Datasets:

OBF

/

text-ds

like 0

Martin Shkreli, the guy who was once called “the most hated man in America” and “a morally bankrupt sociopath” after obtaining the manufacturing license for the anti-parasitic drug Daraprim and raising its price from $13 to $750, got booted off Twitter on Sunday for the “targeted harassment” of Teen Vogue writer Lauren Duca, who scored points with progressives when she complained straight to Twitter CEO Jack Dorsey about his antics. Shkreli had facetiously tweeted her he wanted to take her to the presidential inauguration, and had posted a collage of photos of her on his Twitter profile. One of them was photo of Duca with her husband that had Shkreli’s face where Duca’s husband’s was supposed to be. It was a juvenile prank, but in the Internet troll community—of which Shkreli is a member—that sort of thing is considered harmless good fun. The purpose is to get a rise out of the target, and Duca predictably took the bait, going straight to the principal's office. Dorsey—also predictably—came through for her, booting Pharma Bro off his social media platform, probably without offering him the simple, reasonable option of deleting the offensive material from his profile and maintaining his account. Duca had options in dealing with this “high school” issue. She could’ve simply ignored his puerile attempts to provoke her, blocked him, or turned the tables and mocked him mercilessly. Instead, she chose to have a straight white male protect her from her tormentor, tweeting to Dorsey, “Why is harassment an automatic career hazard for a woman receiving any amount of professional attention? Question for @jack & also society!” This got her sympathy, but she didn't mention that she'd taken the first personal shot at Shkreli in August, tweeting a photo of him drinking a beer, along with, “Martin Shkreli is literally at Guy Fieri’s Flavor Town right now. I don't even know.” The writer followed that with, “I left right away. I feel sick,” and later, “I felt so gross. I still feel so gross.” A feminist warrior in New York City is so sensitive she has to leave a restaurant because she can't share the same air with someone she hates, and over three hours later still feels “gross”? Maybe writing for Teen Vogue about no-bake unicorn cheesecake and Kim Kardashian's lip ring at the Christmas party leads to one taking on the persona of the targeted readership and induces Valley Girl talk. Regardless of your opinion of Shkreli, is it shocking that he might want to take a swipe back at her after she'd obtained a degree of fame from with her contentious appearance on Tucker Carlson’s Fox show? Isn't it targeted harassment to use Twitter to single out someone who’s minding his own business in a restaurant and making him even more of an object of scorn? Duca didn't mention that part to Dorsey because she's skilled at playing the victim card, as so many modern feminists are. Self-proclaimed victimization by the patriarchy comes in handy in immunizing Duca from tweets like, “Friendly reminder that there's an uneven playing field, and straight, white men are generally trash,” and then explaining that with, “Look, I can make fun of white men because I have slept with several of them! Also, the white supremacist patriarchy.” Imagine her outrage at a man referring to white women as trash, regardless of the circumstances. On the same day that Ivanka Trump, who in many ways is a feminist exemplar, got harassed on an airplane while accompanied by her children by an angry guy, Duca tweeted, “Ivanka Trump is poised to become the most powerful woman in the world. Don't let her off the hook because she looks like she smells good.” Tucker Carlson called her out on this, and she disingenuously replied that she hadn't even mentioned the plane situation, though the reference was undeniable. During their spirited exchanges, Duca complained to Carlson that he was talking over her, which he wasn't, and also called him a partisan hack simply because he challenged her fairly. At the end of the segment, an annoyed Carlson shot back with, “You should stick to the thigh high boots,” a reference to one of her Teen Vogue articles, and she called him “a sexist pig.” Carlson makes cutting remarks like that all the time, regardless of gender. That's his signature move. Calling him a sexist makes Duca seem the victim though, which plenty of media accounts of their battle confirmed. Feminist Duca wants to be the hard-edged woman (sample tweet: “I’M GOING TO KILL THE NEXT RANDOM MAN THAT TALKS TO ME”), but as soon as anyone pushes back she plays her victimized little girl role. She's had to turn to the patriarchy now—Jack Dorsey, another straight white male—to defend her against a little online trolling, so it appears she still needs men to fight her battles for her.

Gamers are a funny bunch. Board gamers, doubly so. We treasure our board games. We put plastic sleeves on our cards to keep our games immaculate and pristine. We do not tolerate spilled drinks. So writing on the board (in permanent marker!), placing stickers, and ripping up cards is both incredibly disturbing, and therapeutically cathartic. Welcome to Seafall. A Lesson In Object Permanence The first ever “legacy” game, Risk Legacy, had this sticker sealing the box: “what is done can never be undone”. It is the most dramatic piece of board-game packaging I’ve encountered, and it proclaims boldly: here is something new. Risk Legacy is the greatest version of Risk you’ve never played, and a high watermark in Hasbro’s extensive catalogue. Designed by Rob Daviau, it is a fusion of avant-garde performance art masquerading as a respectable, mass-market board game (alongside Monopoly, Risk is one of most recognisable board game titles in the world). Nothing like this had ever been done before. Advertisement Normal board games are like The Simpsons. No matter what craziness ensues in an episode, the next episode starts the same way with the family on the TV couch, and there are never any lasting changes. Bart is trapped in pre-adolescent rebellion, and Homer will never age enough to lose another hair. The central conceit of legacy games is that the game doesn’t reset. Not precisely. Now we’re watching The Wire, or Arrested Development, or Archer, and changes stay changed. Games accumulate history. Games accumulate scars. Like the North, The Game remembers. The reality is that Seafall, and legacy games in general, are the beautiful lovechild of board games and Dungeons and Dragons. Playing a board game is now a season-long campaign, and both board and players will have scars aplenty by the end. What is done can never be undone, and the “legacