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Analytical solution of metapopulation dynamics in a stochastic environment. We study a discrete stochastic linear metapopulation model to understand the effect of risk spreading by dispersion. We calculate analytically the stable distribution of populations in different habitats. The simultaneous distribution of populations in habitats has a complicated self-similar structure, but the population in each habitat follows a log-normal distribution. A class of discrete stochastic matrix models was mostly dealt with numerically. Our analytical predictions are robust in the wide range of parameters. Qualitative predictions of the current results should hold in the case of multiple habitats. We thus conclude that environmental stochasticity always promotes dispersal.

The Cube of Fate is a shared dungeon that you can enter as long as you're level 40+. There are 50 rooms in the puzzle dungeon (and 10 more extra rooms), each with its own unique challenge to complete. Once you complete a room's challenge, you will receive a random die 6 roll that will move you forward through the dungeon. The objective is to reach room 50; however, if you fail a challenge or are killed along the way, you will respawn back in room 1 with the options to either exit the Cube or start the puzzle all over again. While the Cube can be very frustrating at times, it can also be very rewarding. You could spend a few million coins and come out empty handed, or you could spend 100k and come out with a few million coins, 20 Mysterious Chips, and over 350,000 XP! It's completely random, though patience and persistence will certainly help. You can only do this quest once per day (well, on the days you can afford it), since it takes a Duty Badge.Requirements * Level 40+ to enter.* 1 Badge of Wisdom, which you can get once per day from the Adventure Assistants/Khatru Pup in each of the 6 major cities.* 10-30 Mirage Celestones. Each Celestone can be exchanged for 2 Dice Tickets, and each room requires 1 Dice Ticket to begin the challenge. Some rooms have very difficult challenges, and can be bypassed by paying additional Dice Tickets.* 400-600k coins. Several rooms require 100-200k coins to pass, although usually you are given a chance to win additional coins back.* Patience. Some days it's going to be really easy, and some days it will be impossible to finish. Understand that going in, the Cube is completely random! Rewards * XP! * Money. Several rooms have a chance to win either 1 million or 5 million coins. * Mysterious Chips. Up to 20 per run (5 per room, 4 chip rooms), can be traded for Legendary Molds or gold TT items at the Mysterious Vendor in Thousand Streams City.* Pages of Fate. At level 90+, XP reward (1m XP) for completing the Cube of Fate, and do get pages of fate that you can trade for your Demon/Sage skill books. 1. Fate's BeginningTrade your Duty Badge for a Puzzle Cube at the Room 1 Teleport Master. Use the Forge beside him to repair, buy potions, and exchange Mirage Celestones for Dice Tickets. Choose 'Start the Challenge' to exchange your Puzzle Cube and 1 Dice Ticket, for a random die (1-6)Right click on the die in your inventory, and you'll move forward that many rooms, i.e. if you get a 5 die and you're in room 1, you'll end up in room 6. 5. Count the ApplesCount either the red, white, or blue wisps. Choose correctly, get a die. 6. Open SesameKill the boss mob in this room, who does a very weak AOE dmg. When he dies a Teleport Master spawns, talk to him to get a die. The boss will respawn in about 20 seconds, so make it fast and don't AFK on auto attack for too long. 7. Have a ListenTalk to the butterfly NPC to start the challenge. The goal is to find out which monsters have sound effects, the ones with the fire noise will 1 hit kill you, so slowly approach them until you find the monsters with no sound, and run through them to the other side. Try the 2 mobs against the left hand wall. 8. Try Your LuckCosts 100k, open 10 chests and receive either a Sadness Card (sells for 1 coin), or a Ecstasy Card (sells for 1,000,000 coins). 9. 100 Second StandStay alive for 100 seconds. The mob in the center does AOE dmg, while the moving mobs do weak physical. Run to the corner of the room and kill any monsters that follow you, then just tank the AOE dmg. 10. Bombs Away!A time bomb is attached to you and will detonate in 10 minutes. Once you reach the NPC in room 17 (or higher) ask him to diffuse the bomb. If you fail before the bomb goes off, make sure you have the NPC in room 1 diffuse the bomb. 12. Choices of FateReceive a random token, either 1 room back, or 1-6 rooms forward. Right click to use it like a die. 13. Squad of SixEither talk to the NPC while having 5 squad mates in the room, or pay 3 Dice Tickets to bypass the challenge. 14. I Don't Wanna LeaveThe objective of this room is to get a die once someone in the room dies, so, you can either wait for someone to enter and then PK them. The reward NPC will only appear if someone has died in this room. You may also pay 4 do-all card to pass through. Or simply get yourself killed and start over at room 1. To kill yourself, run into the corner with the plant mob, which will debuff your HP by 80%, then agro the mob in the middle. 15. Mystical MessengerFirst of four rooms where you can get Mysterious Chips (up to 5 per room). You have 60 seconds to kill as many mobs as you can. You must turn the quest in at the middle NPC before (!) the timer runs out, or you get 0 chips. You can only do the Kill for Thrills quest once per day, in each of the four rooms, for a maximum of 20 Mysterious Chips per run. 16. Fight the DemonMust kill a very tough mob. Or you can pay 3 dice tickets to bypass the challenge and get a die. 18. Not Enough YetWhen you enter, you're given 9 Robber cards, but you need 10 to complete the quest and move on. You can either wait for someone else to come in and give you one of their cards, buy missing card from people (there are some catshops usually), or trade 1 do-all card for robber card at NPC, or Use your Town Portal skill to go back to room 1. 19. Happy Hold-upTalk to the NPC, get 5 extra Dice Tickets, and a die. 20. Another Choice of FateReceive a random token, either 1-3 rooms back, or 1-6 rooms forward. Right click to use it like a die. 22. Mystical MessengerSecond of four rooms you can get Mysterious Chips in, same challenge, 60 seconds to kill 1-5 mobs. 23. Real or FakeMust kill 1 mob, some are weak, most are hard, kite, use pots, not too difficult. 24. ConsequenceOpen 5 chests, get a die. You can change the amount of chests required to complete the challenge (after you have finished your own quest), to either 5, 20, or 100 chests. 25. Dragon GateRun through the exploding hands, simply wait for them to explode them move through the circle. Reach the opposite corner and talk to the NPC for your die. 26. Death JudgeMust loot 5 chests, guarded by a mob that can 1 hit kill you. The mob moves very, very slow, so you can have him chase you to the corner of the room. Then run back and loot 2 chests, rinse, repeat until you have all 5. Holy path or any other running skills may be helpful here. 27. Try to Listen EXSame as the previous listen room (7). 28. Count the Apples EXSame as the first room (5), count either the red, white, or blue wisps (it's random which one the NPC will ask for). 29. Slaughterhouse EXKill 5 mobs, no time limit. 30. 100 Second Stand EXSame as room 9. Stay alive for 100 seconds, the AOE does more damage in this room. 31. Mystical MessengerThird of the four Mysterious Chip rooms. Kill as many mobs as possible within 1 minute. 43. Take Down the DemonKill a mob, or pay 10 dice tickets to bypass. The higher your lvl is, the easier to kill it. 44. Bomber ManiaA time bomb is attached to you, must reach room 50 in 10 minutes or less. Talk to the NPC in room 50 to diffuse the bomb. 45. Open, open sesame!Same as room 6, kill a boss mob. 46. Still not EnoughSame as room 18, get 9 Bully Cards, need 10. Either hope someone comes in and gives / sells you one of theirs, or trade your 2 do-all cards for missing bully card, or Town Portal back to room 1 and start over. 47. 100 Seconds, Bring It On!Stay alive for 100 seconds, same as the previous two 100 second stand rooms (9 & 30). Mob in the middle does significatly more AOE dmg. 48. Chest Unlocker HardcoreOpen 15 chests, get a die. 49. Prize RaidHave 2 minutes to kill as many mobs as you can, each mob is worth 5000 XP and 1000 Spirit. Don't forget to turn in quest BEFORE the time is over, or else you will be teleported to room 1. 50. Fate's EndThe final room, receive your XP, Spirit, and a chest that contains 1-3 Mirage Celestones, with a 5% chance to get a Badge of Dexterity (need 10 to make a Sign of Dexterity, need 1 of each Sign type to get the level 90+ Sage weapons). Mysterious ChipsIf you visit the Mysterious Merchant in Thousand Streams City, left of the city elder, you can trade chips AND coins for legendary molds and items. You can also trade chips and coins for legendary materials from Twilight Temple, Lunar Glade, and the Warsoul (end game) weapons.

Opinions on games, movies, series and fantasy. Posts Tagged ‘Games’ Amanita Design‘s latest is the adventure game Machinarium. Like their earlier games it is also a point-and-click adventure with a lot of puzzles thrown in. Unlike, say, Samorost 2, the action revolves more strongly around the game’s hero, the little robot Josef, who possesses many qualities useful in an action game protagonist: He has telescopic hands and a body that can be adjusted either higher or lower, a lot of storage space and most importantly has a mission. Josef’s adventure begins at a waste deposit outside an aged robot town. As the game progresses you find out that the city is being terrorised by a group of evil robots, who refer to themselves as the Black Hat Society. They plan to blow up a tower in the city and have taken Josef’s girlfriend as a prisoner and are using her as a cook. The plot may sound like the archetypal videogame tale of princesses with men trying to save them, but there are many details that set Machinarium apart from any other video games you might have played. First off the setting. All the game surroundings are handdrawn and look stunningly beautiful. Screenshots of the game, mind you, do not do the game justice: There are so many small details hidden within every area you stumble into. Instead of just static backgrounds there can be a small waterfall, or some funny character animations. There is a surprising amount of depth to Machinarium’s robotic characters as you find out throughout the story. Instead of dialogue or text, all communication between Josef and the other robots is relayed with a bubble that plays a simple animation, which can tell the player what is needed to solve a puzzle or appease a certain character and sometimes simply tells us more of them. The animations detailing Josef’s relations to the evil robots especially come to mind. Another thing I was taken aback by in the game was how emotional and engaging the story was. There is something very cute and moving about Machinarium’s robots. It is the heartrending imagery of the Black Hat Society committing increasingly evil deeds and also the animation and subtle sound effects that help in this. Also every new area, especially towards the end, began to create a feeling of awe. And awe is the word best describing Machinarium. Everyone who has played a point-and-click adventure at some time or who likes puzzles will love this game. People not fitting the earlier description should try the demo out, but keep in mind that the three first levels don’t give a good picture of the sweetness toward the mid and end-parts of the game. An instant classic. Go play it already. Over on Offworld, a great blog on videogames, there was a feature some time ago on Machinarium. I finished the game last week and have to say that it is definitely something different. Anyone who likes their adventure games should definitely try it out. Also in the post on Offworld there are links to most of the projects of Amanita Design, the Czech indie-studio behind Machinarium. The skecthes are also interesting. I will see if I get around to posting a review here of Machinarium, but while you wait for that go check the feature out. You can also try out the first couple of levels here. The newest episode of Tales of Monkey Island brings a much needed change of scenery to the series. The two first episodes repeated each other with an island setting and both even had a forest maze. Compared to them a giant manatee’s stomach is very original. In the end of Siege of Spinner Cay Guybrush, his sole crewmate and pirate hunter Morgan LeFlay got swallowed by a giant manatee. In its mouth our heroes find treasure hunter Coronado DeCava who is also after the Lesponga Grande, which will fix the voodoo pox infecting Guybrush himself and other pirates . The problem Guybrush faces this time is the ear of the manatee. A part controlling its sense of direction has been stolen and is being held by DeCava’s mutinous crew of four. They have formed a brotherhood which Guybrush must join if he wishes to heal the manatee and get the sponge. The game world being essentially a stomach the area in which to walk and interact is a lot smaller, solving a lot of the problems with the control scheme, a big problem in the earlier episodes. Walking up and down the same staircase because of a wronglytimed press of the mouse, as often happened in Siege of Spinner Cay, is gone. Also gone is the time consuming running around. There is even a possibility to use tubes in the manatee’s stomach (don’t ask me) for speedier travel. With the control problems all but gone the player is free to concentrate on what makes Monkey Island so good: The dialogue and humor. When it comes to these two Telltale ups the ante considerably. Lair of the Leviathan presents four new characters and they’re all very funny, my personal favorite being Moose, sort of a surfer-type hippie pirate. A friend from older Monkey Islands also makes an appearance. Different from the earlier episodes is that the characters have a lot more facial animation and many of the jokes involve more facial expressions, instead of only leaning on dialogue. Piratehunter Morgan LeFlay for example grows very disappointed in Guybrush as the episode progresses and makes faces to Guyrush each time he walks past her. The episode even includes a competition of making scary pirate faces, or just downright dumb expressions. AHOY, SPOILERS AHEAD Many of the puzzles deserve an honorary mention. Guybrush playing the part of a wingman to the giant manatee with the help of a manatee speaking horn was my personal favorite. As it happens the horn is a tourist edition and the player needs to figure out which available answer fits best with a female manatee’s comments. With choices varying from “I have nothing to declare” to “I want to go to the theater” this is not necessarily an easy task. In a way the puzzle is a reinvention of insult swordfighting, without the grind. While many of the puzzles were amusing, Launch of the Screaming Narwhal’s puzzle in LeSinge’s lab remains my favorite in the series. END OF SPOILERS Lair of the Leviathan, with very little to complain about, is the funniest episode so far. At some points I actually paused and thought something on the lines of: “Damn, that was amusing”. Perhaps because I was not stuck in the puzzles for as long as in the earlier episodes I also thought the pacing of the game was a lot better. If you have doubts about Tales of Monkey Island on the whole at least play Lair of the Leviathan. Amanita design’s Robot adventure Machinarium has a release date: the 16:th of October. If you don’t know Amanita Design you’re missing out on a world of amusement, cuteness and interesting soundscapes. Also new to the Interwebs is a trailer with a bubble in it. Check it out below. You can get a grasp of what their style looks like from a learning game called Questionaut and pick up something while you’re at it as well. That’s right, one of the greatest adventure games of all time came to Good Old Games. If you haven’t played it yet, now is the time to remedy that. April Ryan is one of my all time favorite characters in gaming. With an epic fantasy plot, characters you’ll love, amazing voice acting and a lot of laugh out-loud moments The Longest Journey will make you sad at times. The game managed to move me like no game before it. So go buy and play already. Below a taste of the prologue. Give you a good sense of April Ryan, and pangs of nostalgia if you’ve already played the game. I recently got a beta invitation to League of Legends via Rock, Paper, Shotgun. The game attempts to sell itself as a mix between Defense of the Ancients (DOTA) and an MMO. I’ll give some general info about the game first and then tell about the champion, your avatar in the game, that I’ve been playing with so far. Be warned that I haven’t played any DOTA games before LoL. I’ll add official LoL tips and tricks videos here, which explain the game better than I ever could. League of Legends is divided into a menu part and the actual game. On the menu you can see the available spells, stat upgrades called runes, which basicly give small boosts to your chosen stat, be it damage, mana or health. Also you get a very WoW-like skill tree, giving you choice between a defense, attack and magic build. You get levels from games you win, which give you more skill points, spells and of course power. That’s the MMO part more or less. When you actually get playing, after all the tweaking, the DOTA element comes in, with battles between five or more players on each side. There’s a wide selection of avatars, or champions as the game calls them, to choose from, each with its unique set of skills. The champions are divided as classes might in an MMO. You can choose from ranged and melee dps, spellcasters, tanks and more support focused champions. There’s quite a selection so finding one to your own liking should be easy, if time-consuming. The gameplay is a mix between fighting against opposing minions, which spawn in groups between steady intervals making their way for the enemy base and the human controlled champions. There’s also turrets which defend both team’s bases. The key to winning the game lies with how well you fight the enemy champions. Teamwork is the key word here. A player going solo hardly ever beats two champions. Also important is levelling up quickly and making money in the process, allowing you to buy items, which are perhaps the most important part of the game actually, granting very substantial buffs and bonuses. I tried a couple of the champions briefly but didn’t find a favorite. Then I decided to stick with one champion for a longer time. My first pick was Ashe, an archer with freezing skills. Her skills are a frost arrow that slows enemies down, a cone of arrows that also slows, a passive skill giving more gold when a minion is killed and finally a super arrow that can be aimed at any part of the map, gaining more damage the further it travels and freezing an enemy champion once it hits. Of course the closer you are the easier it is to actually hit a champion, but then you pay in damage. With all skills available my basic tactic is freezing with the super arrow, keeping the enemy in range by slowing with the other skills and letting attack speed do the rest. While Ashe’s arrows do a great deal of damage with the right items, she’s got very little health. Any dps getting too close makes short work of her. Keeping in the right range is the key when playing as Ashe. I like her in that she is rather straightforward in the way you play. With items I’ve been stacking attack and movement speed making me able to run in, do a lot of damage and run away again. Guerrilla tactics you could say. Playing like this I actually won a couple of matches. Most of the game naturally depends on your teammates. At the moment players disconnecting is a big problem. 4 vs 5 isn’t a fair game so even one player not giving everything he has, or worse, leaving entirely, results in a quick loose. Even a little teamplay gives you the upper hand. Another problem with the game is that I’m forced to play with random people. Of course you never know who you’ll be facing. Also there’s no telling what level people you play against. A match between someone 26 and 6 isn’t all that fair. If I ever get enough buddies in League of Legends to play with a team I know, the game will be a lot more fun. With random people LoL doesn’t really get to it’s full potential. Even though the game is in it’s beta I’ve had some fun playing it and once I find a character that sticks… well who knows how big a time sink LoL might become. After Ashe I think I’ll try a melee dps, expect a post on how that goes later, concentrating more on the champion now you know how the basics about the game. If you want to try it out, apply here and don’t hesitate to add me as a buddy, look for ironanno. Been some time since a trailer rocked this much. The music, the footage, the crazy comic style, all come together wonderfully, creating an overall Wild West mood. Guns, cars, a desert, bad guys to kill and good ones with an attitude? I can’t wait till October and getting to play Borderlands. Thanks for the heads up to Rock, Paper, Shotgun and may I link to you again. Get watching already.

sakura i though she was loud and annoying and pretty much ignored her until she fought to save her teamates and cut her hair in the chunin exams after that i started respecting her and am now a sakura fan

Welcome to Bimmerfest -- The #1 Online Community for BMW related information! Please enjoy the discussion forums below and share your experiences with the 200,000 current, new and past BMW owners. The forums are broken out by car model and into other special interest sections such as BMW European Delivery and a special forum to voice your questions to the many BMW dealers on the site to assist our members! I am not sure my answer will be "by the book", but when I shift into DS, but leave it in automatic mode, the transmission does indeed downshift to 5th. However, that may be more a function of what speed you happen to be driving at when you select the DS/auto mode. Of course, pulling the gear-selector forward or back while in DS/auto will take you into a manual shift mode, where you actually have to shift by hand. My problem with this car is that it's so quiet at speed, it's difficult to tell when to shift! But, still good to have on a steep downhill grade, etc. Hope this helps. Thanks for your reply. You're right that it's really quiet...but I watched the RPM gauge and no change at all. I remember my e92 shifted into 5th gear. Or maybe im just going senile ;( Anyone else? Runnerman is correct: it's entirely speed and load dependent. For instance, if I'm going into my neighborhood at 35-40 or so (up a hill), rpm is sitting at 1200 rpm or so in 4th gear. Shifting to DS causes a downshift into 3rd to get revs up to about 1800-2000 rpm, which sits more in the middle of the torque band. It also is high enough to spool up the larger turbo (the small turbo is effective from idle to around 1500.) I do mostly highway driving. 100% of the time, if I move into DS mode at legal highway speeds, it will downshift into 5th. I do not know what would happen if moving into DS mode above 65mph as I don't switch into DS mode at that speed. I just tried it at lower speeds and it seem to work but on the highway when I wanna pass...it doesn't. Why is that? So do u think it's normal or should I have it looked at? Can't you just kick down on the gas pedal to pass? Doing that alone should downshift. DS is a sport mode that extends the gears for optimum performance. While it does downshift the transmission most of the time, It is not for meant for downshifting on the spot. Just pressing down on the gas pedal all the way is quicker, requires less thinking and yields the same results. It won't downshift to 5th when in DS mode on the highway because we got mad torque yo. I just press my paddle shifters down one gear to pass in 5th. hah ... I tried this morning and mine does when doing around 60mph but when doing 80 it does not. Not sure why it matters if it does or does not though. Quote: Originally Posted by Itinj6 Can't you just kick down on the gas pedal to pass? Doing that alone should downshift. DS is a sport mode that extends the gears for optimum performance. While it does downshift the transmission most of the time, It is not for meant for downshifting on the spot. Just pressing down on the gas pedal all the way is quicker, requires less thinking and yields the same results. Heck you do not have to put it all the way down to get a downshift out of these cars. DS does seem to either change the power or the responsiveness of the throttle by wire. I notice when at a dead stop and leaving a light with just moderate to normal throttle levels the car is more responsive in DS than D. I am assuming it is just more "throttle lag" with the throttle by wire setup when in D for emissions/economy reasons. At 80 you're at 2,000 rpm and the big turbo is spooled up. At 60, you're in the borderline region between the small and large turbos. Yes, I know but I still do not see what the concern here is on if it does or does not downshift when going in DS. The original question does not even state at what speed this is a concern but I question why is it ever a concern. If I am doing 60 and I need it to downshift I press down on the throttle some and it downshifts. It is not like I am driving an E350 Bluetec where I have to smash the throttle to the floorboard to get it to downshift at 60. The transmissions in these 335d cars, to me at least, are extremely responsive to throttle/driver needs. And I am dead serious about the E350 Bluetec comment, it's inability to downshift without major throttle was the prime reason I passed on that car. I'm okay with whatever it does. I was just trying to figure out if something was defective on my new vehicle. I'm pretty sure that my e92 did down shift (at all speeds) and it was noticable when I put DS mode. Yes, I know but I still do not see what the concern here is on if it does or does not downshift when going in DS. The only concern is that DS attempts to keep the engine speed in a realm where more torque (power) is available. If a downshift is required to get things moving, a downshift occurs. If you're already in the fat part of the torque curve, no downshift is needed (unless throttle position demands it.) The only concern is that DS attempts to keep the engine speed in a realm where more torque (power) is available. If a downshift is required to get things moving, a downshift occurs. If you're already in the fat part of the torque curve, no downshift is needed (unless throttle position demands it.) And that is why I had my second sentence that you left out: Quote: The original question does not even state at what speed this is a concern but I question why is it ever a concern. I can understand if at some low rpm cruising speed then a concern when going into what I'd call "sport mode" does not change the gear selection by default. But if I were at a speed where I already in a "sporty" position for driving then I'd lack any concern at all. The way the original question was written it is rather hard to tell what conditions the car even is in to speculate if anything should be happening. All we know is that it must be cruising at a speed that would normally be in 6th gear.

Q: Correctly writed in Db, but "Illegal operation on empty result set." error by Sql I'm making an INSERT on a sql database. And a strange thing happens: when I run the downer code, the DB is correctly writed but the compiler give me an error of java.sql.SQLException: Illegal operation on empty result set. I've yet searched about it and I found that it may due to a bug of JDBC driver (but I don't think so). So I decided to post here. Firstly I give you database tables: table subject +------------------+----------------+------------+ | subjectCode | SubjectName | teacherCode| +------------------+----------------+------------+ | 1 | Maths | 10 | | 2 | English | 20 | | 3 | Greek | 30 | +------------------+----------------+------------+ table class +------------------+----------------+ | ClassCode | ClassName | +------------------+----------------+ | 1 | Class1 | | 2 | Class2 | | 3 | Class3 | +------------------+----------------+ table lesson (row and col are the rows (hours) and columns (days) of a timetable, that univocally determine the lesson in timetable; for example: hour 1 is the first hour of the day) +------------------+----------------+------------+-----------+-------+-------+ | LessonCode | SubjectCode | teacherCode| ClassCode | Day | Hour | +------------------+----------------+------------+-----------+-------+-------+ | 1 | James | 10 | 1 | 1 | 1 | | 2 | John | 20 | 2 | 1 | 2 | | 3 | Frank | 30 | 3 | 1 | 3 | +------------------+----------------+------------+-----------+-------+-------+ Code: private void writeLesson(String subjectName, String className, int column, int row) { try{ int subjCode; String query="SELECT subjectCode from subject WHERE subjectName='"+subjectName+"';"; rs = st.executeQuery(query); rs.next(); subjCode = rs.getInt("subjectCode"); int teacherCode; String query1="SELECT teacherCode from subject WHERE subjectName='"+subjectName+"';"; rs = st.executeQuery(query1); rs.next(); teacherCode = rs.getInt("teacherCode"); int classCode; String query2="SELECT classCode from class WHERE className='"+className+"';"; rs = st.executeQuery(query2); rs.next(); ClassCode = rs.getInt("classCode"); String query3 ="INSERT INTO lesson (subjCode, classCode, teacherCode, day, hour) " + "VALUES ('" + subjCode + "'," + "'" + classCode + "'," + "'" + teacherCode + "'," + "'" + column + "'," + "'" + row + "');"; PreparedStatement statement=con.prepareStatement(query3); statement.executeUpdate(); statement.close(); } catch (Exception ex){ System.out.println("Error db: "+ex); IMPORTANT : the method writeLesson is in a cycle. I've tested this code not in a cycle and it works. Why In your opinion? SOLUTION : the problem was that in the cycle in which is the method writeLesson I passed to it "blank" strings, causing the error (that's why writing on DB worked, but there were errors). A: Did you checked the result sets from your select statements? Isn't one of them empty? rs.getInt() will throw this exception, if rs is empty (rs.next() returns false in this case)

Direct Evidence for a [4+2] Cycloaddition Mechanism of Alkynes to Tantallacyclopentadiene on Dinuclear Tantalum Complexes as a Model of Alkyne Cyclotrimerization. A dinuclear tantalum complex, [Ta2 Cl6 (μ-C4 Et4)] (2), bearing a tantallacyclopentadiene moiety, was synthesized by treating [(η(2) -EtC≡CEt)TaCl3 (DME)] (1) with AlCl3 . Complex 2 and its Lewis base adducts, [Ta2 Cl6 (μ-C4 Et4 )L] (L=THF (3 a), pyridine (3 b), THT (3 c)), served as more active catalysts for cyclotrimerization of internal alkynes than 1. During the reaction of 3 a with 3-hexyne, we isolated [Ta2 Cl4 (μ-η(4):η(4)-C6 Et6)(μ-η(2):η(2)-EtC≡CEt)] (4), sandwiched by a two-electron reduced μ-η(4):η(4) -hexaethylbenzene and a μ-η(2):η(2)-3-hexyne ligand, as a product of an intermolecular cyclization between the metallacyclopentadiene moiety and 3-hexyne. The formation of arene complexes [Ta2 Cl4 (μ-η(4):η(4)-C6 Et4 Me2)(μ-η(2):η(2)-Me3 SiC≡CSiMe3)] (7 b) and [Ta2 Cl4 (μ-η(4):η(4)-C6 Et4 RH)(μ-η(2):η(2)-Me3 SiC≡CSiMe3)] (R=nBu (8 a), p-tolyl (8 b)) by treating [Ta2 Cl4 (μ-C4 Et4)(μ-η(2):η(2) -Me3 SiC≡CSiMe3)] (6) with 2-butyne, 1-hexyne, and p-tolylacetylene without any isomers, at room temperature or low temperature were key for clarifying the [4+2] cycloaddition mechanism because of the restricted rotation behavior of the two-electron reduced arene ligands without dissociation from the dinuclear tantalum center.

Search Don’t ask me why, but I have always had a thing for fast estate cars. Couldn’t explain it to you. Perhaps it’s a latent love for Rickard Rydell honing about in the British Touring Car Championship in a Volvo 850 estate. Or hearing the V6 burble of the Audi RS4 the guy at the end of our road used to own. I actually think that, to explore the real reason that I love fast estate cars, you have to look at my penchant, as a boy, for Swiss Army knives. Here was something which fitted in your hand and was convenient to carry around, but could replicate the experience of owning a saw, or a pen, or a knife, or a magnifying glass. By replicate, I really mean ‘do an impression of’. Because if someone presented me with a piece of wood and said ‘OK pal, you have to cut this and you could either use a real saw or spend the next 7 months of your life eroding the wood away with the saw in this Swiss Army knife,’ I know which one I’d pick. It’s the saw, by the way. My first crush, Rickard Rydell Now those of you whose brains aren’t entirely starved of oxygen should be able to make this analogical leap with me. If someone gave you a racetrack and said ‘OK pal, you can either go around it in a Lotus Exige or a BMW M5 Touring’, you’d probably take the Exige, because its entire raison d’etre, if I might be so pretentious, is to go around a racetrack, just as the saw’s job is to saw through wood. BUT! If I was dropped in a forest somewhere and was only given a saw, I’d think longingly about that Swiss Army knife with all of its flawed features all snugly collapsed into its red body. And similarly, were I to be told that I was only allowed to own one car ever again and found myself owning a Lotus Exige and trying to fit my hypothetical future wife and two small children into it, I think that I’d rather begin to miss that M5 Touring. A Swiss Army knife, earlier today And this is what’s so great about fast estates. They’re the only car you’re ever going to need in the real world. You can go down to Homebase and buy some curtain rods and on the way home you can outdrag a Ferrari and totally remasculate yourself! No, they’re not as sharp as a sports car around a track, and they’re almost certainly not as economical as a Nissan Micra on the road, but if you’ve only got space for one car in your garage and you’re a petrolhead, a fast estate should win out every time. So anyway, that long preamble is by way of discussing the daddy of powerful estates and the subject for today’s little monograph: the Mercedes-AMG ‘Hammer Wagon’. Now for starters, if you’re going to drive around in something, it may as well be called a Hammer Wagon, right? Right. And the Hammer aspect does accord with the engineering principles behind earlier AMGs, namely stick a very large, very powerful engine in the car and then….sell it. In the case of the original Hammer Wagon, AMG started with a W124 E-Class chassis, into which they dropped a 5.6l 360bhp V8. Yes, it may have had the cornering ability of a train, but it packed a hell of a punch when it was released in 1986. It would pack a hell of a punch now….although you rather feel that a modern engine tuner could extract more power out of a 5.6l engine. And because it was a Mercedes estate, you could have two people in the front seats, three in the middle and ANOTHER two on the weird, flip up, probably now illegal bench in the boot. And then you and these six other people could travel at 186mph down the autobahn. Wunderbar! Homoerotic Hammer saloon But why should I mention the Hammer Wagon at all? Well, for one, because I like educating you all out there, dear Readers, about these fabulous cars. But also, I’ve recently written a couple of articles for a BMW modifying magazine and, reading the publication that my articles appeared in, have had the hitherto largely unknown world of car modification illuminated to me. I think I had rather written off car modification as the preserve of sex-starved adolescents from some of the England’s lesser-known counties. But it can be done with taste and with discretion. And this has got Carficionado’s little grey cells ticking. Could I buy a W124 estate and turn it into my own Hammer Wagon? There must be thousands of boggo W124s out there, and no shortage of written-off cars just waiting to have the V8’s scraped out of them. Mercedes themselves are famed for their collection of spare parts for their old models, so sourcing them wouldn’t be a problem. Then just buy some tasteful AMG bodykit and wheels (tasteful, mind), upgrade the suspension, and there you have it: a Hammer Wagon! And then you could drive it around and feel like an 80s banker, or murderer, or something. I can only see two flaws in my plan. One of them is money. The other is that there are bonobos with a greater flair for engineering and mechanics than me. Maybe it will just be a little pipe dream then <sigh>. Either way, ladies and gentlemen, doff your caps if you will to the Mercedes-AMG Hammer Wagon. Italian cars can come in a multitude of colours and look sexy. Let’s take Ferraris as an example. Now, if I ever perchance to buy a 355, I would buy one in red, naturally, and the same will probably be true when I get my Enzo, and almost certainly true when I get my F40. But what if I were to buy a 456? I’d get that in dark blue. A 550? Silver. My 250 Lusso? Did they do it in British Racing Green? Travel north to Germany, however, and things are a bit different. I know I seem to give Germans a bit of a hard time about taste, but they do get it badly wrong sometimes. And, seeking to emulate their Italian automotive counterparts, they sometimes produce their cars in postbox red, or bucca delle lettrerosso, if you’re in Rome. And nearly every one looks, in the immortal words of Samuel Pepys, “bleedin’ ‘orrible”. Would you drive a red E-Class estate? A red R8? A red 5 Series? I thought not. But sometimes, there is a synergy of colour and teutonic car that transcends nationality and just looks excellent. And so below is my run down of the Top 5 German Cars in Red, in no particular order: 1. Porsche 959 The Porsche 959. In a quarry of some kind. What a great looking car this is. Like a 911 turned up to….well, 11. Sparred in the 80s with the aforementioned F40 for the title of World’s Fastest Production Car and yet, unlike the F40, it was also used for rallying and is thus imbued it with some fairly major kudos. And it looked good in red, hence its presence here. 2. Audi Quattro "Fire up the....." blah blah blah Originating in the heady days of Group B rallying, when no limits were put on a car’s maximum output, the Audi Quattro has emerged as something of a legend. It was the first car to introduce four-wheel drive into rallying, which would have been a comfort to the driver, given that some Quattrtos had close to 600 horsepower. Homologated for the road, the car offered a tantalising mixture of performance and discretion that made it the ultimate Q car of the 1980s. Unless you got it in red. Which it looks good in. 3. BMW M1 The BMW M1. In a sexy puddle Originally built in 1978 as a collaboration between BMW and Lamborghini, the M1 was essentially a homologation special intended for competition (kind of like the Porsche 959. And the Audi Quattro). It was mid-engined, had a cool slatted roof, was designed by Giugiaro and….looked good in red. 4. Mercedes 190SL Mercedes 190SL. Looks good in red..... We’ve been hanging out in late 70s/early 80s Germany so far for this list, so let’s take it back a bit. The 190SL, essentially a cheaper, slower, less roofed and thus less gullwing-doored, version of the 300SL, was an archetype of graceful 1950s style. It only had a 1.9 litre engine, as its name suggests, which meant that your only option was to cruise slowly around the Riviera, with the top down, taking in the sights. Sounds terrible. Quite nice in red, too. 5. BMW Isetta The BMW Isetta. Plus man. OK, not a German car in the strictest sense, as the car was licensed to BMW by an Italian firm. But BMW put a lot of their own bits on and in it, it had a BMW badge, and that’s good enough for us. Released in the same year as the 190SL, but entirely different, the Isetta is a little cutie pie, albeit a cutie pie that uses the flexibility of your knee joints as its crumple zone. It seems ironic that, despite all our advancements in the automotive industry, automakers are now (non leg-based safety devices aside) trying to emulate the simplicity of the small cars of the 1950s like the Isetta, as well as the Mini and the Fiat 500. All of which look good in red. But only one of which can be counted as German. The Isetta. In red. Well there you have it. And I appreciate that whether or not a German car looks good in red is subjective (well, it’s objective really, but for politeness’ sake let’s say it’s subjective). But then again, this is my blog, so lump it. Or, better still, tell me your Top 5. Comments welcome! I met with Uli Kranz, the head of BMW’s new sub-brand BMW i, at the Frankfurt motor show last month to discuss the unveiling on their first two cars, the i3 and i8. The i3 is an all-electric city car, whilst the i8, already mentioned in these hallowed pages, is a plug-in hybrid sports car which will be able to outperform an M3, whilst returning a claimed 104mpg. Both introduce some seriously futuristic design language into the BMW brand, or will do when they go on sale in 2013. Are hybrids and electric cars becoming sexy? Dear Lord…..Anyway, take it away, Herr Kranz! Carficionado: As BMWs, the i cars are surely going to have to be pure drivers’ cars. Presumably you haven’t been been sending them around the Nordschleife, but will BMW i cars still be “pure driving machines”? Uli Kranz: I can simply answer ‘yes’. These cars will keep the BMW sheer driving pleasure alive because this is key and this is why we introduced the sub-brand as BMW i. We did our homework on that, because if you see the BMW i3, this is a car with a powerful electric engine installed in the rear and we have rear-wheel drive which is perfectly fine for a BMW. We have an architecture of the vehicle which puts the centre of gravity very low, because in the middle, there’s the battery which is really low above the floor. And we’ve put our focus on lightweight materials. We reduced dramatically the weight of the vehicle by using carbon fibre for the passenger cell and for the drive module we are using aluminium spaceframe. So we have a very light car and with the material choice, we could really offset the additional weight of the battery. So I can assure you that this car will have the BMW DNA and it will be a perfectly dynamic, fun-to-drive vehicle. Carficionado: Surely one of the big problems you have to overcome with starting a sub-brand like this is that you have to entice people in who won’t be enticed solely because you are using electric power – you’ve got to sell it to them in a unique way. Has that been the main problem to overcome? Uli Kranz: We had to make sure that [the i3] is a premium vehicle, that it is a BMW and for that reason we also decided very early to develop the complete powertrain, including the battery, gearbox, power electronics and the electric motor in-house and we do all the application in-house with our experts at BMW. And we know how to build cars that are really fun to drive. And the same applies to the i8. The i8 is a plug-in hybrid super sports car that will have performance comparable to an M3 but with a fuel consumption below 3 litres per 100km and we think this is a very good answer for our customers [so that] they see that the future BMW programmes will still be fun and that we will keep the sheer driving pleasure alive with both cars as well. Carficionado: Why has it taken BMW, who have been seen as a leader in every other aspect in the automotive industry, so long to bring in hybrid systems or electric systems when the Toyota Prius is already 15 years old? Uli Kranz: We always actually worked with different powertrains, and you will have seen in 1972 with the Olympic Games in Munich we introduced an electric 1602. So we have always worked on very efficient combustion engines and also electric engines, and we introduced also some concept cars like the E1 in the 90s. The reason why we decided now to go into serious production is, of course, the battery technology, because all the batteries we had in the past, they were not as good as we [needed] them to be and the thing with lithium ion technology is that we could overcome all the problems with memory effects and difficulties in charging. With lithium ion batteries we can offer our customers a reliable, good-working car with good performance. This is the reason why we started now with electric vehicles like the i3 and i8. But in parallel we always work on even more efficient diesels and combustion engines. And we’ve introduced the complete EfficientDynamics package with start-stop engines, brake-energy recuperation and on top of that, we focus on low-rolling resistance tyres and also on very efficient aerodynamics. And this all, in combination with the new lithium ion batteries, gives us a very good opportunity to introduce the next step towards the future. Carficionado: So it was a question of you not wanting to inconvenience your customers by using sub-standard technology? Carficionado: The i Division is obviously at the other end of the spectrum to the M Division. But do you feel that there’s any room for this modern technology creeping into motorsport, or are they mutually exclusive? Uli Kranz: What we are doing with the BMW i sub-brand and with the M, which is a sub-brand also, is perfectly balancing the core of the BMW brand. The BMW brand benefits from the M division because they highlight even more performance and even faster, quicker and more dynamic [cars]. On the other side, the BMW i is supporting BMW in new technologies and new design language and both sub-brands benefit from the core brand of BMW. So in the future we will benefit from both, so that means that some of the ideas that we develop you will see in the M division or the BMW core brand. Just think about the lightweight materials; this is something that the core brand will see in the future and will use in the M division as well. Carficionado: How much money has been put into the i Division? Uli Kranz: I cannot give you a figure on how much money we have put in, but I can assure you that we have the task to make money. Carficionado: But you’d like to see the technology from the i brand trickle down into other BMWs? Uli Kranz: Of course. One of the tasks we got within Project i is to pave the way towards new technology but not only focussed on the vehicles, also on the production and the production process, introducing new materials and new processes, and this is what we are doing with the electric powertrain, as well as the carbon fibre lightweight materials. Carficionado: Has there been any co-operation with the German government in terms of incentives for the company? Uli Kranz: No. Carficionado: Would you like to have had incentives? Uli Kranz: Actually we are not asking for incentives because we do our developments in-house. On the other hand, what we expect from the government is that we have clear rules and standards. This is key because then we have reliable targets to work towards. Standardisation is key for electric vehicles because at the moment there’s still different standards in Asia, the US and in Europe, but we would be happy if we had three clearly divided standards for where our customers could plug-in and charge the vehicles. Infrastructure is key. Carficionado: Do you think the same customer who buys an M3 will buy an i8? Uli Kranz: We will still have customers, I’m sure, who will opt for an M3, because an M3 is a very emotive car. But with the i8 we have the opportunity to bring new customers into the BMW brand and this was also the reason why we established BMW i, because one of the targets we got from the board at the very beginning is to bring new customers into the BMW brand. And this is what we think we can fulfil with the i8, because the i8 is a real sports car but at the same time has a very low fuel consumption and the complete vehicle architecture is very sustainable and the compete production process is very sustainable as well. So therefore I guess we are talking to a different audience with the i8, and this is the reason why we decided to establish a sub-brand. And the same goes for the i3, because we are absolutely convinced that it we will bring new customers to the BMW brand. Carficionado: Do you envisage a future where there will be an i1, i2, i3, i4 and so on? Uli Kranz: We are focussed now on the i3 and the i8, but there is enough room between these two figures, 3 and 8, for additional derivatives, even above and below. This is all I can say at the moment. BMW unveiled their new 3 Series at a special event in Munich last Friday. And it’s a bit of a cracker. Obviously the unveiled car was red because, as previously mentioned in this blog, our Teutonic friends sometimes drop the ball on matters of taste (incidentally, I can count on the fingers of one hand German cars that look good in postbox red – but perhaps that’s a blog for another day). But the car itself looks great. For me, the most interesting aspect of the new 3 Series is that it points to the future direction of BMW’s design language, joining the dots between the current range and the rather fabulous i8, a petrol-hybrid produced by BMW’s cannily named sub-brand Project i, which is scheduled for release in 2013. The forthcoming i8. Note the similarities And, having personally been disappointed by the styling of the new 5 Series (which hasn’t grown on me at all) it’s nice to see BMW being a little bit edgier with its styling. Well, at least with the front fascia. See the way the lights blend into the front grille? Very i8. Admittedly the rest of the car looks like a smaller 5 Series, but at least it has a handsome face. 5 Series. Yawn. The car will be powered by the usual array of BMW engines, with the 320d looking likely to be the volume seller in Europe, as it was with the previous-gen model. Will there be an M3, I hear you cry? Yes, probably. But ecological conditions being what they are, BMW won’t be shouting about that at this stage, preferring instead to talk about the EfficientDynamics options on offer for the car, such as brake energy recuperation and oil and water pumps that only operate when required. What will it be like to drive? Well, doubtless it will be like most BMWs, that is, very very good. You’ll just have to wait and see if they let old Carficionado have a go in it (advice: don’t hold your breath). So what do you, dear Readers, think of the new 3 Series? Carficionado appreciates any comments! Oh, and as for the aforementioned i8 (and its baby sibling the i3), I’ll be bringing you an exclusive interview that I conducted with Uli Kranz, direction of Project i, in the coming days…. Audi have unveiled their new RS3. And it looks pretty good, in the rather staid way that all Audis these days look pretty good. But its figures are faintly staggering. I was in the pub at the weekend watching Tottenham vs Arsenal and there was a man at the bar whose scarf I would have quite willingly used to throttle him. And this man kept going on and bloody on about how he wasn’t a stat man but if you look at Peter Crouch’s scoring record for England blah blah blah. Now, I’m not a stat man, but if you look at the Audi RS3’s….well, stats, they beggar belief. To-whit….. Price – £40,000 0-60 – 4.6 seconds BHP – 335 OK, this is very nice. But not trouser immolating. This makes it faster than a BMW M3, itself a very fast car. It puts the little Audi in amongst supercar territory. But I can’t help thinking that I’d rather have something with a bit more joie de vivre. I mean, we’re talking £40,000 for a start, not to mention high insurance. Have a look on pistonheads.com and see what you can get for £40,000 – a most enjoyable, saliva-inducing game by the way. A £39,000 blue Ferrari 355 with 40,000 miles on the clock, which leaves you a grand to spend on a Ferrari bicycle, or skis or whatever crap they’re pedaling (arf) to their customers these days. A 45,000 mile Aston Martin DB9. Why not buy a brace (brace mind) of Volkswagen Phaetons? What about a 1959 Rolls Royce Silver Cloud? Now of course, all this is a bit silly. For a start, those cars aren’t new, and thus miss out on warranties and all the appeals that having a new car brings. And frankly, people in the market for an Audi RS3 probably aren’t in the market for Rolls Royce Silver Cloud. But even its competitors seem more interesting than it. I walked passed a Focus RS on the South Bank the other day, and I felt a tremor of vaguely homo-erotic excitement at its muscular haunches and implied potency. And even I, basher of Bimmers, fancy the similarly priced, similarly powered 1 Series M Coupe more than this. But, at the end of the day, there’s little doubt that the Audi will be very good. I just hope that a bit of Lamborghini spirit has drifted through the Volkswagen-Audi group and seeped into it. So, I expected to see some interesting Soviet rubbish/bits of curios lying around Mongolia. But to see a new car that I’d not yet glimpsed in Europe yet, and to be honest hadn’t been aware of at all, on the streets of Ulaanbaatar was slightly disconcerting. What was even more disconcerting was that it was this lumpen pile of crap. Regular readers of this blog (hi Mum) will already know that I feel that the Germans’ attempts to create EVERY possible variation of the car is cynical and faintly intolerable. Sadly, it appears the good folks at Mercedes didn’t read this blog, or at least for some reason, they do not fear the derision of Carficionado. Well derided they must be. I’m not going to talk about how the thing drives because…..well, because I haven’t started reviewing cars in that way yet. So let’s talk looks, which are subjective, but hey, get your own blog if you don’t like my subjectivity. Now imagine, if you will, a steamy late night romp on a second-hand car forecourt between a Mitsubishi Pajero Junior and a Subaru Forrester. Now imagine the lovechild of this illicit act. Now put a Mercedes grille on it. Are you with me, are ya, are ya? Father Mother How could this have happened? I know, I know, BMW got to make the X1 and Audi got to make the Q5 so where’s Mercedes’ baby 4×4 that’s slightly smaller than the M Class and much smaller than the woefully misjudged GL. But I’m sorry, why are we all slowly creeping back into baby 4x4s again anyway, like a class of school children who are told in no uncertain terms to shut the hell up and in spite of the explicit telling off slowly start to chatter amongst themselves again. I mean what, is it 1996? Are we all going to end up back in Suzuki Vitara 3 doors and baby blue Toyota Rav4s listening to the Spice Girls? Hey Mercedes! Let BMW and Audi have that market. Bugger ’em! In fact, why don’t you not make stupid Mitsubishi/Subaru look-a-likes and then get someone in your PR department to say “well, we could have built a baby 4×4, of course we could, we’re Mercedes, but in an age where making 4x4s (or at least tall cars, maybe the damned thing is 2-wheel drive) for mums to then drive around Esher (or German equivalent) is a bit, well, massively backwards, we’re actually going to focus on making cars that deal with the problems that the world is facing, unlike BMW and Audi who have shown themselves to be the Flintstones to our Jetsons. We’re light-years ahead of those stupid suckers.” Spin the hell out of it. Then, when you’re done spinning, go and make that delicious looking Shooting Brake and that electric SLS. Don’t bend to the whims of these Esherians! Esherites? Whatever. Where’s your dignity Mercedes? Don’t let them trample all over you like that. Would Fangio have been proud of that? Moss? Hakkinen? Schumacher? Heikki Kovalainen? OK, not him. Mercedes are trying to make themselves der Über-Manufakturer, and thus be as successful as they can be. And as Jack Kerouac wrote: “You kill yourself to get to the grave before you even die, and the name of that grave is success, the name of that grave is hullaballoo boom boom horseshit.” I forgot to mention that I was going to Mongolia. My bad. Now in terms of Carficionadoing, that’s much more interesting than going to Greece due to the number of Soviet cars and bikes kicking about the place. Without really having a camera to my name and with disposable cameras seeming to be non-existent in Ulaanbaatar, photographing the things might be tough but Carficionado will, as ever, try his hardest. Speaking of Soviet motorbikes, I’ve been riding some. Last Saturday, Tony from Thirsty Horse Motorcycles here in Ulaanbaatar (let’s call it UB shall we?) invited us down to have a play on some of his old Ural bikes in the Mongolian wilderness. The scenery was truly epic and even though the bastard things were a mite unreliable, it was still an excellent trip. The difference between a Ural and my Bonneville is really the analogue quality of the Ural. A gear change is not a mere flick of the toe, but a hefty kick of the heel onto the heel-toe gear lever to pull it up into second. It all felt very manly as we stood around priming engines and kick starting the bikes (another thing my Triumph doesn’t have). And these bikes had sidecars too, and you don’t need to wear helmets, so it was very pleasant to be able to sit and talk to someone whilst having a good old hoon around. There’s talk of a 4 day motorcycle trek in a week or so, too. Watch this space…. Anyway, for the uninitiated (as I was), here is what a Ural looks like, I believe that the Soviets nicked the design from BMW probably in the 40s, as evidenced by the lateral mounted engine. Just a hunch though….(further research tells me that the Ural is based on the BMW R71)

917 S.W.2d 193 (1996) In the Interest of J.M.L., C.E.B., K.L.B., and M.R.B., Minors. JUVENILE OFFICER, Respondent, v. K.A.B., Natural Mother, Appellant. No. WD 50879. Missouri Court of Appeals, Western District. March 5, 1996. *194 Beverly Sue Riordan, Columbia, Guardian ad Litem. John Damron Smith, Columbia, for appellant. Elizabeth K. Magee, Columbia, for respondent. Before ULRICH, P.J., and BRECKENRIDGE and SMITH, JJ. ULRICH, Presiding Judge. K.A.B. (Mother) appeals the court's termination of her parental rights to her four minor children. § 211.447, RSMo 1994. She claims that the trial court erred in terminating her parental rights in that the order was not in literal compliance with the termination statute and that the order was against the weight of the evidence. In both arguments she emphasizes that the court considered her conduct during the years of 1990-1993 instead of the "current situation." The judgment is affirmed. RELEVANT FACTS The three oldest children were originally brought to the attention of the Division of Family Services (DFS) after Mother was arrested for prostitution. DFS was also concerned with Mother's drug use and lack of stable housing. The children were found to be within the jurisdiction of the court pursuant to section 211.031.1(1), RSMo 1994, in August of 1990, and made wards of the court on October 29, 1990. J.M.L. and C.E.B. were placed in the custody of their mother, and K.L.B. was placed in foster care. In February of 1991, mother moved to Columbia, Missouri, with the two children in her custody to attend a drug and alcohol treatment program. She was discharged from the treatment facility in April before completion because she tested positive to a drug screening test. M.R.B. was born on July 16, 1991, in Columbia. Mother admitted use of cocaine and heroin during her pregnancy with M.R.B. The three children were removed from Mother's custody again on November 25, 1991. She had left the children without suitable supervision while she went to a drug house. Mother acknowledged that she was earning extra money for the family by selling contraband drugs. In March of 1992, Mother began a treatment plan with DFS which required Mother to overcome her drug and alcohol addictions, maintain stable housing, maintain stable employment and end her dependence on various paramours to reunite with her children. The plan included family counseling, drug screening, weekly contacts with DFS, and home visits. A caseworker was assigned to Mother's case in 1993. She testified that when she began supervising the case the same issues that existed when jurisdiction was exercised in 1990 still existed. Throughout the case, Mother was involved in several drug treatment programs. However, she acknowledges her continuing drug problem. She admits smoking marijuana at a party only three weeks prior to the termination hearing. She attended therapy sessions sporadically. One of Mother's therapists terminated sessions on April 1, 1993, for Mother's failure to attend scheduled sessions. On May 20, 1994, the juvenile officer filed petitions to terminate Mother's and the natural fathers' parental rights with all four children. Hearings were held on the petition in January of 1995. The court found that the children had been within the jurisdiction of the court for more than a year and that the conditions that led to assumption of jurisdiction still persisted and little likelihood existed that those conditions could be remedied at an early date to allow reunification. The court terminated Mother's and the fathers' parental rights on February 15, 1995. Mother appeals. ISSUES PRESENTED Mother raises two points on appeal, but the core of each argument is substantially the same. Therefore, the arguments are addressed together. Mother argues that the order of the trial court terminating her parental rights did not strictly comply with the *195 termination statutes and that the order was against the weight of the evidence because the court based its termination upon facts that significantly pre-date the termination proceeding. STANDARD OF REVIEW The trial court's order will be affirmed unless no substantial evidence supports it, it is contrary to the weight of the evidence, or it erroneously declares or applies the law. Murphy v. Carron, 536 S.W.2d 30, 32 (Mo. banc 1976); In the Interest of T _ M.E _, 874 S.W.2d 552, 559 (Mo. App.1994). On review, the facts and all reasonable inferences therefrom are viewed in the light most favorable to the trial court's order. In Interest of E.B.S., 876 S.W.2d 8, 10 (Mo.App.1994). This court will reverse only when left with a firm belief the judgment is wrong. Id. DISCUSSION The trial court may terminate parental rights where one or more of the statutory grounds set forth in section 211.447, RSMo 1994, is found by clear, cogent and convincing evidence and where termination is in the best interest of the child. In Interest of L., 888 S.W.2d 337, 339 (Mo.App.1994). The trial court found that termination of Mother's parental rights was in the best interest of the children and appropriate under section 211.447.2(3), RSMo 1994 which states that the court may terminate parental rights if: The child has been under the jurisdiction of the juvenile court for a period of one year, and the court finds that the conditions which led to the assumption of jurisdiction still persist, or conditions of a potentially harmful nature continue to exist, that there is little likelihood that those conditions will be remedied at an early date so that the child can be returned to the parent in the near future, or the continuation of the parent-child relationship greatly diminishes the child's prospects for early integration into a stable and permanent home. The statute contains findings that the trial court shall make when terminating rights under this section.[1] The statute further states additional factors for the court to evaluate in terminating parental rights under this section.[2] Mother contends that although the trial court made detailed findings of fact as required by the statute, they were based *196 on occurrences between the years 1990 through 1993. She argues that the court should not have utilized these facts but instead should have made its determination based on her current situation. The court complied with the statute in considering the years preceding the hearing in determining whether Mother's parental rights should be terminated. All grounds for termination must to some extent look to past conduct. D.G.N. v. S.M., 691 S.W.2d 909, 912 (Mo. banc 1985). Otherwise, a parent can always argue that she has reformed since the filing of the petition, reformation usually occurring while the child is away. Id. A parent's conduct after the petition to terminate her parental rights has been filed cannot constitute the sole consideration of the court's decision. In Interest of J.N.C., 913 S.W.2d 376, 380 (Mo.App.1996). The past provides vital clues to the present and future. In the Interest of M.L.W., 788 S.W.2d 759, 762 (Mo.App.1990). Past events shape the future. "To allow only review of very recent events is both short sighted and dangerous." Id. Substantial evidence was presented supporting the trial court's judgment. Mother has failed to maintain stable housing as required by the DFS service plan. The assigned caseworker testified that Mother still experienced considerable turnover in her housing. Just a few weeks prior to the hearing, Mother moved again and DFS did not have her new address (evidently, she and her companion moved into a one bedroom apartment). Mother also failed to maintain stable employment as required by the service plan. From 1989 to April of 1994, Mother held eleven jobs and experienced job turnover between April and the hearing date in January of 1995. Mother was unemployed at the time of the hearing. Despite Mother's employment at various jobs during the pendency of these cases, she has not made any contribution to the support of the children since they were first placed in the custody of DFS. Contribution, no matter how minimal, demonstrates a parent's intent to continue the parent-child relationship. In the Interest of M.H., 828 S.W.2d 951, 955 (Mo.App.1992); In the Interest of M.L.K., 804 S.W.2d 398, 402 (Mo.App.1991). Mother acknowledges her long history of drug addiction. Mother's drug addiction was a major factor leading to DFS involvement originally. She claims that prison has changed her and that she learned much about herself while incarcerated. However, Mother made similar statements in a PPT meeting in the early part of 1994 when she was informed that DFS was recommending termination of parental rights. Credibility of witnesses and weight of testimony is a matter for the juvenile court. In the Interest of M.H., 859 S.W.2d 888, 894 (Mo.App.1993). At the time of the hearing, eight weeks had passed since Mother's release from prison, yet she admits to smoking marijuana only three weeks prior to the hearing. This event cannot be categorized as stale as it reflects on Mother's claimed rehabilitation and her current ability or willingness to refrain from drug dependency. The requirements for reunification have remained evident since the inception of the case. Mother failed to abide by the terms of the service plan. Her attendance at both drug treatment and therapy has been incomplete, she has provided no support for her children, and she has not stabilized her life. All of this evinces a lack of commitment to the children. DFS has exhausted all services that would likely bring about an adequate adjustment enabling return of the children to Mother within an ascertainable period of time. Therefore, substantial evidence was presented for the trial court to find that termination of K.A.B.'s parental rights was appropriate under section 211.447. Although evidence was presented that mother has improved her situation, the trial court found such evidence insufficient to countervail the evidence supporting termination. Presence of evidence in the record that might support another conclusion does not necessarily establish that the trial court's decision is against the weight of the evidence. R.L.P. v. R.M.W., 775 S.W.2d 167, 170 (Mo.App.1989). The judgment of the trial court is supported by competent, substantial evidence *197 and is not contrary to the overwhelming weight of the evidence. The judgment is affirmed. All concur. NOTES [1] Section 211.447.2(3). In determining whether to terminate parental right under this subdivision, the court shall consider and make findings on the following: (a) The terms of the social service plan entered into by the parent and the division and the extent to which the parties have made progress in complying with those terms; (b) The success or failure of the efforts of the juvenile officer, the division or other agency to aid the parent on a continuing basis in adjusting his circumstances or conduct to provide a proper home for the child; (c) A mental condition which is shown by competent evidence either to be permanent or such that there is no reasonable likelihood that the condition can be reversed and which renders the parent unable to knowingly provide the child the necessary care, custody and control; (d) Chemical dependency which prevents the parent from consistently providing the necessary care, custody and control over the child and which cannot be treated so as to enable the parent to consistently provide such care, custody and control. [2] Section 211.447.3.[T]he court shall evaluate and make findings on the following factors, when appropriate and applicable to the case: (1) The emotional ties to the birth parent; (2) The extent to which the parent has maintained regular visitation or other contact with the child; (3) The extent of payment by the parent for the cost of care and maintenance of the child when financially able to do so including the time that the child is in the custody of the division or other child-placing agency; (4) Whether additional services would be likely to bring about lasting parental adjustment enabling a return of the child to the parent within an ascertainable period of time; (5) The parent's disinterest in or lack of commitment to the child; (6) The conviction of the parent of a felony offense that the court finds is of such a nature that the child will be deprived of a stable home for a period of years; provided, however, that incarceration in and of itself shall not be grounds for termination of parental rights; (7) Deliberate acts of the parent or acts of another of which the parent knew or should have known that subjects the child to a substantial risk of physical or mental harm.

The expendables? World's 100 most endangered species listed - lx http://www.guardian.co.uk/environment/2012/sep/11/100-most-endangered-species-listed ====== cup >The list, published on Tuesday at the World Conservation Congress in South Korea, the quadrennial meeting of the International Union for Conservation of Nature (IUCN), was compiled by 8,000 scientists, and is the first of its kind. What I hate most about news articles is when they fail to link to the actual source they're discussing.

Q: sphinx generate class modules overview I'd like sphinx to generate a module overview similar to the one generated by doxygen, here is an example I can't find how sphinx can do that I could use Graphviz to generate some sort of graph, but I can't find a way to get a clickable object in the graph that operates in the same way as the example above. Is there any way to do that in sphinx directly or some hack to make it work as the doxygen module overview? A: Sphinx has a built-in extension called sphinx.ext.inheritance_diagram that uses Graphviz. It defines one directive: inheritance-diagram. Here is an example of how you could use it in an .rst file: .. inheritance-diagram:: mymodule.MyClass1 mymodule.MyClass2 :parts: 1 Here are some examples of inheritance diagrams in documents generated by Sphinx: http://matplotlib.org/1.3.1/devel/documenting_mpl.html#inheritance-diagrams http://openalea.gforge.inria.fr/doc/vplants/PlantGL/doc/_build/html/user/math.html#class-inheritance-diagram There is also a "generic" sphinx.ext.graphviz extension for embedding graphs in documentation.

High resolution imaging of the knee on 3-Tesla MRI: a pictorial review. The recent introduction of 3-Tesla MRI offers substantial advances in musculoskeletal applications. High resolution images can now be obtained with shorter data acquisition times. This article provides a pictorial review of 3-Tesla imaging in the knee with descriptions of both normal anatomy and the more common lesions involving the menisci, ligaments, and articular cartilage. A discussion of the issues associated with imaging at higher field strengths is also included.

**To get the information about a specific API key** Command:: aws apigateway get-api-key --api-key 8bklk8bl1k3sB38D9B3l0enyWT8c09B30lkq0blk Output:: { "description": "My first key", "enabled": true, "stageKeys": [ "a1b2c3d4e5/dev", "e5d4c3b2a1/dev" ], "lastUpdatedDate": 1456184515, "createdDate": 1456184452, "id": "8bklk8bl1k3sB38D9B3l0enyWT8c09B30lkq0blk", "name": "My key" }

Systemic vasculitis. Diagnostic clues to this confusing array of diseases. Systemic vasculitis can be difficult to recognize because of the many types of the disease and the conditions that can mimic it. However, early identification and initiation of treatment (often empirical) are important to avoid severe morbidity. In this symposium article, Dr Bush clearly describes the most common types of vasculitis according to current nomenclature based on the size of affected vessels. Illustrations of common signs of the various types of vasculitis are also included.

Spatio-temporal variations of carbon dioxide and its gross emission regulated by artificial operation in a typical hydropower reservoir in China. Supersaturation and excess emission of greenhouse gases in freshwater reservoirs have received a great deal of attention in recent years. Although impoundment of reservoirs has been shown to contribute to the net emission of greenhouse gases, reservoir age, geographical distribution, submerged soil type and artificial regulation also have a great impact on their emissions. To examine how large scale reservoir operation impact the water column CO2 and its air-water interface flux, a field study was conducted in 2010 to evaluate potential ecological processes that regulate the partial pressure of CO2 (pCO2) in the water column in the Pengxi River backwater area (PBA), a typical tributary in the Three Gorges Reservoir, China. Measurements of total alkalinity (TA), pH and water temperature were applied to compute the pCO2. And this approach was also validated by calculation of pCO2 from the dissolved inorganic carbon data of samples. Partial least squares (PLS) regression was used to determine how the dynamics of the water pCO2 were related to the available variables. The estimated pCO2 in our sample ranged from 26 to 4,087 μatm in the surface water. During low water operation from July to early September, there was an obvious pCO2 stratification, and pCO2 in the surface was almost unsaturated. This phenomenon was also observed in the spring bloom during discharge period. Conversely, there was no significant pCO2 stratification and the entire water column was supersaturated during high water operation from November to the following February. Significant correlation was observed between the magnitude of pCO2, DO and chlorophyll a, suggesting that phytoplankton dynamics regulate pCO2 in the PBA. The average areal rate of CO2 emissions from the Pengxi River ranged from 18.06 to 48.09 mmol m(-2) day(-1), with an estimated gross CO2 emission from the water surface of 14-37 t day(-1) in this area in 2010. Photosynthesis and respiration rates by phytoplankton might be the dominant processes that regulated pCO2 in the water column. We conclude that pCO2 values in the surface water of Pengxi River could be regarded as potential sources of CO2 to the atmosphere were smaller or similar to those that have been reported for many other reservoirs to date.

Judgment in Death (In Death, #11) by J.D. Robb Download Judgment in Death (In Death, #11).pdf You got here right here in search of e-book Judgment in Death (In Death, #11), written by writer J.D. Robb. You can discover it in class Mystery. We hope you take pleasure in it. You can download it or read it on-line. About the book: ‘She stood in Purgatory and studied dying. The blood and the gore of it, the ferocity of its glee. It had come to this place with the wilful mood of a kid, full of warmth and keenness and careless brutality.’ In an uptown strip joint a cop is discovered bludgeoned to dying. The weapon’s a baseball bat. The motive is a thriller. It’s a case of great overkill that pushes Eve Dallas straight into overdrive. Her investigation uncovers a personal membership that’s greater than a sizzling spot. Purgatory’s a final probability for atonement the place everyone seems to be judged. Where your final destiny is dependent upon your most intimate sins. And the place one cop’s hidden secrets and techniques are about to plunge harmless souls into vice-ridden damnation…

Android fans who've been waiting for a stable edition of CyanogenMod 10.2 can finally start their downloads. Cyanogen has just released its final version of the custom firmware, giving the curious a (relatively) safe way to try the company's take on Android 4.3. Don't expect future support from Cyanogen beyond the usual bug and security fixes, though. The stable 10.2 release marks the formal end to development of Jelly Bean-based ROMs -- after this, the coding team is shifting its attention to CyanogenMod 11, the first release based on Android 4.4 KitKat.

High-throughput real-time PCR for detection of gene-expression levels. While many high-throughput screening campaigns involve the measurement of protein levels or locations, at times it is desirable to measure the levels of gene expression in response to small molecules. Here, we describe a method for capturing mRNA in multiwell plates following compound treatment and measuring gene expression using real-time PCR. This streamlined protocol provides complementary information to conventional phenotypic cell-based assays, and is especially useful in cases where the gene of interest is thought to serve a regulatory function in downstream cellular phenotypes.

CAMPAIGNERS say that tourism could be badly damaged if a new oil rig decommissioning plant on the Clyde is given the go ahead. Over 300 people turned up at Fairlie Village Hall to a Peel Ports consultation about a potential yard being earmarked for Hunterston. Douglas Coleman, programme director at Peel Ports, spoke to campaigners and tried to allay their fears regarding environmental concerns, stating that the site would be ‘fully contained’. As reported last week, over 2,000 people have signed a petition calling for a full environmental impact assessment into the overall development. Campaigner Caroline Briggs, inset, said: “I think the whole project has lacked transparency. “Residents are a major stakeholder in what goes on around them and it has a direct impact on resident’s lifestyles. “Tourism is a major industry - one that the council and the government are trying to develop. “We have Inverclyde Sports Centre, the new campus, Olympic sailors, and the new marine field studies centre on Cumbrae now. “The nature and wildlife is absolutely outstanding in this area - we have had orcas up the Clyde this summer. “We need to make sure that we are not doing anything which would permanently jeopardise that.” Activists have criticised the approach to the development and believe it has been handled in a way that avoids the kind of major consultation exercise which they would like to see. Caroline told the News: “Peel Ports have got quite a reputation UK-wide as being exceedingly profitable and exceedingly powerful - and they need to be exceedingly responsible. “You can’t take a big project, and then apply the regulations in small segments; the regulations need to be applied to the whole project. Holly Atterson, 22, who helped set up the petition against the development, added: “The problem about the consultation is that they just want to talk about the smaller aspects. “What is the bigger plan, and the bigger picture for the Hunterston construction yard? Independent councillor Ian Murdoch says he has asked North Ayrshire Council why was it necessary to give an environmental impact assessment for the extension to the ferry terminal at Ardrossan Harbour but not for the proposed decommissioning yard at Hunterston. He said: “I am not protesting against the project or the investment or the job creation. “What I do have concerns about is that local environment. “The amount of the sea bed silt in the seabed which is going to be dredged is across a massive area and there are grave concerns on the impact on the Site of Special Scientific Interest and the wider environment.” West of Scotland list MSP Jamie Greene attended the public meeting and says he was struck by the unease of local people about the proposal. He said: “I think it’s important that we do find a viable solution for the Hunterston site which adds to and improves local economic output. “But what was clear from the public meeting I attended in Fairlie is the sheer strength of feeling from many hundreds of local residents who have concerns about the possibility of oil rig decommissioning at the site. “Many of those concerns were environmental as well as questions being raised about the realistic quantity and quality of employment opportunities. “My hope is that the planning process is open, transparent and gives all stakeholders more than ample opportunity to have their views and voices heard. “Hunterston is a unique opportunity, there is a very real potential for converting the derelict site into something meaningful. “Its deep water ability should be taken into account but not be the only deciding factor. “At the end of the day, it is local residents who have to live with it on their doorsteps so it is right that they are given a proper platform to air their views. I would expect the Scottish Government to give due regard to all the environmental, social and physical aspects of the outcome before deciding on a final strategy.” Campaigner Ron Gilchrist says he wants to see the 700 acre site transformed into a technology and enterprise park. He added: “Fairlie last Wednesday showed that, after decades of nuclear, iron ore, coal dust and ultrasound pollution, it is saying ‘no’ to any further environmental contamination.” A Peel Ports spokeswoman said: “Peel Ports remains committed to utilising Hunterston PARC’s unique advantages as a deep-water port to deliver economic growth, job opportunities and benefit to the local area, North Ayrshire and the wider Scottish community. “The future vision for Hunterston PARC is currently being drawn together and developed within a 20-year Masterplan, which will be shared and consulted on before the end of 2018. “In the meantime, Peel Ports has taken the proactive decision to regenerate the site by investing in and improving the existing facilities, to unlock the potential of the site.”

FIND US Map Directions For directions to Prested Hall, click the red bubble on the map above. On the box that appears, select the link labelled “To Here”. A new box will appear below the map. In the text box labelled A – please type your postcode, choose any further options and click “GET DIRECTIONS“. If these directions are suitable, please select “PRINT DIRECTIONS” if required. By Car From London and the south: join M25 (avoiding congested A12 south of M25), and exit at Junction 28, following A12 northbound (direction Chelmsford, Colchester). After approx 45 mins, pastChelmsford and Witham, exit at Kelvedon. Stay on road for 2 miles through Kelvedon and Feering. On leaving houses behind, veer right, following signs to Prested Hall. Watch for traffic from the left before crossing over into the drive. From Colchester and the north: Follow A12 south past Mark’s Tey, taking Kelvedon/Tiptree sliproad. Entrance to Prested Hall is on the slip road. From Stansted Airport: Take A120 eastbound towards Braintree/Colchester/Harwich. After Bradwell Village take right turn to Coggeshall. Follow road through and out of village (about 2 miles), turning right to (slightly concealed) lane to Feering. After approx 2 miles at T junction turn left. Soon veer off to the right, following signs to Prested Hall.

An abdominal approach to the repair of post-hysterectomy vaginal inversion. An abdominal operation is described using a Mersilene mesh bridge for the correction of post-hysterectomy vaginal inversion. Four cases are reported in which a satisfactory anatomical and functionally effective repair has been achieved.

This ICSR Insight provides background on ICSR’s research and the issues that Maher hopes to raise in tomorrow’s hearing. A video summary can be watched here. Policy and Priorities At the hearing, Maher will emphasise the following points, which our research suggests should be addressed as a matter of priority: • Government should explore ways of empowering security agencies to disrupt the travel plans of potential fighters before they leave the country. Based on our understanding of foreign fighters’ travel trajectories as well as numerous conversations with law enforcement personnel, we believe that current legislation does not offer sufficient support for doing so. • Instead of relying on a purely punitive approach, the Government’s priority should be to reconfigure its Channel Project, so it can deliver targeted support and interventions for a much broader range of extremists, including returning foreign fighters. Research has shown that only a minority of foreign fighters will become involved in domestic terrorism, and Channel – not blanket sentencing – will provide the appropriate (and sufficiently calibrated) tool for mitigating potential risks. • New Prevent initiatives should seek to dampen intra-Muslim tensions. As a result of Syria and political instability in the Middle East, the narratives and motivations of violent extremists have come to emphasise a strong sectarian element (Sunni vs. Shia) which, in some cases, has overtaken the idea of the “West at war with Islam”. In our view, seeking to prevent any spill-over into British communities will be a key concern for Prevent practitioners in years to come. Background Maher will draw on ICSR’s extensive research on the Syrian conflict and – specifically – the involvement of Europeans as opposition foreign fighters: • In April last year, ICSR was the first research organisation to provide a credible and comprehensive estimate of the number of foreign fighters engaged in the Syrian conflict. (Our numbers were confirmed and adopted by several governments and the EU’s Counterterrorism Coordinator). • In October, we published an overview of British foreign fighters in Syria, outlining their profiles and motivations. • In November, we documented a number of individual cases (here and here) of British foreign fighters in Syria, revealing that a much higher number than previously known had died in battle. (The Foreign Office subsequently launched an official probe into the issue). • That same month, we also published a list of urgent questions and concerns, which we believe Government needs to address in order to mitigate potential future risks from returning fighters. (These questions have since been put to senior government officials by Members of Parliament and the Home Affairs Select Committee). • In December, we published a new estimate, concluding that – by then – up to 11,000 non-Syrians (up to 2,000 Western Europeans) had gone to fight in Syria. • In March, ICSR will release a research paper on the networks that are involved in facilitating and supporting European foreign fighter travel. ICSR is engaged in a multi-year research project on the consequences of the Syrian civil war. For more information, please consult www.icsr.info, and sign up to our newsletter and updates.

Q: Git push failing HTTP 500 curl 22 The requested URL returned error: 500 Internal Server Error I have just setup git with bit bucket for my windows machine. Git pull works properly, where as git push fails with below error. $ git push Counting objects: 10, done. Delta compression using up to 4 threads. Compressing objects: 100% (10/10), done. Writing objects: 100% (10/10), 174.03 KiB | 0 bytes/s, done. Total 10 (delta 6), reused 0 (delta 0) error: RPC failed; HTTP 500 curl 22 The requested URL returned error: 500 Internal Server Error fatal: The remote end hung up unexpectedly fatal: The remote end hung up unexpectedly Everything up-to-date Any help is of great use. Thanks A: Increase the Git buffer size to the largest individual file size of your repo: git config --global http.postBuffer 157286400

Follow-up survey of children and adolescents with chest pain. The purposes of this study were to identify the outcome of chest pain in children and to identify the incidence of recurrent chest pain and the need for further medical services. A telephone survey was conducted of pediatric patients evaluated in the cardiology clinic for chest pain. In the majority of patients (53 of 55), chest pain was thought to be noncardiac in origin. Fifteen patients were offered therapy, and all followed the therapy. Most (10 of 15) thought the therapy was helpful. Forty-one (75%) were satisfied with the explanation given to them. Twenty-six had recurrent chest pain, 12 had pain that was severe, 13 thought the pain interfered with daily activities, and 10 sought further medical care. With the secondary evaluation of chest pain, the diagnosis changed in 9 of 10 cases. Chest pain in children is generally benign. However, chest pain can be recurrent and severe, interfering with activities of daily life.

Q: how to handle missing json objects types when reading a JSON to a DF in spark how to handle missing JSON object types when reading a JSON to a DF in spark to a case class case class userInfo(user_id:String,name:String,div_id:String,div_Name:Option[String]) example json: {"user_id":"123ABC","name":"john","div_id":"Business"} {"user_id":"44wsxer","name":"Valenico"} {"user_id":"33qwe","name":"Jmayar"} {"user_id":"121ioi","name":"xyzz","div_id":"Support"} how to read above json to DF and assign null for the div_Name object A: There are two steps required: Make sure that fields that can be missing are declared as nullable Scala types (either Option[_] or Java boxed types) in the class definition. In your case all fields are String so no additional changes are required. Make sure you provide a schema argument and not depend on schema inference. You can for example use Encoder: import org.apache.spark.sql.Encoders val schema = Encoders.product[userInfo].schema spark.read.schema(schema).json(...)

When comparing Thunar vs Pantheon Files, the Slant community recommends Thunar for most people. In the question“What are the best Linux file managers?”Thunar is ranked 6th while Pantheon Files is ranked 13th. The most important reason people chose Thunar is: Use Custom Actions to add right-click options to do things like Open as Root, Open Git GUI, etc. You can filter the file types and filename patterns that the actions will show up for. To add an "Open as Root" action, go to Edit, Configure custom actions. Assign a name and a description. Set Command as "gksudo xdg-open %f" (you'll need to install gksudo since pkexec won't work). Pick an icon (I prefer "changes-allow"). Under Appearance Conditions, select Directories, Text Files, and Other Files. Ranked in these QuestionsQuestion Ranking Pros Pro Custom actions are easy to set up Use Custom Actions to add right-click options to do things like Open as Root, Open Git GUI, etc. You can filter the file types and filename patterns that the actions will show up for. To add an "Open as Root" action, go to Edit, Configure custom actions. Assign a name and a description. Set Command as "gksudo xdg-open %f" (you'll need to install gksudo since pkexec won't work). Pick an icon (I prefer "changes-allow"). Under Appearance Conditions, select Directories, Text Files, and Other Files. Pro Supports renaming files in bulk Pro Can assign custom shortcuts to scripts in XFCE Thunar can use the editable accelerator feature of XFCE. Run xfce4-appearance-settings in terminal, go to settings tab, check "enable editable accelerator". Now open any command in Thunar menu, hover to a command, i.e. your custom "places" or your custom command, then press any combination to assign a shortcut to it.be careful tho, cause it will also remove the shortcut from other command. Pro Easy to use Pantheon files (like the Pantheon IDE) is very stylish and minimal. It's minimal and very easy to use. The most useful commands are there in plain sight, on the toolbar or the sidebar. Cons Con Tree sidepane missing features When the sidepane is in Tree mode, it does not show Places (Favorites). It also doesn't collapse folders (like Windows Explorer), adding to clutter. Con Simplified action bar The action bar on Thunar is very simple and doesn't have as many features and buttons as other file managers. It only has a back, forward, up, and home buttons as well as the folder path. Con Requires plugins for some basic functions of modern file managers Con Requires GNOME dependencies to support common features Thunar relies on GVFS to support mounting disks or accessing web folders, however since GVFS is a third party GNOME library and made for the use in the GNOME environment its often incompatible to Thunar stable releases which results into crashes and other issues Con No Split View without a patch, which can be a deal breaker This limitation can be quite annoying indeed.. thanks for the heads up! Con Does not integrate well into Gnome Con Slightly unstable Thunar crashes some times on file moves, copy-pasting etc. The developers are working on it, but it's taken a while. Con Image thumbnails sometimes wrong There seems to be a bug where sometimes images get the wrong thumbnail, this can lead to data-loss. Con Not very advanced Pantheon files (like Elementary OS itself) does not offer many advanced features since it's mostly aimed at beginners.

Q: Update values inside an object doesn't work I created some objects from the class and set default values to its attributes. Then I changed that same objects attribute values to different values. But that update doesn't work for me in the output. Container* container = TestValueInventor::getContainer(); container->print(); std::vector<ContainerEntry> cont_entry_vector = container->getContainerEntries(); for (vector<ContainerEntry>::iterator it = cont_entry_vector.begin(); it != cont_entry_vector.end(); it++) { it->updateAmount(6.0); } cout << "After the update...." << endl; container->print(); int pause; cin >> pause; return 0; Above is the main method code. There through the first print() it will display the default values. Then after the second print() it should be printed the updated value. But it's still displaying the default value. I have tried to add the pass by reference concepts. But doesn't work for this. Container * TestValueInventor::getContainer(){ ContainerEntry row1; row1.setAmount(10); ContainerEntry row2; row2.setAmount(50); Container* container = new Container(); container->addContainerEntry(row1); container->addContainerEntry(row2); return container; } Above code is the implementation of getContainer() static method which is in the main method. void Container::print(){ for (ContainerEntry &row : containerRecord) { cout << "value:- " << row.getAmount() << endl; } } Above code is to print the output in the terminal. Inside the main function there are two print functions because first one is to print the default values and second one to print the updated values. There both output is the same which is the issue for the client. std::vector<ContainerEntry> Container::getContainerEntries() { return this->containerRecord; } Above is the implementation of getContainerEntries() method. void ContainerEntry::updateAmount(double amo) { this->amount = amo; } Above is to update the default amount to 6.0. Then at last it will not print not 6.0 but the default values which were assigned previously. So how I can make it correct? A: The Container::getContainerEntries function returns a copy of the vector. It should return a reference instead: std::vector<ContainerEntry>& Container::getContainerEntries() { ... } And of course you need to assign it to a reference, otherwise you make a copy again: std::vector<ContainerEntry>& cont_entry_vector = container->getContainerEntries();

Q: Can the US president hand-off the nuclear football to the vice president? It's been reported that the nuclear football will be coming with President Obama during his historic visit to Hiroshima. Could a president decide to give the nuclear football to the vice president instead? As well as being more diplomatic in this scenario, there could be other instances such as when the president is visiting a hostile nation where not carrying the nuclear football would be advisable. Even though the secretary of defense also has to authorize a nuclear strike, having the control codes in certain scenarios might be overly high risk. A: As far as I could tell, the President could decide to do whatever he wants with the "football" (in terms of where it is, anyway), but it would be useless if not near him and so would defeat the entire purpose. The football by itself is just a communications device and the relevant documentation for emergency options (nuclear and otherwise). It's less talked about, but the Vice President also has his own copy.1 The actual authentication codes (not launch codes!) to verify the President's identity are carried on a separate index card which the President carries with them. The Vice President also has codes, for the same purpose - they authenticate the VP to whoever's at the other end of the football's communication link, thereby allowing him to order a strike if he has the authority to do so (i.e. is Acting President). The briefcase has been with Presidents in both Soviet Russia and the Vatican.2,3 It's also been left behind or misplaced on occasion, although never for long. The aide doesn't necessarily have to stand next to him at all times, but just be close by for ease-of-access. Presumably, when he's actually asleep on a trip, the aide carrying it is in the next room with the rest of his bodyguard detail. So it would be unheard of for Obama to order it out of his immediate vicinity, although he could likely instruct the aide to hang back somewhat to avoid being in photographs.

163352: He opens an account on a downloading website, then he rents this account to others There are websites for downloading files from the Internet. On these sites, the user opens accounts for quick and unlimited downloading, in return for a monthly subscription fee. Some friends and I set up a downloading website connected to all these downloading sites, in return for a monthly fee paid to our website only, and it is lower than the monthly fee on only one of these websites. The cost of subscription to the Rapidshare website is forty dollars. Subscription to Megaupload is thirty dollars. Subscription to our website (for downloading from all of these sites) is only twenty dollars. Please note that downloading will be done from our website through accounts that are already paid for on each of these websites. What is meant is that we have accounts on each of these sites for downloading through them, and we pay for that, but of course after that we will cover these costs with the income we generate. Please note also that some of these websites do not allow sharing accounts for more than one user. I hope that I have explained clearly. Praise be to Allaah. It is permissible for the one who opens an account on a downloading website to allow others to share his account for free or in return for payment on condition that the downloading website has not stated that sharing accounts is not allowed, because “the Muslims are bound by their conditions,” as was narrated by Abu Dawood (3594) and classed as saheeh by al-Albaani in Saheeh Abi Dawood. And because sharing accounts may lead to overcrowding and putting a lot of pressure on the website and slowing down its operation. So if it is stated that that is not allowed, it is obligatory to adhere to that, even though the basic principle with regard to hiring or renting is that the one who rents something may benefit from it himself or allow others to do so. But the fact that harm maybe caused in this case dictates that it is not allowed, unless the one that is renting it out gives permission or does not say anything. See also the answer to question no. 105749 for the ruling on selling or renting out download services on the Internet.

Roasted red pepper hummus recipe with step by step photos. I wanted to try this red pepper hummus recipe since long time. I have made regular chickpea hummus many times to serve with crackers or veg fingers (my favorite). I usually do not use tahini for my hummus, I just add a generous dose of toasted white sesame seeds. I have seen this roasted red pepper hummus recipe in many websites and magazines. The pale orange color of the red pepper hummus was so lovely and I badly wanted to prepare it. I was sure it would taste good as we love the flavor of roasted red pepper in this soup and pasta.We just loved the way the roasted bell pepper hummus turned out, the color was so pleasing with a silky smooth texture and smoky flavor from the roasted bell pepper. While blending hummus generally olive oil is added to bring it to the required consistency, if you do not want to add lots of oil, you can reserve the stock used for cooking chickpeas or even plain warm water while blending and add few spoons of olive oil to the roasted red pepper hummus while serving. To make roasted red pepper hummus recipe, I roasted the red pepper in direct flame, so the flavor was so smoky and too good, you can even roast the bell pepper in oven if you wish. I have peeled the chickpeas after cooking, that is surely a daunting task but the taste and texture of the finished hummus was superb, if you have the time and patience do peel the skin of the chickpeas. Serve roasted red pepper hummus with thinly sliced veggies(carrot,cucumber, bell peppers etc), this is my favorite way to serve hummus. Otherwise you can serve with pita bread, crackers or use hummus as spread for sandwich or wraps. Here is how to make easy and tasty roasted red pepper hummus recipe, do try this when you have red pepper handy! Roasted red pepper hummus recipe with step by step photos: 1. Soak 1 cup chickpeas in water for 6-8 hours. 2. Drain and pressure cook the chickpeas with 3 cups of water up to 3-4 whistles. Drain the cooked chickpeas and reserve the stock. You can use this stock for blending roasted red pepper hummus. Rub and peel of the skin of chickpeas if desired. 3. While the chickpeas are cooking, you can roast the red pepper. Apply olive oil all over the red pepper and roast over direct flame using a tong. Roast till chars appear on all the sides. 4. Cool for few minutes and peel of the skin of roasted red pepper as far as possible. Chop roughly. 5. Dry roast sesame seeds until nice aroma wafts out. Let cool. 6. Take the roughly chopped red pepper, cooked chickpeas, toasted sesame seeds and peeled garlic pods in a blender jar. Add some reserved chickpeas stock and blend for few minutes. 7. Add required salt and 1/4 cup olive oil and blend thoroughly. Check the consistency, add more olive oil and blend again if needed. Serve roasted bell pepper hummus topped with more olive oil. Serve with crackers or veggies or pita bread. Roasted red pepper hummus recipe card below: Roasted red pepper hummus recipe Harini Roasted red pepper hummus, easy,tasty dip made with roasted red peppers and chickpeas! 5 from 3 votes Print Recipe Pin Recipe Prep Time 20 mins Cook Time 10 mins Total Time 30 mins Course side Cuisine Middle Eastern Servings 1 1/2 cups Calories 367 kcal Ingredients 1x 2x 3x 1 cup chickpeas 1 medium red bell pepper 2 tablespoons white sesame seeds 3-4 garlic pods peeled 2 teaspoons lemon juice Salt 1/4 cup + 2 tablespoons olive oil. Instructions Soak 1 cup chickpeas in water for 6-8 hours. Drain and pressure cook the chickpeas with 3 cups of water up to 3-4 whistles. Drain the cooked chickpeas and reserve the stock. You can use this stock for blending roasted red pepper hummus. Rub and peel of the skin of chickpeas if desired. While the chickpeas are cooking, you can roast the red pepper. Apply olive oil all over the red pepper and roast over direct flame using a tong. Roast till chars appear on all the sides. Cool for few minutes and peel of the skin of roasted red pepper as far as possible. Chop roughly. Dry roast sesame seeds until nice aroma wafts out. Let cool Take the roughly chopped red pepper, cooked chickpeas, toasted sesame seeds and peeled garlic pods in a blender jar. Add some reserved chick pe stock and blend for few minutes. Add required salt and 1/4 cup olive oil and blend thoroughly. Check the consistency, add more olive oil and blend again if needed. Serve roasted bell pepper hummus topped with more olive oil. Serve with crackers or veggies or pita bread. Notes 1. You can add ready made thahini instead of sesame seeds. 2. You can add chili flakes if you wish while blending. 3. instead of adding water or chickpea stock, you can use olive oil alone for blending the hummus too. Nutrition Calories: 367 kcal Tried this recipe? Mention cookclickndevou or tag cookclickndevour

//---------------------------------------------------------------------------- // Anti-Grain Geometry (AGG) - Version 2.5 // A high quality rendering engine for C++ // Copyright (C) 2002-2006 Maxim Shemanarev // Contact: [email protected] // [email protected] // http://antigrain.com // // AGG is free software; you can redistribute it and/or // modify it under the terms of the GNU General Public License // as published by the Free Software Foundation; either version 2 // of the License, or (at your option) any later version. // // AGG is distributed in the hope that it will be useful, // but WITHOUT ANY WARRANTY; without even the implied warranty of // MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the // GNU General Public License for more details. // // You should have received a copy of the GNU General Public License // along with AGG; if not, write to the Free Software // Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, // MA 02110-1301, USA. //---------------------------------------------------------------------------- #ifndef AGG_WARP_MAGNIFIER_INCLUDED #define AGG_WARP_MAGNIFIER_INCLUDED namespace agg { //----------------------------------------------------trans_warp_magnifier // // See Inmplementation agg_trans_warp_magnifier.cpp // class trans_warp_magnifier { public: trans_warp_magnifier() : m_xc(0.0), m_yc(0.0), m_magn(1.0), m_radius(1.0) {} void center(double x, double y) { m_xc = x; m_yc = y; } void magnification(double m) { m_magn = m; } void radius(double r) { m_radius = r; } double xc() const { return m_xc; } double yc() const { return m_yc; } double magnification() const { return m_magn; } double radius() const { return m_radius; } void transform(double* x, double* y) const; void inverse_transform(double* x, double* y) const; private: double m_xc; double m_yc; double m_magn; double m_radius; }; } #endif

Four-time winners of major international race test positive for PEDs Four members of an elite racing squadron–a squadron that is among the most dominant in the history of racing sports–tested positive for Tramadol, a prescription opioid pain-reliever last spring, with that revelation only now coming to light. His legacy now called into question, team leader Dallas Seavey has denied involvement in his athletes’ positive tests, claiming that an unknown saboteur is the likely culprit in the positive tests. This theory might hold water if the athletes all unanimously have denied any wrong-doing as well, but that’s not the case. Could his athletes have taken the Tramodol under their on volition, unbeknownst to Seavey? Well, no. No, they couldn’t, because–you see–the athletes are dogs… literal dogs… they are animals who can’t really exercise free will. Now if you’re like me, your brain is already broken to the point of this story not really registering at all. Doping allegations and scandals are so commonplace that they no longer serve to shock or infuriate–they simply bounce off our retinas after being denied entry into the already full part of our brains meant to process that sort of disappointment. Not even the fact that actual pet dogs are now the subject of potentially sport-altering doping allegations can break us of the general feelings of resignation we must cope with constantly as fans of sport. Stories like this one only push us past the point of no return. The dumbest, silliest, and most eye-popping instance of alleged doping in the history of sport has already happened. We’ve been to the edge and stared into the abyss. What’s left to push us over the ledge? Paul Snyder Meme-disparager, avid jogger, MS Paint artist, friend of Scott Olberding, Citius Mag staff writer based in Flagstaff. Supplying baseless opinions, lukewarm takes, and vaguely running-related content. Once witnessed televison's Michael Rapaport cut a line of 30 people to get a slice of pizza at John's on Bleeker at 4am. You can follow Paul on Twitter at @DanielDingus.

Hello All, if any of you are interested how to solve the problem with the current version of the API, here's the solution: 1. Define the following in your code typedef struct tls_impl { const char *ti_name; } tls_impl; extern tls_impl ldap_int_tls_impl; 2. Now check the ti_name to discover which crypto lib has been linked: if(strncmp(ldap_int_tls_impl.ti_name, "MozNSS", 6) == 0) { // NSS } else if (strncmp(ldap_int_tls_impl.ti_name, "GnuTLS", 6) == 0) { // GnuTLS } else if (strncmp(ldap_int_tls_impl.ti_name, "OpenSSL", 7) == 0) { // OpenSSL } else { // Unknown } I hope this will help other people in building more portable binaries... :D Cheers, Max On 06/10/2011 01:37 AM, Massimiliano Pala wrote: Hi all, I have a little problem. I am implementing an application that uses the OpenLDAP libraries. Until not too much time ago, linking with OpenSSL was sufficiently safe (on almost every Linux distros) and providing my own verification function through the SSL_CTX (by using the ldap_set_option(m_ldap, LDAP_OPT_SERVER_CERTIFICATE, _my_verify)) was easy. Now, Linux distros started to use GnuTLS, NSS, and OpenSSL as the crypto API. My question is: how do I develop an application that when deployed on different systems might need to use functions and data structures from different crypto-api (e.g., when I distribute the binaries of my app) ? How can I retrieve that info *at runtime* (I'd like my binaries to be compatible) ? At least, is there a function that allows me to know which crypto APIs are expected by libldap_r (so that I don't pass in the wrong data structure since it is a (void *)) ? Or at least, is there a way to set/get options so that I would know which API is in use ? Thanks,

Abnormalities of auditory evoked magnetic fields and structural changes in the left hemisphere of male schizophrenics--a magnetoencephalographic-magnetic resonance imaging study. Functional and structural changes in 10 DSM-III-R male schizophrenics and 10 healthy volunteers were investigated using magnetoencephalographically (MEG) detected long-latency (N100 m) auditory evoked fields (AEFs) and magnetic resonance imaging (MRI). The AEFs were characterized by single moving equivalent dipoles, which were superimposed on MRIs. There were significant differences in dipole orientations and in AEF latencies in the left hemisphere of schizophrenics, when compared to the controls. The MEG-detected alterations were found to be associated with a bilateral volume reduction of the posterior superior temporal gyrus (pSTG), which was more pronounced in the left hemisphere. Separate analysis of white and gray matter has shown that the pSTG volume reduction resulted from decreased gray matter volumes without white matter changes. Both the functional and the morphological data indicate a left-hemispheric disturbance in our patients.

Storm Caroline To Disrupt Weekend Action? Fans are being urged to pay attention to the weather reports this weekend with parts of the United Kingdom set for snow. Storm Caroline has already seen large winds hit parts of the UK and today Northern Ireland, Scotland and the north of England were blanketed in snow and it’s expected that this will continue tomorrow and possibly in more southern areas as well. That’s not withstanding any potential freeze owing to the temperatures. The Met Office expect Saturday to be another day of ‘frequently blustery snow and hail showers’ in northern and western parts of the UK in particular – with the expectation that Wales and the West Midlands will certainly be hit. The Wolverhampton Wanderers vs Sunderland game is already in doubt with staff and fan volunteers welcomed to the Molineux early on to help clear any snowfall and that certainly won’t be the only game that faces an early pitch inspection. A statement from Wolves read. ‘At this stage, advice to fans is to start making plans to arrive as early as possible ahead of the game as the inclement weather will disrupt travel plans and will increase congestion around the stadium.’ Again, they won’t be the only club encouraging fans to turn up early this weekend.

Gasoline prices could fall up to 25 cents a gallon by the end of July. Gasoline prices could fall up to 25 cents a gallon in parts of the USA within the next two weeks, thanks to slumping crude oil prices, weakening demand and robust supplies. Now averaging $3.64 a gallon - vs $3.48 last July -prices could soon drop to $3.50, with some Southern states falling below $3, says Patrick DeHaan, senior petroleum analyst for price tracker gasbuddy.com. Crude oil prices are down again Wednesday, with benchmark West Texas crude off 84 cents to $102.56 a barrel and Brent crude off 62 cents to $108.32 - a ninth straight daily drop. "The tipping points were cooling tensions in Iraq and Hurricane Arthur come and being no big deal,'' says DeHaan. "Oil bulls had no where to go, and oil prices are higher than they should be and unjustified at this level." With Iraqi output still strong and Libya expected to boost exports, supplies are also ample. U.S. output is also surging. Horizontal drilling and hydraulic fracturing has pushed U.S. crude oil production to 8.5 million barrels a day, the most since 1972, according to the Energy Information Administration. "We continue to produce oil at mult-decade highs and have ample supplies in storage, so that gives the market less of a need to rally prices,'' says Platts oil futures editor Alison Ciaccio. "Futures prices have fallen from highs seen in June, and that translates to lower prices at the pump." The expected drop in prices is coming nearing two months after gasoline prices typically peak for the year. California, which was again hampered by refinery woes, should see the biggest price drops. Now averaging $4.13 a gallon, prices could fall 25 cents. That would be below year-ago levels averaging $3.98. Still, the run up that kept 2014 prices higher and longer than normal could push the year's average above 2013's $3.49, the lowest annual average since 2010.

Writer, Designer Category Archives: Games Hello, everyone! The Scarred Lands Player’s Guide has officially gone to press, which means you can get hard copies very soon! Stay tuned for the upcoming Pathfinder adventures: Dagger of Spiragos and Ring of Spiragos. A few weeks ago, I started working on a one-page RPG system that could be adapted to several popular genres. What I came up with was Tango. Check out some of the implementations and let me know what you think! The very rough first draft of my new RPG, D6 Dungeons is live and has its own website. For all you gamers out there, especially those with kids who might love the hobby (but not the overly complicated rules of most old school RPGs), it could be something your whole family enjoys. Check it out and send any feedback you have my way via the subreddit or by contacting me directly. The Pathfinder version of the Scarred Lands Player’s Guide is done and will be going out soon! This project was an absolute blast to work on, as it’s a revision of my very first publication when I was still in college, many years ago. Check out the updated version and all the fun, new stuff we added! If you’re interested in learning about writing for video games and you’re in the Atlanta area on Friday, May 27th, come see us at MomoCon! I’ll be speaking on a panel at 10:00am in room A-404-405 with a few other game industry veterans. To be quite honest, we usually start out with a positive message about how to write good fiction for video games, but these things almost always devolve into trading horror stories from our time in the business. So, you’ll probably learn a few things but, for those of you hoping to get into making games someday, you’ll might just begin to question that goal. The one thing I can promise, however, is that it’s going to be a lot of fun! See you all at MomoCon! One of the projects I’m currently working on in my sparse free time is a book of 10 new classes for Pathfinder. Now, instead of trying to go wild with how far I can stretch the rules or reinvent the wheel by modifying the existing classes, what I’m aiming to do is “fill in the blanks,” so to speak, by making classes that I think the official Paizo material has overlooked. For example, the tinker: a staple of the fantasy genre that somehow got overlooked in official material. The same goes for a dedicated shapeshifter class, one that’s not tied to arcane magic or druidic ideology. For this project, the art is being supplied by the phenomenally talented Eric Kenney, and when it’s done, it’s going up on DriveThruRPG. If you’re interested in play-testing this material, send me a message and I’ll hand out SRD-style first drafts as soon as they’re ready! Thanks to the great people at Onyx Path, this awesome fantasy RPG setting is making a big comeback! It’s a project that’s dear to me, as I worked on it both last year and 15 years ago. As my first publication in the RPG business, it launched my career as a professional writer and game developer. Check it out!

Re: Question about virtual destructor Hello! Me class derives from class, which doesn't provide virtual destructor. I declared virtual destructor in my class. Would object destruction work the same as in class derive from class with virtual destruction? Re: Question about virtual destructor Hi, When you add virtual destructor it works as other virtual methods. So if you use a pointer to a base class object, which refers to derived class object and call delete on this object you will get ~Derived() and then ~Base(). And that is a correct behavior. If you don't have a virtual destructor in Base class you will not be able to destruct an object of Derived class through the pointer to Base.

Cedar Hopperton, a Hamilton anarchist who's been behind bars following a heated speech at a city hall public meeting, will continue to have their parole revoked. Hopperton, 33, has been in jail since June 22. That's when police arrested Hopperton following a speech about violence between far right demonstrators and a group of people in pink masks at a Pride festival a week earlier. Initially, Hamilton police said Hopperton was at Pride and included both allegations as violations of parole conditions in its submission to the board. But Hopperton's lawyer, Asaf Rashid, say the allegation of being at Pride got little attention at the parole board hearing. Instead, the board ruled on whether Hopperton was inciting violence in an anti-police speech. Rashid argued that Hopperton had a right to freedom of expression, especially in Hamilton city council chambers. "It basically baffles me," Rashid said. "It's a very disappointing decision, and it basically speaks to the very poor recognition of the rights of a person that is on parole." Hopperton — who uses the pronoun they — gave the speech after several people were injured at a June 15 Pride festival at Hamilton's Gage Park. A group of self-appointed street preachers with homophobic signs arrived at the park with loud speakers and cameras. A masked group of people associated with The Tower, a local anarchist social space, blocked the protesters with a large black portable barrier. The incident devolved in a violent clash between the people with homophobic signs and Pride supporters. A week later, police arrested Hopperton, who was on parole for their role in anti-gentrification vandalism on Locke Street a year earlier. The Crown described Hopperton as "the ringleader" of the Locke Street incident. In a June 22 media release, police said Hopperton violated parole "in (the) Pride Hamilton disturbance" for "participating in a public demonstration where peace was disrupted." Police eventually admitted, however, that Hopperton's speech at a June 18 "community conversation" held by city council's LGBTQ advisory committee was part of why they reported Hopperton to the Ontario Parole Board. In the provocative speech, made amid numerous frustrated speeches from LGBTQ residents, Hopperton said they are "not part of any community that includes police." Hopperton urged the LGBTQ community not to rely on police for protection against hate groups. Instead, "let's figure out how to use measured force ourselves and figure out when it's appropriate to do so." Hopperton also told the deputy chief of the Hamilton Police Service to "get the f--k out." The case has attracted widespread attention, particularly since police have arrested and charged three counter-protesters and only one protester. Of the three counter-protesters arrested, two are affiliated with the Tower and were also on probation for convictions related to the Locke Street vandalism. The one protester arrested is charged with assault. Police say to deal with possible assaults by protesters seen on video they need victims and witnesses to be more willing to come forward to co-operate with their investigations, and have made several public calls for that. On Monday, 100 academics from various Ontario universities signed a letter expressing concern about how police and the city have handled the Pride incident. A group of McMaster University faculty have expressed similar concerns, as have various unions, the Hamilton District Labour Council and the Council of Canadians. Hopperton told CBC News last month that their sentence ends in late August.

Q: implement stack with freelist feature in Python 2.7 Design a stack with free list feature (i.e. after a node is popped, its space is reusable by future push operation, and kept in free list). The code is simplified and does not make sense in some perspective, and I just use below code to show the general idea of stack with free list (as a prototype). My question is about how to design pop operation. My confusion is since a reference to a node is returned after pop operation, for example in my code there is node1 = stack.pop(), the reference to a node might be used by client who call pop, and the same node reference is reclaimed in free list and might be used by other push operation, how to resolve such conflict and wondering for general advice for design free list feature with stack, linked list or queue. MAXSIZE = 100 freeListHead = None class StackNode: def __init__(self, value, nextNode): self.value = value self.nextNode = nextNode class Stack: def __init__(self): self.top = None self.size = 0 def peek(self): # return StackNode return self.top def push(self, value): global freeListHead if self.size >= MAXSIZE: raise Exception('stack full') node = freeListHead node.value = value freeListHead = node.nextNode node.nextNode = self.top self.top = node self.size += 1 def pop(self): if self.size == 0: return None node = self.top self.top = self.top.nextNode self.size -= 1 return node if __name__ == "__main__": # initialization for nodes and link them to be a free list nodes = [StackNode(-1, None) for i in range(MAXSIZE)] freeListHead = nodes[0] for i in range(0, len(nodes)-1): nodes[i].nextNode = nodes[i+1] stack = Stack() stack.push(1) stack.push(50) stack.push(100) stack.push(200) print stack.peek().value node1 = stack.pop() print node1.value print stack.peek().value A: You could simplify your code by returning the value given to push instead of StackNode holding the value. There are no concerns of memory consumption since you can set node.value to None in pop before returning the result. Below is simple example on how this would work in the practice: class Node: def __init__(self): self.nextNode = self.value = None class Stack: def __init__(self, maxSize): self.maxSize = maxSize self.size = 0 self.top = self.free = None def push(self, value): if self.size == self.maxSize: raise Exception('Stack full') if self.free: node = self.free self.free = node.next else: node = Node() node.value = value node.nextNode = self.top self.top = node self.size += 1 def pop(self): if not self.top: raise Exception('Stack empty'); node = self.top self.top = node.nextNode node.nextNode = self.free self.free = node self.size -= 1 result = node.value node.value = None return result stack = Stack(3) for i in range(3): stack.push(list(range(i + 1))) while stack.size: print(stack.pop()) Output: [0, 1, 2] [0, 1] [0]

School is in session and Orlando Bloom, Jay Chou, Kate Hudson, Jessica Chastain and Cara Delevingne are your classmates We're calling it: Katy Perry threw the birthday/Halloween party of the year. The singer, who turned 32 on 25 October, threw a '50s high school-themed party where she presided as principal (that's Principal Hudson to you) of Hudson High. There was a classroom-themed photobooth, a giant Twister board, a pie-eating contest that Cara took part in, a hula hoop competition, and performances by impersonators dressed as Marilyn Monroe, Elvis Presley and The Supremes. Nothing beats actually having been at the party, but we mortals just have to make do with what's on social media (and that's already impressive enough).

Holly Wootten As we all know, one of the most popular and most consumed foods in the world would be cake, which is not surprising as everyone is a cake lover! No one can say no to a good piece of cake and that why cake is an important part weaved in to most cultures and events in our lives. Even though many people do not think about it, cake is a beacon of celebration and this is why we cannot hold an event without a cake being present there! Even though we can buy a regular cake from a cake store for our functions it is not going to be the same as buying a custom made cake at all. A custom made cake is made directly for us and can even be designed just the way we want which adds more specialty to an event! It is also something that can add a hint of personality to an otherwise regular event! So here are three events that we all experience that can be benefited from beautiful custom made cakes! They can make birthday parties unforgettable! Keep in mind that one’s birthday party is all about them and not about anyone else which is why better custom cakes are going to be an important aspect to any birthday party! People want their birthday parties to be unique and the spotlight to be on them which is why a custom made cake, which reflects what they are, is going to help them do so! So if you want your birthday party to be an unforgettable one, make sure to buy a custom made cake without fail! They can make your wedding more special! A wedding is something that you are going to celebrate only once in your life which is why every single detail regarding a wedding has to be incredibly special! And what is more special than wedding cakes South Auckland that are custom made just for your big day? You can easily contact a professional store in the country in order to custom design your special cake for your wedding and you will realize just how much of a change it can really make! A custom made cake will truly add to the specialty of the whole thing and make your wedding a truly special day for everyone! They are fit for exciting anniversary celebrations! Anniversaries, much likes birthdays, come around each year but unlike birthdays an anniversary is an event of love and bond between two people which is why it is a special thing! So why not celebrate that special moment with a custom made cake? Birthdays are special occasions that are celebrated and valued by all of us. Even if we do not celebrate our own ones, we make it a point to wish, buy gifts and host parties for our loved ones in order to have a great time with them. Celebrations organized for birthdays of children can be extremely pleasant and adorable since there are various themes that can be used and they tend to be colourful and bright. If you are about to organize your little one’s special day, you may feel a little nervous about getting everything ready properly and on time since it can be a little tough to handle everything while taking care of your child. There are a few tips that would be helpful to you while you organize such a celebration. Budget It is important to make a list of expenses in order to budget your event. The budget is not something that you can neglect. This is an important thing that should be prepared initially in order to avoid any mishaps. When you know the amount that you can spend on the preparation of the celebration, it will be easier for you to plan things out. For an instance, there are various kids birthday party venues. Hence, knowing the amount you can spend will help you in finding a place that is suitable for your requirements. Decide a venuePeople tend to choose various places to host parties for children. Make sure to find a venue that is both easy for people to reach and has required services such as space, proper seating, restroom facilities and etc. These are mandatory to be there in a venue and, if the food is also provided by them, make sure to check if their food is good in quality and tastes good as well. Since children are going to be there, it is important that you let them know about it and decide on child- friendly food items and beverages. Some Newcastle function venues tend to not have their own catering services. Hence, it would be wise to choose places such as restaurants in order to host such events. Additionally, by choosing such places, you will not have to worry much about the food as well. Keep it vibrantSince it is a children’s party, it is important that you make sure to decorate the place according to a certain theme or how the little one likes it. Try your best to make sure that the decoration items are child- friendly since wires and other sharp items may tend to wound children. Make sure to use colourful decoration. You can even easily make them by yourselves or even order them at low costs. The above will be helpful when you organize your little one’s party. Additionally, make sure to make a guest list in order to make other choices easier. There are many instances on which you would always love to complete a full project by yourself. This could leave you happy and proud of yourself or could leave you with a failed event. There are many types of events and many things to consider at planning stage. Some events could be really tough and you would need the help and support from others while there could be events you could host by yourself. Therefore, it is important to understand what you need to consider at planning stage to make sure that you host a successful event that would satisfy and make everyone happy. The following are some things to consider in order to make a decision on whether you need to outsource different parts of the event. Size This is the most important aspect to consider. Most of the other items you need to consider depends on the size of your event. If you are planning on hosting a large scale event with over hundred people, it would be ideal if various parts of the event could be given to people to hold them responsible. This way you do not have to worry too much on everything in detail. Further, it is obvious that party food catering for over 100 people is not going to be an easy task unless you focus on a few jobs including the meals. See this page for more info on party food catering Sydney. Place The place you are planning to host an event should also be considered in order to host a proper event. Sometimes there are many instances where the venue is too far for the outsourced corporate catering company to deliver or that they are unable to accommodate all your guests. This can most often happen when you the venue is a private property or a house. Therefore, is this is the case it should be ensured that a new place is chosen and that it is more convenient for everyone and also that all guests could be accommodated. Meals If you have never prepared the meals for an event, it is highly suggested that you outsource the job to an expert to avoid falling into a disastrous situation. Meals are one of the most important aspects of an event and therefore, you need to make sure that you make sure that it is done right. A discussion with an expert would leave you with a successful outcome and even save some money and these expert already have the required labour and material for these activities. Therefore, it is important to make sure that the above is considered and activities are outsourced when you are hosting an event. As the owner of a cafe you are probably constantly looking for ways to make sure that your cafe is improved. There are many things that you can do in order to make sure that you improve your cafe. For an instance, if you think that hiring new employees or adding new things to the menu will improve your cafe, then you should ensure that you get this done. In addition to this ensure that you do not do anything that will cost you a lot of money but not bring you anything in return. The aim of this article is to give you some tips on what you can do in order to improve you cafe. Here they are. Hiring New Employees If you want to expand your cafe, you should think about hiring new employees. If you have been running your cafe in a small place with just one or two employees, you have to understand that this is not going to work with a bigger space. It will only take time to serve the customers and this will result in slow service and bad reviews. Therefore, ensure that you hire new employees who have gone through the spiegelau perfect serve collection http://www.great-earth.net/en/brand/spiegelau so that they are experienced and know what they are doing as well. Purchase New Equipment The other thing you should do is to purchase new equipment. It is important that you purchase new equipment and that you improve the standards of your cafe, if you are thinking of making it better. You can think about getting new things like lavazza coffee machine at Great Earth International Company Limited so that you will be serving better quality coffee. Ensure that you go to a proper place and purchase the new equipment. Purchase New Seating The seating in your cafe is of vital importance. This is because; the seating has to be done properly and methodically. If the couches and seats in your cafe are uncomfortable, your customers are bound to leave soon and not return again. You will also run the risk of getting some bad reviews. Therefore, ensure that you purchase new and proper seating that is very comfortable. Redo the Image of Your Cafe Another thing you can do is to redo the image of your cafe. For an instance, you can give your cafe a paint job with interesting colours that will make the place pop and attract more people. You can make your advertising campaign a little better and you may want to invite a few critiques to come and review the place. This will be good in terms of improving your cafe. Hong Kong is not a shoddy tourist destination .But having said that, with little bit of extra planning and innovativeness, you can spend a pleasant day in the city on a tight budget. Outside spaces, road shows, museums and markets take up to a majority of this beautiful city, and many of these are open for tourists for free. Hong Kong is an energetic and active city of eight million occupants thus, can be overwhelming for some guests, particularly those not used to swarmed places. What’s more, with such a great amount to do here, one can scratch their head on where to begin all together get the most out of their outing. If you are travelling to Hong Kong on a budget, we have a list of things you shouldn’t miss. Go on a Big Bus Tour. Hop on to a Big Bus and enjoy 24 or 28 hour access to Hong Kong’s open top tourist transport services and see the greater part of the city’s seminal historic points and places at your own pace. Your pass permits you to explore on 3 diverse sightseeing trails through Kowloon and Hong Kong Island. Go along the Hong Kong Island course, known as the Red Route, investigate the Blue Route of Kowloon, and take the Green Route through Stanley to glance through the breathtaking city view of metropolitan Hong Kong. Walk through the Kowloon Market Hong Kong is plentiful with busy markets, and you’ll find the best of them on as you walk through the busy streets of Kowloon. From the signature Kowloon flower market to the Yuen Po Street Bird Garden, you are likely to find amazing deals or get away from the turmoil of the city. Kowloon market is also best known to be home for many great seafood restaurants in Hong Kong. Make sure to stop by and enjoy signature Hong Kong cheesy lobsters. Link here http://www.tgifridays.com.au/find-us-forest-hill-chase/ offer a tasty food that you can satisfied. Take a street food tour Find the heavenly food on a tasty street meal tour and check out some of the finest Asian street food on the go. Hong Kong’s street food is amazingly divine and adored by local people and guests alike. Make sure to stop by roadside burger places in Hong Kong and enjoy local Blue Butcher. Enjoy the turquoise beach Whether it’s surfing or a sun bath, Hong Kong’s shorelines offer a free and charming break from the city. Simply bring sunblock and music for a shabby but a lovely gathering. 21 happens only once and it is your big day. Turning 21 means that you are also entitled to do a lot of things you were not able to do before. In other words, there is nothing you can ‘not’ do now. Whether you are looking to spend your 21st birthday with your family, friends or significant other, it should be a memorable occasion that you will want to remember for the rest of your life. Here are some ways how you can celebrate this important birthday and have the best time of your life. House Party Celebrating your 21st at your home with everybody you love is a great idea. You can invite as many friends as you like and have a ball. If you have had house parties before, look for ways to make your 21st birthday house party unique from the rest you have had. You can decorate the house to a grown up theme, get a DJ to play music and have fun without limitations. Dine somewhere you have not been to before. Going out for dinner can be quite expensive, so select a bunch of your closest friends and head to best rooftop restaurant in town. You can order your favourite cuisine, open up a bottle of wine and engage in endless chatter and laughter with your friends. After all, being 21 is a big deal and you deserve to dine at a Michelin star restaurant with your favourite people on this day. Indulge in Booze 21 means that you are also of legal age to purchase alcohol, so why not head to a Italian restaurant in Bangkok and do some shots with your friends? If it is your first time drinking know your limits but, still have fun. This is also the perfect opportunity for you to learn about different drinks and how to mix them. At the bar, you can book a private space for you and your friends and have an incredible time. Hit the Club Once you are 21, you can officially enter a nightclub. Dancing the night away is a great way to start a new chapter in your life. Gather your friends, pour yourself a drink and step into the dance floor like a boss. But, stay within your limits as you want to remember everything that happens on the night of your 21st birthday. These are the top 4 ways to celebrate your 21st and make is a memorable day. It doesn’t matter where you go or what you do, what matters is that you spend time with the people you love. Shopping for gifts can be very hectic, especially if you are someone who leaves to do it the last minute. Running down every aisle trying to figure out what would be a good present can be very tiring. Thanks to today’s technology we have methods to do all our shopping online, as there are a variety of shopping websites available for us to choose a suitable present for everyone. Retail shops There are many websites that give you a selection of Clothes, handbags, shoes and accessories to choose from, they give you information from what brand it is to what material has been used to make them, it offers you with an easy alternative from having to take time off and going all the way to the store, by simply letting you browse a lot of products online at one go. It allows you to pick a product that is suitable for your occasion and have it delivered to your doorstep without having to leave your home. Personalized Items A personalized item is having a name written on a cup or putting a picture of the both of you on a frame, key tag, cup, or even a puzzle. A personalized gift is one of the most meaningful gifts anyone could receive but many people disregard the idea, as it can take hours purchase. Good news is that it is now available online, and it’s the simplest thing ever, as all you have to do is upload the picture, select which item you want it on and enter the address you want to have it delivered. Gift Hampers There are wide ranges of hampers to choose from, these allow you to order flowers, fruits, skin care products and the best of all it allows you to best Australian wine. You have the opportunity to select a hamper and put multiple products in it, both flowers and skin care products or fruits, chocolates and a good bottle ofred wine. There is a huge variety of products to choose from, and you get to pick each detail, such as the type of flower in the hamper and also be able to choose from the different types of wine, which will leave you with the perfect hamper that will be suitable for the occasion you are sending it for. With the information given above you will understand that there are many advantages when you purchase your gifts online, as you can browse online till your heart’s content leaving you with the perfect present and allowing you to have it delivered to their doorstep, making shopping for gifts a very easy task! People follow many kinds of diets these days. It can have different kinds of names, such as vegan diet, weight watcher’s diet, raw food diet, etc. There are many reasons why individuals want to follow this procedure. The majority takes this procedure seriously if they are overweight, heart diseases, cholesterol, etc. This helps a lot of people to recover from many critical sicknesses. A specific eating regimen might be looked for weight reduction or weight picks up. Changing a subject’s dietary admission or beginning the day with a better consumption timetable, can change the vitality amend and increase or decrease the amount of obese put away by the body. A few sustenance are particularly prescribed, or even modified, for adjustment to the necessities of a specific eating regimen. These eating regimens are regularly prescribed in conjunction with exercise. Having a solid eating regimen is an approach to forestall medical issues, and will give the body the correct adjust of vitamins, minerals, and different supplements.To make a diet more interesting you can add sweetness and fruitiness to flavor up your meals. For sweetness you can always buy gourmet chocolate which is typically characterized by the cocoa rate, yet a decent definition would cover the accompanying viewpoints: Fixing quality – for an instance, the nature of the beans, regardless of whether cocoa margarine is substituted by vegetable oil, readiness –for an instance, broiling, last blend, and Imaginativeness – for an instance, plan of chocolate, bundling All viewpoints are vital when taking a gander at chocolates, for example, bonbons or pralines made by a chocolate creator, however, just the initial two are vital while surveying chocolate, for example, couverture chocolate made by a chocolatier. For the fruitiness rich flavor and health, you can always buy gluten free muesli which is enlivened by the conventional Swiss grain. This dazzling mix of gluten free oats, dried organic products, nuts, and seeds can be appreciated a plenty of courses: with yogurt, drain, or squeeze, hot or cool, straight out of the pack or splashed overnight.It is a non-Swiss Standard German a breakfast and early lunch dish in view of crude moved oats and different fixings like grains, crisp or dried organic products, seeds, and nuts, that might be blended with cow’s drain, soy drain, almond drain, other plant drains, yogurt or natural product juice. This is an eating regimen rich in crisp leafy foods as a basic piece of treatment. It likewise can be newly arranged utilizing either dry moved oats or entire grain oats that have been absorbed water or natural product juice. Other regular fixings are extra ground or cleaved new organic product e.g., bananas, apples, berries, grapes, mango. Purchasing fish from the market to bring home to cook your favorite dishes can be quite alluring. But not many know the hardships that go through as these fisherman take a higher journey to invest for their needs whether it be family or house support. The rough patches in their tiresome life these young or middle aged men carry out these jobs with great determination, as without such determination they will not adhere to fish and take over these jobs. Due to the global warming effects the world has been undergoing recently the fish have relatively reduced and they do arrive in smaller sizes and they don’t have much nutrients to absorb to be of a healthy type of fish. Around the world most fishermen find it difficult to navigate across seas, oceans and lagoons to go in search of where fresh seafood Preston are inhibited in large amounts and can be fetched easily from their tying nets so that they receive a greater fee in the market and also competition ties up among their revenues and cash clashes involving not much of a profit gain after a hard working day which they are only working and earning money through the problematical way to only ensure to get a reasonable profit. In additional restaurants fish are consumed in a greater capacity known for its great taste it produces and together making dishes as a side dish served with rice and a soup or noodles added with spicy sauce or even tortillas. Most places you may also find raw fish eaten with cold rice and slices of lime to add a tangy taste. The most re-known and popular dish known as fish and chips paves the way for young adults as they like to enjoy it with a fruit juice and or other fizzy drinks. This dish is great as a serve for grilled and batter fried fish resulting in a great and quality taste ensuring maximum satisfaction. Homemade style fish with recipes to manufacture the different sauces and the various types of fish which can be consumed will be the best feeling you ever would have experienced. Tantalize your taste buds with sautéed fish, roasted and tossed clams/oysters, fried fish available at the most exclusive restaurants and pick your favorite dressing such as salads or sweet, spicy, garlic flavored sauce as an added extra dish and a meal including a rice bowl and a dough wrap which will invite you to have a different set of taste buds. Enjoy the flavor that the fish gives you and purchase from your fish market today. Deciding on a place to have dinner may not pass as one of humans most crucial selections, and It doesn’t mean that you should resolve to the nearest place which serves food for the sake of eating either. Food cannot be categorized as a simple physical necessity because it is one of life’s most valuable pleasures and therefore should be enjoyed in the best of possible way. And it only makes sense that you give enough priority when choosing a place to have a nice meal. This guide is carefully picked and arranged to help you make a good choice the next time you want to have a fulfilling meal and a good memory altogether. Starting off with the basics one of the initial steps into finding a good place is to check on the cleanliness. Before worrying if it’s under the list of best restaurants in Melbourne, or the amount of star reviews the business is currently showing. The least of the things a restaurant should offer is the cleanliness because nobody would want to worry about the later digestive problems while in the process of having their food. Be on the outlook for the conditions of the eatery such as if there are incontrollable number of flies hovering around or if they have messy tables and walls and most of all the sanitary check on the level at which their restrooms are maintained, because if the places that are visible to you aren’t clean it could only mean worse for the places you can’t see. Another sign to help you determine if the place is good is by the number of customers they have maintained throughout since the day of the start of business. Because relying on the self-proclaimed label of having their name under the top 10 restaurants in the city could sometimes be a very well mark of being misled. If the place has a steady number of customers are most likely to provide good food and drinks. You can also ask your friends and peers for their recommendations and opinions but it’s always a good sign to keep in mind that options of others are constructed based on their palates which necessarily might not match with yours. You can also shortlist few places of your choice and personally go to them and check the state of the place and make sure that it matches the type of moment you are planning to have be it business related or personal romantic. You can check the menu of the place or talk to the bartender or manager and then check the atmosphere and the level of sounds to obtain a basic knowledge. The easiest option available nowadays is the websites that are online provided by restaurants for further information and inquiries. These websites also help you go through ratings, menu, facilities and pictures of the place if provided. Some websites also let you make reservations which could come in handy if you have busy schedule to run and have no time to step out. One of the joys of visiting another country is getting to know of its cuisines, both at the national and local levels. The cuisines of Europe, such as those of Italy, France and Spain, are well known for their delicacies, as are the Asian cuisines of China, Japan and India. Every country has its very own cuisine, with a large repertoire of dishes – and accordingly, it is often recommended to try the local dishes when visiting another country for a holiday. For example, you might want to try traditional Lebanese food when in Lebanon or attempt to try the sushi dishes when in Japan. Cuisine is, after all, a major part of travelling to another country. However, you need to keep in mind that you might not very well be used to foreign dishes and that you could cause problems for your gastrointestinal system if you are not too careful. Below are some common tips that you could follow in order to avoid being locked in a bathroom abroad: • The common food types to avoid – when travelling abroad, there is a general consensus on food types that would better be avoided, unless you wish to run into a number of diseases. The number one example here is raw seafood, which is a potential harbour for bacteria of all types (and even amongst seafood, you need to avoid clams, oysters and the like). Uncooked meats and unpasteurized dairy products are also a source of concern, as are any raw vegetables and fruits that you did not attend to personally. • Exotic cuisines? – Every country has their very own ‘exotic’ dishes: food types that sometimes, even the locals do not attempt to eat. It may be the monkey brains of Africa, the grasshoppers of Japan or even the blood pancakes of Finland – basically, every country has a few weird dishes. Now, the question you need to ask yourself is whether you are sure your stomach can handle them. No? Then better not attempt to try them. • Learn the food language/ Use a translator app – previously, you would either have to learn the language quite well, or have a notebook with translations of the various food names and types in order to understand a menu of a foreign country. After all, even a general understanding of a foreign language is often not enough to understand a menu, which can feature different names of fish species, dressings and other untranslatable words, such as the different methods of cooking. However, nowadays we have the smartphone app translators, and you can generally depend on them to get a close enough translation. Make sure to use them (or learn the language, if you want to) when dealing with a menu of a foreign restaurant. With the loads of work that you have to deal with, the responsibilities and less free time will fill yourself with stress. You cannot stop stress but what you can do is to get rid of the stress that you are dealing with and to refresh yourself. Stress is not anything that is easy to deal with. A majority will suggest that you take a long holiday but there are way in which you can say bye to the harmful stress in the little time that you have. Food for the heart Sometimes, food is the answer to everything. In the little free time that you get, what you can do is to visit a French food restaurant with your family. The relaxing environment, the comfort, the mouthwatering dishes and everything less will make your day better and in turn, the stress in your body will be perishing way. Moreover, French food is loved by people from all around the world and there is no reason that you will not. If you have not tried the French cuisine, it is the time that you do. when you spend time with some that you love while eating a mouthwatering dish to please all your senses, you will be living your life in the little time that you get and yes, you will fall in love with this type of an experience that you will make it a habit to make your life better. Visit http://lavache.com.hk/menu/ Go for a run No one of us are too busy and we do have some time left in our schedules that we can use to make our lives better because that is essential to everyone’s life. The best ways of getting rid of stress is to run for it. If you are really too busy, ten minutes a day will be just fine. When you run, you will not only be getting rid of the stress that is a major negativity to your life but your body is always given a good cardio exercise, which in in turn will enhance your health. Get a good sleep You will be getting sleep everyday but what you have to make sure is that you are getting a good sleep. Most of us are sleeping at night but are we really sleeping well? It is important that you arrange your bedroom so that can have a better sleep. When you sleep better, your whole life will become better and you will feel in it your body when you get rid of the stress with your sleep. With the help and support of internet the day to day needs are met extensively. The computer at your place is no more a simple electronic box for playing video games or watching movies. With the help of the internet you can carry out the all the basic needs and even get lots of offers and services at your door. The online marketing adds up much to your comfort level and provides you with a range of products. You can shop online and they are delivered at your place with a stipulated time. The new inclusion in that list is the fresh meat delivery. Earlier you could have ordered for any online dress or designs for your own need but now you can even order your grocery items as well as regular foods online. Meats are also available for online delivery. They are well kept and fresh products. It is not that they will some arrange a previous meet and complete your order. Various types of meats are available online and at an affordable price. Add to the advantage of free home delivery. There are many retail butcher in NSW. They make sure you get all the quality and genuine products. The meat manufactured or dealt with them are all fresh and without any chemicals used in it for long preservation purpose. Generally the technique that is taken to preserve or keep them meats fresh for a longer duration of time is the flash freezing. It helps to keep the meat fresh and good enough for longer duration. The meat is kept in the refrigerators for storage purpose and is usually designed for the suitable shipping processes. In that way you get the quality item and at low price as well. The other positive aspects of them are that they provide special meats which are hardly available in the market all the time. In such online stores you can get those any time. These are the good features of an organic buthcher in Sydney. Moreover they are best suited for special menus and occasions. You can order your desired type of meat and can enjoy them. In NSW chefs are more eager to add special items in their menu and this forces them to take the help of online service. So you can get any item at any point in time. Moreover in the present time where there is tremendous competition in the market you can get a variety of foods at different restaurants. These are the result of online ordering and sustainable butcher. So you too start ordering for different variety of meats and take the pleasure of preparing the special dishes for your family members. There are several places where you could have a wedding. So how do you decide on where to have your special and memorable event of your life? When it comes to deciding where to have your wedding, there are some ways you could come to a conclusion that would be in line with the wishes of both individuals. Put your heads together Everyone has dreams of how they want their wedding to be. For that reason, both the bride and the groom need to put forward their dream wishes and see what would be possible to execute. In most cases the budget would determine which dream destination for the wedding one could realize. Today it is also easy to find online today function venues South Yarra. You can browse through the different banquet halls and venue lists in your area to get an idea of the different wedding venues that are available. Making a budget Once a couple has arrived at, a destination for their wedding they can then decide what kind of costs they would incur. Every destination would have different costs. For instance, if you have decided to have the marriage party in your home backyard, you would be saving on the rental that comes when you check out for function venues. At the same time, function venues at hotels and resorts will differ their prices as per their brands, luxury ratings, amenities you ask for and so forth. If you have an outstation wedding there would be accommodation aspects to take care of additionally. Look at your options Once you have a budget as to how much you can spend on your wedding you can then look at the places that would fit that. There is no need to go overboard simply because you have a dream destination in mind. It would be wise to set a reasonable budget for the wedding venue asthere would be other costs to cover as well. You could always keep the marriage small and splurge on the honeymoon destination for both of you. The above points help you arrive at the ideal destination for your wedding. There would be other aspects to look at, such as availability or accessibility of the venue for your guests, accommodation requirements and so forth. The service and food as well as other entertainment and décor aspects need to be looked into as well. These points need to be mesh well as your ideal wedding destination and it should be a place that will remain memorable for both of you for years to come. Hervey Bay in the country of Australia is known to manufacture the most delicious of sausages that are really worth digging into on the part of those who are avid foodies and who live to eat rather than eat to live. The gourmet sausages in Hervey Bay are served in most of the gourmet dining destinations in the city which open for breakfast, lunch as well as dinner. Customers are not likely to suffer from food poisoning when they opt for the consumption of these sausages whether rarely on or a frequent basis. For the best gourmet sausages in Gold Coast, it would be a good idea to visit some of the well known super markets in the major cities and towns over here. Sausages are sold in both uncooked form as well as in ready to eat form and consumers can buy any one of the two depending on their preferences. It would be a better idea to buy the sausages that are uncooked as one can get to fry this using cooking oil at one’s own home and thereby ensure that these are cooked in a healthy manner or way. The services for smoked food catering Burleigh heads is known to have sausages as a part of the many gourmet food items that are provided to customers. The sausages are sold both as snacks as well as a part of the main course. The sausages which are offered as snacks are cocktail sausages and are quite small in size. These are first deep fried after which they are dipped into some sweet sauce in order to add flavor to them. One will be able to consume four to five of these sausages at a given time without any trouble. For affordable catering Burleigh heads one has to carry out an advance booking as it is those who do this who get to avail of discounted rates on the catering services as a whole. The rates of discount which are offered on the catering services are about ten to twenty percent. At the time of booking catering services one should ensure that one has a ready function venues Canberra to provide the caterers with in which they can organize and cook the food and also serve it to the guests on time. Without an adequate venue requesting for catering services would not be a worthwhile thing to do. Payment for gourmet catering services needs to be made on cash down basis so that caterers are in a position to get started on the catering work immediately. Find a Canberra Italian restaurants for your delicious food. Attending wine tastings and going on winery or vineyard tours is exciting for a lot of people, because not only do they get to experience the actual making and production of wine, but they also get to sample the product at the end of the tours. Whether you’re looking to go on tour to a vineyard to see the endless fields of grapes, or you want to go to a winery to see the process of making wine, we’ve got the best tour line-ups around. If you’re curious about how wine is made, or just want to see what a vineyard or winery looks like, then take up one of our great tours today! Join us for one of our amazing vineyard tours in Melbourne and we’re sure you’ll have a blast. Every vineyard is different, so don’t assume you’ve been to them all if you’ve been to one already! Give us a chance to show you just how different each vineyard really is by inviting you on a tour of our great vineyard in Melbourne. Our great company is ready to show you around the best wineries in Yarra Valley, so if you’re in the mood for wine, or just want to go for a short and sweet trip, join us for some great Yarra Valley wine tours! During our great tour, you’ll get to speak with friendly employees and meet the owner of the winery, as well as get to taste a few of our best selections! If you’re interested in our great winery tour in Yarra Valley, then call us up today and book a tour for you and your closest friends! Going to a winery is fun and a great way to spend the day with the people you love, even if it’s with just one other person. Book a tour today and ensure that you and your friend, or family member, have one of the best days off ever! Even if you’re only able to make a part of the tour, we guarantee that you won’t regret a single minute of it. Although you may regret having to miss the rest of the tour! But don’t worry, you can always book another tour and come right back when you next have time off. Do you live in the Mornington Peninsula area and are looking for something a little closer to home? We have a great winery available just waiting for you to book in a tour today! Our Mornington Peninsula wine tours are listed as some of the best tours you’ll ever attend in Australia, so stop dawdling and putting off actually going on that tour! If you want to go on a tour, go for it! They’re not expensive and every minute of it will be a blast, even if you go alone! We’ll ensure that your entire trip is worth every cent you paid and that you leave with a smile on your face! For all the coffee lovers out there in the world, getting a coffee maker is one of the best investments to make. You can then be able to have all those cups of copy when you want it and how you want it. Even if you are not a lover of coffee drinks, it may still be important to have a maker at home. This will help you cater for all your guests. There are many different types of coffee makers in the market and most of these can be bought at affordable prices. If you are new to coffee makers, there are a couple of things to look out for when you decide it is time to buy a coffee maker. These will help you in your choice for the right machine to buy. Type of maker Coffee makers come in different styles and makes. There are those that are single pods and others that are the normal drip models. There some specialty brands like the espressos and the cappuccino. For those who are new to coffee, this may not make any sense. However coffee lovers would easily understand that the type of machine you buy will determine the kind of brew you can make with it. The most popular machine that is used by many is the drip machine. Either way each machine has its advantage and its disadvantage. Capacity Depending on whether you are looking for a maker which can make single cups of coffee like the when you buy nespresso pods Australia or those that can make up to 12 cups you can search online or from the shops. The capacity that may please you will depend on whether you are buying a maker that will serve only you or guests too. There are those 4 cups coffee makers which are good for travelling and there those that can make up to 24 cups and suitable for buffet. Must have features There are other features that you should look out for when buying a coffee maker. These include; • The auto off switch; no matter what type of coffee maker you are buying, you should check to ensure that this safety feature is included. • There is a brew interrupt feature that allows the user to stop the brewing cycle and get coffee. • Some coffee makers can come with programmable features. You can program the machine to brew coffee only when you want. • Other features include the brew selector. Hopefully you will be able to get the right maker to suit your needs. It is often advised that even if you stay alone, you should get a maker that can serve more than four cups. That way, you can serve your guests when they come over. Family is the most important thing in the whole world. If there is one person that keep the family happy and united, is a mother. Being a mother isn’t easy: she has to carry her baby in her stomach for 9 months and then take care of her god given gift for the rest of her life but a mother never takes it as a burden. A mother always helps her family members to uplift their mood, motivates them, helps them take the right decisions in life and are always by their side. Having a mother is truly a blessing. Make your family happy with a delicious meal Who doesn’t love a delicious meal? Yes, everyone does, especially when it’s made by our own mother. Every food becomes tastier when mother makes it because she mixes her love into the food. If you’re a mother who wants to take good care of your family members and if you love seeing your family members happy, the best thing you should do give them is a delicious plate. If you are not happy about your cooking skills, you can take a good group cooking classes in Sydney. Siting in the dining table together, helps to build up the family bond. After a hard day at work, your husband comes home looking for relaxation, he will love it if he gets surprised by a lovely and so will your kids. Spend quality time with your family Maybe you don’t have time to spend with your family because you are stuck with your work but that is not an excuse; family should always come first. The attention given by the mother and the father contributes a lot to the mental wellbeing of the child. Make sure that your children doesn’t feel neglected. Be understanding Its better being a flexible mother than a strict mother. You should always talk to your children and you should bring out their feelings. The more you talk to them, the more you’ll know their desires and what they are up to in life. If your child dreams of being a musician when he grows up, you should motivate and supply him with the necessary equipment. If your child wants to do something which is not healthy, instead of just giving them a ‘no’, you can explain why it is bad and what effects it will have on their future. even a mother explain, every child will understand but when the mother chooses to simply say no, children will start questioning your love for them. When your office or home is situated you can be rest assured that is you want to arrange a party at home, you do not need to panic about the food services. Simply leave it to the professionals and you spend quality time with your guests. There are many catering companies. The catering companies emphasize on – quality service, customer satisfaction and repeat orders. Starting from the chairs, table, marques, table linens and crockery they provide everything. Now there can be carious types of party like- wedding, birthday, anniversary celebration, and college reunion and even corporate. Professional companies know what sort of decor to arrange the type of food to served on the table. Spit roast parties have become a recent trend. Mobile food trucks is a specialised service and it needs the right choice of chair, table and dull coloured decor. The decor has to be smart. Drinks, starters, main course, side dishes and desserts comprise the main attraction of the party. In case of corporate dinners it consists of round tables or centre table with a dais where the speaker stands and addresses the crowd. The theme colour of the party should be selected as a dark one or extremely light. Generally colourful decor is not preferred for this purpose. Party caterers create such an ambiance and mood so that the guests are bound to enjoy and cherish each and every moment of it. Generally the menu differs from corporate party and a fun filled casual party. Theme parties are also very common and popular. The food may be more or less the same but the difference is brought about in the mood of the party. Boat party is a very popular concept for wedding or other occasions. The party caterers should be responsible for creating vibrant ambiance and make it memorable for the guests. Catering services are a good business but all you need to do is serve the customer to the hearts content, create an atmosphere of friendship and see that the clients will definitely remember you and give a call for the next party. Small gifts like key rings, menu cards and show pieces can be considered a good means of branding for the catering company. These sort of low scale BTL activities are useful both for the catering company and the client. So, when you are determined to have a party at your home, simply get the menu from your friend. Then it’s time for you to decide over the menu. Generally for a 3-4 course meal you should have 10- 12 types of menus. If you want to go for a budget party then 7-8 types of menu is enough. The count of people should be determined and you should ask for a quote from the catering manager. In case of cocktail party, the drinks section should be separate and a separate budget for drinks should be prepared. For cocktail party side dishes and snacks should be truly exclusive. So, get indulged into the fantasies of a party in your house that will be remembered for its service, food and fun filled ambiance. Lets friends talk about your memorable party for years to come. I have often heard it mentioned that different types of wine can be personified as different kinds of stereotypical individuals. A Cabernet Sauvignon is a military general, due to its bold and stolid flavour that is somewhat heavy-handed. A Shiraz is gypsy-style woman who is free in spirit and lives life on a whim due to its fruity and indulgent taste. A Chardonnay is well-dressed woman of style who is very prim and proper, due to its crystalline colour and subtle flavours. Whether or not this type of person would drink the wine matching their description, I do not know. However, it does seem a very good way to differentiate between wines and more so, to gift wrap them. Wine gift boxes are often very plain in style. Thinking of wines as people is a very good idea to dress up these gift wrappings. If you are giving a Cabernet Sauvignon as a gift, dress the gift box up as a military general, using cut-outs and various other scrapbooking materials. You may also decide, however, that this is a silly idea. This is no matter because most of the people I drink different types of wines. And so, why not make that wine their signature drink. When you give it to them as a gift, dress up the gift bag as something that is typically them and then in the gift card write out a description of how their personality matches the wine they love so much. I am sure that you can buy wine gifts NZ in every colour and so finding a suitable background shouldn’t be an issue. A Sauvignon Blanc is a very fresh and natural tasting wine and so maybe you can buy a green gift box and dress it up with pressed flowers and dried leaves. A Riesling or a dessert wine can be decorated with brightly coloured, candy-themed decorations to match its natural sweetness. You could also attach a few sweets onto the outside of the wrapping to the recipient can enjoy their wine with something nice to go with it. In fact this is a good idea for any wine. Whatever a specific wine is supposed to pair with, attach something along that theme or write a little note explaining what would be best to drink it with. There are thousands of ideas to choose from. This is a fantastic idea as both wine and people are so versatile. These gift boxes will be so beautiful that the person receiving them may even keep them to use for something in their home to remind them of you and themselves, as opposed to throwing them away or using to give wine to someone else. If you are someone who loves fashion and has a knack for the fashion world, you would consider choosing that world as your career. If you are good at show casing the beauty of clothes and accessories by wearing them properly and have an interest in walking the ramp, you can try becoming a model. If your talent lies in designing new clothing ideas then, you can become a fashion designer with the proper training and education. This is the same with any field. Becoming a business owner is choosing the world that you love in order to be successful. Right now in the business world, there are multiple opportunities that you can use. If you look at the beverage industry in Australia, there is a fast growing franchise based on tea. If you can become a part of that franchise, that will also be good. You can try entering the business world on your own. If you have enough capital and a good plan that can make you successful you can try entering the business world. If the branch in the business world that you are trying to enter is the beverage industry, you should first start by looking for a place where there is a market for such a service. You can find out what types of drinks people like to drink. This is all relevant for someone who is thinking about starting a place that supplies fresh beverages. If you find it difficult to enter into the beverages industry on your own you can look for other options. For example, if you take a look at the bubble tea outlet franchise they are ready to help you become a franchisee for them. You need to contact them. After a simple process you can be looking at becoming a part of a growing business. You will of course have to face an interview and undergo training if you are chosen. However, that is fine because at the end of the day your dream of entering the beverage industry is realized. If you are someone who has a passion for beverages and wants to enter that world as a business person, you have two choices. First choice is staring a beverages business of your own. Second option is joining a franchise that is already flourishing and is ready to help out those who have your desire. Starting your day off the wrong foot can set the tone for how your entire day will go. Every now and then even the simplest things can make all the difference, like stubbing your toe getting out of bed, or just having a cold cup of watery java. The act of making that perfect cup of Joe can make the day so much easier for the average working person or college student. Here are a few tips to make sure you improve that brew. Fresh Roast Most people just buy some generic beans or mix from a local store and stick it in a pot or a Chemex Classic coffee maker for a little while. This is just not enough for that perfect blend. Take a bit of time to find some fresh, flavourful roasted java. Experiment with a few so that you can find something unique and delicious. Make sure to buy fresh because flavour tends to break down fast. The process of selecting the flavours and the choice you finally make will be your inspiration every morning. Store in Air Tight Containers That espresso may not taste so good because you’re storing your beans in the wrong containers. Roasted beans should not be exposed to oxygen as they will deteriorate and the flavour will just about vanish. Even the airtight packaging the beans come in can cause oxidation from the air inside. This is why you should check the date they were roasted on. The fresher the beans, the better the taste. Also, you should not be storing your beans in the refrigerator. The best storage option is an airtight glass jar. Ditching the Sugar Do you find yourself ditching the sugar because you are worried about the calorie content, even though you dislike the bitterness of a black brew? Well, then it’s time to switch your machine to just a pot and a Hario V60 copper dripper because it helps to improve your coffee station. This is the ideal pourover option because it uses slow extraction to give you a sweeter taste without having to add heaps of sugar. Water You’d be surprised how much your water defines the taste of your brew. You should taste the water you are using and check if there is a chlorine or rusty taste. If there is, you need to purify it. Boil or filter your water to make sure it is pure, and then use it for your brews. These tips will instantly make your mornings (and therefore your days) so much better!

Get Your Weekly Digest Channels International More More from Complex Networks 6-17-23 #12 Air Jordan 6-17-23 Release Date: 2011 Complex Says: This model takes characteristics from the Air Jordan VI and XVII (which equals 23, hence the name) using the VI’s main body mixed with the XVII’s heel and lacing system. The glossy midsole and icy outsole set it off for a pretty sick sneaker. You may have seen Kemba Walker hurting feelings in these as of late. No Articles Found. Try Our Search Here: Now Trending COMPLEX participates in various affiliate marketing programs, which means COMPLEX gets paid commissions on purchases made through our links to retailer sites. Our editorial content is not influenced by any commissions we receive.

Pages Wednesday, July 18, 2012 Busy, like a, whataya call it? That rat thing with the flat tail. Like's trees. Buck teeth. Busy like one of those. By George and Bob-howdy, I have been keeping busy! You won't hear me complain (unless I'm complaining, that is), but man ALIVE! Here are the highlights from the last eight-to-ten weeks. My good friend Joel was lucky enough to marry a lovely wife, who later brought along a sweet daughter. With Joel's birthday and Father's day fast approaching, Erin asked me to make this, which turned out lovely. That's Grace up on his shoulders, and everything was going great until I mailed it. See, all of the zip codes in Lawrence, Kansas (where I used to live) go 606**, whereas all of the Chicago zips go 660**. I'm a feeble-minded young man, so I'll leave you to put the puzzle together and guess how I DERAILED a nice gifting experience. It took about two months to straighten itself out, and happened to get delivered while I was having a beer with Joel himself, in Kansas, just a few miles from his home. I could have biked it there faster! But it got there, and he loved it. FTW! Then, of course, there is this one. I'll keep it short: He hated it. End of story. I never heard if he went through with using these dolls as a vehicle for a marriage proposal, which was their intent. Custom artwork can be tricky, and I am more than pleased to say this is my second (#2) dissatisfied customer EVER. In the end, his dissatisfaction had to do with the likeness, in that they looked old and fat, which, you see, nesting dolls, their general shape is... Oh, well. Back to happy! These kids turned out to love their portrait, all suited up to fight crime. It was a gift for the oldest childs' birthday (he's batman, there in the middle). The parents and kids were all very happy with it, I am pleased to share. Next came the singularly most random and fun-to-paint wedding invitation OF ALL TIME. What you see here is the result of a request for a wedding invitation image that was to encompass, and I am quoting here, "mummies, sarcophagi, a T-Rex named Ivan, shrunken heads, the Berlin wall, something from the Revolutionary and Civil Wars, the two grooms, and (their) cat, Carrie Fisher." Basically, awesome. They loved it, and I wish them a long and happy marriage! You may recognize the fellows and their cat from a previous post, in which they were made into little, adorable peg people. MUNCHIE! He's into adventures, apparently, which are chronicled verbally by my friend John and his wife, for whom this was a gift. We are all curious, John, and when the time comes, I expect to be considered for the illustration half of the award winning children's book. MASKS! On toddlers! So very cute. These were commissioned as take-away party favors for a very special fourth birthday party. They were a hit! There was also a fox mask, which I somehow managed not to photograph. So cute! I made this elephant last night! I think I'll be pumping a few out to try to unload at Renegade Craft Fair, which I will again be participating in! Oh, boy, so much to do. This giraffe happened today, and they are great friends, he and the elephant. I know because they TOLD ME. I need to sleep. Oh no they're CONSPIRING AGAINST ME! Sorry for the 'instagramminess' of some of these photos, I try not to use them outside of the 'gram itself, but it had to happen if I wanted to get this up tonight. No comments: Get Personal Benjamin RumbackAn emerging artist in the neighborhood of Lincoln Square, in the city of Chicago, in the state of Illinois, which is part of the United States of America and the world at large... located in the milky-way galaxy in the universe.

Centrifugo-Magnetophoretic Purification of CD4+ Cells from Whole Blood Toward Future HIV/AIDS Point-of-Care Applications. In medical diagnostics, detection of cells exhibiting specific phenotypes constitutes a paramount challenge. Detection technology must ensure efficient isolation of (often rare) targets while eliminating nontarget background cells. Technologies exist for such investigations, but many require high levels of expertise, expense, and multistep protocols. Increasing automation, miniaturization, and availability of such technologies is an aim of microfluidic lab-on-a-chip strategies. To this end, we present an integrated, dual-force cellular separation strategy using centrifugo-magnetophoresis. Whole blood spiked with target cells is incubated with (super-)paramagnetic microparticles that specifically bind phenotypic markers on target cells. Under rotation, all cells sediment into a chamber located opposite a co-rotating magnet. Unbound cells follow the radial vector, but under the additional attraction of the lateral magnetic field, bead-bound target cells are deflected to a designated reservoir. This multiforce separation is continuous and low loss. We demonstrate separation efficiently up to 92% for cells expressing the HIV/AIDS relevant epitope (CD4) from whole blood. Such highly selective separation systems may be deployed for accurate diagnostic cell isolations from biological samples such as blood. Furthermore, this high efficiency is delivered in a cheap and simple device, thus making it an attractive option for future deployment in resource-limited settings.

1. Field of the Invention The present invention relates to sending and receiving facsimile documents via a facsimile machine, and more particularly to sending and receiving secure facsimile documents via a facsimile machine such that the receiving party cannot directly read the received facsimile document. 2. Description of Related Art At present, when a standard facsimile (FAX) machine is utilized to send important, sensitive information, such as financial, legal, personal or sensitive business data, the intended receiving party may not be the only party/person who views the received FAX document. In many cases a received FAX document may be handled and viewed by FAX room personnel, hotel personnel, or various corporate staff members prior to the received FAX arriving in the hands of the intended recipient. Thus, the important, sensitive information on the received FAX document may be seen or reviewed by parties who should not be viewing the document. Having sensitive information viewed by unintended viewers could result in a tremendous negative impact on an individual or corporation. The drawback of the standard system for sending and receiving FAX documents is that the intended FAX recipient does not need to be present when the FAX document is received and printed or displayed. One technique for solving the problem is for the sender and intended recipient of the FAX document to arrange a mutually convenient time for sending/receiving the FAX document so that the intended recipient can wait by the FAX machine for the document to be received and printed. This will insure that the intended recipient is the only viewer of the received FAX document. A drawback of this solution is that it can be inconvenient for both parties to set up a mutually acceptable time. It is further inconvenient for a traveling party who is receiving a FAX document at a hotel, client""s business location, or, other location that is not in the control of the intended recipient. What is needed is a method and/or apparatus for sending and receiving FAX documents in a manner that disables the ability of people, other than the intended recipient, from viewing the received FAX document. It is an object of the present invention to provide a method and apparatus which allows a FAX document to be sent and received wherein the received FAX document cannot be interpreted by anyone casually glancing at it. It is a further object of the present invention to provide a FAXing system and method that provides a hard copy of a secure FAX that is not legible to a human, but that can be decoded by an intended recipient of the same FAX. It is a further object of the present invention to provide a method for encrypting the body of a FAXed document and to provide an unencrypted heading on the received FAX document. The encrypted heading informs a FAX operator who the encrypted FAX is for. These and other objects, which will become apparent after reading the specification and studying the drawings, are accomplished by encrypting the body of a document using a code provided by the sending party. An unencrypted header is provided. The unencrypted header and the encrypted body of the FAX document are FAXed as a normal FAX via a system capable of transmitting a FAX document. When the FAXed document is received, it may be printed out as a normal FAX. The receiving party, who may not be the intended recipient of the FAXed document, will not be able to read the encrypted body of the received FAX document. The receiving party will be able to read the unencrypted header. Via the header, the received FAX can be delivered to the intended recipient. The intended recipient can scan the received encrypted FAX into a computer and provide a decode code. The computer, via software will decrypt the encrypted body of the received FAX document with the decode code to produce a facsimile of the original document for the intended recipient.

Finding the Right Hearing Aids For Your Needs Gone are the days where hearing aids are embarrassing. Nowadays, they are so small and unnoticeable; many people won’t even notice that you have hearing aids until you tell them. So how do you choose the best audiologist for open fit hearing aids Charlotte? There are only a few audiologists in the area, but every one of them has the knowledge and expertise to get you fitted for the right hearing aids. Making a choice may be intimidating, but if you follow a couple of steps, the choice is quite simple. Before you choose an audiologist for hearing aids, make a couple of phone calls. Here are some of the questions that you should be asking: How much does an appointment cost? Do you take my insurance? How much are hearing aids? Do you have any specials or discounts? What are your office hours? How much experience does your company have? Getting the answers to these questions will help you determine which audiologist(s) are right for your needs. Many times, the secretary at the audiologist office will have the answers to these questions, or they will have the audiologist call you back in a timely manner if you have questions that they cannot answer. There are plenty of options for you to choose from when it comes to getting the aids that you need. Take the time to look into what is out there and to learn about what can be done to make the whole process easier on yourself. Then, you will be in a better position when it finally comes time for you to go ahead and see what your insurance will cover and what you can afford to get to make life just a little bit easier for your future.

Q: What is a good mastering chain to use in a DAW? I realise that there is no one 'correct' answer to this (so maybe this can be marked community wiki), but as a hobbyist with a small home studio I would be interested to hear how others set up their mastering chains within their DAW to finish off recordings, along with the rationale behind it. Links to plugins are appreciated. My current setup tends to consist of a multiband compressor (Sonitus multiband or ReaXComp) followed by a limiter (Kjaerhus Classic Master Limiter or Yohng W1). The kind of things I am interested in: Do you include EQ, and if so, where in the chain? If you use multi-band compression, how many bands do you typically use? Do you add reverb? Do you use any analogue/tape saturation simulation plugins? Do you use any metering plugins and if so, how do they help? A: Mark, While "sims" in your comments is correct that it does depend on the source material, and I've never met two professional mastering engineers with the same signal paths, I will give a shot at trying to answer your question based on my own mastering work. Generally my chain ends up in blocks, in the following order, though any block may be in or out at any given time: Minimum Phase EQ Linear Phase dynamics Pre EQ Dynamics blocks Linear Phase EQ - post dynamics Ambience Stereo width Final eq Limiting I also tend to use a good amount of mid-side processing (see my blog for a long primer on mid-side) To answer your specific questions: a) I'll use eq where ever I feel like it, and almost always on either side of my dynamics to pre and post shape the audio into the dynamics to get them to do what I desire. b) I tend to use multi-band compression as little as possible. Generally the better the incoming mix, the less I use. Multiband can be a useful bandaid for poor mix balance, but it's not a substitute for mixing chops. My most common use of multiband is typically a single band to fix a specific problem. For instance, if there is a particular frequency band that needs a lot of eq to fix balance issues, sometimes a multiband before that eq will smooth the band enough to make the eq correction less apparent. c) Ambience with a reverb or delay is a rare, but sometimes used item. More common is tailored dynamics to shape the ambience in the original recording. d) When I find a tape plugin that I like, then maybe. e) I don't use a level metering plugin. First, many of the don't correctly apply a reconstruction filter, and therefore useless for detecting intersample overs. Second, because of the phase shift near nyquist in some implementations of the various lossy codecs that people use almost exclusively to listen to music, the final peak levels of the wav/aiff will not correlate to the final peak levels of the mp3/aac. Almost inevitably you have to print the lossless file a little lower in level, convert it, and then look for intersample overs in the resulting file, and adjust the print level of the final product to give as much as possible without those intersample overs.

Fast Facts: › Curiosity is using its wheels, as well as its science payload, to investigate sand that forms active dunes on Mars. › Plans call for the rover to scoop up and sieve sand for onboard laboratory analysis. NASA's Curiosity Mars rover has begun an up-close investigation of dark sand dunes up to two stories tall. The dunes are on the rover's trek up the lower portion of a layered Martian mountain. A view of the rippled surface of what's been informally named "High Dune" is online at: http://www.jpl.nasa.gov/spaceimages/details.php?id=PIA20168 A wheel track exposing material beneath the surface of a sand sheet nearby is at: http://www.jpl.nasa.gov/spaceimages/details.php?id=PIA20169 The dunes close to Curiosity's current location are part of "Bagnold Dunes," a band along the northwestern flank of Mount Sharp inside Gale Crater. Observations of this dune field from orbit show that edges of individual dunes move as much as 3 feet (1 meter) per Earth year. The rover's planned investigations include scooping a sample of the dune material for analysis with laboratory instruments inside Curiosity. Curiosity has been working on Mars since early August 2012. It reached the base of Mount Sharp in 2014 after fruitfully investigating outcrops closer to its landing site and then trekking to the mountain. The main mission objective now is to examine successively higher layers of Mount Sharp. For more information about Curiosity, visit: http://mars.jpl.nasa.gov/msl News Media Contact Guy WebsterJet Propulsion Laboratory, Pasadena, [email protected] Brown / Laurie CantilloNASA Headquarters, Washington202-358-1726 / [email protected] / [email protected]

Flavoring components are utilized in a wide variety of food and beverage products to impart, provide, modify, or improve the flavor or taste to the product. Such components often inherit some undesirable characteristics due to processing of the raw materials. Also, it is possible that desirable flavor characteristics can be lost or degraded after processing or storage over time. All these undesirable characteristics result in lower quality of products to which these components are added. For example, coffee aroma derived from Robusta coffee beans is perceived as harsh, rubbery, or earthy, and is undesirable for some consumers. Coffee aroma from low grade Arabica coffee beans is also perceived to be fermented, baggy, or cereal in nature. Another example, delicate coffee aroma is often degraded, lost during processing as seen in instant coffee and ready-to-drink manufacturing methods. Also, coffee aroma is known to be very unstable. As coffee aroma degrades, it generates unpleasant and non-coffee-like notes that are undesirable. This degradation substantially reduces the perceived quality of the product. For this reason, special attention must be paid to the preparation and storage of flavoring components such as coffee aroma so that desirable aroma components are enhanced or undesirable components are reduced or eliminated. The prior art recognizes that various flavor protective agents can be added to food or beverage products in order to preserve, maintain, or improve the flavor characteristics of such products. It is well known in the art that sulfites can be added to beverages such as beer or wine to preserve the flavor of such beverages. Generally, sulfites act as antioxidants to prevent deterioration of the flavor. For example, sulfites can react with oxygen to prevent deterioration of the flavor of the product due to oxidation of the flavoring component. Also, Japanese patent application 08/196212 discloses the addition of sulfite, catalase, cysteine, or glutathione to a coffee beverage when liquid is added to reconstitute the beverage. This is not very effective as the sulfite simply dissolves in the beverage without significantly improving or preserving the aroma because the sulfite is added into the whole food matrix and is integrated therein. Instead of adding the sulfites directly to food products, U.S. Pat. No. 4,536,409 discloses that sulfites may be incorporated into the packaging to prevent absorption of oxygen into the packaged food. Again, oxidation of the flavor component is reduced so that the desired flavor of the food is retained for a longer period of time. U.S. Pat. No. 3,540,889 discloses that methyl mercaptan can be added to an aqueous extract of soluble coffee solids prior to drying the extract to a stable moisture content for improving the flavor of this extract when it is reconstituted as a coffee beverage. Despite these disclosures, there still remains a need for improvement of aromas by enhancing desirable aroma components, reducing undesirable components, and preserving volatile flavoring components in order to improve their ability to impart the desired flavor, taste, and other sensory characteristics to foods to which they are added. The present invention now provides a number of practical solutions that satisfy this need.

St. Patrick pitcher Anna D'Aquilla throws against Philadelphia during the first inning of their 3A softball playoff game at St. Patrick on Monday, May 1, 2017. D’Aquilla helped lead St. Patrick past Philadelphia on Tuesday. The 2-1 series win sends the Irish to the Class 3A South State series. John [email protected] St. Patrick pitcher Anna D'Aquilla throws against Philadelphia during the first inning of their 3A softball playoff game at St. Patrick on Monday, May 1, 2017. D’Aquilla helped lead St. Patrick past Philadelphia on Tuesday. The 2-1 series win sends the Irish to the Class 3A South State series. John [email protected] Prep roundup: St. Patrick, Long Beach forced to work with South State at stake St. Patrick and Long Beach had to work Tuesday but in the end, both Coast softball powers did enough to advance to the Class 3A and 5A South State series. The teams entered Tuesday leading their respective best-of-three series 1-0. St. Patrick fell to Philadelphia 3-1 in Game 2 before rallying in Game 3 to win 7-6. Likewise, Long Beach dropped Game 2 against Brookhaven 3-2 before winning convincingly 11-5 in Game 3. Marissa Hanley led the Irish (22-4) with three hits in the first game of the day. Morgan Redmond (2-1) went the distance in the Game 2 loss. Both the Irish and Philadelphia traded shots throughout Game 2 with an insurance run in the seventh ending up as the difference maker. Raven Blackwell led the Irish with a double and a triple. Raylen Blackwell and Anna Grace Castanedo also added doubles. Hanley had a team-high two RBIs. Morgan McCrea added two singles. Anna D’Aquilla (20-3) picked up the complete game win, striking out two. Be the first to know. No one covers what is happening in our community better than we do. And with a digital subscription, you'll never miss a local story. South State will start Friday at Choctaw Central. The series will head to St. Patrick on Saturday for two games if necessary. Bearcats moving on Malayna Cruz and Faith Peterson led LBHS with two hits apiece in Game 2. Savannah Bryant struck out one in the loss. Game 3 was a much different beast as Abbey Fisher rapped out four hits, including one double. Peterson and Allie Dubuisson recorded a single and a double. Dayna Jordan added two singles. Bryant and Peterson led Long Beach’s offensive outburst with two RBIs apiece. Bryant earned the complete-game win, striking out two. LBHS will play the winner of Wayne County and Picayune in the Class 5A South State series. Picayune travels to Long Beach on Thursday. East Central 5, Newton County 3: Kaleigh Fillingame led ECHS (24-6) with a double and two RBIs. Ashlynn Vice added a two-run homer. Taylor Lawson earned the complete-game win. Games 2 and (if necessary) 3 will be Thursday. Winner advances to play North Pike/Lawrence County winner.

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631 S.E.2d 408 (2006) 279 Ga. App. 352 LILES v. INNERWORK, INC. No. A06A0239. Court of Appeals of Georgia. May 12, 2006. *409 George L. French, Atlanta, for appellant. Douglas C. Dumont, Bruce A. Taylor, Jr., Drew, Eckl & Farnham, Atlanta, for appellee. RUFFIN, Chief Judge. Debra Liles was injured at a corporate retreat while participating in a "team-building" activity organized by Innerwork, Inc. Liles sued Innerwork, claiming gross negligence by its employees. The trial court granted summary judgment to Innerwork, concluding that Liles had assumed the risk of injury by participating in the activity. We agree with the trial court and affirm. We review a grant of summary judgment de novo, "giving the opposing party the benefit *410 of all reasonable doubt and construing the evidence and all inferences and conclusions therefrom most favorably toward the party opposing the motion."[1] So viewed, the evidence shows that as part of a retreat sponsored by her employer, Liles took part in a team-building program organized by Innerwork. She was assigned to a group led by Jay McLeod, an Innerwork employee. Liles executed a release relieving Innerwork of liability for any injury she might suffer unless that injury was caused by gross negligence or wilful misconduct. After engaging in several other activities, Liles' group was to perform an activity called "Over, Under, Through." The group was placed in an imaginary box whose boundaries were indicated by stakes and strips of caution tape. Members of the group were to assist each other in getting out of the box. Liles had some concerns about the safety of this activity, but agreed to participate. She had declined to participate in at least two of the previous activities because she felt they could be dangerous. Liles was the first participant to be lifted over the tape, which was estimated to be eight feet high. Liles expected McLeod to assist her once she was lifted over the tape. Prior to being lifted up by her teammates, Liles saw McLeod standing on the other side of the tape. Once she had been lifted up, however, she realized McLeod was not there to assist her. Liles jumped to the ground and injured her knee. Innerwork moved for summary judgment on Liles' claim, relying on an affidavit by McLeod and depositions given by Liles and Greg Newell, one of the people who had lifted her. Liles submitted an affidavit in response to the motion for summary judgment that, she argues, created genuine issues of material fact as to whether Innerwork was grossly negligent and whether she assumed the risk of injury. The trial court granted Innerwork's motion, and Liles appeals. 1. Liles first contends that the trial court erred in failing to consider as evidence her affidavit submitted in response to the motion for summary judgment. The trial court found that Liles' affidavit was self-serving and conclusory and thus did not create an issue of fact for trial. In order to be considered by the trial court, [a]ffidavits supporting and opposing summary judgment must be made on personal knowledge and must set forth such facts as would be admissible in the evidence. All hearsay evidence, unsupported conclusions, and the like, must be stricken or eliminated from consideration in a motion for summary judgment. A self-serving, conclusory affidavit not supported by fact or circumstances is insufficient to raise a genuine issue of material fact.[2] In her affidavit, Liles made several statements that contradict her deposition testimony. Specifically, she stated in the affidavit that: "I was told that I must take part in the activity and that I would be the first participant in the activity"; "as members of the group were lifting me over the tape, Mr. McLeod received a radio transmission from the Innerwork base camp"; and "Mr. McLeod moved away from the `box' in order to talk on the radio." In her deposition, however, she testified that she understood she was not required to participate in any activity; she had already refused to participate in two activities she felt were dangerous; and while she had qualms about being lifted by her teammates, she chose to participate, asking her teammates "to make sure that they held onto me the whole time." This was corroborated by Newell's testimony that Liles volunteered to go first because she had been a cheerleader and knew how to land. Liles also testified that she did not know where McLeod had gone when he moved away from the box; rather, she later heard from "somebody" that "he was talking to his girlfriend on his cell phone."[3] And *411 Newell had no recollection of McLeod using a cell phone during the activity. On motion for summary judgment, the court must construe any contradiction between a party's deposition testimony and affidavit against the party, unless the contradiction is satisfactorily explained.[4] "Whether such testimony is contradictory, and whether a reasonable explanation has been offered[,] is a question of law for the trial court."[5] We agree with the trial court that portions of Liles' affidavit contradict her deposition testimony, and the record contains no explanation for these contradictions. As such, the trial court properly refused to consider the contradictory testimony contained in Liles' affidavit.[6] The uncontradicted portion of Liles' affidavit should have been considered in evaluating the motion; thus, to the extent the trial court excluded the entire affidavit, it erred.[7] Any error was harmless, however, as the remaining portions of the affidavit are duplicative of Liles' deposition testimony, which was before the trial court.[8] 2. The trial court found that Liles assumed the risk of her injuries even if, as she stated in her affidavit and deposition, she believed that McLeod was going to assist her and he did not. Liles, however, contends that she cannot have assumed the risk because she relied on McLeod's assurances in deciding to participate and thus was misled about the safety of the activity. Summary judgment on the issue of assumption of the risk is appropriate "where the evidence shows clearly and palpably that the jury could reasonably draw but one conclusion."[9] In order to establish assumption of the risk, the evidence must show that Liles "(1) had actual knowledge of the danger; (2) understood and appreciated the risks associated with such danger; and (3) voluntarily exposed [herself] to those risks."[10] We agree with the trial court that Liles had actual knowledge of the danger associated with the activity and appreciated the risk involved, "as any reasonable person would understand the danger inherent in allowing oneself to be dropped from a height of eight to ten feet." We have repeatedly held that "no danger is more commonly realized or risk appreciated . . . than that of falling."[11] Moreover, Liles' testimony that she understood there was a risk of falling even if McLeod assisted her undermines her claim.[12] And when Liles was being lifted and saw that McLeod was not there, she did not ask to be lowered back to the ground, but instead chose to jump. The evidence, construed most favorably to Liles, shows that she voluntarily engaged in the activity knowing that she risked injury from falling.[13] Thus, the trial court did not err in granting summary judgment to Innerwork on the basis of Liles' assumption of the risk.[14] 3. Based on our holding in Division 2, we need not determine whether a genuine issue of material fact exists as to the gross negligence of Innerwork. The trial court found that Liles had assumed the risk of injury even if Innerwork was grossly negligent, and *412 assumption of the risk is a valid defense to gross negligence.[15] Judgment affirmed. SMITH, P.J., and PHIPPS, J., concur. NOTES [1] Gibson v. Symbion, Inc., 277 Ga.App. 721, 627 S.E.2d 84 (2006). [2] (Citations and punctuation omitted.) Sherrill v. Stockel, 252 Ga.App. 276, 278, 557 S.E.2d 8 (2001). [3] This testimony is inadmissible on hearsay grounds. See Dalton v. Jones, 260 Ga.App. 791, 793(2), 581 S.E.2d 360 (2003). [4] See Walker v. Brannan, 243 Ga.App. 235, 237, 533 S.E.2d 129 (2000); see generally Gentile v. Miller, Stevenson, & Steinichen, Inc., 257 Ga. 583, 361 S.E.2d 383 (1987) (outlining "contradictory testimony rule"). [5] Worley v. State Farm Mut. Automobile Ins. Co., 208 Ga.App. 805, 807, 432 S.E.2d 244 (1993). [6] See Lipton v. Warner, Mayoue & Bates, P.C., 228 Ga.App. 516, 517-518(1), 492 S.E.2d 281 (1997). [7] See Fieldstone Center v. Stanley, 216 Ga.App. 803, 804(1), 456 S.E.2d 61 (1995). [8] See Moody v. Dykes, 269 Ga. 217, 218(1), 496 S.E.2d 907 (1998). [9] Sones v. Real Estate Dev. Group, 270 Ga.App. 507, 509(1), 606 S.E.2d 687 (2004). [10] Vaughn v. Pleasent, 266 Ga. 862, 864(1), 471 S.E.2d 866 (1996). [11] (Punctuation omitted.) O'Neal v. Sikes, 271 Ga.App. 391, 392, 609 S.E.2d 734 (2005); see also Barnes v. Fulton, 213 Ga.App. 806, 807, 446 S.E.2d 213 (1994). [12] See Fowler v. Alpharetta Family Skate Center, 268 Ga.App. 329, 332(3), 601 S.E.2d 818 (2004). [13] See id. [14] See id.; Jekyll Island State Park Auth. v. Machurick, 250 Ga.App. 700, 701-702(1), 552 S.E.2d 94 (2001). [15] See Muldovan v. McEachern, 271 Ga. 805, 809(2), 523 S.E.2d 566 (1999) ("a plaintiff's assumption of the risk will bar his action even though there was wilful and wanton misconduct on the defendant's part") (punctuation omitted).

EPISTEMIC CONTRASTIVISM (penultimate version of an entry for the Routledge Encyclopedia of Philosophy, 2017) Peter Baumann Contrastivism about knowledge is the view that one does not just know some proposition. It is more adequate to say that one knows something rather than something else: I know that I am looking at a tree rather than a bush but I do not know that I am looking at a tree rather than a cleverly done tree imitation. Knowledge is a three-place relation between a subject, a proposition and a contrast set of propositions. There are several advantages of a contrastivist view but also certain problems with it. 1. Contrastivism 2. Pro Contrastivism 3. Contra Contrastivism 1. Contrastivism According to an orthodox view, knowledge is a binary relation between a subject and a proposition. Contrastivism about knowledge (or "contrastivism") is the view that 2 knowledge is rather a ternary relation between a subject, a (true) target proposition and a (false) contrast proposition (or a set of contrast propositions) which is incompatible (but cf. Rourke 2013, sec.2) with the target proposition. The form of a knowledge-attributing sentence is "S knows that p, rather than q" rather than "S knows that p" (see Sinnott-Armstrong 2004 and 2008, Schaffer 2004a, 2005, 2007a, 2007b, 2008, Karjalainen and Morton 2003, Morton 2013; see also Morton 2011 and Schaffer 2012a). To say, for instance, that Jean knows that there is a dog in front of her, is elliptical and short for the claim that Jean knows that there is a dog in front of her rather than, say, a cat. This is compatible with Jean not knowing that there is a dog in front of her rather than a wolf. Contrastivism shares certain similiarities with relevant alternative views according to which knowledge does not require that the subject can rule out all alternative possibilities but only the "relevant" ones. Relevant alternatives views, however, typically stick with a binary analysis of knowledge (see, e.g., Dretske 1970). Some contrastivists embrace contextualism, the view that the meaning of a knowledge sentence varies with the context of the speaker; they claim that the set of contrast propositions is determined by the speaker's context (see, e.g., Schaffer 2005; for a non-contextualist contrastivism see Sinnott-Armstrong 2002, 2004). Before epistemologists developed contrastivist accounts of knowledge (and other epistemic relations) philosophers of science proposed contrastivist accounts of explanation or causation (see, e.g., Hitchcock and Schaffer in Blaauw 2013b). Recently, some authors have developed contrastivist accounts of practical reasons 3 and of related notions (see Snedegar 2013 and Sinnott-Armstrong 1996, 2006; see also Sinnott-Armstrong, Driver and Snedegar in Blaauw 2013b). There are also contrastivist views about justification or confirmation (see Fitelson in Blaauw 2013b and Sinnott-Armstrong 2002, 2004, 2006, ch.5) or about belief (see Blaauw 2013a and Baumann 2008, appendix). 2. Pro Contrastivism Contrastivists take some encouragement for their views from data about ordinary usage of terms like "knowledge" (see, e.g., Schaffer 2008 or 2005, sec.3). However, recent experimental data have not led to much agreement here (see Schaffer and Knobe 2012 but also Pinillos 2011, DeRose 2011, Gerken and Beebe 2016). Other kinds of arguments seem to carry more weight. Jonathan Schaffer has presented a couple of linguistic arguments (see Schaffer 2004a, 77-79, 2005, sec.3). First, even though knowledge ascriptions often have an explicitly binary form there is reason to assume that there is a hidden variable for contrasts because there are also explicitly ternary forms of knowledge ascriptions. Second, there are phenomena of binding by quantifiers which suggest a hidden variable for contrasts ("On every test, Jones knows that the substance is A" is analyzed along the lines of "For every test and for every alternative substance in the test, Jones knows that the tested substance is A rather than the alternative"). Third, contrast preservation under ellipsis also suggests a hidden contrast variable: If, e.g., Holmes knows that Mary stole the bicycle rather 4 than the wagon, then "Holmes knows that Mary stole the bike, and Watson does too" preserves the contrast in the case of Watson. Fourth, focus differences suggest hidden variables for contrasts: "Mary STOLE the bike" suggests a contrast with borrowing etc. while "Mary stole the BIKE" suggests a contrast with wagon etc. Fifth, the assumption of hidden contrast variables can explain surface paradoxes (see also Schaffer 2004a, 81). Suppose that Jill can distinguish between dogs and cats but not between dogs and wolfs. Facing a dog, one wants to say both that she knows that there is a dog (rather than a cat) and that she does not know that there is a dog (rather than a wolf). For a detailed critique of all these arguments by Schaffer see Rickless 2014. A further, semantic argument concerns the relation between knowledge and questions (see Schaffer 2005, sec.1-3, 2007a, 2007b and Sawyer 2014, sec.2): Knowing some proposition is knowing the (correct) answer to a (contextually salient) particular question. Since "all well-formed questions are multiple-choice questions" (Schaffer 2007a, 240), the known answer to a question is contrastive in nature, and thus also the knowledge of the corresponding proposition. One might wonder whether "knowing is knowing the answer" (Schaffer 2007b, 383). Even if knowing only requires knowing the answer (still a controversial claim) it is not obvious that knowledge inherits contrastivity from the latter or from the contrastive nature of the question. Apart from that, not everyone does agree that all questions are multiplechoice questions. 5 Adam Morton has argued that since tracking of objects is contrastive (I can see that you went into the kitchen rather than the bathroom but I cannot see which part of the kitchen), the corresponding knowledge is contrastive, too (see Morton 2013, sec.1-2). Similarly, since evidence is contrastive (I have evidence that I am talking to Chuck rather than Jill but not that I am talking to Chuck rather than his twin brother), the corresponding knowledge is contrastive, too (see Morton 2013, sec.3). However, since characteristics of a necessary condition of some X need not be characteristics of X, too, it would be interesting to see more detailed arguments here (see also Sawyer 2014, sec.2 here with respect to perceptual knowledge). Contrastivism also offers solutions to major epistemological problems like the following skeptical puzzle (containing plausible premises and an implausible conclusion): Jay does not know that he has not been deceived by some Cartesian demon into falsely believing that he has hands; if he does not know the latter, then he does not know that he has hands; hence, Jay does not know that he has hands (see, for many, DeRose 1995, 1). This easily generalizes with respect to subjects, propositions and sceptical scenarios. The conditional premise is usually supported by some principle of epistemic closure under known entailment (schematically and roughly: If S knows that p, and if S also knows that p entails q, then S knows that q). Given knowledge of the relevant conditional (If I have hands, then I have not been deceived by some Cartesian demon into falsely believing that I have hands), the second, conditional premise of the skeptical argument follows. 6 The contrastivist has an elegant solution for this skeptical paradox (see Schaffer 2004, 80, 2004b, 2005, sec.5). If one makes the relevant contrasts explicit, then the premises and the alleged conclusion have to be reformulated. It turns out then that Jay does not know that he has hands rather than being deceived by some Cartesian demon into falsely believing that he has hands; however, it also turns out that Jay knows that he has hands rather than, say, stumps. No sceptical argument goes through and the paradox is resolved. By limiting the scope of both common sense and scepticism, the contrastivist can make the two views compatible with each other: Subjects do know ordinary propositions like I have hands but cannot know that they are not in a sceptical scenario. The contrastivist can do this while holding on to a principle of closure (for a contrastivist closure principle see especially Schaffer 2007a). The contrastivist response to scepticism is in some ways very similar to contextualist responses and is as controversial as the latter (see the exchange between Luper 2012 and Blaauw 2012). Does common sense not contain stronger claims ("I just know that I have hands, period!") than the weaker contrastive ones ("Sure, I know that I have hands rather than wings!")? And is not the point of scepticism its damaging effect on ordinary knowledge claims rather than just the denial that one can know that one is not in some extravagant sceptical scenario? Finally, it has been argued that contrastivism can capture and describe the stage and progress of inquiry: It can explain in detail what is known and what is not (yet) known – which (multiple-choice) questions can be answered at a certain stage and 7 which not (see Schaffer 2004a, 81, 2005, 237). Contrastivism thus describes the epistemic abilities and accomplishments of subjects in more detail than binary accounts. 3. Contra Contrastivism There are alternatives to contrastivist explanations of the way people talk about knowledge. Some people argue that the relevant contrasts concern knowledge's content, correctly characterizable as adjunctive ("p rather than q"; see Blaauw 2008, sec.2), as conjunctive ("p and not q"; see Jespersen 2008 and also Kallestrup 2009, sec.1), or as conditional ("if p or q, then p"; see van Woudenberg 2008, 283, passim; see against this kind of strategy Schaffer 2008). A more serious threat to contrastivism is, perhaps, the objection that the contrastivist leaves something important out when they ascribe knowledge that p, rather than q: The subject might typically work with the assumption that either p or q is true (see Becker 2009, 253-254). If the corresponding (multiple-choice) question ("p or q?") provides information and testimonial knowledge to the subject that one of the two is true (see Montminy 2008, 130-131), then there is still a good case for a binary knowledge attribution (the subject knows that p by disjunctive syllogism). Schaffer has replied that the subject need not be aware of the question and also does not need to trust the would-be informants (see Schaffer 2005, 250, fn.20; see also Steglich-Petersen 2015 on the role of presuppositions). 8 A further objection says that contrastivism makes knowledge "too easy" in many cases. Somebody who has next to no clue about Mongolia could still know that Ulan Bator rather than Vatican City is the capital of Mongolia (see Montminy 2008, 130132). Intuitions diverge on this: Some (see, e.g., Schaffer 2005, 257) hold that this is not so implausible. As long as one does not deny the difficulty of knowing some things, it might be fine to accept the easiness of knowing some other things. A related objection (see Becker 2009, 255-256) says that the contrastivist analysis is vulnerable to a problem of "lucky questions". For instance, someone who finds themselves unwittingly in fake barn county but happens to look at one of the few veritable barns might thus count as knowing that there is a barn rather than a farmhouse in front of them. However, the belief that there is a barn is true only by luck and thus cannot qualify as knowledge. This constitutes another way in which knowledge might come "too easily", given contrastivism. The contrastivist could reply that while the subject does not know that there is a barn rather than a fake barn in front of them, they still know that it is a barn rather than a farmhouse. Apart from that, the contrastivist could embrace the view that knowledge is compatible with this kind of luck. A contrastivist account of belief might offer additional resources to escape this objection: The belief that that's a barn rather than a farmhouse might not qualify as lucky. Even if contrastivism is somewhat plausible one might wonder whether all knowledge is contrastive. What for instance is the contrast proposition for knowledge that 2+2=4? 2+2=4 rather than what? There does not seem to be a plausible answer 9 to this question. Similar things can be said about basic logical knowledge (I know that everything is self-identical rather than what?) or semantic knowledge (I know that vixen are female foxes rather than what?). It does not help to say that in such cases the contrast proposition is simply the negation of the target proposition; this would trivialize contrastivism and make it collapse into a binary view (see Morton and Karjalainen 2008, 272 but also cf. Buenting 2010). So, contrastivism might only have some plausibility for certain kinds of knowledge, like knowledge based on discriminatory cognitive abilities (e.g., perceptual ones), but not for others (see Becker 2007, 83, Baumann 2008, sec.1, and Luper 2012, 56; on the role of discrimination here see Schaffer 2004b, Morton and Karjalainen 2008, and Sawyer 2014, sec.2). Finally (echoing certain objections against contextualism), one could point out that normally subjects are blind to the contrastivity of knowledge attributions. Does the contrastivist then have to offer a convincing error theory which explains the systematicity of the mistake? It might be an open empirical question whether people are or are not aware of contrastive effects. Apart from that, one might also simply accept and even defend the claim of semantic blindness (see Schaffer and Szabó 2014, 533-535). But, one might follow up, how is thought and communication about knowledge possible when speakers and hearers are blind to the existence of a third relatum? Are they then even talking or thinking about it at all (in the full sense)? On the other hand, how is thought about knowledge possible when they are not blind to the contrasts: 10 Would not normal subjects be overloaded by the additional complexity? And how then is communication possible if (as perhaps usual) the contrasts the speaker has in mind are not made explicit to the hearer (and vc. vs.)? Can one simply rely on the idea that normally speakers and hearers share the same context and thus the same set of contrast propositions? At least some of these open questions can only be answered on an empirical basis. See also: CONTEXTUALISM, EPISTEMOLOGICAL; EPISTEMIC RELATIVISM; KNOWLEDGE, CONCEPT OF; RELEVANT ALTERNATIVES; SCEPTICISM; SUBJECT-SENSITIVE INVARIANTISM References and further reading Baumann, P. (2008) 'Contrastivism Rather than Something Else? On the Limits of Epistemic Contrastivism', Erkenntnis 69: 189-200. (Critique of contrastivism, including the claim that contrastivism does not apply to all kinds of knowledge; includes an appendix on contrastivism about belief) ------ (2012) 'PS: Response to Schaffer's Reply', S. Tolksdorf (ed.), Conceptions of Knowledge, Berlin: de Gruyter, 425-431. (Response to a reply by Schaffer to the author's criticism) Becker, K. (2007) Epistemology Modalized, New York & London: Routledge. 11 (Important monograph on modal epistemology and reliabilism; includes a brief passage on contrastivism (80-86)) ------ (2009) 'Contrastivism and Lucky Questions', Philosophia 37: 245-260. (Presents the Lucky Questions objection) Blaauw, M. (2008) 'Contra Contrastivism', Philosophical Issues 18: 2-34. (Criticizes Schaffer's rejection of the adjunction strategy in Schaffer 2008) ------ (2012) 'Defending Contrastivism', International Journal for the Study of Skepticism 2: 59-64. (Replies to Luper's critique of contrastivist responses to scepticism) ------ (2013a) 'Contrastive Belief', M. Blaauw (ed.), Contrastivism in Philosophy, New York: Routledge, 88-100. (Perhaps the most detailed attempt to apply contrastivism to beliefs) ------ (ed.) (2013b) Contrastivism in Philosophy, New York: Routledge. (Representative anthology on contrastivism in different areas of philosophy) Buenting, J. (2010) 'An Epistemic Reduction of Contrastive Knowledge Claims', Social Epistemology 24: 99-104. (Proposes to analyze the contrast proposition as the negation of the target proposition and argues that a binary account results from this) DeRose, K. (1995) 'Solving the Skeptical Problem', Philosophical Review 104: 1-52. (Important discussion of recent Cartesian skepticism; develops a contextualist response) ------ (2011) 'Contextualism, Contrastivism, and X-Phi Surveys', Philosophical Studies 156: 81-110. 12 (Discussion of experimental work relating to contrastivism and contextualism; also comments on Schaffer and Knobe 2012) Dretske, F. (1970) 'Epistemic Operators', Journal of Philosophy 67: 1007-1022. (Classic paper on closure as well as on relevant alternatives) ------ (1972) 'Contrastive Statements', Philosophical Review 81: 411-437. (On contrasts; in many ways a precursor of some aspects of contrastivism) Gerken, M. and Beebe, J.R. (2016) 'Knowledge in and out of Contrast', Noûs 50: 133164. (Critical discussion of experimental work relating to contrastivism) Hughes, M. (2013) 'Problems for Contrastive Closure: Resolved and Regained', Philosophical Studies 163: 577-590. (Defends principles of contrastivist closure) Jespersen, B. (2008) 'Knowing that p rather than q', Sorites 20: 125-134. (Discusses the conjunctive analysis of contrastive knowledge attributions) Johnson, B.C. (2001) 'Contextualist Swords, Skeptical Plowshares', Philosophy and Phenomenological Research 62: 385-406. (Contains some remarks on the contrastivist nature of relevant alternative accounts of knowledge) Kallestrup, J. (2009) 'Knowledge-wh and the Problem of Convergent Knowledge', Philosophy and Phenomenological Research 78: 468-476. (Discusses interrogative knowledge-wh ascriptions and the problem of "convergent knowledge"; also discusses conjunctive strategies of analyzing contrastive knowledge attributions) 13 Karjalainen, A. and Morton, A. (2003) 'Contrastive Knowledge', Philosophical Explorations 6(2): 74-89. (Early proposal of contrastivism by two of its major defenders) Kelp, C. (2011) 'A Problem for Contrastivist Accounts of Knowledge', Philosophical Studies 152: 287-292. (Criticizes Schaffer's contrastivist closure principle) Kvanvig, J. (2007) 'Contexualism, Contrastivism, Relevant Alternatives', and Closure, Philosophical Studies 134: 131-140. (Contains a discussion of contrastivist closure) Luper, S. (2012) 'Contrastivism and Skepticism', International Journal for the Study of Skepticism 2: 51-58. (Critique of contrastivist repsonses to scepticism) Montminy, M. (2008) 'Cheap Knowledge and Easy Questions', Grazer Philosophische Studien 77: 127-146. (Critique of contrastivism; includes the objection that it makes knowledge "too easy") Morton, A. (2011) 'Contrastivism', S. Bernecker and D. Pritchard (eds.), The Routledge Companion to Epistemology, London etc.: Routledge, 513-522. (Exposition and defense of contrastivism) ------ (2013) 'Contrastive Knowledge', M. Blaauw (ed.), Contrastivism in Philosophy, New York: Routledge, 101-115. (Exposition and defense of contrastivism; includes a discussion of the contrastivity of tracking and of evidence) 14 Morton, A. and Karjalainen, A. (2008) 'Contrastivity and Indistinguishability', Social Epistemology 22: 271-280. (Discussion of different kinds of contrastive expressions and of closure; defense of a restricted contrastivism about beliefs on pp.278-279) Pinillos, N.Á. (2011) 'Some Recent Work in Experimental Epistemology', Philosophy Compass 6: 675-688. (On relevant experimental work; also on Schaffer and Knobe 2012) Rickless, S.C. (2014) 'The Contrast-Insensitivity of Knowledge Ascriptions', Philosophy and Phenomenological Research 88: 533-555. (Detailed critique of Schaffer's linguistic arguments for contrastivism) Sawyer, S. (2014) 'Contrastive Self-Knowledge', Social Epistemology 28: 139-152. (Defends contrastivism about self-knowledge and about perceptual knowledge; argues for contrastivism about belief in sec.3) Schaffer, J. (2004a) 'From Contextualism to Contrastivism', Philosophical Studies 119: 73-103. (An early defense of contrastivism by one of the most important contrastivists; contains linguistic arguments for contrastivism) ------ (2004b) 'Skepticism, Contextualism, and Discrimination', Philosophy and Phenomenological Research 69: 138-155. (Discusses contrastivism with respect to scepticism as well as discriminatory abilities) ------ (2005) 'Contrastive Knowledge', T.S. Gendler and J. Hawthorne (eds.), Oxford Studies in Epistemology, vol.1, 235-271. 15 (Exposition and defense of contrastivism; contains a discussion of question-relativity as well as scepticism and closure; discusses contrastivism about belief in sec.4) ------ (2007a) 'Closure, Contrast, and Answer', Philosophical Studies 133: 233-255. (The most detailed proposal of a principle of contrastivist closure) ------ (2007b) 'Knowing the Answer', Philosophy and Phenomenological Research 75: 383-403. (On interrogative knowledge-wh ascriptions and the problem of "convergent knowledge; defends the claim of the question-relativity of knowledge) ------ (2008) 'The Contrast-Sensitivity of Knowledge Ascriptions', Social Epistemology 22: 235-245. (Defends contrastivism and criticizes the conjunction, conditional and adjunction strategy) ------ (2012a) 'What Is Contrastivism?', S. Tolksdorf (ed.), Conceptions of Knowledge, Berlin: de Gruyter, 353-356. (Brief exposition and defense of contrastivism) ------ (2012b) 'Contrastive Knowledge: Reply to Baumann', S. Tolksdorf (ed.), Conceptions of Knowledge, Berlin: de Gruyter, 411-424. (Reply to Baumann's critique of contrastivism) Schaffer, J. and Knobe, J. (2012) 'Contrastivism Surveyed', Noûs 46: 675-708. (Discusses contrastivism and its alternatives with respect to experimental data) Schaffer, J. and Szabó, Z.G. (2014) 'Epistemic Comparativism: A Contextualist Semantics for Knowledge Ascriptions', Philosophical Studies 168: 491-543. (Proposes a semantics of knowledge attributions) 16 Sinnott-Armstrong, W. (1996) 'Moral Skepticism and Justification', W. SinnottArmstrong and M. Timmons (eds.), Moral Knowledge? New Readings in Moral Epistemology, Oxford: Oxford University Press, 3-48. (One of the earliest defenses of contrastivism, especially moral contrastivism, by one of the most important contrastivists) ------ (2002) 'What's in a Contrast Class?', Analysis 62: 75-84. (One of the first expositions and defenses of contrastivism about justification) ------ (2004) 'Classy Pyrrhonism', W. Sinnott-Arnstrong (ed.), Pyrrhonian Skepticism, Oxford: Oxford University Press, 188-207. (Defends contrastivism about justification while accepting scepticism about the relevant contrast class) ------ (2006) Moral Skepticisms, Oxford: Oxford University Press. (Important monograph on moral epistemology defending moral contrastivism and contrastivism about justification in detail; accepts scepticism about the relevant contrast class) ------ (2008) 'A Contrastivist Manifesto', Social Epistemology 22: 257-270. (Defends the author's own version of epistemic contrastivism) Snedegar, J. (2013) 'Reason Claims and Contrastivism about Reasons', Philosophical Studies 166: 231-242. (Defends contrastivism about practical reasons) Steglich-Petersen, A. (2015) 'Knowing the Answer to a Loaded Question', Theoria 81: 97-125. (Criticizes Schaffer for neglecting the role of presuppositions in knowledge attributions) 17 Swinburne, R. (2001) Epistemic Justification, Oxford: Clarendon. (Mainly on epistemic justification but contains a brief remark (34) suggesting contrastivism) van Woudenberg, R. (2008) 'The Knowledge Relation: Binary or Ternary?', Social Epistemology 22: 281-288. (Argues for a binary account and for the conditional strategy) PETER BAUMANN

A meme directed at Bernie Sanders supporters, purportedly offering them instructions on how to create homemade glow sticks, started circulating on social media in May 2016: The instructions given in the above-displayed meme don’t create glow sticks, however, but rather explosions. Mixing chlorine and isopropyl alcohol creates a violent chemical reaction, which (when it is confined to a sealed container) has dramatic, potentially dangerous results. A video posted by the Backyard Scientist in 2013 demonstrates this chemical reaction: Another video from 2012 shows the result of containing this reaction inside a plastic bottle: The exact origins of the above-displayed meme are unclear, but one of the first mentions we were able to uncover was posted to the /pol/ section of the web site 4chan in March 2016. The meme was shared again in May 2016, along with a message encouraging forum members to spread it on social media in an apparent attempt to prank Bernie Sanders supporters: Hey guys! Let’s trend this on Twitter and my FaveBook. Even though I like Hillary the mostest I still think this is a fun idea for a truce between the Democrat groups! Who’s with me!? Hehehehe While some forum members found this “joke” funny, others reported the meme to the FBI:

Nas & Jungle's Artist Kiing Shooter Has Reportedly Died Kiing Shooter, who is currently signed to Nas and Jungle’s Mass Appeal offshoot Street Dreams Records, has died. HipHopDX confirmed the news with Street Dreams Records. Fellow Hip Hop artist Big Twins was informed the Queensbridge native was hospitalized for liver problems. There’s speculation he possibly contracted COVID-19 while in the hospital, however his official cause of death has yet to be confirmed. “Kiing Shooter was one of the new guys coming up in Queensbridge,” Big Twins told HipHopDX. “Nas just signed ‘em to Street Dream Records. He was coming with it. What’s crazy is that Alchemist just hit me three days ago, asking me, ‘Who’s this dude Shooter? He’s nice.’ “He was the one that broke through the most, getting hundreds of thousands of views on YouTube and really coming with it. Me and his father go way back … we used to play basketball together and he used to date my older sister. But Shooter next up to represent the Bridge … I’m stunned today. Rest in peace Shooter.” On April 24, Shooter — real name William Daniels — shared an Instagram photo of himself laying on a hospital bed. In the caption, he insinuated alcohol had become a serious issue. “This Can’t Be Life,” he wrote. “I Said Henny Was Stronger Than The Rona I Ain’t Kno It Was That Strong. No More Drinkin For Me.” Shooter was an affiliate and longtime friend of Harlem MC Dave East. In 2017, he released several freestyles with East and eventually released his own single in June 2018 called “They Say.” His debut EP Fucc The Doubters arrived a couple of months later and featured from East, Don Q and Mac. He followed up with his second EP No Turning Bacc last April 20 and his debut solo album Still Outside in March. Shooter was 24. Subscribe to DX Newsletter Get The Most Important Stories Of The Day Straight To Your Inbox Thank You! Thank You! Thank You! You’re Far Too Kind To complete the subscription process, please click the link in the email we just sent you.

For more than a century, the Distillerie TESSENDIER has been located in the heart of the town of Cognac and has played a major role in the Cognac economy, by participating actively in the main organizations that regulate the Cognac region :

Love dating service 20 Divine Caroline talked to relationship expert April Masini to find the top dating sites for millennials. Best for No Cost: Ok Cupid Ok Cupid is full of 20-somethings looking for relationships of all kinds, so it's great for people looking to dive into the dating pool without emptying their pockets. Based on responses to a lengthy questionnaire, Ok Cupid calculates your compatibility percentage with other users. If you follow the first three tips, you should already have plenty of better choices. Know More at the Official Website of Thai Friendly Thai Cupid Popularity: Thai Cupid is a one of the largest and most popular Thai dating sites. Jen Brit Millionaire dating has become one of the trends in recent years with the popularity of the TV show Millionaire Matchmaker. The reason is that more and more singles hope to find millionaire singles with stable financial status and well-educated. You can join niches like non-smoking, organic, psychic, cigar, coffee, mullets and classical (music). The site is mostly for verified college students and alumni. If you can fit the bill, however, the site gives you awesome features. Every day, the site sends users six matches based on compatibility, but it leaves much of the matching up to the user.I free like I can not meet anyone because I am not a super model. As the name suggests, Meeting is an online dating site exclusively for millionaires and their admirers.Powered by segment leader Millionaire Match, this site is one of the most reliable dating sites on the market.Free Online dating sites are becoming more and more popular. We’ve done a huge research and picked the safe and virus free sites. Plenty of Fish True to its word, POF has the highest number of users in this list. You get the full package for free but like other free sites, there are a plethora of premium packages that you can buy such as seeing when other users read your messages.According to statistics, one third of all married couples in the US met online. POF was among the first online dating sites and as such, they have been able to refine the site to up user experience. Like POF, the site is free with added features for premium members (otherwise referred to as A-list members). Leave a Reply You don’t want to be the guy who gets walked all over in relationships or in friendships. So if you're an example of any of the signs below, it may be time to reassess where you stand as a man in this thing we call life. Every now and again, you’ll find it freeing and, dare I say, liberating.

GOG.com is a digital distribution platform – an online store with a curated selection of games, an optional gaming client giving you freedom of choice, and a vivid community of gamers. All of this born from a deeply rooted love for games, utmost care about customers, and a belief that you should own the things you buy. What is GOG.com about? Hand-picking the best in gaming. A selection of great games, from modern hits to all-time classics, that you really shouldn’t miss. GOG.com is a digital distribution platform – an online store with a curated selection of games, an optional gaming client giving you freedom of choice, and a vivid community of gamers. All of this born from a deeply rooted love for games, utmost care about customers, and a belief that you should own the things you buy. What is GOG.com about? Hand-picking the best in gaming. A selection of great games, from modern hits to all-time classics, that you really shouldn’t miss. Filterless fashionista Pipiro and poindextrous punster Pokkle are ordinary step-siblings facing an ordinary day in their ordinary little burg...until a grand theft macguffin occurs and they decide to become unlikely heroes for cash and glory (in that order). This goes about as well as you’d expect.... Filterless fashionista Pipiro and poindextrous punster Pokkle are ordinary step-siblings facing an ordinary day in their ordinary little burg...until a grand theft macguffin occurs and they decide to become unlikely heroes for cash and glory (in that order). This goes about as well as you’d expect. SD Anime-Style Characters Inhabiting a Colorful Hand-Drawn 2D World Boasting beautiful painterly art rife with detail and animations, and populated with an equally colorful cast of super-deformed anime characters who are constantly on the move, the world of Arges feels perpetually alive and energetic. Fast and Chaotic Combat Featuring a Plucky Duo of Protagonists (and One Pet) Fend off merciless enemies in real time with Pokkle’s melee attacks and Pipiro’s myriad magics, and solve puzzles to progress through the game’s many dungeons, all while either flanked by a loyal pet or while monitoring said pet from afar as it goes off on its own adorable little journeys. Food-Based Leveling System Allowing Players to Challenge the Game on Their Own Terms Eat food to level-up, or hoard your food so you can exchange it in town for even better food down the line that grants even more experience. Will you stay low-level and challenge dungeons well beyond your means for the promise of more level-ups to come, or will you engorge yourself on demand to make the road ahead a little easier? Minigames, Music, Achievements, Art, and More, Creating the Definitive Zwei Experience Play an Ys-inspired typing tutor, an adorable yet savage aeroplane shmup, or a block puzzler that rewards you for not making combos – or maybe just take the time to help guide your pet through the harsh wilderness for various spoils! If that’s not enough, why not try for one of the myriad new achievements, seek out one of the newly illustrated character bromides, or switch out the regular soundtrack for its 2008 arranged version? You can even play the game with Japanese text if you want! Add to that a bevy of control improvements and other modernizations, and you have the ultimate update to this unsung Falcom classic!

"Government has decided to honour the contribution of Atal Bihari Vajpayee": Defence Ministry (File) The government will name the strategic tunnel under Rohtang Pass after former prime minister Atal Bihari Vajpayee on his birth anniversary on Wednesday. The historic decision to construct a strategic tunnel below the Rohtang Pass was taken on June 3, 2000 when Atal Bihari Vajpayee was the prime minister. "Government has decided to honour the contribution of former prime minister Atal Bihari Vajpayee by naming the strategic tunnel under Rohtang Pass after him on December 25," the defence ministry said. The 8.8-km-long tunnel is the world's longest above an altitude of 3,000 metres.

Tag Archives: Education Reform ….. a Grade Two student at a private primary school in Kiambu County, gets upset every evening that his father, Joseph Mutiga, returns home without a printer. His homework involves printing assignments almost on a daily basis, and his dad has promised him that he will buy a colour printer to make it easier for him to deliver on the assignments. print outs must be done in full colour. The Mutiga household’s story is replicated in most Kenyan households that have school going children in Grade Three and below, who are undertaking the new Competency-Based Curriculum (CBC). The curriculum, which is set to replace the 8-4-4 system that was criticised for being too theoretical and exam-focused, has won admirers and critics in equal measure. A small home colour printer costs about Sh10,000, which Mr Mutiga says is a new item on his budget. He is also contemplating installing a home internet connection that will add about Sh2,500 to his monthly budget. Critics, including the Kenya National Union of Teachers (Knut), have however warned that the new curriculum will entrench inequalities where only children of the rich and middle class families will afford to provide their children with the relatively expensive learning materials. Public schools, and especially those in rural areas and urban slums, are most affected as their student populations cannot afford the materials required for the new curriculum. In Kirinyaga County, Jerry Mworia says his son previously brought home class assignments that only required him to use a pencil and a book. After the new curriculum took effect, he is now regularly required to buy items that are not stocked in his neighbourhood shops such as modelling clay. “I had to make a two-hour round trip to Kerugoya, the nearest place I could find plasticine (a brand of modelling clay). I bought a kilogramme for Sh150. Kenya’s CBC is a caricature of isomorphic mimicry. Teachers are not ready. Parents are not ready. The government is not ready. It all sounds like a sophomore project gone awry. Yet millions of Kenyan pupils will be subjected to this disaster of a policy. It is not hard to see how the new system will worsen class-based differences in education outcomes. The curriculum is totally divorced from the lived experience of the vast majority of Kenyans. Now it would be one thing if the Kenyan government had the capacity to pull it all off. However, the government merely implemented what “consultants” and “advisors”, many of whom obviously had very little local knowledge, suggested. It has done precious little to prepare the country for the policy. Most reputable education professionals in Kenya oppose the shift. The textbooks are a disaster. Teachers have not been trained. Add this to the list of failed “development” projects that are completely divorced from the objective realities of their intended beneficiaries. Roll-out of the curriculum has taken off poorly, especially in public schools that do not yet have books and other learning materials. Teachers in some public schools were yet to get instruction kits as of late last week. “From the CBC training, we are required to take videos, pictures and in some lessons use the television as a teaching tool, but we do not have any of the supporting equipment and books at my school,” said Mrs Jackline Mueni, a Grade Three teacher in a public school. WHICH has provided a better return in recent decades: America’s stockmarket or education? The latter, according to a research review by George Psacharopoulos and Harry Patrinos for the World Bank. The two economists looked at 1,120 studies, across 139 countries, and came up with an annual average “rate of return”—actually a pay premium, the increase in hourly earnings from an extra year of schooling—of 8.8%. The analogy is inexact, but for comparison America’s stockmarket returned an annual 5.6% over the past 50 years. Their figure excludes social gains, such as lower mortality rates associated with greater education. The premium is higher for girls and for primary education. It is also higher in poor countries, presumably because the smaller the share of educated people, the higher the pay they can command. The same reasoning suggests that the return should have dwindled as educational attainment rose. Instead, it has stayed strong, especially for higher education. Education attainment appears to be trending in the right direction across the globe (see image). However, the rate of improvement over the last three decades has been higher in some regions than in others. For example, while in 1992 Africa and South Asia had 42% and 38% of the out-of-school children of primary age, respectively, by 2014 the comparable figures were 57% and 19%. Clearly, African states need to do more. The Bill & Melinda Gates Foundation has recently announced its foray into education. If done well, the Foundation’s involvement in the education secctor has the potential to nudge policy makers in the right direction, while also generating valuable data for cross-country comparisons. More than half of the tigers that Thai authorities confiscated in 2016 from an infamous Tiger Temple tourist attraction have died from a viral disease because their immune systems were weakened by inbreeding, media reported. Yemen's Iran-aligned Houthi group said it attacked two plants at the heart of Saudi Arabia's oil industry on Saturday, knocking out more than half the Kingdom's output, in a move expected to send oil prices soaring and increase tensions in the Middle East.

the remainder when 68 is divided by r. 12 Let x(g) = 2*g**2 + 33*g + 48. What is the remainder when 30 is divided by x(-15)? 0 Let p(u) be the third derivative of -11*u**4/24 - 8*u**3/3 - u**2. Calculate the remainder when p(-7) is divided by 21. 19 Suppose -5*q = -3*d + 24, -8 = -d - q - 2*q. What is the remainder when (13/(-5))/(6/(-30)) is divided by d? 5 Let t(b) = -b**3 + 10*b**2 + 10*b + 7. Let w be t(11). Let x be (w/(-12))/((-3)/(-18)). What is the remainder when 61 is divided by (-122)/(-6) - x/(-3)? 19 Suppose -2*y + y = 0. Suppose y = -b + 1 + 26. Suppose b = -f + 2*f. What is the remainder when f is divided by 10? 7 Let t(k) = k**2 - 3*k - 1. Let g be t(4). Suppose g = n - 21. Let v = -1025 - -1118. What is the remainder when v is divided by n? 21 Let a = 733 + -592. Let o = 84 + -55. Calculate the remainder when a is divided by o. 25 Let o(p) = 384 + 4*p**2 + 5*p + 2*p**2 - 380 - 4*p**2. Suppose -n - 2 = 2. What is the remainder when 47 is divided by o(n)? 15 Suppose -3*k - 40 + 160 = 0. Calculate the remainder when 148 is divided by k. 28 Suppose 0*n + 4*g = n + 5, 0 = 4*n - g + 35. Calculate the remainder when 29 is divided by ((-12)/18)/(1/n). 5 Let j be 23/5 + 2/5. Suppose -6*g - 8 = -2*r - 2*g, -3*r - j*g = -23. What is the remainder when 6/(48/21 - 2) is divided by r? 3 Suppose 2*l = 2*m + 56, -11*l - 71 = -13*l + 5*m. Let t(s) = 2*s**2 - s + 5. What is the remainder when t(-5) is divided by l? 14 Let x be (-42)/(-63) + (-587)/3. Let z = x - -277. Let o(h) = -h**2 - 10*h - 7. Calculate the remainder when z is divided by o(-6). 14 What is the remainder when 144 is divided by 2842/87*18/14? 18 Suppose 0 = n - 3 + 18. Let m(i) = -i + 16. Let x be m(10). Calculate the remainder when 43 is divided by n/x*(-22)/5. 10 Let j(f) = -2*f**2 - 7*f + 44. What is the remainder when 24 is divided by j(3)? 4 Let r(f) = 2*f**3 - 2*f**2 - 2*f. Let x be r(2). Calculate the remainder when 38 is divided by x/(-6)*-3 + 26. 10 Let t = 128 + -75. Let z = -48 + t. What is the remainder when 5 is divided by z? 0 Suppose 3*v + 9*y = 13*y + 268, -5*v + 2*y + 470 = 0. Calculate the remainder when v is divided by 21. 12 Let y = 174 + -102. Suppose 45 = g + l, -y = -5*g + l + 147. What is the remainder when g is divided by 8? 4 What is the remainder when ((-89955)/225)/((-2)/(30/3)) is divided by 22? 19 Suppose 35 = -6*o + 137. Calculate the remainder when 32 is divided by o. 15 Let k(s) = s**2 - 20*s + 32. Calculate the remainder when 26 is divided by k(19). 0 Suppose -95 = -5*o - 4*l, -7*l = -5*o - 14*l + 110. Let b(z) = -z + 26. What is the remainder when b(0) is divided by o? 11 Let k = 1 + 1. Suppose 0 = -k*x + 18 - 2. Let a(l) = -l**3 - 84*l**2 - 162*l + 167. Calculate the remainder when x is divided by a(-82). 2 Suppose 4*n - 5*n = -2. Suppose 0*v - 12 = -n*v. Suppose -y = 2*k - 1, -3*k + 12 = y + 4*y. Calculate the remainder when v is divided by y. 0 Calculate the remainder when 6/(466/1484 - 44/154) is divided by 38. 22 Let b(u) = 10*u. Let g be b(4). Suppose -8*s + g = -4*s. Calculate the remainder when 57 is divided by s. 7 Let j be (-1 + 6/4)/((-1)/2). What is the remainder when 32 is divided by 99/36*(-4)/j? 10 Suppose -960 = -15*b + 75. What is the remainder when 77 is divided by b? 8 Suppose -8*r + 197 - 37 = 0. What is the remainder when r/14 + 1/14*-6 is divided by 1? 0 Let w(o) = o**3 + 6*o**2 - 11*o - 7. Let g = -46 - -36. Let n = g + 22. Calculate the remainder when w(-7) is divided by n. 9 Let k(v) = -v**2 + 6*v + 2. Let n be k(7). Let s = 52 + n. Let y(l) = 4*l - 28. What is the remainder when s is divided by y(10)? 11 Let i = -131 + 147. What is the remainder when i is divided by 9? 7 Let j = -1 - -1. Let d = j + 2. Let f(k) = k**2 - 45*k + 377. Calculate the remainder when f(11) is divided by d. 1 Let m(o) = 3*o + 9. Suppose 5 = q - 5*n, 5*q = 3*n - 4 + 7. What is the remainder when m(q) is divided by 4? 1 Suppose -15*c + 14*c = -79. Suppose 53 = 4*m + 5*i, -4*i + 36 = 3*m + i. Calculate the remainder when c is divided by m. 11 Suppose -2*a - 4*r + 158 = 0, 3*r = -13*a + 10*a + 225. Calculate the remainder when a is divided by 22. 5 Suppose 3*y - 6*y - u - 38 = 0, -u = y + 12. Let b = y + 26. Calculate the remainder when b is divided by 8. 5 Let i = -175 - -188. What is the remainder when 35 is divided by i? 9 Let z(t) = 12*t + 142. Calculate the remainder when 181 is divided by z(-8). 43 Suppose -2*j - 90 = -2*p, -j + 86 = 4*p - 69. What is the remainder when 106 is divided by p? 26 Suppose 5*g - 212 = 123. Let y(j) = -16*j + 1. Let b(a) = a**3 - 4*a**2 - 1. Let r be b(4). Calculate the remainder when g is divided by y(r). 16 Let j = 153 + -33. What is the remainder when j is divided by 43? 34 Let a be (2/(-4))/((-2)/(40 + -4)). Suppose -a*b - 44 = -11*b. Calculate the remainder when b is divided by 4. 2 Let m be -3*1/(-2)*2. Suppose -10 = 8*f - m*f. Calculate the remainder when (f/3)/(5/(-75)) is divided by 3. 1 Let z(w) = 48*w**3 + w - 1. What is the remainder when z(1) is divided by (-2 + 7 - -4) + 5 + -4? 8 Suppose -9*c = c - 2300. Calculate the remainder when c is divided by 77. 76 Suppose 0 = 7*l - 18*l + 1661. Calculate the remainder when l is divided by 49. 4 Let l = 2 + -1. Suppose -5*f + 9 + 6 = 0. Calculate the remainder when l is divided by f/6*-1*-2. 0 Suppose m + 1 = 2*m. Let o = m + 8. Suppose 0 = 9*q + 63 - 351. Calculate the remainder when q is divided by o. 5 Suppose 3*i = 5*g - 335 - 425, 5*g - 2*i - 760 = 0. Calculate the remainder when g is divided by 51. 50 Let p(k) = 6*k - 60. What is the remainder when 115 is divided by p(15)? 25 Let i(j) be the third derivative of -1/6*j**3 + 0 + 3*j**2 + 0*j - 19/24*j**4. What is the remainder when 35 is divided by i(-1)? 17 Let k be 2*(-1 + (-37)/(-2)). Let r = k + -31. Suppose -13 = -l - g, -31 = -4*l + r*g + 5. Calculate the remainder when 20 is divided by l. 9 What is the remainder when 15 is divided by 60/(25/5) + -6? 3 Let d(y) = y**2 + 35*y + 336. Calculate the remainder when d(-27) is divided by 37. 9 Calculate the remainder when 151*(18/(-90) + 12/10) is divided by 77. 74 Let n = -59 - -65. Suppose -z = -i - 4, n = z + 2*i + 2. Calculate the remainder when 15 is divided by z. 3 Calculate the remainder when -4 - -320 - 4/(-8)*-6 is divided by 17. 7 Let i(c) = -13*c - 1 + 28*c**2 + 13*c. Let w(v) = -v. Calculate the remainder when i(1) is divided by w(-7). 6 Let i = 10 - -22. Suppose -25 - 136 = -23*a. What is the remainder when i is divided by a? 4 Suppose -4*a + 40 = d - 4*d, -4*a = d - 72. Suppose -m - 12 = 2*m, -4*w + 28 = 4*m. Calculate the remainder when a is divided by w. 5 Let q(x) = -x**3 - 7*x**2 + 8*x + 19. What is the remainder when 45 is divided by q(-8)? 7 Let d be -47 - (0 - 1)*-2. Let a = -12 + -22. Let q = a - d. Calculate the remainder when 59 is divided by q. 14 Let u be 66*2/(-4)*-1. Let y = u - 31. Calculate the remainder when -1 - 1*7/(-1) is divided by y. 0 Suppose -991*m = -993*m + 460. Calculate the remainder when m is divided by 110. 10 Let q(b) = -b**3 + 18*b**2 - 38*b + 28. What is the remainder when q(14) is divided by 57? 52 Let u = -7 + 3. Let l be 3 - 1/1 - -2. Let z = l - u. Calculate the remainder when 21 is divided by z. 5 Let d(x) = 3*x + 51. What is the remainder when 164 is divided by d(-9)? 20 Let u be (19/(-76))/((-1)/12). Suppose -u*h = 4*x - 2*h - 108, -5*x + 3*h = -135. Calculate the remainder when x is divided by 15. 12 Suppose 4*g - 116 = 4*a, a + 0*g = 3*g - 37. Calculate the remainder when 2*a/(-2) + (0 - -3) is divided by 16. 12 Let p(r) = 4*r + 5. Let v be p(0). Suppose 0 = 3*u - 4*c - 127, 3*u = v*u + 3*c - 62. Calculate the remainder when ((-73)/(-3))/((-2)/(-6)) is divided by u. 36 Suppose 8*a - 12 = -4*a. Calculate the remainder when -4 + 22 + a + 3 is divided by 12. 10 Let l(h) = -h**3 + 26*h**2 + 58*h - 43. Calculate the remainder when 22 is divided by l(28). 9 Let j = 4 - -7. Let p(f) = f**3 - 7*f**2 - f + 10. Let q = 51 - 44. What is the remainder when j is divided by p(q)? 2 What is the remainder when (-4088)/(-280) - (-6)/(-10) is divided by 2? 0 Let q(g) = 4*g + 7. Suppose 9 - 3 = -3*k. Let v = k - -11. Calculate the remainder when q(2) is divided by v. 6 Let k = 62 - -2. Calculate the remainder when

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A 35-second track of Lady Gaga‘s, allegedly called “Stupid Love”, has been leaked to Twitter, leading many to speculate that LG6 may be just around the corner. The track itself, which is super rough audio quality, seems reminiscent of something you’d hear on Born This Way, but it’s now quite difficult to find online due to Gaga’s management being rather scrupulous about removing any traces of the snippet from the internet. Now, there’s lots of hear-say doing the rounds at the moment. There’s a rumour that “Stupid Love” will be the lead single set for a February 7 release, which management has since allegedly denied. There’s another rumour that “Stupid Love” actually did belong on Born This Way originally and, although it’s now being re-recorded for LG6, what we’re hearing now is the old 2011 version. At this point, who the fuck knows? It’s no secret that us Lady Gaga fans have been (im)patiently waiting the arrival of LG6, but this latest leak has well and truly pushed us over the edge (of glory). Whatever the future holds for LG6 and “Stupid Love”, the leak has given rise to an abundance of cracking tweets. Let’s check ’em out. Me to @ladygaga after listening to bad quality leaked snippets of Stupid Love pic.twitter.com/3JwNz7rNK3 — Lady Gaga Facts (@LGMonsterFacts) January 18, 2020 interscope taking down the leaks and trying to do damage control over stupid love leaks pic.twitter.com/UblizdNTp0 — karlo (@mxdern_ecstasy) January 18, 2020 Gaga confronting the gays to remove the Stupid Love leaks pic.twitter.com/boQ1yw8x1D — Josh (@NerveOfJosh) January 19, 2020 Me bopping to dead silence because I can’t find Gaga’s Stupid Love leak pic.twitter.com/OUAwZLysvR — ✨finn✨ (@_sweeteaner) January 18, 2020 Gaga when she comes to Twitter to see Stupid Love #LG6 pic.twitter.com/R7t84K5gLs — Angel (fan account) (@_Angel160_) January 19, 2020 Lady Gaga to the person who leaked Stupid Love: pic.twitter.com/R08IXAPLzA — ???????????????????????????????????????? (@shawnthemartian) January 19, 2020 "Stupid Love" has HIT written all over it. pic.twitter.com/6EbUJVI2pn — An Ungrateful Minx (@yosoymichael) January 19, 2020

The relationship of x-linked primary immune deficiencies and autoimmunity. It is well-known that autoimmunity is significantly more prevalent in females. Growing evidence indicates that genes located on the X chromosome may play a role in autoimmunity and immune dysregulation, as also indicated by the frequent association of autoimmune phenomena in patients with X-linked primary immune deficiencies (PIDs). Hence, this group of genetic disorders is of particular interest to study PID-causing genes in the setting of more complex autoimmune disorders. This review focuses on the mechanisms leading to the autoimmune phenomena that are associated with the different X-linked PIDs, and on the intriguing interplay between immune dysregulation and immune deficiency in this unique setting.

Background {#Sec1} ========== Inflammatory Bowel diseases, comprising of Crohn's disease (CD), Ulcerative colitis (UC) and IBD-unclassified (IBD-U), are multifactorial in their etiology. In the last two decades, the introduction of the anti-tumor necrosis factor-α (anti-TNFα) drugs (e.g. infliximab and adalimumab) has expanded the treatment arsenal with drugs potent for both inducing remission as well as maintaining remission \[[@CR1]--[@CR3]\]. Although these immunosuppressants are increasingly used, the need for intestinal surgery remains unchanged, with 25--61% of newly diagnosed IBD requiring surgery at least once within the first 5 years after diagnosis \[[@CR4]--[@CR6]\]. Additionally, anti-TNFα treatments are not effective in 20--40% of IBD patients and loss of response and/or is seen in a substantial proportion of the patients \[[@CR1], [@CR7]--[@CR10]\]. While it has been suggested that earlier treatment with anti-TNFα could improve disease outcome \[[@CR11]\], we were previously unable to confirm a benefit for earlier anti-TNFα treatment on IBD-disease complications \[[@CR12]\]. The most likely explanation appeared to be that an inappropriate selection of patients eligible for therapy had led to suboptimal treatment and subsequently outcome. Genetics play an important role in IBD, as IBD shows a large hereditary component and genetic variants may influence cellular functions, the innate immune system and thereby both disease activity and response to treatment \[[@CR13], [@CR14]\]. Genome-wide association studies (GWAS) have identified over 163 single-nucleotide polymorphisms (SNPs) that are associated with IBD \[[@CR15], [@CR16]\]. Based on their known function in normal cellular settings, efforts have been made to cluster these SNPs into functional categories in order to glean insight into the mechanistic aspects of IBD pathology \[[@CR17], [@CR18]\]. Key pathways identified so far are innate immunity, defective epithelial barrier, autophagy, IL10 signaling and adaptive immunity, although these definitions are not always clear-cut, with many genes acting in more than one of these categories. While the general role of these genes in cellular processes is in most cases known, it is as yet largely unclear how the IBD-associated SNPs in these genes affect cellular function, or how such changed cellular functions would contribute to the development of IBD. However, there are some positive exceptions. For instance, the IBD-associated variants in the *NOD2*, *ATG16L1* and *IRGM* genes affect cellular autophagy processes and bacterial clearance in (innate) immune cells, and may affect bacterial composition of the gut in patients with IBD \[[@CR19]--[@CR22]\]. In addition, SNPs in the interleukin 23 receptor gene (*IL23R*) were recently shown to affect expression of the anti-microbial peptide DMBT1 in intestinal epithelial cells in IBD \[[@CR23]\]. Our own studies demonstrated that an IBD-associated SNP in the neutrophil cytosolic factor 4 (*NCF4*) gene results in a decreased antimicrobial function of granulocytes, as demonstrated by a reduced production of reactive oxygen species by these cells \[[@CR24]\]. In light of the immune-cell modulatory properties of several of the known IBD-associated SNPs, it is likely that these SNPs may affect response of patients to immune-modulatory drugs as well. Identifying associations between patients' genetics and characteristics and response to treatment would open up the possibility of implementing personalised treatment strategies. Tailored strategies in the future could include treatment according to the individual patients' genetic profile. With this study we aimed to identify patients likely to benefit from anti-TNFα treatment, based on their genetic profile. Methods {#Sec2} ======= All patients of whom DNA was available at the Erasmus MC University Medical Center, and the diagnosis of IBD could be confirmed according to the Lennard-Jones criteria, were included in this study \[[@CR25]\]. Disease characteristics were scored according to the Montreal criteria \[[@CR26]\]. Patients having had a liver transplantation or suffering from auto-immune hepatitis or PSC and who were treated for these conditions, were excluded from analysis. Data on patient and disease characteristics were obtained from the patients' medical charts. For each patient, the following characteristics were retrieved: date of birth, date of IBD diagnosis, age at diagnosis, date of first visit to the Erasmus MC University Medical Centre, IBD phenotype, gender, comorbidities, familial IBD status, disease location, disease behavior, extra-intestinal manifestations, fistula and abscesses and the amount of surgery. SNP carriers were compared to non-SNP carriers for above mentioned parameters. For disease location and behavior, patients with IBDU were classified as patients with UC. Maximum disease extension and disease characterization were scored according to the Montreal criteria \[[@CR26]\]. Number of flares during follow-up were scored based on clinical and endoscopic parameters. End of follow-up was January 1st, 2013. This study was approved by the institutional medical ethical board of the Erasmus MC (MEC-2012-245). Of all patients, records pertaining to infliximab (IFX) and adalimumab (ADA) use were perused. Of the treatments, their use, side-effects and primary non-response and loss of response were evaluated. Primary nonresponse to biologic therapy was defined as an absence of symptomatic improvement with persistently high levels of C-reactive protein (CRP) after induction treatment. Long-term sustained response to biologics was defined as improvement of the symptoms lasting at least 1 year without any further adjustments of the therapeutic regimen. Failure of the therapeutic regimen was defined by an absence of improvement of the symptoms of disease and by a decision of the treating physician to add steroids, add another immunosuppressor, switch to another immunosuppressor, switch to another anti-TNF medication (adalimumab), or refer for CD-related surgery. Several immune-regulatory genes were selected for this study. We focused on genes involved in innate immunity/autophagy/bacterial clearance in both in blood immune cells and Paneth cells (*IRGM*, *NOD2*, *LRRK2*, *ATG16L1*, *XBP1* and *NCF4*) \[[@CR19], [@CR24], [@CR27], [@CR28]\] and genes affecting adaptive immune responses (*IL23R*, *STAT3*, *CCR6*) \[[@CR29], [@CR30]\]. Rs13361189 (*IRGM*), rs10210302 (*ATG16L1*), rs2066844, rs2066845, rs2066847 (*NOD2*), rs35873774 (XBBP1), rs11175593 (*LRRK2*), rs11465804 (*IL23R*), rs2301436 (*CCR6*), rs744166 (*STAT3*) and rs4821544 (*NCF4*) SNP status were determined by KBiosciences, UK. Inconclusive SNP analyses were excluded, accounting for the variable number of patients analyzed per SNP (Additional file [1](#MOESM1){ref-type="media"}: Table S1). Different SNPs in *NOD2* were combined for analysis, as these SNPS have been shown to alter cellular function in a similar manner \[[@CR31], [@CR32]\]. Due to the low number of patients homozygous for the SNPs, patients heterozygous for the risk allele were analysed together with patients carrying two risk alleles of the same gene, thereby comparing carriers and non-carriers of the IBD-associated alleles. Statistical analyses were performed using descriptive statistics, independent t tests, Mann--Whitney nonparametric tests, Chi square (Χ^2^) tests and Fisher's exact test. Independent samples t tests were used to compare means. Proportions were compared using the Χ^2^ test or Fisher's exact test. Two-sided p values \< 0.05 were considered significant. Associations were assessed using a logistic regression using the enter method expressed as odds ratios (OR) with 95% confidence interval (CI). Correction for multiple testing was applied to logistic regression analysis, with two-sided p values of \< 0.0055 considered significant correction for multiple testing. Overall logistic analysis associating IFX to the SNPs in the IBD related genes were corrected for age, IBD subtype and fistulising disease. Subanalyses in CD patients were corrected for fistula and age. Subanalyses for UC were corrected for age. Logistic analyses aiming to associate ADA to the SNPs were corrected for extra-intestinal manifestations, age, and IBD subtype. Subanalyses in CD patients were corrected for extra-intestinal manifestations, fistula and age. Subanalyses in UC patients were corrected for extra-intestinal manifestations and age. Statistical analyses were performed using SPSS for Windows software (v23.0, Chicago, IL). Results {#Sec3} ======= Patient and disease characteristics {#Sec4} ----------------------------------- Of the 591 eligible patients, 19 were excluded due to liver disease or liver transplantation, one patient was not suffering from IBD, and one patient was excluded because of multiple kidney transplantations, leaving a total of 570 patients. Thede included 411 CD (71.9%), 148 UC (26.0%) and 11 IBDU (1.9%) patients. Patient and disease characteristics are shown in Table [1](#Tab1){ref-type="table"}. The median age at IBD diagnosis was 27 years (range 5--79). Median age at diagnosis was 25 years in CD, 26 years in UC, and 32 years in IBDU. Of our patients 54.7% were female. The mean duration of follow-up was 9.2 years (range 0.1--49.1). Four patients developed colorectal cancer during follow-up.Table 1Patient characteristicsTotal\ N = 570CD\ N = 411UC\ N = 148IBDU\ N = 11Follow-up Length, mean, range9.2 yrs (range 0.1--49.1)9.5 yrs (range 0.1--49.1)8.6 yrs (range 0.2--32.3)4.9 yrs (range 0.8--10.5) Length, median6.9 yrs7.0 yrs6.9 yrs4.8 yrsGender Male258 (45.3)169 (41.1)85 (57.4)4 (36.4) Female312 (54.7)242 (58.9)63 (42.6)7 (63.6)Age at diagnosis Mean, range27 yr (range 5--79)27 yr (range 5--79)28 yr (range 8--69)32 yr (range 17--47) Median25 yr25 yr26 yr32 yrDisease location CD L1---terminal ileum99 (24.1) L2---colon90 (21.9) L3---ileocolon120 (29.2) (+) L4---upper GI tract63 (15.3) Other0 (0) Unknown21 (5.1) No inflammation18 (4.4)Disease location UC E1---proctitis8 (5.0)7 (4.7)1 (9.1) E2---left sided colitis69 (43.4)64 (43.2)5 (45.4) E3---pancolitis73 (45.9)69 (46.6)4 (36.4) No inflammation3 (1.9)3 (2.0)0 (0) Other2 (1.3)1 (0.7)1 (9.1) Unknown4 (2.5)4 (2.7)0 Backwash ileitis35223 Rectal sparing19161Disease behaviour CD B1---luminal disease126 (30.7) B2---stenosis89 (21.7) B3---abscesses and/or fistula181 (44.0) P---perianal disease144 (35.0) Unknown15 (3.6) Extra-intestinal172 (30.2)134 (32.6)36 (24.3)2 (18.2)Family history of IBD Yes127 (22.3)98 (23.8)25 (16.9)4 (36.4) No380 (66.7)267 (65.0)108 (73.0)5 (45.4) Not documented63 (11.0)46 (11.2)15 (10.1)2 (18.2)Family history of CRC Yes36 (6.3)22 (5.4)13 (8.8)1 (9.1) No469 (82.3)342 (83.2)119 (80.4)8 (72.7) Not documented65 (11.4)47 (11.4)16 (10.8)2 (18.2)All numbers are presented as n (%), unless stated otherwise*CD* Crohn's disease, *UC* ulcerative colitis, *IBDU* unclassified inflammatory bowel disease, *CRC* colorectal cancer, *IBD* inflammatory bowel disease, *yrs* years In total 211 patients were treated with IFX and 179 with ADA, with 111 patients receiving both treatments. A total of 126 patients developed side effects while treated with IFX and 89 did so while on ADA. Fifty-nine patients experienced loss of response to IFX and 26 to ADA. Twenty-seven patients were primary non-responders on IFX and 14 never responded to ADA. CD patients were more likely to be treated with IFX (p = 0.022, OR 1.6, CI 1.1--2.3) or ADA (p \< 0.0001, OR 7.6, CI 4.2--13.9) compared to UC/IBDU patients. IFX treated patients were less likely to achieve mucosal healing than patients not requiring this medication (p \< 0.0001, OR 0.48). Both IFX (p \< 0.0001, OR 2.5) and ADA (p = 0.002, OR 1.8) treated patients were more likely to undergo bowel resection, compared to patients not receiving these medications. However these associations were no longer significant after correction for fistula and disease phenotype. Furthermore ADA treated patients suffered from extra-intestinal manifestations (p \< 0.012) more often than patients who were not treated with ADA, which remained significant after correction for disease phenotype (p = 0.047, OR 1.5, CI 1.0--2.2). Genetics {#Sec5} -------- SNPs in nine IBD related genes were evaluated. Distribution of the genetic profiles can be found in Table [2](#Tab2){ref-type="table"}. The minor allele frequency known in literature and the frequency in this cohort can be found in Table [3](#Tab3){ref-type="table"}.Table 2Genetic profile patientsGeneSNPTotalHomozygous: no SNPHeterozygous, one SNPHomozygous, two SNPs*IRGM*C56843012018*ATG16L1*T559103272184*NOD2*T, C, C57042812814rs2066844T559484714rs2066845C567539271rs2066847C561513480*XBP1*C, protective567510543*LRRK2*/*MUC19*T562532300*CCR6*A558135280143*IL23R*G, protective564524382*STAT3*T56221826678*NCF4*C57028222563Number of patients that could be analysed for each gene, and the distribution of risk alleles in these genes. All numbers are expressed as n Table 3Minor allele frequencies of investigated SNPs in general population (controls), as reported for IBD (IBD) and in the IBD cohort described here (cohort)TreatmentSNPMAF controls \[[@CR31]\]MAF IBD \[[@CR31]\]MAF cohort*IRGM*C0.130.180.14*ATG16L1*T0.480.40 \[[@CR44]\]0.57*NOD2*T, C, C----rs2066844T0.070.140.07rs2066845C0.010.050.03rs2066847C0.020.110.04*XBP1*C, protective0.040.040.05*LRRK2*/*MUC19*T0.020.030.03*CCR6*A0.470.480.50*IL23R*G, protective0.080.020.04*STAT3*T0.420.410.38*NCF4*C0.330.38 \[[@CR31], [@CR45], [@CR46]\]0.31*MAF* minor allele frequency, *SNP* single nucleotide polymorphism An association between the *ATG16L1* risk allele and Crohn's disease (p = 0.007) and younger age at IBD diagnosis (26.83 vs 29.93, p = 0.032) was observed. Sub analysis per disease phenotype showed that UC or IBDU patients carrying the *ATG16L1* risk allele were less likely to achieve mucosal healing (p = 0.027). In CD patients, *ATG16L1* SNP carriers were significantly more likely to have a family member with IBD (p = 0.004). Carrying the *IRGM* risk allele was associated with male gender (p = 0.034) and younger age at diagnosis (25.84 vs 27.90, p = 0.048). Sub analysis for IBD phenotype did not how any differences between SNP carriers and non-carriers. *NOD2* risk allele carriers more often suffered from CD (p = 0.002) and carrying the *NOD2* SNP was associated with colonic disease in these patients (p \< 0.0001). Carrying the *CCR6* SNP was associated with achievement of mucosal healing in UC patients (p = 0.009). CD patients carrying the *NCF4* SNP were more likely to suffer from stenosing disease (p = 0.005, OR 2.0, CI 1.2--3.2), even after correction for age (p = 0.004, OR 2.0, CI 1.2--3.3), although no association with fistula or non-stenosis-non-fistulising disease was observed. *IL23R* CD SNP patients were also more likely to suffer from stenosing disease (p = 0.023). There were no differences in basic clinical parameters between patients carrying risk alleles of the *XBP1*, *STAT3* and *LRRK2*/MUC2 genes and patients who did not carry these risk alleles. None of the risk alleles were associated with the number of flared (corrected for follow-up time). Genetics versus treatments {#Sec6} -------------------------- The only significant association between anti-TNFα use and genetic risk variants was found for *ATG16L1*. While there were no associations between *ATG16L1* risk allele carriers and IFX use/response, neither in the entire cohort, nor in CD and UC sub analyses, IBD patients carrying the *ATG16L1* SNP were significantly more prone to use ADA (p = 0.004, OR 2.4, CI 1.3--4.4, corrected for age, extra-intestinal manifestations, IBD subtype and multiple testing). In CD patients, this correlation also remained true (p = 0.005 OR 2.6 CI 1.3--5.0). Other, nominally significant associations are listed below. Logistic regression analysis after correction for age and IBD phenotype showed that patients carrying the *IRGM* risk allele were more prone to develop primary non response to IFX (OR 2.4, CI 1.0--5.7, p = 0.048). In sub analysis per disease phenotype, it was apparent that in particular UC patients carrying the SNP in the *IRGM* gene were more prone to suffer from primary non response to IFX (p = 0.009, OR 12.2, CI 1.2--78.8, corrected for age) whereas there were no associations between the *IRGM* risk allele and IFX use and response in CD patients (corrected for age and fistula). Regarding ADA, patients carrying the *IRGM* risk allele more often used ADA, compared to patients who did not carry this risk allele (p = 0.021, OR 0.58, CI 0.36--0.92 corrected for age, IBD subtype and extra intestinal manifestations). Sub analysis for CD patients only did not show any associations between the *IRGM* SNP and ADA. *XBP1* risk allele carriers responded less to IFX (p = 0.016, OR 3.7, CI 1.2--10.8) and patients carrying a *STAT3* SNP more often had side effects on IFX (p = 0.021, OR 0.30, CI 0.11--0.83). No associations were found between the risk allele carriers of the *NOD2*, *LRRK2*/*MUC19*, *CCR6*, *IL23R* and *NCF4* genes and response to anti-TNFα. As only 13 UC + IBDU patients were treated with ADA, no further analysis could be performed. An overview of the outcomes of the logistic regression can be found in Table [4](#Tab4){ref-type="table"}.Table 4SNP versus treatment logistic regressionTreatment*IRGMATG16L1NOD2XBP1*LRRK2/MUC19CCR6IL23*STAT3*NCF4Requirement InfliximabnsnsOR 0.62, CI 0.41--0.95nsnsnsnsnsns AdalimumabOR 0.57, CI 0.36--0.91OR 2.4, CI 1.3--4.4nsnsnsnsnsnsnsSide-effects InfliximabnsnsnsnsnsnsnsOR 0.19, CI 0.05--0.78ns AdalimumabnsnsnsnsnsnsnsnsnsLoss of response Infliximabnsnsnsnsnsnsnsnsns AdalimumabnsnsnsnsnsnsnsnsnsPrimary non response InfliximabOR 2.8, CI 1.1--7.0nsnsOR 3.8, CI 1.2--12.0nsnsnsnsns AdalimumabnsnsnsnsnsnsnsnsnsLogistic regression analysis showing the association between the different IBD risk genes and clinical response to anti-TNFα treatments*SNP* single nucleotide polymorphism, *ns* not significant, *OR* odds ratio, *CI* confidence interval Discussion {#Sec7} ========== Personalized medicine for IBD is called for, as a lack of identification of the appropriate patient group may result in underestimation of clinical results of some treatments. For instance, studies with the granulocyte colony stimulating factor (GM-CSF) sargramostim have been controversial \[[@CR33]--[@CR35]\]. However, granulocytes of CD patients carrying the *NCF4* risk allele were recently shown to be less sensitive to stimulation with GM-CSF, suggesting that only a subpopulation of patients may actually benefit from this treatment \[[@CR24]\]. Similarly, trials on the use of interferon-β-1α (IFN-β-1α) in IBD initially did not seem to be effective \[[@CR36], [@CR37]\], while on closer inspection, Croatian and Russian patients were shown to have high remission and response rates using this treatment, while Western European populations experienced the opposite \[[@CR36]\]. These studies emphasise the diversity in IBD, and suggest that in study populations, genetic variants could be used to stratify groups of patients, potentially leading to a tailored treatment model. The purpose of our study was to investigate putative links between IBD-risk alleles and the effect of anti-TNFα treatment, something which has received relatively little attention to date. For five of the nine investigated genes, no association was found with treatment response, whereas with three other genes (*IRGM*, *XBP1*, *STAT3*) associations were found, but were not strong enough to survive multiple testing corrections. The strongest association observed was a tendency for *ATG16L1* SNP carrying patients to be treated with ADA, with increased odds for using ADA when carrying two *ATG16L1* risk alleles (not shown). Recently, a retrospective study of 588 IBD patients investigated 41 IBD risk genes, including the nine in the current study, and showed that only the *XBP1* variant was nominally associated with start of IFX/ADA \[[@CR38]\]. However, unlike the current study, this study was performed in a pediatric cohort. Interestingly, a prospective study testing 31 risk-alleles (including *NOD2*, *ATG16L1* and *IL23R*) in 102 patients showed that only polymorphisms in *ATG16L1* correlated to clinical response, with patients carrying the *ATG16L1* risk alleles having significantly better response to ADA. Although *ATG16L1* SNP status was associated with use of ADA in our study, we did not find primary non-response, side-effects or loss or response to anti-TNFα to be modulated by any of the SNPs studied. However, unlike the other three measured outcomes, treatment use in itself is not likely a parameter that is influenced by patient genetics, as treatment of patients is decided by physicians and SNP status in this study was not available to treating physicians. Hence, these results hint at an underlying disease phenotype which is not captured by the currently used parameters (Montreal score, disease location, disease severity). If true, this would suggest that based on genetics, it might be possible to define patient groups with subtly different disease, that cannot otherwise be distinguished, which opens up an interesting avenue of investigation. Attempts have already been made to categorize CD patients into genetic-based Crohn's disease subgroups according to SNPs in 46 disease susceptibility loci \[[@CR39]\]. Surprisingly, these genetic-based subgroups could not be explained by clinical phenotypic variables such as disease location and behaviour, suggesting that patients had been categorized into previously un-identified sub-groups by genetically-determined pathways rather than the currently used classifications that are mostly based on disease location \[[@CR39]\]. A direct comparison between genetic studies is complicated by differences in either cohort size, disease phenotype and age of onset. Furthermore, differences in genetic associations between disease location and behaviour might be found in a different minor allele frequency distribution between cohorts. While *NOD2* and *ATG16L1* variants are some of the most consistently observed IBD-associated loci, association studies differ per cohort. We have investigated only nine of the \~ 200 IBD related risk genes, while interactions between SNPs in different genes might also account for specific phenotypes \[[@CR40]--[@CR42]\]. Only around 13 and 8.2% of disease variance of CD and UC, respectively, has been explained by the risk loci identified to date, and other genes or epigenetic events may contribute to various extents in these cohorts \[[@CR15], [@CR43]\]. Conclusions {#Sec8} =========== In conclusion, genetic polymorphisms in the *ATG16L1* gene correlate with ADA treatment, for which a previously unidentified disease phenotype may be responsible. This suggests that genetic make-up of IBD patients may in future help physicians decide on personalized treatment strategies. Further investigation will need to elucidate the implications of these findings and identify the corresponding disease phenotype. Additional file {#Sec9} =============== **Additional file 1: Table S1.** SNPs versus treatment, number of patients per group. **Electronic supplementary material** The online version of this article (10.1186/s12967-017-1355-9) contains supplementary material, which is available to authorized users. VN, literature search, study format, writing protocol, collecting data, processing data, data interpretation, analysing data, writing manuscript; MP, literature search, data interpretation, commenting on manuscript; JW, literature search, study format, writing protocol, data interpretation, commenting on manuscript; GF, literature search, study format, data interpretation, writing manuscript. All authors read and approved the final manuscript. Acknowledgements {#FPar1} ================ The authors thank K. Diederen and L. Vellekoop for their help with retrieving patient data, and Katya Mauff from the Erasmus MC Department of Biostatistics for help with statistical analyses. Competing interests {#FPar2} =================== VN received an unrestricted educational grant from Dr. Falk Benelux B.V. JW has received consultancy fees from MSD, Abbvie, Pharmacosmos, and Ferring and an unrestricted educational grant from Dr. Falk Benelux B.V. Availability of data and materials {#FPar3} ================================== The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Consent for publication {#FPar4} ======================= Not applicable. Ethics approval and consent to participate {#FPar5} ========================================== Ethics approval was obtained from the institutional review board (MEC-2012-245). Funding {#FPar6} ======= No funding was obtained for this study. Publisher's Note {#FPar7} ================ Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

2nd Victim Dies In Eldred Twp. Motorcycle Crash A 28-year-old Saylorsburg-area man died yesterday at Lehigh Valley Hospital, Salisbury Township, from injuries sustained in a motorcycle accident in Eldred Township on Thursday. Patrick Sokolowski of Saylorsburg R.3 died of multiple traumatic injuries, according to Lehigh County Coroner Wayne Snyder. He was a passenger on a motorcycle that was involved in a head-on collision with a pickup truck on Kunkletown Road. The driver of the motorcycle, Martin Motto, 27, of Kunkletown was killed in the crash. State police at Lehighton said the motorcycle was westbound when it was struck by a pickup, driven by Mark Lane, 23, of Saylorsburg, which was westbound. Police said Lane's vehicle entered the east lane as it rounded a curve, hit the motorcycle, then went through guard wires and down an embankment. Lane was treated at Pocono Medical Center.

// // HTTPRequest.cpp // // Library: Net // Package: HTTP // Module: HTTPRequest // // Copyright (c) 2005-2006, Applied Informatics Software Engineering GmbH. // and Contributors. // // SPDX-License-Identifier: BSL-1.0 // #include "Poco/Net/HTTPRequest.h" #include "Poco/Net/NetException.h" #include "Poco/Net/NameValueCollection.h" #include "Poco/NumberFormatter.h" #include "Poco/Ascii.h" #include "Poco/String.h" using Poco::NumberFormatter; namespace Poco { namespace Net { const std::string HTTPRequest::HTTP_GET = "GET"; const std::string HTTPRequest::HTTP_HEAD = "HEAD"; const std::string HTTPRequest::HTTP_PUT = "PUT"; const std::string HTTPRequest::HTTP_POST = "POST"; const std::string HTTPRequest::HTTP_OPTIONS = "OPTIONS"; const std::string HTTPRequest::HTTP_DELETE = "DELETE"; const std::string HTTPRequest::HTTP_TRACE = "TRACE"; const std::string HTTPRequest::HTTP_CONNECT = "CONNECT"; const std::string HTTPRequest::HTTP_PATCH = "PATCH"; const std::string HTTPRequest::HOST = "Host"; const std::string HTTPRequest::COOKIE = "Cookie"; const std::string HTTPRequest::AUTHORIZATION = "Authorization"; const std::string HTTPRequest::PROXY_AUTHORIZATION = "Proxy-Authorization"; const std::string HTTPRequest::UPGRADE = "Upgrade"; const std::string HTTPRequest::EXPECT = "Expect"; HTTPRequest::HTTPRequest(): _method(HTTP_GET), _uri("/") { } HTTPRequest::HTTPRequest(const std::string& version): HTTPMessage(version), _method(HTTP_GET), _uri("/") { } HTTPRequest::HTTPRequest(const std::string& method, const std::string& uri): _method(method), _uri(uri) { } HTTPRequest::HTTPRequest(const std::string& method, const std::string& uri, const std::string& version): HTTPMessage(version), _method(method), _uri(uri) { } HTTPRequest::HTTPRequest(const HTTPRequest& other): HTTPMessage(other), _method(other._method), _uri(other._uri) { } HTTPRequest::~HTTPRequest() { } HTTPRequest& HTTPRequest::operator = (const HTTPRequest& other) { if (this != &other) { HTTPMessage::operator = (other); _method = other._method; _uri = other._uri; } return *this; } void HTTPRequest::setMethod(const std::string& method) { _method = method; } void HTTPRequest::setURI(const std::string& uri) { _uri = uri; } void HTTPRequest::setHost(const std::string& host) { set(HOST, host); } void HTTPRequest::setHost(const std::string& host, Poco::UInt16 port) { std::string value; if (host.find(':') != std::string::npos) { // IPv6 address value.append("["); value.append(host); value.append("]"); } else { value.append(host); } if (port != 80 && port != 443) { value.append(":"); NumberFormatter::append(value, port); } setHost(value); } const std::string& HTTPRequest::getHost() const { return get(HOST); } void HTTPRequest::setCookies(const NameValueCollection& cookies) { std::string cookie; cookie.reserve(64); for (NameValueCollection::ConstIterator it = cookies.begin(); it != cookies.end(); ++it) { if (it != cookies.begin()) cookie.append("; "); cookie.append(it->first); cookie.append("="); cookie.append(it->second); } add(COOKIE, cookie); } void HTTPRequest::getCookies(NameValueCollection& cookies) const { NameValueCollection::ConstIterator it = find(COOKIE); while (it != end() && Poco::icompare(it->first, COOKIE) == 0) { splitParameters(it->second.begin(), it->second.end(), cookies); ++it; } } bool HTTPRequest::hasCredentials() const { return has(AUTHORIZATION); } void HTTPRequest::getCredentials(std::string& scheme, std::string& authInfo) const { getCredentials(AUTHORIZATION, scheme, authInfo); } void HTTPRequest::setCredentials(const std::string& scheme, const std::string& authInfo) { setCredentials(AUTHORIZATION, scheme, authInfo); } void HTTPRequest::removeCredentials() { erase(AUTHORIZATION); } bool HTTPRequest::hasProxyCredentials() const { return has(PROXY_AUTHORIZATION); } void HTTPRequest::getProxyCredentials(std::string& scheme, std::string& authInfo) const { getCredentials(PROXY_AUTHORIZATION, scheme, authInfo); } void HTTPRequest::setProxyCredentials(const std::string& scheme, const std::string& authInfo) { setCredentials(PROXY_AUTHORIZATION, scheme, authInfo); } void HTTPRequest::removeProxyCredentials() { erase(PROXY_AUTHORIZATION); } void HTTPRequest::write(std::ostream& ostr) const { ostr << _method << " " << _uri << " " << getVersion() << "\r\n"; HTTPMessage::write(ostr); ostr << "\r\n"; } void HTTPRequest::read(std::istream& istr) { static const int eof = std::char_traits<char>::eof(); std::string method; std::string uri; std::string version; method.reserve(16); uri.reserve(64); version.reserve(16); int ch = istr.get(); if (istr.bad()) throw NetException("Error reading HTTP request header"); if (ch == eof) throw NoMessageException(); while (Poco::Ascii::isSpace(ch)) ch = istr.get(); if (ch == eof) throw MessageException("No HTTP request header"); while (!Poco::Ascii::isSpace(ch) && ch != eof && method.length() < MAX_METHOD_LENGTH) { method += (char) ch; ch = istr.get(); } if (!Poco::Ascii::isSpace(ch)) throw MessageException("HTTP request method invalid or too long"); while (Poco::Ascii::isSpace(ch)) ch = istr.get(); while (!Poco::Ascii::isSpace(ch) && ch != eof && uri.length() < MAX_URI_LENGTH) { uri += (char) ch; ch = istr.get(); } if (!Poco::Ascii::isSpace(ch)) throw MessageException("HTTP request URI invalid or too long"); while (Poco::Ascii::isSpace(ch)) ch = istr.get(); while (!Poco::Ascii::isSpace(ch) && ch != eof && version.length() < MAX_VERSION_LENGTH) { version += (char) ch; ch = istr.get(); } if (!Poco::Ascii::isSpace(ch)) throw MessageException("Invalid HTTP version string"); while (ch != '\n' && ch != eof) { ch = istr.get(); } HTTPMessage::read(istr); ch = istr.get(); while (ch != '\n' && ch != eof) { ch = istr.get(); } setMethod(method); setURI(uri); setVersion(version); } void HTTPRequest::getCredentials(const std::string& header, std::string& scheme, std::string& authInfo) const { scheme.clear(); authInfo.clear(); if (has(header)) { const std::string& auth = get(header); std::string::const_iterator it = auth.begin(); std::string::const_iterator end = auth.end(); while (it != end && Poco::Ascii::isSpace(*it)) ++it; while (it != end && !Poco::Ascii::isSpace(*it)) scheme += *it++; while (it != end && Poco::Ascii::isSpace(*it)) ++it; while (it != end) authInfo += *it++; } else throw NotAuthenticatedException(); } void HTTPRequest::setCredentials(const std::string& header, const std::string& scheme, const std::string& authInfo) { std::string auth(scheme); auth.append(" "); auth.append(authInfo); set(header, auth); } bool HTTPRequest::getExpectContinue() const { const std::string& expect = get(EXPECT, EMPTY); return !expect.empty() && icompare(expect, "100-continue") == 0; } void HTTPRequest::setExpectContinue(bool expectContinue) { if (expectContinue) set(EXPECT, "100-continue"); else erase(EXPECT); } } } // namespace Poco::Net

Q: Cortana skill wasn't triggered by the invocation phrase I created a Azure based Web App Bot using the QnAMaker template and used the 'Test in Web Chat' to test it successfully. To enable voice assistant to the chatbot, I configured the Cortana channel and enabled the 'manage used identity through connected service' option too to link the user's account with the skill. The chatbot wasn't published yet but same Microsoft account has been used in test devices to login to Cortana as the botframework login used to develop the Azure web app bot. However, the invocation phrase doesn't invoke the skill in the Cortana apps running on iOS, Android and Windows 10 PC. I used utterance such as 'Ask purple genie', 'Tell purple genie' only to get the regular search results. I changed the language/region to English/US on all the test devices too. Isn't this change enough for testing this skill when the device is not in US. A: It turns out to be a question of whether web search or skill has the priority in Cortana skill. In the chat I had with Micromuncher from Microsoft, he worked with his dev team to bring the skill invocation phrase to invoke the skill. Apparently Cortana dev team play around with setting priority of phrases to bring up search results instead of invoking a skill.

Photodegradation of decabromodiphenyl ether adsorbed onto clay minerals, metal oxides, and sediment. The photodebromination of decabromodiphenyl ether (BDE-209) adsorbed onto six different solid matrixes was investigated in sunlight and by irradiation with 350 +/- 50 nm lamps (four lamps at 24 W each). After 14 days of lamp irradiation, BDE-209 degraded with a half-life of 36 and 44 days, respectively, on montmorillonite or kaolinite, with much slower degradation occurring when sorbed on organic carbon-rich natural sediment (t1/2 = 150 days). In late summer and fall sunlight (40.5 degrees N, elevation 600 ft), the half-lives of BDE-209 sorbed on montmorillonite and kaolinite were 261 and 408 days, respectively. Under both irradiation schemes, no significant loss of BDE-209 occurred when sorbed to aluminum hydroxide, iron oxide (ferrihydrite), or manganese dioxide (birnessite). Upon exposure to both lamp and solar light and in the presence of montmorillonite and kaolinite, numerous lesser brominated congeners (tri- to nonabromodiphenyl ethers) were produced. Nearly identical product distribution was evident on montmorillonite and kaolinite. Dark control experiments for each mineral showed no disappearance of BDE-209 or appearance of degradation products. These results suggest that photodegradation of BDE-209 on mineral aerosols during long-range atmospheric transport may be an important fate process for BDE-209 in the environment.

Q: Permutations without but also kinda with repitition I'm very new to coding but I was needing some help. My problem is if I have the code: import itertools result = itertools.permutations('ABCD',4) for i in result: print(i) This got me all 24 permutations but how would I code the same thing but if the letters were A B, B and C for example as if you swap the Bs around, it makes no difference? I'd appreciate any help I can get, thank you. A: Just turn it to a set and it will remove the duplicates. If that is what you are asking. import itertools result = itertools.permutations('ABBD',4) result = set(result) for i in result: print(i)

Zachary Corlew Blog posts : "best beginner yoga boulder" One of the most debilitating things to affect humans is depression. Depression bring affected people into a moody state where they might lose sight of goals in life and lose any hope for their future. If you need help battling depression, then focus on the recommendations in this post.

AM I THE ONLY ONE AROUND HERE 122 shares

Anarchist blog boy freed After the longest stretch ever served in the joint for refusing to disclose a source, blogger/activist Josh Wolf is a free man. Wolf spent 226 days, nearly 7 1/2 months, in the Federal Penitentiary in Dublin, California after refusing to testify before a grand jury and withholding footage of a 2005 anarchist rally in San Francisco from federal prosecutors. The feds supposedly wanted the video and testimony as part of an investigation into events at the rally after a San Francisco policeman suffered a head injury and there was some indeterminate fire damage to a city police car. California has a reporter shield law that might have protected Wolf, but the feds claimed jurisdiction over the investigation on the thin premise that the car was partially funded by federal money. Federal law contains no reporter shield, so Wolf had no protection against the subpoena. Wolf has claimed throughout the whole affair that the feds weren't interested in the squad car at all, but really just wanted him to name names about the anarchists and organizations at the rally. He's had a point, too - the subpoena in question was served on Wolf by a Special Federal Officer of the Joint Terrorism Task Force, which suggests that the feds were more interested in having Wolf do their surveillance for them than in actually getting to the bottom of the police car mystery. Plus, footage of the rally that Wolf sold to local news stations seems to imply that federal agents were at the scene before the events that supposedly conferred jurisdiction on them had even taken place. Wolf has long argued that the uncut video was not useful as evidence in the investigation and that he mainly wanted to avoid testifying before the grand jury so that he would not have to reveal information regarding his sources or contacts at the rally. After the deal reached between Wolf and prosecutors on April 3 and his subsequent release, Wolf posted the entire video on his blog. He claims he would have done it sooner, since it had no damaging information in it, but he wanted to retain a bargaining chip in his negotiations with the feds. Many in the blogosphere are proclaiming Wolf's release a victory for bloggers and journalists, but it is unclear what exactly they have won. The deal entered into the legal record states that Wolf agreed to turn over the video and also answered questions about the rally under oath, which basically gave away the farm since he originally refused to comply with the subpoena specifically to avoid testifying about the rally. Wolf didn't have to appear before the grand jury, though. He did admit in the deal, however, that the government can still serve him with another grand jury subpoena relating to the events at the rally. If and when the government decides to do that, Wolf still has nothing to protect him from another contempt order and another stay behind bars, and the whole thing could start anew. So a momentary victory for Josh Wolf it may be, but a Pyrrhic victory at best for bloggers and journalists in the federal legal system. Still, Wolf did a long stretch in federal prison to protect an ideal, bargained for his freedom with federal prosecutors, and added to the political pressure to create a federal reporter shield law.

EDITORIAL It is my pleasure to introduce to you the eleventh issue of Phenotype magazine! As always, this issue includes contributions from PIs, post-docs and students from across the University. A highlight of this issue is an introduction by Dr Phil Biggin, RCUK Fellow in the Department of Biochemistry, to his research using computational approaches to examine ligand binding to receptor proteins. Also featured is an interview with Prof Adrian Hill, director of the Jenner Institute, in which he shares the highlights (and travels) of his career in tropical medicine thus far. This issue has a strong focus on advances in genetics and how this affects us all. William Brandler starts the discussion by introducing the “500 Genome Project” of The Wellcome Trust Centre for Human Genetics and how whole genome sequencing can be used to identify the genetic basis of diseases. Annabel Morley looks more closely at what can be done once genetic diseases are identified, namely gene therapy. She explores how close this treatment is to becoming a clinical reality, describing recent advances in how gene therapy might be delivered. Finally, Mark Pavlyukovskyy moves the discussion to genetic modifications that can already be accomplished and how we as a society view them, summarising the current state of genetically modified food in the EU and the challenges for the future. Moving away from genetics, Richard Wheeler gives us an insight into how economists view academic science, describing the theory of gift economics. We also showcase a blogger from the Oxbridge Biotechnology Roundtable, Sonya Hanson, who wonders about the future of biotech investment in a post-recession world. Finally, in our Science and Society section, Clara Ferreira introduces us to the Athena SWAN award, which promotes gender equality in the science, engineering and technology sector, and Blanka Sengerová shares her experiences of volunteering at Science Oxford. The image gracing this issue’s cover was submitted by Dr Elizabeth Hartfield and was the winner of last issue’s SNAPSHOT prize. Learn more about her work using skin cells from Parkinson’s patients to first create stem cells, then differentiated neurons, on page 31. There is another chance to win £50 from Oxford University Press this issue and we look forward to your research-inspired images. Congratulations to our regular contributor, Penny Sarchet, for her recent win of the Wellcome Trust science writing prize! Read her past contributions, Ghost Forest in Issue 8 and Bugs that eat Oil in Issue 9. If you are considering a career in science journalism after the DPhil, or you just love to write, Phenotype is the place to hone your talents while at Oxford. If you would like to get involved in any aspect of the magazine, from writing to editing to design, please contact us at [email protected]. This issue is a result of the hard work and dedication of our team of students and post-docs. Thank you for making my job an easy one, and producing what I’m sure everyone can agree is a superb issue! Jennifer de Beyer Department of Biochemistry n Monday 13 February, OUBS is hosting Prof Peter Leadlay from the Department of Biochemistry, University of Cambridge. He is currently researching the molecular genetics and chemistry of polyketide antibiotic biosynthesis. Polyketides are a large class of microbial metabolites produced by soil-based bacteria such as Streptomyces spp.. They comprise useful antibiotics such as erythromycin A, anticancer drugs such as doxorubicin and antiparasitics such as avermectin. Polyketide production is one of the major branches of the pharmaceutical industry and such compounds comprise 20% of the top-selling drugs. Work by Leadlay’s group revolves around the production of new polyketides with improved or novel pharmacological properties, a process favoured by the modular nature of polyketide synthases. Polyketides are classified both on the basis of their structure and their mode of biosynthesis. The most interesting polyketides for genetic engineering are the reduced polyketides, in which the first linear chain is constrained by macrocyclisation into a biologically active conformation. This promotes targeted and precise interaction with their protein partners. Reduced polyketides are further subdivided into macrocycles and polyethers. Macrocycles contain a lactone or lactam ring, while polyethers bear a carboxylate group and two to five ether oxygen atoms. Genes coding for polyketide synthases have a modular organisation. Polyketides are built on a molecular assembly line with an enzymatic domain for each biosynthetic step. The modules are organised into multimodular subunits, with a typical subunit containing two or three modules. Many polyketide synthases receive their substrates from enzymes that catalyse prior steps in the synthesis and not by diffusive loading, implying that the enzymes have not been under an evolutionary pressure to develop strict substrate specificities. Indeed, genes coding for individual domains or entire modules can be replaced or substituted to generate chimeric genes coding for engineered polyketide synthases. These in turn generate polyketides with altered stereochemistry or functionality. However, there are currently caveats that hamper the creation of novel polyketides. Many domains have degrees of substrate specificity that prove difficult to change, and controlling stereochemistry is complicated by a complex interplay between ketosynthase and ketoreductase domains. The spatial relationship between domains within the modules that enable them to cooperate sequentially is not well understood, but must be conserved in engineered enzymes. The structure of polyketide synthases is not well characterised, making it hard to arrange correctly positioned subunits for synthesis solely of targeted products. Lastly, engineering polyketide synthase systems is tedious due to the large size of polyketide gene clusters. by Maria Mogni Nonetheless, Leadlay’s group has contributed to the development of several new polyketides, as well as to the understanding of the pathways behind their synthesis. For example, an analysis was performed of the role in stereochemistry of certain amino acids in the active site of a ketoreductase. It was found that additional factors such as tethering of the substrate to an acyl-carrier protein might play a role in ketoreductase stereospecificity (1). Furthermore, a study was conducted in order to isolate and identify intermediate species which are usually covalently attached to their biosynthetic enzymes (2). This led to the development of a chemical strategy based on a competition effect between carba(dethia) substrates and acyl carrier proteins, the former causing the premature release of intermediates from polyketide synthases. The group has also contributed to the identification of new enzymes involved in the biosynthesis of specific polyketides, such as an enzyme acting on chorismate for the synthesis of the important immunosuppressant drug rapamycin (3). Resveratrol, a phytoalexin found in grapes and other food products, was shown to have cancer chemopreventive activity. This snapshot of Professor Peter Leadlay’s research underlines the important role of polyketides in biomedical research, whereby combinatorial biosynthesis is key to the generation of novel compounds. References: 1. Kwan D, et al. (2011) Insights into the stereospecificity of ketoreduction in a modular polyketide synthase. Org Biomol Chem 9(7):2053–2056. 2. Tosin M, et al. (2011) In vivo trapping of polyketide intermediates from an assembly line synthase using malonyl carba(dethia)-N-acetyl cysteamines. Chem Commun 47(12):3460–3462. 3. Andexer J, et al. (2011) Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin involves a previously un-described family of enzymes acting on chorismate. PNAS 108(12):4776–4781. Hilary 2012 | Phenotype | 5 A selection of recent life sciences research from the University of Oxford Glutamine analogs promote cytoophidium assembly in human and Drosophila cells Cellular compartmentalisation of CTP synthase enzyme in structures termed cytoophidia occurs in bacteria, yeast and fruit flies. More recently, such filamentous structures have been identified in humans. Cytoophidia in human cells were found by immunostaining HeLa P4 cells with antibodies against CTP synthase, revealing filamentous structures. The conservation from prokaryotes to eukaryotes indicates that cytoophidia have a crucial function within cells. CTP synthase is an essential metabolic enzyme involved in pyrimidine biosynthesis from both de novo and uridine interconversion pathways. The rate-limiting reaction catalysed by CTP synthase is the hydrolysis of glutamine in a glutamine amidotransferase domain to produce ammonia. Glutamine analogues such as 6-diazo-5oxoL-norleucine (DON) inhibit enzyme activity by acting as a receptor antagonist irreversibly binding to the enzyme’s catalytic centre. In the bacterium Caulobacter crescentus, DON abolishes cytoophidium formation. Surprisingly, in human cells DON treatment increases the occurrence of cytoophidia. This difference is puzzling, but could be explained by the differences between prokaryotic and eukaryotic cells, or the exposure time of DON in the studies – bacterial treatment was shorter than its human and fly counterparts. It is hypothesised that the induction of cytoophidium formation by DON might be a compensation mechanism responding to its inhibition of CTP synthase activity. Another glutamine analogue, azaserine, had comparable effects to DON. Clonal analysis by CTP synthase RNA interference (RNAi) showed that CTP synthase expression levels are crucial for cytoophidia formation. Nevertheless, DON promotes cytoophidium assembly when CTP synthase levels are low. Experiments showed DONinduced cytoophidium formation in flies occurs in a wide range of tissues, including larval and adult testes, and trachea and larval epithelial stem cells. Increased CTP synthase activity is observed in many cancers, hence inhibitory DON has been trialled as an anti-tumour agent. Further studies are also needed to ascertain whether the abundance of cytoophidia is a potential cancer biomarker. Cytoophidia occurrence in human cells increases upon treatment with DON, responding in a Vitamin D–gene interactions in multiple sclerosis Gene-environment interactions can be crucial in disease risk. Vitamin D (VitD) deficiency has been linked to multiple sclerosis (MS), but the molecular mechanisms are unclear. VitD is a group of fat-soluble steroids that function as prohormones in humans; it is primarily synthesised by the body as vitamin D3 and then enzymatically converted to its active form 1,25dihydroxyvitamin D (known as calcitrol). VitD mediates its biological effects by binding to the vitamin D receptor (VDR), which is principally located in the nuclei of target cells. After binding to the retinoid-X receptor, this complex binds to specific genome sequences called VitD response elements (VDREs) in the nucleus where it can regulate transcription of multiple hormone-sensitive genes. The incidence of MS rises with increased latitude and decreasing levels of UVB radiation, which correlates to VitD levels. To ascertain the molecular basis for this association, Berlanga-Taylor et al. searched for VDREs in regulatory elements within the major histocompatibility (MHC) class II region. In silico analysis showed that a VDRE existed close to the promoter region of HLA-DRB1, the main risk variant for MS. Recruitment of VDR to this region was also indicated. Furthermore, increased expression of HLA-DRB1*15 occurred upon VitD stimulation. These findings provide strong molecular evidence for an environmental factor directly interacting with the highest MS risk variant. A genome-wide map of VDR binding, using chromatin immunoprecipitation and DNA sequencing, identified 2776 VDR binding locations. Many other genes associated to MS were discovered to be regulated by VitD, including IRF8 and CD226. There is considerable evidence in support of VitD deficiency underlying risk for several diseases, including MS, rheumatoid arthritis and type I diabetes. With the molecular mechanism for action of VitD in MS now revealed, the evidence could lead to disease prevention studies. The dynamics of receptors H by Dr Phil Biggin ow do receptor proteins transmit a signal? Knowledge of this process, which usually involves a change in conformation, is useful not only for our basic understanding of how these proteins work, but also for improving our prospects for drug design. Indeed there is an increasing feeling that modulation of receptors rather than outright block will become the way forward for novel drugs. My group uses computational methods to explore the dynamics of receptors with a long-term view to developing alternative strategies for drug design. Receptors are dynamic Receptors are a class of macromolecules that specifically and directly convey a signal, typically in the form of a smaller molecule, between or within cells. A receptor must not only recognise the particular molecule that activates it but also, when recognition occurs, alter cell function. This invariably involves the receptor undergoing a conformational change such that other proteins can now interact with the receptor, leading to a cascade of signalling events that might, for example, lead to a change in transcriptional activity. Alternatively, the conformational change can lead to the opening of ion-channels to allow the depolarisation of the cell. Examples of the latter are the ionotropic glutamate receptors (iGluRs). The iGluRs are responsible for the majority of fast neurotransmission in the brain and central nervous system and therefore are involved in memory and learning (1). Because of their centrality to brain function, it is perhaps unsurprising to find these receptors implicated in many neurological diseases including Parkinson’s, Huntington’s and epilepsy. The receptors are ligand-gated ion channels situated in synaptic membranes. Glutamate, the agonist, is released from the pre-synaptic neuron, diffuses across the synaptic cleft and binds to iGluRs. The binding event leads to ion channel opening, which then allows sodium ions to pass into the cell. This in turn depolarises the membrane, initiating an action potential which continues down the length of the neuron. After prolonged exposure to glutamate, the receptors desensitise, undergoing further conformational changes to close even though glutamate is still bound. Determining iGLuR structure The iGluR family, which can be divided into three sub-families based on their response to different pharmacologically relevant compounds, are large tetrameric assemblies. Each subunit has an unusual modular architecture (Figure 1A). In particular, the ligand-binding domain (LBD) appears to have a complete potassium-channel fold inserted into its polypeptide sequence. Both the amino-terminal domain (ATD) and the LBD have an overall structure similar to periplasmic-binding proteins and are essentially the shape of a Pac-Man or a clam-shell. This provides the first clue as to how the receptor is 10 | Oxford University Biochemical Society able to couple the binding of a neurotransmitter into mechanical work that allows the transmembrane (TM) pore to open. The modular nature of the receptor allowed a ‘divide and conquer’ approach to be taken in terms of obtaining structural data. Arguably the most significant step was to make a protein construct that corresponded to the LBD alone, maintained the binding properties of the full-length receptor, and could be readily crystallised (2). More recently a fulllength crystal structure of a tetramer has been solved (3) which supports not only the crystal structures of the isolated domains, but also the expectation that the TM region would be similar to potassium channels (Figure 1B). The full length structure also revealed that the TM region exhibits true four-fold symmetry which appears to break down as the protein exits the membrane, such that the extracellular domains are best thought of as a dimer of dimers. Finally, the ATD appears to exhibit domain swapping, although whether this is a genuine feature in vivo or an artefact of the crystallization process remains to be seen. The combination of structural data with years of mutagenesis and pharmacological studies has led to an overall cartoon of channel function (Figure 1C). Glutamate binding allows the LBD to pull open the TM pore. After a period of time, the receptor undergoes desensitisation and that is thought to reflect a change in the dimer interface allowing the pore to close even though glutamate remains bound. Despite a huge amount of experimental data, the precise nature of the conformational changes remains little more informed than our low-resolution cartoons. In part, this is because there are few, if any, experimental tools that can address these dynamic questions at atomic resolution. This is where computational techniques, and in particular molecular dynamics, can be used to gain further mechanistic insight. Molecular dynamics Molecular dynamics (MD) computes the movement of atoms as a function of time. The potential energy of the configuration of the system, given by the atomic coordinates, is described by a force-field. The forces acting on the atoms are computed using Newton’s equations and this is used to drive the evolution of the system forwards in time. The end result is a trajectory, or ‘movie’, comprised of several snapshots at each time interval. This alone can provide enormous insight into the behaviour of proteins in general. - + O O We and subsequently others have shown that the overall flexibility of the LBD is also directly related to the type of agonist bound (7, 8). Full agonists appear to induce a more ‘rigid’ LBD, which might be important for how efficiently the binding signal is transmitted to the TM domain. MD also predicted that the LBD could readily open to a more open structure than had been observed by X-ray crystallography, supported by small-angle X-ray scattering (SAXS) data (9). Detailed free energy calculations suggested that 9-12 kcal/mol becomes available upon binding glutamate to drive the conformational change that is required to open D1 O The structures of the LBD revealed that agonists and partial agonists bind to the middle of the clam-shell, thus stabilising a closed-cleft conformation (middle panel of Figure 1C). Partial agonists appear to stabilise the clam-shell with a degree of domain closure directly proportional to the efficacy of the agonist. In other words, the more efficacious the agonist, the ‘more closed’ the clam-shell is (4, 5). Conceptually this was attractive because one can imagine that a full agonist would induce full domain closure which in turn would pull on the pore-lining M3 helices to a maximal opening. Partial agonists would do the same but to a lesser extent. However, single channel experiments reveal that partial agonists are capable of opening up the channel to the same conductance levels as full agonist, but also, and rather importantly, that this occurs less frequently (6). Thus, partial agonists are less efficient at inducing channel opening and the static picture from the crystal structures is a bit misleading. ATD NH 3 Beyond cartoons So what can MD contribute to our understanding of iGluR function? The first area where simulation has been applied extensively is to understanding the role that dynamics might have within the LBD. B O However, molecular dynamics can provide much more information than just the “wiggling and jiggling”, as Richard Feynman might have put it. With recent increases in computational power, we can also obtain free energies of processes such as conformational change and binding events. Quantities such as free energy reflect an ensemble of states. According to the ergodic hypothesis, the time average provided by MD should be the same as the ensemble average. This allows us to relate what we see for a single molecule to an experiment that records an ensemble. The only proviso is that we must have performed the dynamics for a long enough time-period. This is sometimes called the ‘sampling problem’ and is the main reason why many of these calculations were hitherto prohibitive. A D2 OUT M1 M3 M4 M2 IN C D1 D1 D2 D2 OUT M3 IN M3 Resting Open Desensitized Figure 1. (A) Schematic cartoon of the ionotropic glutamate receptor subunit topology. The LBD comprises two discontinuous regions of polypeptide chain that form two structural lobes or sub-domains (D1 and D2). The LBD and ATD have similar overall folds. Note that the architecture of the transmembrane region resembles that of an upside-down potassium channel. (B) Cartoon of the X-ray structure of the full-length structure. Chains are coloured green, blue, gold and red. The structure shows domainswapping in the ATD relative to the rest of the protein. (C) A schematic cartoon of the major changes in conformation as we imagine them. Only two subunits and the LBD and M3 from the TM domain are shown for clarity. The receptor starts off in the resting state with the channel closed (pinched off by the ends of the M3 helices). Upon ligand-binding, the D1 and D2 lobes move together allowing mechanical work to be done to pull the M3 (and M1) helices to open the pore. After a period of time, despite the continued presence of agonist (glutamate), the receptor closes into a desensitised state, thought to be due to a rearrangement of the interface between the D1 lobes of adjacent subunits. the channel (10) and more recently, we have been able to identify a single salt-bridge rearrangement that appears to control whether the cleft will close or remain open (11). Thus, we are beginning to put some dynamic detail on critical motions of the LBD. Unanswered Questions The full-length structure solved in 2009 generated more questions than answers. For example, the cartoons for the mechanism of opening suggest that closure of the LBD opens the channel by pulling on the M1 and M3 helices. Yet initial MD simulations reveal that this mechanism is not immediately compatible with the solved structure. The full-length crystal structure was solved with an antagonist bound Hilary 2012 | Phenotype | 11 A teepee formed by the M3 helices (Figure 2C). It is clear that additional motions are required to allow the M3 helices to move far enough apart to allow ions to flow through. Thus the mechanism by which LBD closure leads to channel opening remains far from obvious and will keep us busy for some time yet. Figure 2. (A) Overlay of pore-lining TM helices from the closed state of the KcsA potassium channel (red) with the pore-lining helices from the glutamate receptor structure (cyan). The similarity supports the view that the crystal structure is in the resting (closed) state. (B) Overlay of the M1-M3 of the glutamate B receptor (cyan) with the KcsA potassium channel in a partially open (gold) and open (green) state, illustrating the potential direction the pore-lining helices might be expected to travel in to open the channel. (C) A view from the synapse showing the position of the pre-M1 cuff (grey) which appears to hinder the postulated opening motion of the glutamate receptor. M3 (pore-lining) helices are shown C in cyan, M1 helices are red and M4 are shown in gold. I thank Dr Ranjit Vijayan for some of the figures used in this article and Dr Maria Musgaard for helpful comments. References: CLASH! in the ligand-binding clefts. This corresponds to a resting, closed state. However, we do have crystal structures of the isolated ligand-binding cores with agonists bound, corresponding to the open state of the channel, so by overlaying the D1 sub-domains we can get an idea of the direction that the forces exerted by the LBD should act in. Furthermore, because the TM domain of iGluRs is evolutionarily related to potassium channels, comparison to crystal structures of the open-states of those channels can be used to infer how the iGluRs might open (Figure 2A & B). However, when this is examined with MD the M3 helices that line the pore hardly move at all, even when artificially ‘pushed’ in the postulated directions (Figure 2B & C). There are two reasons for this. Firstly, the linker regions are quite long, unstructured sections of protein which appear to dissipate the mechanical work done by the LBD. Secondly, the TM region is ‘locked’ by the presence of a so-called ‘pre-M1 cuff ’, which acts like a ring on the top of the Dr Phil Biggin is the RCUK Fellow in Structural Bioinformatics and Computational Biochemistry in the Department of Biochemistry, University of Oxford. Hilary 2012 | Phenotype | 13 Six billion to one ASS TO GAS How whole genome sequencing can improve our health and even help us find love by William Brandler Our evolution has shaped us to choose partners based on subtle cues that reflect both their genetic fitness and compatibility with us. As our understanding of human genetic variation becomes more complete, we could skip this imperfect system and go straight to the source, our genetic code. Internet dating websites could spring up where lonely hearts are matched up using not only their personalities and interests, but also their genetic compatibility. Couples could be paired to maximise the likelihood of their offspring having user-specified ‘desirable traits’, while minimising the risk of genetic diseases – the end result being ‘designer babies’. Regardless of the ethical and moral considerations, the pace of the genetic revolution is such that this could be a reality in the next few years. The Genetic Revolution Before the sequencing of the human genome in 2001, next to nothing was known about the genetics of common human traits. Moving forward just 10 years to June 2011, there were 1,449 published mutations identified that influence variation in 237 human traits (1). Prior to 2001, the molecular basis of approximately 100 rare, monogenic disorders was known. This number has jumped 30-fold such that we now know the genes behind almost half of the 7,000 known monogenic disorders (2). These numbers have been increasing exponentially as the cost of genome sequencing technologies has nosedived (Figure 1). As Richard Resnick, CEO of genetic software firm GenomeQuest puts it (3), this drop in the cost of genome sequencing “is the equivalent of filling up your car with gas in 1998, waiting until 2011 and now you can drive to Jupiter and back, twice.” It will not be long before this analogy can be pushed beyond our solar system. The human genome project was a monumental international effort that cost upwards of £2 billion. As of October 2011, the biotech firm Illumina was offering whole-genome sequencing for as little as £5,000 for people with a life-threatening genetic disease and for around £7,500 for people with cancers that require the sequencing of both tumour and non-cancerous cells (4). Soon it will be affordable for the NHS to routinely sequence the genomes of patients. Jay Flatley, CEO of Illumina, believes that all babies born a decade from now will have their genetic code mapped at birth (5). Personalised medicine This freefall in cost is driving a revolution in medical genetics that is catalysing a shift in the understanding, prevention, and treatment of genetic diseases. The information gathered from genome sequencing is ushering in an era of personalised medicine, where individuals are given treatments 14 | Oxford University Biochemical Society tailored to their genetic makeup. This is because some drugs are only effective if patients carry specific mutations. For example, mutations in the epidermal growth factor receptor gene, EGFR, are present in around 15% of lung cancers (6). The anti-cancer drug gefitinib is only effective in this 15% of patients (6, 7), but costs more than £15,000 for each course of treatment. In 2005, France decided to pay for the treatment of every citizen who would benefit from targeted drugs like gefitinib (8) and screened 15,000 patients for mutations in the EGFR pathway, of which 1,700 tested positive. These patients were given a full course of treatment at a cost of around £30 million (8). To give every patient an initial eight week course of gefitinib to see if they would respond, and then only continue treating those who did, would have cost nearly triple this figure. There are 15 drugs like gefitinib that have already been approved by the European Medicines Agency (8) and many more will follow. Personalised medicine will make medical practice more effective and efficient. Whole genome sequencing for disease diagnosis To effectively treat a disease, you first need to know its cause. Clinical geneticists have therefore started offering whole genome sequencing to individuals with unexplained life-threatening genetic disorders. For example, a team led by Dr David Dimmock at the Medical College of Wisconsin in Milwaukee sequenced the genome of an infant diagnosed with acute liver failure and identified mutations that affected both copies of a gene called TWINKLE (7). Mutations in this gene have previously been shown to cause progressive neurological and eye disorders, with two cases also presenting with liver disease. In this case, the child was not recommended for a liver transplant and died six months later. As Dimmock explains, “This was not a happy ending – but in a sense it was” (4). A child was spared a gruelling, costly and unnecessary treatment, the parents were spared false hope, and a liver was saved for another child who may have had greater need. Following on from these initial results, larger scale sequencing of human genomes has now begun. In August 2011, The Wellcome Trust Centre for Human Genetics in Oxford teamed up with Illumina to sequence the genomes of 500 people with various genetic diseases, ranging from cancer to immunological disorders and rare inherited diseases (9). Knowing the cause does not guarantee a cure Despite these technological advances, whole genome sequencing provides a wealth of data that is incredibly challenging to interpret and convey to patients. It requires sifting through the six billion letters that make up our genetic code, searching for one, or a handful of, causative mutations. Even if the gene responsible can be identified, it may not be treatable. For example, Tay-Sachs disease is a progressive neurological disorder caused by mutations in the HEXA gene, for which there is no cure. For many genetic disorders, short of using gene therapy to replace the defective copy of the gene in every cell in your body before it has an irreversible effect, there will be no cure. Furthermore, the results of genome sequencing may throw up some unwelcome incidental findings. You may not want to know your fate if it turns out you carry mutations that cause an incurable Mendelian disorder like Huntington’s or early onset familial Alzheimer’s disease. Genes are not our destiny For more common, multigenic disorders like heart disease, diabetes and cancer, the letters of your genes do not spell out your destiny. If you know the risks, you can make lifestyle changes to minimise them. However, even the largest scale studies have yet to do more than scratch at the surface of understanding the genetic basis of common human traits. For example, a study of human height in 180,000 individuals has found variants that account for only 10% of the observed phenotypic variation (10). As we perform ever larger and more sophisticated studies, we will begin to close the gap on this ‘missing heritability’ of genetic traits. Companies like 23andme have sprung up in the last few years offering to genotype specific regions of the genome that are associated with known human traits and diseases. As costs plummet, there is no doubt that these companies will offer whole genome sequencing. It is only a matter of time before internet dating websites join them. Figure 1. The cost per human genome has dropped significantly since the completion of the human genome project (11). This has far outstripped Moore´s law, which describes the doubling of computer power every two years. Wetterstrand KA. DNA Sequencing costs: Data from the NHGRI Large-Scale Genome Sequencing Program. Available at www.genome.gov/ sequencingcosts. Accessed January 2012. William Brandler is a 3rd year DPhil student in Prof Anthony Monaco´s laboratory at the Wellcome Trust Centre for Human Genetics, University of Oxford. Hilary 2012 | Phenotype | 15 Gift economics and science by Richard Wheeler Y ou will have heard of gifts and of economics, but probably not of gift economics. This economic structure completely ignores bartering and money. Instead, you are expected to give away your time, skills or belongings for free. In a gift economics world, instead of going to work and earning money in return, you spend the day working for free and when you head home, you stop at the supermarket and pick up a bag full of shopping without paying. This economic system is the complete inverse of capitalism and in today’s world, which is driven by trade, seems very backwards. There are now very few communities that base their everyday lives on gift economies. Hundreds, if not thousands, of years ago, the vast majority switched from giving gifts to bartering and trade. Given this, you can be forgiven if you have not heard of gift economics. However you may be surprised that the research conducted at Oxford University is actually part of one of the biggest gift economies active in the world today. Figure 2. Gift economies. Many of the most recognisable gift economies today are knowledgebased and conducted over the internet. Imagining how a gift economy works can be tricky. Thinking back a few thousand years to huntergatherer communities where gift economies were prevalent is helpful. When a hunter makes a kill, he feels obliged to share his meat in support of his community and he does so with no expectation of receiving anything in return. If the hunter fails to make a kill in the future he will not go hungry as a fellow hunter will feel the same moral obligations and share his winnings, thus balancing the situation. It is difficult to insert this alternative to trade into today’s capitalist world. However, there are actually many instances in which members of a community share their time, skills and belongings as gifts rather than for trade. Consider the gifting of support and advice in a group of friends, the gifting of information and knowledge to others via Wikipedia and the gifting of programming skills to create free and open source software for others to use. The prestige, interest and respect that arise from the free sharing of a person’s effort can be viewed as the currency of a gift economy. But how does gift economics link to science? The world’s academic scientific research is one big gift economy. The principle of research lies in the open exchange of ideas by publication and the value of this gift to the researcher is that of a self-organising collaboration. By sharing their results, others are inspired to ‘return the favour’ by completing their own research and giving the data away. This cycle is one of the key driving forces behind the emergence of exciting new fields in science. Importantly, a person never has to pay to stand on the shoulders of giants. The support is given freely. This situation is particularly fascinating, as giving away (publishing) scientific research has genuine monetary value. For example, many next-generation sequencing facilities offer two ways to use their sequencing services. A researcher can either pay a commercial fee, or enter a formal collaboration and give the sequencing facility part-ownership of the intellectual content of the research. A sequencing facility may give £20,000 in running costs, reagents and working hours to be included on a research paper, and then give this intellectual content away for free in an article. The opportunity to give the gift of this scientific data is literally worth £20,000. To understand this counterintuitive situation of giving something worth money away, you need to imagine the real currency of a gift economy. While giving away your ideas and results may seem altruistic, an individual is actually likely to profit from increased prestige and interest in their field in the long run. The uneasy interface between capitalist investment and academic research Unfortunately, the features which make a gift economy work for scientific research are also the features which make scientific research a difficult investment for a capitalist economy, especially as 16 | Oxford University Biochemical Society research is an inherently risky investment. From a capitalist point of view, there is no value in giving away research results. In fact, patents exist specifically to protect intellectual property from being given away without some kind of trade, the precise opposite of the gift economy. Capitalism also views the value of scientific research to others as a reason to protect and hide it, via patents and trade secrets, in order to ensure that it retains value in a trade. Freely sharing this intellectual property is rarely considered. This fundamental conflict of interest is one of the underlying difficulties in interactions between academic and commercial research. A classic complaint from commercial pharmaceutical companies is the lack of patent protection on drug candidates discovered in universities. From the researcher’s point of view, it is advantageous to share their results to promote research in the field. However, from the drug company’s point of view, it is vital to obtain patent protection as quickly as possible to ensure it retains commercial value. Neither the capitalist nor gift economy can be viewed as more ‘right’. In isolation both approaches are perfectly effective, but for a usable drug to be generated in the long term, researchers must usually acquiesce to the commercial nature of the drug industry. Like any economy, gift economies can break down. The example of a hunter-gatherer society illustrates the instabilities of a gift economy well. If resources become scarce, selfishness will become a key motivation. During times of drought hunting becomes difficult. If a hunter is lucky enough to make a kill, he will be less inclined to share, to prevent his own starvation. He would only give away meat in return for something and would only consider a trade. This situation can easily occur in the scientific research gift economy. If research becomes difficult, for example due to a lack of resources, the motivation shifts away from free sharing. Hoarding the data, either by protecting it with patents or by accumulating it for high impact publications to secure future funding, becomes preferable. This is arguably why the ‘publish or perish’ attitude, quantifying research output by number and impact of papers in order to use it in a trade for further funding, has become common. So do we need a scientific gift economy bail-out? Academic scientific research has undoubtedly suffered from the recent turmoil in the capitalist economy. The banks have had bail-outs; does the scientific gift economy need a bail-out too? It makes sense to support gift economies when the capitalist economy is weak, since there is no sense in building a patent portfolio when there is no money available to invest in the inventions. It could be far more advantageous to publish those discoveries quickly to promote further research in that area. But what form would a bail-out in a gift economy take? The health of a gift economy is measured in a similar way to a capitalist economy. If more gifts are being given, analogous to increased productivity, the economy is healthier. By this logic, should we be promoting pre-publication services, like arXiv.org for physics research, which allow open peer access and review prior to publication? And should shorter times between discovery and publication, or more presentation of ongoing research in conferences, be promoted? Is it time to promote sharing of reagents and methods? Gift economies may seem unusual but it is important to support them. Imagine a world where Einstein did not give away his theory of general relativity for free but instead stayed working ‘9 ‘til 5’ in a patent office for cash... But don’t cut up your credit card just yet. The capitalist model of patent protected research is also extremely effective as shown by the ongoing revolution in high-throughput DNA sequencing. References: 1. Barnes B & Edge D (1982) Science in context: readings in the sociology of science. MIT Press. 2. Kovac J (2007) Moral rules, moral ideas, and use-inspired research. Science and Engineering Ethics 13(2):159–169. 3. Mauss M (2002) The gift: the form and reason for exchange in archaic societies. Routledge. 4. Raymond E (2001) The cathedral and the bazaar: musings on Linux and Open Source by an accidental revolution. O’Reilly Media, Inc. Richard Wheeler is a 4th year DPhil student in the Gluenz and Gull laboratories,The Sir William Dunn School of Pathology, University of Oxford. Hilary 2012 | Phenotype | 17 Targeting the problem: advances towards effective gene therapy W by Annabel Morley hen treating genetic disorders such as cystic fibrosis and haemophilia, a fundamental issue is that every cell in the body possesses a copy of the defective DNA responsible for the disease symptoms. A successful therapy must target the defective gene in all cells, either to replace it, modify it or insert a functioning gene into the cells’ DNA to compensate for the expression of the faulty gene. Scientists have responded to this problem by developing a solution: gene therapy. This is the delivery of a functioning copy of the gene in question to cells via a vector, usually an inactive virus or a plasmid that carries the gene to target cells, inserting the functional gene into an unspecified area of the cells’ DNA. However there are still the dilemmas of how to guarantee the vector’s success in delivering the gene to each cell in the body; how to ensure that the gene is not rejected as a foreign body; and how to make the treatment a more permanent solution as once the gene is delivered to a percentage of cells, other cells which still possess the non-functioning gene are dividing and so the disease remains. Since the emergence of gene therapy in the 1990s as a viable tool for treatment, progress appeared to stagnate with limited advancement beyond discovering that a vector can be used to deliver a specific gene and the proposal of various methods to distribute this around the body, for example via aerosol spray for lung centred diseases such as cystic fibrosis. However, 2011 has seen a flurry of activity with the publication of numerous papers highlighting new vectors, methods to increase permanency, and techniques to improve vector delivery and success rates. Vector delivery improvements For many diseases, such as amyotrophic lateral sclerosis (ALS), there are no effective therapies currently available. However, promising progress is being made. For example, research using RNAi and antisense oligonucleotides in animal models has shown suppression of two genes linked to ALS pathogenesis, SOD1 and Fas (1). So far however, clinical applicability has not yet been shown and the effects on SOD1 have only been demonstrated when injections are administered directly to the central nervous system (CNS). Many other treatments currently being developed for ALS suffer from similar issues relating to delivery to the correct site. Without direct injection into the CNS these treatments, whether pharmaceutical inhibitors or vectors, have limited success in crossing the bloodbrain barrier, while injection directly into the CNS has shown success in different animal models. 18 | Oxford University Biochemical Society Several studies have investigated how to increase the area which is targeted by the CNS injections (2, 3). Using a ‘convection-enhanced’ delivery technique, which utilises a pressure gradient that generates a mass flow of these agents through the interstitial fluid space, the delivery of therapeutic agents across a wider area can be achieved. This propulsion of agents across a wider space has resulted in the capability to target a larger area of the brain, showing a promising advancement for the future. In a recent review, Salegio and co-workers emphasised the benefits of using anterograde axonal transport as a transport mechanism for vectors (4). This is the movement of molecules from a cell body to the synaptic junction, moving larger cargo objects such as microtubules or proteins to a target area. When associated with an adeno-associated viral (AAV) vector, genes or agents applied with this method are detected in high levels in the thalamus. However, a severe lack of any expression in the cortex will need to be addressed before further clinical trials can be conducted. Gene therapy may also be utilised in other disorders, where rather than replacing a faulty gene it would be used to insert a gene to increase or decrease levels of specific proteins or chemicals. Cederfjäll and others reviewed the efficacy of utilising gene therapy to administer a constant supply of DOPA, the precursor of the neurotransmitter dopamine, to Parkinson’s sufferers in order to improve motor problems caused by the disease (5). Once again, though preclinical studies have presented promising results, there are still issues to be addressed. For example, improvements to allow DOPA to be delivered continuously are needed, especially using the current AAV vector systems. Vector alternatives Historically, much gene therapy research has been aimed at treating cystic fibrosis, where a thick mucus layer in affected areas inhibits access to target cells. Viruses such as the human papilloma virus and the Norwalk virus were used as delivery vectors. However, a recent study investigating the success rate of a number of vectors utilised in gene therapy discovered that most AAV vectors are below average in accessing target cells when confronted with human mucus secretions. This may be a reason why treatments for cystic fibrosis, specifically aimed at the lungs, have not been hugely successful, and highlights the importance of selecting the appropriate vector (6). EQUINOX GRAPHICS This data provoked research into non-viral vectors that could more effectively reach their target cells, and deliver the gene more permanently and safely than the viral options currently available. One such non-viral vector option is the use of chitosanDNA-FAP-B nanoparticles, which exploit the ability of the fibronectin attachment protein of Myobacterium bovis (FAP-B) to target epithelial cells, for delivery to the lungs (7). After nebulising the nanoparticles, Mohammadi and others administered the particles to the lungs via an aerosol spray and discovered that this increased gene expression 16fold compared with chitosan-DNA-nanoparticles. This type of vector is appealing as the particles are nonpathogenic. Therefore, the problems linked to the use of viral vectors, including the potential reversion “... most adenoto pathogenic states or rejection by the immune associated viral system, are avoided. In addition, the use of an aerosol vectors are below provides a non-invasive technique unlike direct average in accessing injections, as used in previously discussed research. 2. Bobo R, et al. (1994) Convection-enhanced delivery target cells...” of macromolecules in the brain. PNAS 91(6):2076– Looking forward to gene therapy 2080. It is safe to say that the current increase in clinical 3. Hadaczek P, et al. (2006) The “perivascular pump” trial successes and the increased ability to target driven by arterial pulsation is a powerful mechanism specific diseases indicate that gene therapy may well for the distribution of therapeutic molecules within become a valid clinical strategy in the future. Though the brain. Mol Ther 14(1):69–78. there is a greater body of evidence documenting the 4. Salegio EA, et al. (2011) Guided delivery of adenouse and reliability of viral delivery vectors, there has associated viral vectors into the primate brain. Adv been an emergence of several promising non-viral Drug Deliv Rev doi:10.1016/j.addr.2011.10.005. options. There has also been increasing research into 5. Cederfjäll E, et al. (2011) Key factors determining effective options for accurately targeting the affected the efficacy of gene therapy for continuous DOPA areas of specific diseases. However, there are risks delivery in the Parkinsonian brain. Neurobiol Dis associated with invasive techniques such as direct doi:10.1016/j.nbd.2011.10.017. injection of the vectors into the CNS and as such 6. Hida K, et al. (2011) Common gene therapy viral further research is required before they can be fully vectors do not efficiently penetrate sputum from accepted as a viable method for patient treatment. cystic fibrosis patients. PLoS One 6(5):e19919. In conclusion, gene therapy research has rapidly 7. Mohammadi Z, et al. (2011) In vivo transfection increased to a point where it is entirely possible study of chitosan-DNA-FAP-B nanoparticle as a new that sufferers of many genetic diseases may have non viral vector for gene delivery to the lung. Int J an effective treatment in the near future and the Pharm 421(1):183–188. possibility of curing such diseases via gene therapy may be a very distant but potential goal. References: 1. Nizzardo M, et al. (2011) Research advances in gene therapy approaches for the treatment of Amyotrophic Lateral Sclerosis. Cell Mol Life Sci doi: 10.1007/s00018-011-0881-5. Annabel Morley is a Research Assistant in Prof Charles Godfray´s laboratory, Department of Zoology, University of Oxford. Hilary 2012 | Phenotype | 19 Is biotech a fad? T by Sonya Hanson he reasons for our interest in science can be broken down into two main categories: we want to know how things work and we hope that our discoveries will prove useful. The expectation of life science’s ability to be useful has surged remarkably in the last two decades. With the investment of billions of pounds by governments and venture capitalists in biotechnology often correlating to media-driven hype, it is sometimes difficult to see the logic behind the excitement. While it is easy to see the essential role biotech plays in bringing science ‘from bench to bedside’, the relatively few successes among a sea of failures beg a closer look into the sustainability of ‘biotech’. In the beginning… The birth of biotech could be marked by the brewing of beer or, more recently, milk pasteurisation. Dr Tamas Bartfai suggests that technically biotech was born in 1922 when the injection of insulin, crudely purified from foetal calf pancreas, successfully treated a dying diabetic 14-year-old boy in Toronto. But biotech as we know it today began in the 1970s, when Stanley Cohen and Herbert Boyer first produced and purified human insulin from bacteria using recombinant DNA technology. From that Bay Area discovery sprung Genentech, the leviathan that anchored the world’s biotech capital. Still, by 1988, only four more proteins from genetically engineered cells had been approved by the United States Federal Drug Administration (FDA) (1). Wait, how much? However, the ball had been set rolling and by the end of the 1990s over 125 proteins from genetically engineered organisms had been approved. Among these was alpha-interferon, commercialised by Biogen for the treatment of multiple sclerosis. Another development was the production of humanised monoclonal antibodies by Sir Greg Winter. While antibodies had been used to treat syphilis since 1910, broadening the same idea towards effective treatment of diseases such as hepatitis B and C, auto-immune disorders and cancer has been invaluable to the medical community and has been recognised by multiple Nobel Prizes. $6.4 to $12.6 billion over the 30 years it [would] take to pay off the state bonds used to fund it” (2). A later analysis showed that this was a gross over-estimation of the benefits, especially given that the study did not take into account that advances in medicine tend not to lower the cost of health care, but often raise it as treatments are piled on top of each other (2). While we remain decades from knowing if the investment in stem cell research will pay off, other examples of government support have fallen flat. In the late 1980s and early 1990s when companies like Genentech and Biogen were hitting it big, a phenomenon of ‘biotech clusters’ arose in which these companies thrived off the rapid local exchange of ideas and technology. This phenomenon was misguidedly embraced by many local governments hoping to improve their economy by building biotech clusters of their own, with little more than fancy buildings and tax incentives. Unfortunately, places like the Texas Research Park, which broke ground in San Antonio in 1987 with dreams of attracting 30,000 jobs yet 15 years later had only sustained 300, were by no means an exception. The strategy did work for a lucky few, such as Florida’s funding of $510 million towards a biomedical research facility in Palm Beach County built by the Scripps Research Institute (3). While one cannot deny the benefits of combining good science and good business to make a successful biotech company, nothing happens in a vacuum. The early successes of biotech – sheep cloning, mapping the human genome, stem cell therapy and now personalised medicine – generated a media frenzy. It is easy to forget that these successes were by no means certain and took years of investment to show results, while many other avenues funded at the same level and for the same duration failed. Despite the potential risks and long-term nature of these investments, and a slew of articles every few years predicting the ‘pop of the biotech bubble’, biotech has remained afloat, buoyed in part by the regular appearance of new and exciting innovations to entice investors. However, with the recent economic downturn, and what must now be an increasingly aware set of investors and governments regarding the likelihood of immediate returns, biotech startups may now need to look beyond venture capital and one-off federal investments. Nowadays, even the viability of the venture capital fund of the man heralded as starting UK biotech, Sir Christopher Evans, is in question (4). In the mid-2000s, New York invested $1 billion in stem cell research. This was based primarily on a 2004 study that predicted that “stem-cell research would generate state revenues and health-care savings of or not’ to a more targeted approach, with distinct strategies toward certain emerging markets. This trend coincides with venture capital’s changing focus towards biotech companies in their later, safer stages of development. It is hoped that venture capital investment in early stage biotech will recover with the economy, but this seems unlikely unless certain standards are set in place to help stabilise start-ups. This known risk is an important reason why start-ups tend to follow trends, which appear safer, but this is not the ideal climate for the development of the drugs that are really needed. Dr Tamas Bartfai spoke to OBR about this gap between science and drugs. Pharma and biotech focus disproportionately on targeting diseases such as diabetes and cancer, simply because the science in these areas is already well established, clinical trials are quick and thus risks are low and profit more likely. Antipsychotic drugs and new antibiotics to combat an impending ‘superbug’ are ignored as they are riskier and more expensive to develop. This is a gap that a commercial approach to medical science is not prepared to fight head-on and that must be tackled with the help of government health funds and academic scientists. With Dr Francis Collins’ creation of the National Center for Advancing Translational Sciences at the NIH in Bethesda, MD, and the Royal Society of Chemistry’s recent funding from Parliament to be directed toward drug discovery, there is an obvious push towards reducing our dependence on biotech start-ups to get the drug discovery pipeline moving. Government funding for biotech and biological sciences has been around for a long time, but the recent push to eliminate the hyper-competitiveness of early biotech via formal programmes is new. Some biotechs now engage in ‘pre-competitive alliances’, where companies exchange ideas and technology in a series of agreements. However, these alliances come with heavy regulations and many caveats. Another excellent example of this type of collaboration is the increasing number of graduate programmes, such as that funded by the BBSRC, which allow students to have both an industrial and an academic mentor. With the low-hanging fruits of early biotech now fully developed, and a market that is gradually less impressed by each shiny new breakthrough, perhaps it really is time for biotech to settle into its proper niche between academic and commercial medicine. This theme was even picked up at the Structural Genome Consortium, which is holding a conference in January 2012 titled: ‘Drug Discovery: A job too complex for academic or industry alone’. References: 1. Colwell RR (2002) Fulfilling the promise of biotechnology. Biotechnol Adv 20(3-4):215–228. Dr Tamas Bartfai spoke to OBR about risk-avoidance by pharma and biotech leading to a bias in the kinds of diseases targeted. Oxbridge-London Biotechnology Roundtable (OBR: http://oxbridgebiotech.com) is an intercampus forum connecting industry professionals to academic innovators with a mission to foster an on-campus conversation about biotech, pharmaceutical and the life sciences industry. An expanded version of this article appears on the Roundtable Review (http://www.oxbridgebiotech. com/blog), the online publication arm of OBR. Get in touch with us at blog@oxbridgebiotech. com if you’d like to contribute your own voice to the conversation. Sonya Hanson is a 3rd year NIH-Oxford DPhil student in the Department of Biochemistry. She is supervised by Dr Simon Newstead and Prof Mark Sansom at Oxford and Dr Kenton Swartz at the NIH. Hilary 2012 | Phenotype | 21 European approaches to GM: Understanding the policy dilemma in a global context By Mark Pavlyukovskyy O n 31 October 2011, the seven billionth person on the planet was born in Manila, the Philippines. Both the Russian and Indian governments claimed that babies born in their countries also held this symbolic status, yet this happy occasion highlighted one of the most pressing challenges facing today’s world. With the world’s population projected to reach nine billion by 2050, what rate of population growth is sustainable? Impetus for GM development The consequences of overpopulation are devastating. Resources become scarce and the carrying capacity of the planet is exceeded. Poor farming practices, topsoil erosion and a lack of water lead to desertification, which in turn decreases the proportion of arable land and is indirectly responsible for close to one billion people across the globe going hungry every day. In developing countries, a staggering 30,000 people, the equivalent of the student population of Oxford University, die of hunger every day. Technological advances, including the use of agrochemicals, fertilisers, mechanisation and improved quality of seeds, have helped to double food production over the past several decades, even though arable land has only increased by 10% during that period. However, most of these techniques have negative impacts on the environment, including algal-induced anoxic dead-zones in bodies of water where phosphates and nitrates have run off, as well as the siphoning-off of large quantities of water to irrigate fields, and the harmful effects of pesticides on biodiversity. covered up uncertainties in the evidence while expert advice had downplayed potential risks (1). Following these troubles, there was an attempt by the European Union (EU) to enhance expert credibility and establish a risk-assessment process that was separate from the risk-management process. To this end, new legislative bodies were established, including the European Food and Safety Authority (EFSA), allowing for a more rigorous and transparent evaluation of food safety. It is useful to note that this decision to create a new system to cope with the problems in food safety, including GM crops, was in stark contrast to the decision in the United States to utilise the already-present system in the form of the Food and Drug Administration, as well as the Environmental Protection Agency, to oversee the GM crops approval process. Improved plant breeding strategies, including genetic modification (GM), have been seen as a progressive technological solution with very few negative effects. In the United States, upwards of 85% of cotton, corn and soybean crops are genetically modified. The engineered resistance to herbicides or insecticides allows for higher yield and better quality crops, with decreased use of expensive, non-specific insecticides, making GM agriculture also an economically superior solution. GM crops in Europe: introduction and ban GM crops were introduced and championed in Europe by large agricultural biotechnology companies. The largest and best-known of these are the American company Monsanto and, to a lesser degree, the Swiss company Syngenta. With the food crises of the 1990s in mind, European consumers were very sceptical of large companies altering food crops for the sole purpose of making a profit. Non-governmental organisations (NGOs) like Greenpeace amplified these fears by staging mass media campaigns to alert people to the ‘untested’ and ‘untried’ aspects of GM crops. Moreover, GM crops were easy to vilify due to the type of genetic modifications that are made. European food safety regulation While GM crops have been widely adopted across the Americas and parts of Asia, they are conspicuously missing from Europe. The reasons for this can be traced to Europe’s history with food regulation, which has been notoriously unstable. In Europe, food safety and authorisation have resided primarily in the realm of specialised scientific bodies, which would then give the impetus for policy decisions. Yet as the ‘mad-cow disease’ and dioxin crises in the late 1990s demonstrated, this system was not ideal, since the European Commission had Monsanto, and indeed almost all companies involved in GM crops, produce genetically modified organisms (GMOs) with ‘input trait technology’. Such modifications are exclusively limited to herbicide tolerance or insect resistance. The resulting benefits are realised mainly by farmers through better yields and lower cost, and are felt only marginally by consumers in the form of lower prices. For Monsanto and other companies, there is a huge incentive to produce plants with these traits because in their main market, the United States, growing such crops on an enormous scale offers large profit margins. 22 | Oxford University Biochemical Society For American consumers, who had not experienced food crises on the same scale as in Europe, GM crops were simply a cheaper alternative at the supermarket. By contrast, for European consumers, GM crops were an untested and potentially dangerous product that offered them little, while allowing large companies to make large profits. NGOs like Greenpeace were able to capitalise on this and paint a picture of GMOs as ‘Frankenstein Food’ that had as its sole purpose increased revenue for large foreign companies. These negative attitudes towards GM crops provided the impetus for EU member states to use legal loopholes to avoid authorising GM crops for cultivation in their territories, which created many problems for the European Commission and resulted in a case being brought against the EU for the violation of World Trade Organisation agreements. The irony of the cultivation bans in EU member states is that Europe imports 80% of its animal feed from America and Brazil in the form of soybean and corn, where over 90% of the exported crops are GM. Owing to the large cost to farmers of importing non-GM feed, member states have begun allowing European farmers to use GM feed. This presents the European Commission, the body responsible for authorisation of GM crops, with a dilemma in that home-grown GM crops are no different from imported GM crops and the basis for the GM ban in member states is coming to be seen as very tenuous. To ban or to...? There are several policy alternatives that the European Commission could implement. The most straightforward option would be to allow member states to be part of the decision-making process. This could be achieved by creating a rotating ad hoc ‘Independent Expert Council’ comprising a group of outstanding research scientists representing all EU states. The decision-making process would acquire legitimacy and credibility among member states, ensure representation and incorporate the latest knowledge into the decisions. Another option would be to enter into a dialogue with, and educate, the public through initiatives where people would receive objective comparative information about available agricultural production methods (conventional, organic and GM), along with their advantages and drawbacks in terms of human health and environmental sustainability. People would be offered crops with ‘output trait technology’, including food with increased nutritional value, which would be presented as useful and practical for their needs. Finally, it would be constructive to create publically funded ‘Independent GM Research Centres’, possibly affiliated with a research university, which would conduct cutting-edge research on the use of GM organisms to combat disease and improve human nutrition. This would turn over the control of genetic modification research to the public from the for-profit global corporations. Allowing unopposed scientific investigation, which is presently only possible as a result of funding from large companies, would increase the European public’s trust of GM crops, and encourage more research in this field. “NGOs like Greenpeace were able to capitalise on this and paint a picture of GMOs as `Frankenstein Food`.” Mark Pavlyukovskyy is a 3rd year undergraduate student from Princeton University, working in Prof Jonathan Hodgkin´s lab, Department of Biochemistry, as part of the Princeton/Oxford exchange. Hilary 2012 | Phenotype | 23 BOOK REVIEWS Fungi – Biology and Applications (Second Edition). Edited by Kevin Kavanagh ISBN: 978-0-470-97709-5,Wiley-Blackwell (October 2011), Paperback, 376 pages, £34.95 Reviewed by Jennifer de Beyer Fungi – Biology and Applications is billed as an introduction to all aspects of the fungal world and research, suitable for an undergraduate or newcomer to the field. It covers the diversity of fungal metabolism, physiology and growth, and focuses on how this diversity impacts and is utilised by man through fermentation, therapeutic and biotechnology applications. The text deals particularly well with genetic analysis of fungi and fungal proteomics. Both the molecular biology and protein biochemistry required to generate data and the ‘omics’ analysis tools are covered. Assuming very little prior knowledge, these techniques are explained in the context of specific advances in understanding of fungal physiology, providing a good link between theory and research. Chapters dealing with the economically and medically important aspects of fungi are packed full of facts, yet maintain an easy pace. The authors show good knowledge of both their subject field and their audience, with fascinating discussions exploring exactly how one produces a pint of the perfect hue and the alcohol content of bread dough around the world. Again bearing in mind the intended reader, each chapter closes with a short recommended reading list rather than a lengthy reference section and a useful set of review questions, the answers to which are provided in an appendix. However, a lack of care in production means quality varies significantly between chapters. In most chapters, the layout is clear and the writing style easy to follow and engrossing. In others, convoluted sentence structure and heavy writing leaves the reader confused and bored. Worse, in-text references to images are incorrect. In some cases, captions are incomprehensible due to lack of a key and in others are quite simply wrong. It is a great shame, as the breadth of information contained in Fungi – Biology and Applications and its generally engaging tone should make it well suited as an introductory text. However, the errors are sufficiently numerous and distracting that I would not recommend this book in its current edition. The Magic of Reality: How we know what’s really true Richard Dawkins ISBN-13: 978-0593066126, Bantam Press (15 September 2011), Hardcover, 272 pages, £8.00 Reviewed by William Brandler While growing up I had heard of dinosaurs, DNA and Darwin, but I had no real idea about the evidence for evolution. I believed in it because it was presented to me as a fact in school. In The Magic of Reality, Richard Dawkins shows how science can answer the big questions in which children may be interested, such as: “Why do bad things happen?” and “Who was the first man?” Although it is pitched at 12 year-olds, the broad nature of the topics covered and his elegant style of prose make this book appealing to adults as well. First Dawkins details other attempts to answer these questions. Children may be aware of Adam and Eve, but not of the countless other creation stories in different cultures. What is clear, although he is not explicit in saying so, is that not all of these myths can be true. He then explains the evidence for evolution, which is so compelling and wonderful in comparison, that it makes myths seem absurd. As Dawkins explains, myths don’t tell us “how old the universe is; they don’t tell us how to treat cancer; they don’t explain gravity or the internal combustion engine; they don’t tell us about germs, or nuclear fusion, or electricity, or anesthetics”. He doesn’t skirt around difficult concepts, using complicated words like perihelion and metastasis, explaining them in a clear and unpatronising way. For a child growing up in a community where myths, the supernatural and magic are presented as reality, a book like this can be empowering and I would highly recommend it. 24 | Oxford University Biochemical Society SCIENCE and SOCIETY Volunteering at Science Oxford Have you ever cycled towards Headington and wondered what is in the glass building marked with a purple sign just below the hill? Well, this is Science Oxford, our local science centre which aims to make science more accessible through providing education and engagement activities for the general public. As someone who has been volunteering there for the past couple of years, I wanted to introduce the centre to University of Oxford students and staff who may also enjoy getting involved. One of the most well attended events hosted by the centre is the Thursday evening talk. It sometimes feels like Oxford is saturated with scientific presentations, but the twist with those at Science Oxford is that they are aimed at people without a science background. So anyone can listen to a talk about quantum physics without feeling lost! Volunteers are involved in these regular talks, helping ‘front of house’ prior to the session. This involves mastering the ever-so-complicated till, ushering people to the lecture room, webcasting and recording the talk. Volunteers can also listen to the talks, so you can sign up to help at the events you want to attend. As well as helping at talks, you can volunteer in other ways. Firstly, you can write for the Science Oxford Online blog. This is a depository for sciencerelated articles aimed at the general public and includes reviews of the Science Oxford Live talks. As a volunteer at the event, you are well placed to review the talk afterwards for Science Oxford Online. The blog may also be of interest to budding science writers as any articles are welcome, providing they are scientific in nature and suitable for general consumption. So do think about writing for the blog, even if you do not have time to volunteer at the talks. Although time-consuming, the most satisfying way of getting involved is to present a talk yourself. I have done this and it seemed more challenging than presenting to peers in a departmental seminar or at a conference. You certainly have to be mindful of the diverse levels of knowledge within the audience – you could be talking to anyone from a retired or active Oxonian professor, through to someone whose science education ended at the age of 14. With this in mind, I chose not to talk about the intricacies of my research, but rather ‘science behind the headlines’. For this, I compared the reporting of science articles by different news outlets ranging from BBC News to The Sun. Using the original journal article abstracts, I discussed a number of points to look for in order to assess the credibility of the reporting. To elaborate, I discussed the concept of a fair scientific trial, introducing aspects of control and randomisation with Smarties ‘tablets’, concepts which seemed to be well received by the audience. Finally, the centre hosts a Discovery Zone which Dr Blanka contains science-based, hands-on exhibits open to Sengerová primary school students during the week and the general public on weekends. Using the Discovery Zone and adjacent activity space, the staff at Science Postdoctoral Oxford also run holiday Science Clubs, and have researcher in the recently initiated a Saturday Science Club for DNA Damage and children (some aimed at five to seven year-olds and Repair lab at the others at eight to eleven year-olds). This is another Weatherall Institute great opportunity for volunteers to get involved. of Molecular Medicine. If you are interested in volunteering at the Thursday talks and want to find out when the next training session will take place, you can contact the volunteer co-ordinator, Emma Clare. Alternatively, if you would prefer to get involved on the writing side, the Science Oxford Online blog is run by Carl Anglim. As Forever Young playing on my next door neighbour’s radio echoes in the background, I realise that I am two hours away from the Phenotype article submission deadline. I open a new tab in Firefox: “define: procrastination”. Hello. My name is Andrea and I am a procrastinator. 1st year DPhil student on the Doctoral Training Centre Systems Introducing ‘Piled Higher and Deeper’ (PhD) Comics Biology programme PhD Comics is probably the finest example of a procrastination source for graduate students. It brings together grads from all over the world as they commiserate over the pains and sorrows of being a graduate student. If you have no idea what I am talking about, then you are probably not a graduate student. The comics themselves started off as a means of procrastination for Jorge Cham, then a PhD student in Mechanical Engineering at the University of Stanford, USA. The first comic was published on 27 October 1997 with a new comic appearing on average 2.7 times per week. After completing his PhD, Jorge spent a few years as a researcher at Caltech. He is now dedicated full time to PhD Comics and lately, PhD The Movie. ‘Piled Higher and Deeper’ The Movie Now, some 14 years after the first comic, Jorge has produced a film based on the comics. It was filmed at Caltech without the help of professional actors or producers. The whole project was carried out by graduate students and researchers, with contributions from other staff members at the university. The film aims to provide a more realistic view of the unique and, let’s face it, often funny world of academia. As Jorge points out, there are not enough stories about scientists in popular culture and the existing ones place far too much emphasis on eccentricity and the ‘mad scientist’ stereotype. The film follows the characters from the comic (Cecilia, Mike, Tajel and the ‘Nameless Grad Student‘) in their attempts to find a balance between research, teaching and their personal lives. Auditions were organised at Caltech and standards were high; Alexandra Lockwood who plays Cecilia confesses she has had a long history of involvement with performing arts, ranging from being part of a play in high school, to having sung a (rather bad) song in a musical. 26 | Oxford University Biochemical Society Many people have wondered who the person playing Professor Smith is. He is indeed part of the world of academia, but he is no academic. He is one of the IT officers at Caltech – that’s right, he fixes the computers of Nobel Prize winners. Interestingly enough, the ‘Nameless Grad Student’ was in fact played by a first year undergraduate. This seems to have helped a lot in terms of conveying genuine surprise when faced with certain aspects of graduate life. Perhaps the bad news is that he now wants to become a graduate student. One might wonder how those graduate students in Caltech managed to find the time to get involved in such a project. Alex explains that her supervisor was quite supportive when she told him, last minute of course, that she was going to be in a film: “Weekends and long hours, that’s how I managed it”. Jorge adds that Alex’s tiredness ended up being advantageous for particular scenes in the film. Another unique aspect of PhD The Movie is that it is not screened in cinemas but rather on university SCIENCE and SOCIETY campuses across the world. It is a film made by graduate students and researchers for graduate students and researchers. The Oxford University screening, held in the Examination School, was made possible by the contributions and efforts of the Oxford University Student Union (OUSU) and the Mathematical, Physical and Life Sciences Division, along with a team of enthusiastic graduate students. For those of you who could not get a ticket for the first screening (to be fair, the tickets did sell out in eight hours), all is not lost! A second screening is going to be organised, most likely in Hilary term 2012. People have asked if the film is worth seeing. If you like the comic, then it definitely is! Jorge Cham in Oxford Thus, PhD The Movie came to Oxford. Thanks to a generous contribution from The Times Higher Education, we were able to have Jorge Cham and Alex Lockwood attend and hold a Q&A session after the film. A few of us were lucky enough to spend half a day as their guides. It was a refreshing experience, as if we were showing a couple of old friends around Oxford. After meeting them at the train station, our first destination – before even such Oxford landmarks as Christ Church College – was G&D’s ice cream cafe. Jorge and Alex were impressed and at times amused with the ’Disney world of Academia’ that was unravelling in front of them as the tour progressed. Many people have asked what Jorge Cham was like. “Jet-lagged”, would be my answer. And one would expect nothing less, given that he is zigzagging across time zones to introduce the film. Appearance-wise, you can tell where the inspiration for the ‘Nameless Grad Student’ in the comics came from; the hairstyle is unmistakable. Jorge is a relatively quiet person, although this might have been the jet-lag, and you can most definitely see the distinct humour of a person who has gone through grad school in him. Back to the lab... Procrastination is a serious issue. However, it is arguable that a controlled dose of procrastination helps keep us graduate students sane. When experiments don’t work, when equipment fails, when you haven’t seen actual sunlight for days, you need something to lift you up. This input may not come from your lab mentor, who is probably trying to make the deadline for a paper, your colleague, who needs to stand by his reaction day and night, or your supervisor, who is too busy anyway. It is at this point you begin to venture into ‘the hollow world of the interwebs’ to seek comfort. PhD Comics do a great job in this respect. Many of the comics are inspired from stories e-mailed to Jorge by the readers. “They e-mail me stories and I draw up the comic”, Jorge explains. This way, the comics have become a global project, with contributions from graduates everywhere. The comics give you that pat on the back; they tell you that even though you are the only person in a windowless room, you are not alone. And this gives you the strength to carry on, make the experiment work and write a grant proposal to purchase new equipment, to go out there, show your work to the world and submit the thesis! References: www.phdcomics.com Write for Phenotype? • The deadline for article submissions is Friday of 8th week, 9 March 2012 • We accept articles on any aspect of biological sciences research, books or science education • Articles can be either 650 or 1300 words If interested, please get in touch: [email protected]. Work for Phenotype? If you’d like to get involved in editing, production or management of Phenotype, please get in touch: [email protected]. The Athena SWAN Charter scheme was developed in 2005 to recognise excellence in Science, Engineering and Technology (SET) for women employed in higher education. Its goal is to improve the representation of women in science by placing an effective framework within the workplace for diagnosing gender gaps, drawing up action plans and committing to progress on gender inequality. 2nd year DPhil student in the Department of Anatomy, Physiology and Genetics. Graduate Women’s Officer for the Oxford University Student Union. Our Medical Sciences Division will face a loss of £100 million in National Institute for Health Research (NIHR) funding by 2015 if it fails to show it is taking sufficient and effective action on gender equality by achieving Athena SWAN Award silver status. In a public letter on 29 July 2011, the Chief Medical Officer of the Department of Health, Professor Dame Sally Davies, issued an ultimatum to all medical schools in the UK in which she stated that she was “appalled on behalf of our nation” by the lack of thought that medical schools had put into improving gender equality in science. Award principles Currently, there are 68 members (approximately 51% of eligible higher education institutions) of the Athena SWAN Charter, each awarded either bronze, silver or gold status upon application. The awards recognise the good practice of its members on the recruitment, retention and promotion of women in SET in higher education and research, striving to increase the numbers of women recruited to top posts within SET roles. Awards are made on how well departments and universities incorporate the six Charter principles into their action plans: addressing gender inequalities; changing cultures and attitudes across the organisation; examining the implications of gender homogeneity at management and policymaking levels; tackling the high loss rate of women in SET; recognising that the current system of short-term contracts has negative consequences for the retention and progression of women in SET; and actively considering the personal and structural obstacles to women making the transition from a PhD into a sustainable academic career. The University of Oxford and Athena SWAN Oxford University as a whole holds a bronze award, renewed in 2010, showing its commitment to creating gender equality within its departments. However, only the Zoology department holds a silver award. The university is encouraging its SET departments to apply, as it will only move forward to silver and gold level if it shows a significant record of activity and achievement across the full range of SET disciplines, with a substantial number of departments holding individual awards. 28 | Oxford University Biochemical Society Sarah Hawkes, senior policy adviser at the Equality Challenge Unit, who is responsible for the Athena SWAN award, commented on the achievements: “We are pleased that these successes are encouraging other departments within Oxford to embark on the Athena SWAN process, and we hope that good practice continues to be shared within and outside the institution”. Getting involved with Athena SWAN The key to a successful Athena SWAN application is the support and energy of the department in conducting its Athena SWAN self-assessment, and in delivering on its action-plan. Only by having an overarching view of the problems in maintaining gender equality and diverse ideas on how to address these problems at each step of the academic ladder, from undergraduate level to tenured academics and technical staff, will the gender imbalance be addressed. Everyone is encouraged to get on board. You can get in touch with your Head of Department and volunteer to be a representative on the Committee. You can also hold evidence-gathering consultations or surveys or simply participate in them. Getting involved, in whatever way, means a lot. The award is presented to departments who show they are taking constructive initiatives to make progress on equality, not merely achieving gender parity in staff or student figures. Furthermore, although the Athena SWAN Award is aimed at gender equality policies and initiatives, the best equality-promoting initiatives ultimately improve the experience and atmosphere for everyone in the department. 5´ with... Professor Adrian Hill I was hooked. It was a very exciting time for science – the techniques that were just coming through like PCR were amazing. You realised that everything science had been waiting to do for years, for example sequencing bacterial genomes, we were now going to be able to do. I did two more clinical years and then went back to research. If you were not a scientist, you would be… When I was seven, plan A was to be an astronaut! But to be honest, I would probably be a medic. If you are not in the lab you are… On an aeroplane. Most scientists have two reasons to travel, firstly to go to conferences to present work and secondly to network and build collaborations. But when you work on tropical medicine you have another – you have to travel to get to where the action is. A drian Hill was appointed director of the Jenner Institute in 2005, after co-founding the Oxford Centre for Clinical Vaccinology and Tropical Medicine. His group focuses on the development of prime-boost malaria vaccines. Interviewed by Amy Baxter When did you first decide you wanted to be a scientist? When I was a houseman, I got an MRC training fellowship to work towards a DPhil with Sir David Weatherall. I met with him, expressed my interest in the work that was going on in the lab and asked if I could join his group. He mentioned some collections from Vanuatu that could be of interest and I just said yes. I committed myself without even knowing where Vanuatu was! The first thing I did was go to the library to look it up in an atlas and it didn’t exist, it was only recently renamed and had formally been the New Hebrides. I completed my DPhil analysing the population genetics of Pacific Islanders and after that, What was your worst disaster in the lab? That’s easy. One day a postdoc from the lab walked in almost in tears. She had noticed tumours in one mouse from a vaccine study and hadn’t thought anything of it, but that day she saw tumours in two more vaccinated mice. This was a vaccine type that we were already using in a clinical trial! Obviously, we had to stop the trial and work out what was happening. It was a very scary month until we realised that the mouse strain we were using had a mutation that made them susceptible to spontaneous salivary gland tumours and it was nothing to do with the vaccine. What has been the most memorable finding of your career so far? The most memorable finding was many years ago when we were looking for the first CD8+ T cell responses to malaria. I had made malarial peptides that we had predicted might be recognised by a certain protective HLA type and took them to Africa to test. This was in the days when you made your own peptides, a horrible, smelly procedure that made you very unpopular in the lab. One morning we drove to a village clinic, saw HLA-typed patients and did the assays, testing responses to the peptides that evening. The first few were negative, but then at midnight a critical sample was positive. It was from a woman who had the HLA-type associated with malaria resistance. She had responses against liver-stage malaria antigens, just as we had predicted. It all fell into place. What is your favourite conference location? You need two key things for a great conference – you need the right people and also you need them to be Hilary 2012 | Phenotype | 29 5´ with... Professor Adrian Hill locked away without any other distractions, apart from skiing! Probably the best place for this is Cold Spring Harbor on Long Island in summer and a Keystone ski resort in winter. What is the best advice you have ever received? Work on an important problem. Peter Medawar wrote a book published in 1981 called Advice to a Young Scientist. In it he said, “don’t try to solve piffling problems, because you will get piffling answers”. That was rude language for his generation, but he was right! Do you have a favourite classical experiment? There was a graduate student at Exeter College called Anthony Allison who was in the third year of his DPhil and didn’t really have any data, so decided to go to Uganda to collect some. While he was there he discovered that sickle haemoglobin is protective against malaria – in 1953! It was the only gene he had looked at. However, although he was right, lots of people didn’t believe him. In 1964 he wrote a passionate defence concluding that “I can’t see what further evidence any reasonable person would want to have”. It’s the same way we all feel when a reviewer rejects a paper. In your opinion, what makes a good scientist? The really good ones are prepared to ignore the popular topics, the fashions, and search for something that has been missed, something that would make a difference. They keep going even when it’s difficult, despite what anyone says. Getting a grant rejected doesn’t stop good scientists; it just delays them. How do you imagine biological research will change over the next twenty years? It will become far more computational, like it already is in genetics. It used to be the case that you spent 90% of the time in the lab at the bench and the rest at a computer. Now it’s 90% at a computer and the rest spent sending off samples for high-throughput sequencing. I also think there will be more networking and more ‘big science’. I fear it will be much less about small projects, which is a shame because good science often comes from small groups of determined people with big ideas. Explore the latest books in Cell and Molecular Biology All Phenotype readers can save 20% on books by using promo code LIFE at the checkout www.wiley.com/go/lifesciences Like Cell and Molecular Biology? There’s a button for that! facebook.com/cellandmolecularbiology Digital versions are available online 11 - 3 6 9 2 9 SNAPSHOT Research Image Competition This issue´s winner is... Dr Elizabeth Hartfield A career development fellow in Dr Richard Wade-Martins’ laboratory in the Department of Physiology, Anatomy and Genetics. Her image shows a differentiating neurosphere that was generated from a human induced pluripotent stem cell line. After 45 days of differentiation, cells were fixed and stained for the neuronal marker Tuj1 (red) and nuclear DNA (blue), and images were captured using confocal microscopy. Large neuronal processes can be seen migrating outwards from the centre of the sphere while cell bodies remain within the sphere. In recognition of her contribution, she will receive a £50 book voucher kindly provided by our sponsor Oxford University Press. After completing her PhD in Molecular Neuroscience at Bristol University, Liz joined Dr Wade-Martins’ laboratory in April 2010. Here she is part of a large team of researchers studying neurodegenerative diseases, including Parkinson’s and Alzheimer’s. Specifically, Liz is utilising the latest cellular reprogramming technologies to develop models for early stage Parkinson’s disease (PD). PD is a progressive neurological condition that results in the loss of dopaminergic neurons. The consequent reduction in dopamine levels leads to the symptoms of PD, which most commonly include tremor, rigidity and slow movement. There are approximately 120,000 PD patients currently living in the UK, the majority of whom are over 50. The exact causes of PD remain poorly understood and, although there are drugs available to help relieve the symptoms of the disease to some degree, there is currently no cure. Liz’s research uses small skin samples from both PD patients and healthy donors. Viral vectors are used to deliver five reprogramming factors (OCT4, Sox2, KLF4, nanog and c-myc) to the skin-derived fibroblasts. These factors reset the differentiated status of the cells to a stem cell-like state, producing induced pluripotent stem cells (iPSCs). The iPSCs can then be differentiated into dopaminergic neurons, the cells that degenerate in PD brains. Researchers in Dr Wade-Martins’ group are amongst the first in the world to successfully differentiate functional dopaminergic neurons from iPSCs, which are in turn derived from PD patients. “These cells express midbrain dopaminergic markers, are electrically active, and produce the neurotransmitter dopamine, which is incredible considering that they were once skin cells!” explains Liz. Many valuable insights into the end stages of PD have been obtained using human post-mortem brain tissue. However, post-mortem samples are of limited use when investigating the early molecular mechanisms involved in PD development. The use of reprogrammed cells will allow researchers to obtain human midbrain dopaminergic neurons derived from PD patients for the very first time, enabling the early stages of PD to be studied more effectively. “We are essentially developing a ‘disease in a dish’.” The ultimate aim of this research is to develop improved treatments for this debilitating disease. Win a £50 book voucher kindly provided by Oxford University Press! SNAPSHOT Research Image Compettion Do you have an image from, or inspired by your research? Why not enter it in SNAPSHOT? We are now accepting entries for pictures to be featured on the cover of Phenotype TT 2012. To enter, send images to [email protected] with a brief description (maximum 100 words). Please get permission from your supervisor before sending any images. There is no limit to the number of entries per person. The deadline for the competition is 9 March 2012. PHENOTYPE crossword Enter the competition by sending your answers to [email protected] or leave a paper copy in a sealed envelope in the OUBS pigeonhole at the New Biochemistry reception. Entries received by 9 April 2012 will be entered into the prize draw. The winner will receive their choice of two books reviewed in this issue, generously provided by Wiley-Blackwell.

United Nations Security Council Resolution 677 United Nations Security Council resolution 677, adopted unanimously on 28 November 1990, after recalling resolutions 660 (1990), 662 (1990) and 674 (1990), the Council condemned attempts by Iraq to alter the demographic information of Kuwait and the restrictions on the movement of its citizens. Acting under Chapter VII of the United Nations Charter, the Council also condemned attempts by Iraq to destroy civil records maintained by the Government of Kuwait. Therefore, the resolution mandated the Secretary-General Javier Pérez de Cuéllar to take custody of a population register of Kuwait that has been certified by the "legitimate Government of Kuwait" and which covers the population register until 1 August 1990. It also asked the Secretary-General and the Kuwaiti government to establish a set of rules and regulations governing access to the register. The resolution was adopted in anticipation of the disappearance of Kuwaitis or the influx of non-Kuwaitis as a result of Iraqi policy in the occupied country. See also Foreign relations of Iraq Gulf War Invasion of Kuwait Iraq–Kuwait relations List of United Nations Security Council Resolutions 601 to 700 (1987–1991) References External links Text of the Resolution at undocs.org Text of the resolution at un.org, German translation 0677 0677 Category:Gulf War Category:1990 in Iraq Category:1990 in Kuwait 0677 Category:November 1990 events

TravisVoter Authors The Internal Revenue Service gained by personal exertion $2.3 trillion in 2008. The top 1% of wage earners make payment for more than 40% of all of Americas taxes. Beneath the newfangled system, an estimated 51.6 million human beings (36% of all fil...

Cabernet Sauvignon Cabernet Sauvignon is one of the most popular and widely planted red grapes in the world; from Old Worlds regions like France (Bordeaux), Italy and Spain to New World regions like California, Australia and Chile. Cabernet Sauvignon wines show a great ageing potential because of high tannin which acts as a preservative for these wines. It shows a great affinity for oak. Young wines typically exhibit strong fruit flavours of black cherries and plum while as the wines age they can sometimes develop aromas associated with cedar, cigar boxes and pencil shavings. New World Cabernet Sauvignon wines have more pronounced fruity notes while Old World wines can be more austere with heightened earthy notes. The aroma of black currants is one of the most distinctive characteristic element of Cabernet Sauvignon that is present in virtually every style of the wine across the globe.

Q: Why am I not seeing output in the terminal after executing python script? Im following a tutorial @: https://blog.scrapinghub.com/category/scrapy-tips-from-the-pros/ ~ The code seems to execute fine, but Im not seeing any output to the terminal.. Im still trying to figure out how to use a "stack trace with python..., to see if there is a issue on the back-end", Problem is that I am not seeing any output in the terminal after executing the script.. Any help would be great.. import scrapy class SpidyQuotesViewStateSpider(scrapy.Spider): name = 'spidyquotes-viewstate' start_urls = ['http://quotes.toscrape.com/search.aspx'] download_delay = 1.5 def parse(self, response): for author in response.css('select#author > option ::attr(value)').extract(): yield scrapy.FormRequest( 'http://quotes.toscrape.com/filter.aspx', formdata={ 'author': author, '__VIEWSTATE': response.css('input#__VIEWSTATE::attr(value)').extract_first() }, callback=self.parse_tags ) def parse_tags(self, response): for tag in response.css('select#tag > option ::attr(value)').extract(): yield scrapy.FormRequest( 'http://quotes.toscrape.com/filter.aspx', formdata={ 'author': response.css( 'select#author > option[selected] ::attr(value)' ).extract_first(), 'tag': tag, '__VIEWSTATE': response.css('input#__VIEWSTATE::attr(value)').extract_first() }, callback=self.parse_results, ) def parse_results(self, response): for quote in response.css("div.quote"): yield { 'quote': quote.css('span.content ::text').extract_first(), 'author': quote.css('span.author ::text').extract_first(), 'tag': quote.css('span.tag ::text').extract_first(), } A: The given code has no active execution. This is nothing more than a class definition. To get output, you need to continue in the tutorial to write a driver (main) program that will instantiate an object of the class and make a call or two to actually scrape the given web sites. You don't get a "stack trace" unless your program crashes (elicits an fatal exception). It's not something you implement and "use".

Q: wkhtmltopdf passing variable in html file I use wkhtmltopdf with php, and it works well. Now, i want to add some variables from the php file to the html one, but i don't find a solution. the PHP file: <?php require '/path/vendor/autoload.php'; use mikehaertl\wkhtmlto\Pdf; $pdf = new Pdf(array( 'no-outline', 'margin-top' => 0, 'margin-right' => 0, 'margin-bottom' => 0, 'margin-left' => 0, // Default page options 'disable-smart-shrinking', )); if($_GET['file'] == 'public'){ $pdf = new Pdf('template_public.html'); }else{ $pdf = new Pdf('template_pro.html'); } $pdf->send(); ?> The HTML file: <html> <head> <title>Generated PDF file</title> <meta http-equiv="Content-Type" content="text/html; charset=iso-8859-1"> </head> <body bgcolor="#FFFFFF" leftmargin="0" topmargin="0" marginwidth="0" marginheight="0"> <div> {title} </div> </body> </html> How can i replace the {title} in the HTML file? A: This should replace all of the {variables} in the html files with their values, given an array of parameters. $params = ["title"=>"title_val", "content" => "something", "key" => "value"]; $pdf = new Pdf(); $html = file_get_contents($templateFile); foreach($params as $key=>$value) { $html = str_replace("{".$key."}", $value, $html); } //Renders the pdf directly from the html string, instead of loading the file directly $pdf->addPage($html); $pdf->send();

Q: What is the best c# method you've seen for encapsulating an ADO.Net query We're building a simple ADO.Net infrastructure, and looking for the best practice for creating one or more objects/methods to handle queries to SQL Server. Such a method could for example, take a connection string and a query (or stored proc), and return a datatable, dataset, etc., with the query results. How has this worked best for you in the past? If you could mention what your method signature(s) looked like or include some code, that would be helpful. A: You might want to look at NHibernate, LINQ to SQL, ADO.NET Entity Framework or another ORM. They are mostly mature technologies to interact with ADO. Happy coding

Report: Mets interested in Kluber TSN.ca Staff Corey Kluber , The Canadian Press Two of the most active teams thus far in the Major League Baseball offseason could be cooking up something together. MLB.com's Mark Feinsand reports that the New York Mets, who are currently finalizing the acquisition of Robinson Cano and Edwin Diaz from the Seattle Mariners, have had discussions with the Cleveland Indians, who recently traded Yan Gomes to the Washington Nationals, over ace Corey Kluber. Sources say the Mets have spoken with the Indians about Corey Kluber. The two teams had talked about Yan Gomes before he was dealt to the Nationals, but the Mets' interest now appears to also extend to Kluber, who had Mets manager Mickey Callaway as a pitching coach in Cleveland. Feinsand notes the connection between the two clubs with Mets manager Mickey Callaway having served as Kluber's pitching coach in Cleveland and the teams having engaged in talks over Gomes last week. Kluber, 32, is a two-time Cy Young winner and is coming off of his first 20-win season in his eighth MLB campaign. The native of Birmingham, AL went 20-7 this season with an earned run average of 2.89 and a WHIP of 0.991 in a league-leading 215.0 IP. He struck out 222 batters and walked just 34. There is no word on what a potential package from the Mets would look like. Cleveland is also said to have had talks with the Los Angeles Dodgers over Kluber.

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Using a cell phone for an hour a day increases cancer risk by 500%, study shows (NaturalNews) Studies are increasingly showing that cellular phone use can lead to chronic health problems, including cancer and neurodegenerative disorders. Now a new study in the journal Electromagnetic Biology & Medicine has suggested a biological mechanism that might explain how these health problems develop. The study was conducted by researchers from Indiana University, the University of Eastern Finland, the University of Campinas in Brazil, and the Institute of Experimental Pathology, Oncology and Radiobiology in Kiev, Ukraine. The researchers found that exposure to the radiofrequency radiation (RFR) used by cell phones and other wireless devices causes a metabolic imbalance known as oxidative stress. “These data are a clear sign of the real risks this kind of radiation poses for human health,” co-author Igor Yakymenko said. Enormous increases in tumor risk Health researchers roughly classify radiation into two categories: ionizing and non-ionizing. Ionizing radiation, which includes X-rays, is a variety known to cause DNA damage and cancer. Non-ionizing radiation, including RFR, is believed to be too weak to directly damage cells. Nevertheless, evidence is emerging that RFR does indeed increase the risk of cancer. In 2011, the International Agency for Research on Cancer officially classified RFR as a “possible carcinogen.” This came a year after the international Interphone study found that people who used a cell phone for ten years were 40 percent more likely to develop brain tumors. The risk was 400 percent higher among those who started using phones before the age of 20. Decade-long cell phone users were also more likely to develop parotid gland tumors and 300 percent more likely to develop acoustic nerve tumors. The industry-funded Interphone study has been openly criticized for selecting data in a way that was designed to minimize the apparent risk of cell phone use. For the new study, the researchers reviewed prior studies into cell phone risk. They found that just an hour of cell phone use per day for four years was enough to increase the risk of certain tumors between three and five times. Even 20 minutes of daily use for five years was enough to triple the risk of a certain brain tumor. The risk may be even higher, Yakymenko warned, because some cancers can take 30 years to develop. In addition, little research has been conducted into people who start using cell phones as children. “[Our] data were obtained on adults who used cell phones mostly up to 10 years as adults,” he said. He added that the situation could be much different for children who use cell phones because their biology is more vulnerable to hazards and they will presumably use the devices throughout their lifetime. Cell phones cause oxidative damage One of the major problems in gaining widespread acceptance of these risks has been the fact that RFR simply does not cause the damage seen in cells exposed to ionizing radiation. In reviewing experimental studies on the metabolic effects of low-intensity RFR, the researchers found a surprising trend: regular cell phone, tablet or wireless internet RFR consistently causes oxidative stress in living cells. Oxidative stress is a metabolic imbalance in which the production of free radicals exceeds the body’s ability to remove them with antioxidant activity. The excess free radicals produced in this situation are able to damage cells and DNA. Free radicals have been implicated as causes of many chronic diseases, including cancer, heart disease, and dementia, and they are also responsible for many of the effects of aging. It is well known that the body reacts to aggressive environments with oxidative stress. Now it has been demonstrated that “ordinary wireless radiation” can have the same effect, the researchers said. This could explain not just cancer, but many of the other long-term health effects observed with long-term cell phone use.

Microsoft developed its own online Word procc. years ahead of Google & dumped it - Indyan http://www.pallab.net/2008/06/06/netdocs-story-of-a-missed-oppertunity/ ====== iwwr Is Google Docs making that much money? ~~~ regularfry That barely matters, from Microsoft's position. Any argument that NetDocs (which MS would have had control over) would have cannibalised Office applies even more to Google Docs (which it most certainly does not). ~~~ iwwr OK, I tried MS Web Office (Excel), it's sloow and a missing features, shortcuts that either Excel or Google Docs has. If web docs matter, MS is way behind Google at the moment.

Bill Ray William James "Bill" Ray was the tenth Anglican Bishop of North Queensland in Australia. He was consecrated a bishop in March 2007 and installed as the 10th Bishop of North Queensland on 24 March 2007. He retired as Bishop of North Queensland on 21 September 2018. Born in country Victoria on 19 October 1950, Ray went to teachers college and began life as a primary school teacher, soon becoming head teacher of a rural school. In his young adult years he led a scout troop, contributed to diocesan committees such as the Camp and Conference committee, lead several camps, represented the Diocese of Gippsland on the General Board of Religious Education (GBRE) and studied theology by distance education. During this time he held a lay reader’s license, often taking services of Morning and Evening Prayer in the Parish of Yarram. From 1978 to 1981, Ray worked full-time with the young people of the Diocese of Brisbane, offering Bible studies, camps for various ages and assistance with youth groups, as well as providing training for Sunday school and religious education teachers and youth leaders. He also continued his involvement with GBRE. His ministry as youth and children’s worker in the parish of St Luke’s Toowoomba from late 1981 to 1986, was punctuated by two years at Duke University in North Carolina where he studied for his Masters in Religious Education. He moved back to Victoria at the beginning of 1987 to be the education officer for the Diocese of Gippsland and the regional officer for the Council for Christian Education in Schools. Ray was ordained a deacon in Rockhampton in 1992 during the first few weeks of his five-year ministry as diocesan ministry training officer. He was ordained a priest later that year. He served as a parish priest in the parishes of Wandal (Rockhampton), East Ivanhoe and Croydon (Melbourne) and as Archdeacon of Maroondah (outer eastern suburbs of Melbourne). Over the life of his full-time ministry, Ray has had an active role in the Education for Ministry (EFM) programs at various levels from national trainer, to regional co-ordinator as well as a group mentor. He is also a proponent of the catechumenate program and has led this at both the parish and diocesan levels. He became the Director of GBRE in 2000, being equipped for this position over the years through his membership of the board, the executive and positions on various editorial committees. He has written a number of religious education programs and in recent years authored three Lenten study booklets. Ray holds a Diploma of Teaching from Frankston Teachers’ College; a Bachelor of Education from the Western Australian College of Education; a Licentiate of Theology from the Australian College of Theology and a Masters of Religious Education from Duke University in the United States. Ray is married to Robin and they have two children and three grandchildren. References Category:1950 births Category:Living people Category:Anglican bishops of North Queensland Category:Anglican lay readers

Results of two controlled studies on antiemetic combination against vomiting induced by 5-fluorouracil. A group of 132 patients with different disseminated solid tumors entered two consecutive antiemetic trials in which 5-fluorouracil given in a 120-h continuous infusion was the emetogenic stimulus. The purpose of the trials was to investigate the validity of Peroutka and Snyder's hypothesis. These authors suggested that CNS receptors other than the classical dopamine D-2 (e.g., histamine H-1 and muscarinic cholinergic receptors) were involved in emetic response. Hence, a combination of a phenothiazine (an antidopaminergic drug) with an antihistaminic or a tricyclic antidepressant (H-1 and muscarinic cholinergic blockers) was suggested to be possibly superior to phenothiazine alone against antineoplastic chemotherapy-induced vomiting. The first study showed the antiemetic superiority of a phenothiazine (thiethylperazine) over placebo but failed to show a superiority of the combination of thiethylperazine and an antihistaminic (diphenhydramine) over thiethylperazine alone. In contrast, the second study proved the superiority of the combination of thiethylperazine and a tricyclic antidepressant (amitriptyline) over thiethylperazine alone. In conclusion, tricyclic antidepressants - but not antihistaminics - potentiate the antiemetic activity of thiethylperazine against 5-fluorouracil-induced vomiting.

Early defects, ironically, showed Lexus' commitment to quality What happens when a brand founded on the slogan "The Relentless Pursuit of Perfection" turns out to be imperfect? The newborn Lexus Division suffered its first recall in December 1989, only a couple of months after the first cars went on sale. Better than any English word, the German word schadenfreude(SHAH'-den-froy-deh) probably describes how rival luxury brands such as Mercedes and BMW felt at the news. It means "joy at the misfortune of others." The notion that the much-hyped perfect car brand was forced to announce a recall was so jarring that it made network TV news on Dec. 4, 1989. "It was a big deal," said Dave Illingworth, who was then Lexus Division general manager. RECALL? HERE? Illingworth, now 64, confessed in a recent interview that nobody at Lexus ever imagined they would be faced with a recall. "We thought, 'That's never going to happen,'" he said. But right out of the box, Lexus was confronted with the need for a double-barreled recall: for a cruise-control defect that could cause an accident by making it harder to stop; plus a center high-mounted stop light that could overheat. The problems affected more than 8,000 LS 400s —all that had been sold. At best, it was embarrassing. At worst, it was potentially lethal for the startup Lexus brand. "About two years before that, Audi had the unintended acceleration situation and mishandled it, and sales dropped 50 percent," Illingworth said. Audi was brusque in blaming driver error for accidents, saying drivers mistakenly stepped on the accelerator instead of the brakes. The backlash from Audi's initial reaction and a devastating TV segment on "60 Minutes" nearly drove the brand out of the United States. With the Audi disaster in mind, Illingworth said, he knew it was time to put up or shut up. Illingworth had written the "Lexus Covenant," which was signed by every dealer. The covenant says in part that Lexus cars will be "the finest ever built." It goes on to say, "Lexus will treat each customer as we would a guest in our home." "If that covenant means anything, we do the right thing," Illingworth said. Doing the right thing, Lexus-style, meant picking up the cars, replacing the appropriate parts, filling the cars with gasoline, washing them and taking them back again, in a hurry. It took an all-out, all-hands effort, recalls Steve Haag, who was part of the Lexus field force at the time. "I was working in Chicago, in the Central Region office. I'm not involved in service; there were people that were more technically involved than I was. But they called everybody in, everybody in the field organization ... and mobilized everybody," he says. Haag, 48, is now corporate manager of private distributors. A TURNING POINT Haag says Illingworth told the group, "We can either fail, the brand will fail, or we can grab it and make it a win." At the time, there were fewer than 100 Lexus dealers in the United States. That meant some customers lived hundreds of miles from the nearest dealership. In those cases, Lexus flew in technicians to do the work on the spot, including for one owner in Alaska. According to The Lexus Story, a book the company published in 2003, completing the recall by typical methods could have taken a year. By pulling out all the stops, Lexus got most of the repairs done in a few weeks. James D. Power IV and Chris Denove wrote in their 2006 book, Satisfaction: "We believe this recall marked the day that Lexus was truly born, and not the day it sold its first car. The recall was the day that Lexus showed the world what it really meant to be customer-focused." The recall became a case study in building customer good will. The Lexus Story brags that instead of taking lemons and making lemonade, Lexus had done even better, taking lemons and making margaritas. By New Year's Day 1990, competitors' feeling of schadenfreude was more like "shock and awe."

This Month's Special Tuesday, May 31, 2016 Tour Kick Off: Daughter of the Sun by @zoekalowriter Young Adult Fantasy Date Published: May 2016 Sixteen-year-old Trinity was born during a solar eclipse and left at the doorsteps of a convent along with a torn piece of papyrus covered with ancient symbols. Raised by nuns in the English countryside, she leads a quiet life until she’s whisked away to the Island of Cats and a grandmother she never knew. But before they can get to know each other, her grandmother dies. All that Trinity has left is a mysterious eye-shaped ring. And a thousand grieving cats. As Trinity tries to solve the enigma of the torn papyrus, she discovers a world of bloody sacrifices and evil curses, and a prophecy that points to her and her new feline abilities. Unwilling to believe that any of the Egyptian gods could still be alive, Trinity turns to eighteen-year-old Seth and is instantly pulled into a vortex of sensations that forces her to confront her true self—and a horrifying destiny. A certified bookworm, Zoe Kalo has always been obsessed with books and reading. Reading led to writing—compulsively. No surprise that at 16, she wrote her first novel, which her classmates read and passed around secretly. The pleasure of writing and sharing her fantasy worlds has stayed with her, so now she wants to pass her stories to you with no secrecy—but with lots of mystery… A daughter of adventurous expats, she’s had the good fortune of living on 3 continents, learning 4 languages, and experiencing a multicultural life. Currently, she’s working on a Master’s degree in Comparative Literature, which she balances between writing, taking care of her clowder of cats, and searching for the perfect bottle of pinot noir.

location insurance Medical questions & health advice by board certified doctors "Why do I keep crying even when nothing is wrong?!" Question Sorry if this is weird, but I keep crying and I don't know why or what is wrong with me?? I am a 21 year old girl and in school.I haven't seen a counselor yet, but I don't know what to tell him if I do. It keeps happening every day and taking over my life. I am not on any medication other than birth control pills, but I need this to stop now. Answer I am sorry to hear that you have been having these uncontrollable crying spells. From your description, it is unclear if you have any underlying depressive thoughts, suicidal ideations, thoughts of hurting yourself or others, but if you notice any of these symptoms you should immediately go to your nearest emergency department for further evaluation because depression can be a very serious disease and if these crying episodes are related to depression, then there is concern that this may worsen. It is recommended that you consult a mental health care professional as soon as possible because of these symptoms that you are having. Based upon your clinical exam, they may decide to start you on certain medications to adjust your mood. You do not need to worry about what you will say to a counselor when you see them, because they are trained to care for patients who have symptoms such as the ones you are experiencing. The most important thing to do at this time is to be evaluated so that further work up can be done and the appropriate treatment regimen can begin. They will also examine other facets of your life to see if there are underlying causes for your stress such as family history, high stress jobs, etc. Zocdoc Answers is for general informational purposes only and is not a substitute for professional medical advice. If you think you may have a medical emergency, call your doctor (in the United States) 911 immediately. Always seek the advice of your doctor before starting or changing treatment. Medical professionals who provide responses to health-related questions are intended third party beneficiaries with certain rights under Zocdoc’s Terms of Service. What is Zocdoc? Managing your healthcare is easier than ever before with Zocdoc. Just search for a doctor in your insurance network, see available times, and book an appointment on the spot! You can read real doctor reviews from other patients, see the doctor’s background and education, view photos of the office, and more. It’s simple, secure, and free! Search for answers Zocdoc Answers is for general informational purposes only and is not a substitute for professional medical advice. If you think you may have a medical emergency, call your doctor (in the United States) 911 immediately. Always seek the advice of your doctor before starting or changing treatment. Medical professionals who provide responses to health-related questions are intended third party beneficiaries with certain rights under Zocdoc’s Terms of Service.

A high prevalence of BRCA1 mutations among breast cancer patients from the Bahamas. The Bahamas is a group of islands in the Caribbean with a high incidence of early onset breast cancer. In isolated populations, the identification of founder mutations in cancer predisposing genes may facilitate genetic testing and counseling. To date, six distinct BRCA1 mutations have been found in patients from cancer families from the Bahamas. The frequencies of these mutant alleles have not been measured in a large series of unselected breast cancer patients from Bahamas. We studied 214 Bahamian women with invasive breast cancer, unselected for age or family history of cancer. All patients were screened for six mutations in the BRCA1 gene that have previously been reported in cancer patients from the Bahamas. A mutation was identified in 49 of the 214 breast cancer patients (23%). The mutation frequency was particularly high in women diagnosed before age 50 (33%) in women with a first-degree relative with breast or ovarian cancer (41%) and in women with bilateral breast cancer (58%). Approximately 23% of unselected cases of breast cancer in the Bahamian population are attributable to a founder mutation in the BRCA1 gene-this is the highest reported mutation prevalence for any country studied to date. Genetic testing for these mutations is advisable for all women diagnosed with breast cancer in the Bahamas.

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Yenn and Ciri By Nairiai Watch 159 Favourites 9 Comments 10K Views I keep reading Witcher. I really like to watch the relationship between Yennifer and Ciri. So here's a nice illustration from their lives. IMAGE DETAILS Image size 4831x2929px 10.08 MB Show More Published : Jan 22, 2017

using System; using System.Collections.Generic; using System.Text; using Microsoft.Xna.Framework; using Microsoft.Xna.Framework.Graphics; using Microsoft.Xna.Framework.Input; using OpenC1.CameraViews; using OneAmEngine; namespace OpenC1.GameModes { class OpponentEditMode : GameMode { FixedChaseCamera _opponentCamera; FlyView _fpsView; int _watchingOpponent = 0; public OpponentEditMode() { _opponentCamera = new FixedChaseCamera(6.3f, 2.3f); _opponentCamera.FieldOfView = MathHelper.ToRadians(55.55f); _fpsView = new FlyView(Race.Current.PlayerVehicle); } public override void Activate() { _fpsView.Activate(); MessageRenderer.Instance.PostHeaderMessage("Edit Mode: Opponents", 3); } public override void Update() { if (Engine.Input.WasPressed(Keys.D0)) { _watchingOpponent = (_watchingOpponent + 1) % (Race.Current.Opponents.Count + 1); } if (_watchingOpponent == 0) { _opponentCamera.Position = Race.Current.PlayerVehicle.GetBodyBottom(); _opponentCamera.Orientation = Race.Current.PlayerVehicle.Chassis.Actor.GlobalOrientation.Forward; Engine.Camera = _opponentCamera; } else { Opponent opponent = Race.Current.Opponents[_watchingOpponent - 1]; _opponentCamera.Position = opponent.Vehicle.GetBodyBottom(); _opponentCamera.Orientation = opponent.Vehicle.Chassis.Actor.GlobalOrientation.Forward; Engine.Camera = _opponentCamera; opponent.Vehicle.Chassis.OutputDebugInfo(); } } public override void Render() { if (_watchingOpponent == 0) { Race.Current.PlayerVehicle.Render(); } foreach (OpponentPathNode node in Race.Current.ConfigFile.OpponentPathNodes) { Engine.DebugRenderer.AddCube(Matrix.CreateTranslation(node.Position), Color.White); foreach (OpponentPath path in node.Paths) { Color c = Color.Yellow; if (path.Type == PathType.Race) c = Color.Red; if (path.Type == PathType.Cheat) c = Color.Blue; //Engine.DebugRenderer.AddLine(node.Position, path.End.Position, c); Vector3 offs = new Vector3(0, 0, path.Width); Vector3 s3 = path.End.Position - node.Position; s3.Normalize(); s3 *= path.Width; Vector3 s1 = Vector3.Transform(s3, Matrix.CreateRotationY(90) * Matrix.CreateTranslation(node.Position)); s1.Y = node.Position.Y; Vector3 s2 = Vector3.Transform(s3, Matrix.CreateRotationY(90) * Matrix.CreateTranslation(path.End.Position)); s2.Y = path.End.Position.Y; Engine.DebugRenderer.AddLine(s1, s2, c); s1 = Vector3.Transform(s3, Matrix.CreateRotationY(-90) * Matrix.CreateTranslation(node.Position)); s1.Y = node.Position.Y; s2 = Vector3.Transform(s3, Matrix.CreateRotationY(-90) * Matrix.CreateTranslation(path.End.Position)); s2.Y = path.End.Position.Y; Engine.DebugRenderer.AddLine(s1, s2, c); } } } } }

Q: Why does mining profitability tend towards zero? Why does mining profitability tend towards zero? Is it different for short term miners than it is for long term miners? Example: if I mine now and sell them next year, they may be worth more as next year they'll be harder to mine Thanks A: As with all things related to supply and demand, the market will eventually find its equilibrium, where the cost of generating the Bitoins will be close to their sale price. If the costs were bigger, less cost efficient miners would not mine. If the price was higher, there would be more room for investment that would increase the difficulty, thus increasing the cost to mine every Bitcoin. If you want to calculate how profitable mining is, just put the data into any Profitability Calculator. A: This is a bit of a generalization, since mining profitability is different for different people depending on their comparative advantages. But the profitability of mining is affected by the difficulty, which in turn is determined by the total hashrate of all miners. If at any time the profitability is too high, this will attract more miners causing the profitability to decrease. If it is negative, it will cause miners to quit, increasing the profitability. The result is that there will be very few untapped opportunities to profit from mining. Note that the profitability is only close to 0 if all costs are considered - hardware, electricity, space, maintenance, risk and so on. Every potential miner will have his own costs/benefits analysis. The causality in your quote is reversed - if bitcoins are worth more, they will be harder to mine. (At least, if we ignore the effect of generation reward halving.) A: This is a loaded question, as it assumes that profitability will tend towards 0. However, for any given piece of mining hardware it's almost certainly a fair assumption for the foreseeable future that it's profitability will tend towards zero. This is because, from an overall perspective, as new processing hardware is developed (improving both efficiency and processing power), the cost per hash of mining decreases. While this holds true, there will always be a point in time when the cost of operating a given graphics card (or other processor), with all ownership costs included, exceeds the cost of purchasing new hardware. The most important issue for miners purchasing new hardware is whether the break even point can be reached before the hardware becomes essentially obsolete (because the costs exceed the revenue). Predicting this currently involves taking a gamble on what the future price of bitcoins will be. All this means that the profitability of mining doesn't necessarily approach zero, as long as you continue to optimise your mining equipment to maximise efficiency.

Letters November 27, 1996 By Darrell Stanford Standing Behind The Russian Press The Nov. 6 article, "How Russia Runs Without Yeltsin," presents a concise summary of the current situation in Russia that I find clear and on the mark, except, that is, for the last section on Russian press coverage of Boris Yeltsin's health. In describing Russian TV as "closely controlled by the government for the most part," the article gives a distorted picture of the quasi-independent status of Russian networks. In reality, ORT, NTV, and RTR, the three networks with the widest national distribution, are each owned and controlled by varying combinations of government and business organizations. What these groups have in common is an interest in political and economic stability - not a return to power by communist or nationalist parties that might renationalize the media. This explains their support for Mr. Yeltsin's reelection and their recent character assassination of Alexander Lebed. But these interests did not prompt Russian TV to refrain from "speculation on the president's health" and the political ramifications thereof. True, such wild reports as that of Yeltsin's death were not widely trumpeted, but the Russian analytical programs comparable to PBS's "Newshour" and weeklies such as "Face the Nation" repeatedly dealt in detail with questions of Yeltsin's health. If, as the article states, "all most Russians know is that the president was said to need heart surgery," it has not been for a lack of TV coverage of the issue. Instead, it may be indicative of the average Russian's focus on problems closer to home, such as receiving wages that are often months overdue. Darrell Stanaford Moscow Next up Here are more stories that look at the news with empathy, insight, and hope.

A prospective study of plasma ascorbic acid concentrations and breast cancer (United States). To investigate the association between prediagnostic plasma ascorbic acid concentrations and subsequent breast cancer risk in a nested case-control study. Female volunteer residents of Washington County, MD, donated 14,625 non-fasting blood samples in 1989. Incident breast cancer cases (n = 115) and controls (n = 115) were matched by age, menopausal status at donation, and date and hour of blood donation. Median ascorbic acid concentrations were similar between cases and controls (1.44 mg/dl vs. 1.39 mg/dl. p = 0.78). There was no evidence for a dose-response relationship between higher plasma ascorbic acid concentrations and breast cancer risk [highest vs. lowest fifths: ORadjusted = 0.90, Ptrend = 0.98). Findings from this prospective study do not suggest a protective association between prediagnostic plasma ascorbic acid concentrations and breast cancer risk in the subsequent 5 years of follow-up.

[Decreased prothrombin coagulation activities in breast-fed children?]. Intracranial bleeding due to vitamin K deficiency in infants without prior symptoms of disease has been reported. All of these children were fully breastfed. To evaluate a potential deficit of vitamin K dependent coagulation factors in fully breastfed infants we determined the prothrombin clotting times in healthy babies on the 5th day (n = 204) and in the 5th week of life and correlated the results to the feeding. On the fifth day of life prothrombin coagulation times in fully breastfed infants were significantly longer than in babies receiving formula exclusively or additionally. Vitamin K supply in fully breastfed neonates should therefore be reinvestigated. In the 5th week of life, however, there was no difference in prothrombin coagulation times between fully breastfed infants and infants with exclusive or supplementary formula feeding.

package com.calsignlabs.apde; import android.content.Context; import android.content.DialogInterface; import android.content.Intent; import android.content.SharedPreferences; import android.os.Bundle; import android.preference.PreferenceManager; import androidx.appcompat.app.AlertDialog; import androidx.appcompat.app.AppCompatActivity; import androidx.appcompat.widget.Toolbar; import android.view.LayoutInflater; import android.view.Menu; import android.view.MenuItem; import android.view.View; import android.view.ViewGroup; import android.view.WindowManager; import android.widget.BaseAdapter; import android.widget.Button; import android.widget.CheckBox; import android.widget.EditText; import android.widget.LinearLayout; import android.widget.ListView; import android.widget.RelativeLayout; import android.widget.TextView; import com.calsignlabs.apde.build.Manifest; import com.calsignlabs.apde.build.Permission; import com.calsignlabs.apde.build.SketchPreviewerBuilder; import java.util.ArrayList; import java.util.List; public class PermissionsActivity extends AppCompatActivity { private boolean[] checked; private PermissionAdapter adapter; private boolean isPreviewSetttings; private String startData; protected class PermissionAdapter extends BaseAdapter { @Override public int getCount() { return Manifest.permissions.size(); } @Override public Permission getItem(int position) { return Manifest.permissions.get(position); } @Override public long getItemId(int i) { return i; } @Override public View getView(final int position, View convertView, ViewGroup parent) { if (convertView == null) { LayoutInflater inflater = (LayoutInflater) getSystemService(Context.LAYOUT_INFLATER_SERVICE); convertView = inflater.inflate(R.layout.permissions_list_item, parent, false); } final RelativeLayout layout = (RelativeLayout) convertView; final TextView label = (TextView) layout.findViewById(R.id.permissions_list_item_label); final CheckBox check = (CheckBox) layout.findViewById(R.id.permissions_list_item_checkbox); label.setText(Manifest.permissions.get(position).name()); check.setChecked(checked[position]); View.OnClickListener onClickListener = new View.OnClickListener() { @Override public void onClick(View view) { boolean ck = !checked[position]; checked[position] = ck; check.setChecked(ck); } }; View.OnLongClickListener onLongClickListener = new View.OnLongClickListener() { @Override public boolean onLongClick(View view) { showPermissionDescDialog(position); return true; } }; layout.setOnClickListener(onClickListener); label.setOnClickListener(onClickListener); check.setOnClickListener(onClickListener); layout.setOnLongClickListener(onLongClickListener); label.setOnLongClickListener(onLongClickListener); check.setOnLongClickListener(onLongClickListener); return convertView; } }; @Override protected void onCreate(Bundle savedInstanceState) { super.onCreate(savedInstanceState); setContentView(R.layout.activity_permissions); Toolbar toolbar = (Toolbar) findViewById(R.id.toolbar); toolbar.setBackgroundColor(getResources().getColor(R.color.bar_overlay)); setSupportActionBar(toolbar); getSupportActionBar().setHomeButtonEnabled(true); getSupportActionBar().setDisplayHomeAsUpEnabled(true); getWindow().getDecorView().setBackgroundColor(getResources().getColor(R.color.activity_background)); isPreviewSetttings = getIntent().getBooleanExtra("previewSettings", false); if (isPreviewSetttings) { getSupportActionBar().setTitle(R.string.pref_build_preview_permissions); } } @Override public void onResume() { super.onResume(); final ListView permsList = (ListView) findViewById(R.id.permissions_list); permsList.setChoiceMode(ListView.CHOICE_MODE_MULTIPLE); permsList.setItemsCanFocus(false); checked = new boolean[Manifest.permissions.size()]; for (int i = 0; i < checked.length; i ++) { checked[i] = false; } if (isPreviewSetttings) { loadDataPreviewSettings(); } else { loadData(); } adapter = new PermissionAdapter(); permsList.setAdapter(adapter); } //Displays a permission description dialog private void showPermissionDescDialog(final int perm) { //Inflate the layout LinearLayout layout = (LinearLayout) getLayoutInflater().inflate(R.layout.permission_desc_popup, null); //Populate the layout with permission values ((TextView) layout.findViewById(R.id.permission_desc_popup_title)).setText(Manifest.permissions.get(perm).name()); ((TextView) layout.findViewById(R.id.permission_desc_popup_message)).setText(Manifest.permissions.get(perm).desc()); //Create the alert AlertDialog.Builder build = new AlertDialog.Builder(this); build.setView(layout); final AlertDialog dialog = build.create(); dialog.setCanceledOnTouchOutside(true); if(Manifest.permissions.get(perm).custom()) { ((TextView) layout.findViewById(R.id.permission_desc_popup_message)).setVisibility(TextView.GONE); //TODO custom descriptions Button delete = (Button) layout.findViewById(R.id.permissions_desc_popup_delete); delete.setVisibility(Button.VISIBLE); delete.setOnClickListener(new Button.OnClickListener() { @Override public void onClick(View view) { AlertDialog.Builder builder = new AlertDialog.Builder(PermissionsActivity.this); builder.setTitle(R.string.permissions_delete_permission_dialog_title); builder.setMessage(R.string.permissions_delete_permission_dialog_message); builder.setPositiveButton(R.string.delete, new DialogInterface.OnClickListener() { @Override public void onClick(DialogInterface dialogInterface, int which) { String data = getData(); Manifest.removeCustomPermission(perm, getApplicationContext()); adapter.notifyDataSetChanged(); dialog.dismiss(); setData(data); } }); builder.setNegativeButton(R.string.cancel, new DialogInterface.OnClickListener() { @Override public void onClick(DialogInterface dialog, int which) {} }); builder.create().show(); }}); } dialog.show(); } @Override public void onPause() { if (!isPreviewSetttings) { saveData(); } super.onPause(); } @Override public void onBackPressed() { if (isPreviewSetttings) { promptSaveDataPreviewSettings(); } else { super.onBackPressed(); } } private SharedPreferences getSharedPreferences() { return getSharedPreferences(((APDE) getApplicationContext()).getSketchName(), MODE_PRIVATE); } public void saveData() { getSharedPreferences().edit().putString("permissions", getData()).apply(); } public void loadData() { setData(getSharedPreferences().getString("permissions", "")); } public void loadDataPreviewSettings() { setData(SketchPreviewerBuilder.getInstalledPermissions(this)); startData = getData(); } public void promptSaveDataPreviewSettings() { if (startData.equals(getData())) { // If the permissions haven't changed, then don't worry about it finish(); return; } AlertDialog.Builder builder = new AlertDialog.Builder(this); builder.setTitle(R.string.pref_build_preview_permissions_reinstall_dialog_title); builder.setMessage(R.string.pref_build_preview_permissions_reinstall_dialog_message); builder.setPositiveButton(R.string.pref_build_preview_permissions_reinstall_dialog_button_install, new DialogInterface.OnClickListener() { @Override public void onClick(DialogInterface dialogInterface, int i) { previewReinstall(); } }); builder.setNegativeButton(R.string.pref_build_preview_permissions_reinstall_dialog_button_exit, new DialogInterface.OnClickListener() { @Override public void onClick(DialogInterface dialogInterface, int i) { finish(); } }); builder.setNeutralButton(R.string.cancel, new DialogInterface.OnClickListener() { @Override public void onClick(DialogInterface dialogInterface, int i) {} }); builder.show(); } protected void previewReinstall() { Intent result = new Intent(); result.putExtra("permissions", getDataArray()); setResult(RESULT_OK, result); finish(); } @Override public boolean onCreateOptionsMenu(Menu menu) { getMenuInflater().inflate(R.menu.activity_permissions, menu); return true; } @Override public boolean onOptionsItemSelected(MenuItem item) { switch(item.getItemId()) { case android.R.id.home: if (isPreviewSetttings) { promptSaveDataPreviewSettings(); } else { finish(); } return true; case R.id.menu_new_permission: newPermission(); return true; case R.id.action_settings: launchSettings(); return true; default: return super.onOptionsItemSelected(item); } } private void launchSettings() { startActivity(new Intent(this, SettingsActivity.class)); } public void newPermission() { //Create the alert AlertDialog.Builder build = new AlertDialog.Builder(this); build.setTitle(R.string.permissions_new_permission_dialog_title); build.setMessage(R.string.permissions_new_permission_dialog_message); APDE global = (APDE) getApplicationContext(); final EditText input = global.createAlertDialogEditText(this, build, "", false); build.setPositiveButton(R.string.create, new android.content.DialogInterface.OnClickListener() { @Override public void onClick(DialogInterface dialog, int which) { //TODO let the user customize the prefix and the description String data = getData(); Manifest.addCustomPermission(input.getText().toString(), getResources().getString(R.string.permissions_custom_perm), getApplicationContext()); Manifest.sortPermissions(); adapter.notifyDataSetChanged(); setData(data); }}); build.setNegativeButton(R.string.cancel, new DialogInterface.OnClickListener() { public void onClick(DialogInterface dialog, int whichButton) { } }); AlertDialog alert = build.create(); if (!PreferenceManager.getDefaultSharedPreferences(getApplicationContext()).getBoolean("use_hardware_keyboard", false) && alert.getWindow() != null) { alert.getWindow().setSoftInputMode(WindowManager.LayoutParams.SOFT_INPUT_STATE_VISIBLE); } alert.show(); } public void setData(String data) { clearChecks(); if (data.length() <= 0) { return; } setData(data.split(",")); } public void setData(String[] data) { for (String permission : data) { int index = permission.lastIndexOf("."); checkItem(permission.substring(index != -1 ? index + 1 : 0), true); } } /** * @return the selected values, separated by commas */ public String getData() { // Combine all values StringBuilder out = new StringBuilder(); for (int i = 0; i < checked.length; i ++) { if (checked[i]) { out.append((Manifest.permissions.get(i)).consumableValue()); out.append(","); } } return out.toString(); } public String[] getDataArray() { List<String> permissions = new ArrayList<>(); for (int i = 0; i < checked.length; i ++) { if (checked[i]) { permissions.add((Manifest.permissions.get(i)).consumableValue()); } } String[] out = new String[permissions.size()]; for (int i = 0; i < out.length; i ++) { out[i] = permissions.get(i); } return out; } public void clearChecks() { ListView permsList = (ListView) findViewById(R.id.permissions_list); permsList.clearChoices(); permsList.requestLayout(); for (int i = 0; i < checked.length; i ++) { checked[i] = false; } } public void checkItem(String value, boolean ck) { int index = permissionsPos(value); //We have a problem if (index == -1) { return; } checked[index] = ck; ListView permsList = (ListView) findViewById(R.id.permissions_list); permsList.setItemChecked(index, ck); } //Get the location of the permission in the list private int permissionsPos(String name) { for (int i = 0; i < Manifest.permissions.size(); i ++) { if (((Manifest.permissions.get(i)).name()).equals(name)) { return i; } } return -1; } }

Q: Getting header resend error in node I have following routing: router.get('/blog/:title', function (req, res) { blog.getBlogPost(req, function (data) { res.render('blog', data); }); }); and the function getBlogPost exports.getBlogPost = function (req, callback) { // TODO SAFE PARAM // TODO ERR Handling var title = req.param('title'); Blog.findOne({permaLink: title}).exec(function (err, data) { var date = new Date(+data.timestamp); data.tags = createHashtagsFromCSV(data.tags); data.date = month_names_long[date.getMonth()] + " " + date.getDate() + ", " + date.getFullYear(); callback(data); }); // not found callback({}); }; and strangely I get following Node console log Error: Can't set headers after they are sent. at ServerResponse.OutgoingMessage.setHeader (http.js:689:11) at ServerResponse.header (C:\Users\Michael\Desktop\qcode\node_modules\express\lib\response.js:662:10) at ServerResponse.send (C:\Users\Michael\Desktop\qcode\node_modules\express\lib\response.js:146:12) at fn (C:\Users\Michael\Desktop\qcode\node_modules\express\lib\response.js:896:10) at View.exports.renderFile [as engine] (C:\Users\Michael\Desktop\qcode\node_modules\jade\lib\jade.js:325:12) at View.render (C:\Users\Michael\Desktop\qcode\node_modules\express\lib\view.js:76:8) at Function.app.render (C:\Users\Michael\Desktop\qcode\node_modules\express\lib\application.js:527:10) at ServerResponse.res.render (C:\Users\Michael\Desktop\qcode\node_modules\express\lib\response.js:900:7) at module.exports (C:\Users\Michael\Desktop\qcode\app.js:65:9) at Layer.handle_error (C:\Users\Michael\Desktop\qcode\node_modules\express\lib\router\layer.js:58:5) I have done stuff like this already a few times in my project, but this times it throws this error and I have now clue why? Any idea why? A: Your callback calls twice. So the second one throw header error Make something like Blog.findOne({permaLink: title}).exec(function (err, data) { if (!data) { callback({}); return; } var date = new Date(+data.timestamp); data.tags = createHashtagsFromCSV(data.tags); data.date = month_names_long[date.getMonth()] + " " + date.getDate() + ", " + date.getFullYear(); callback(data); });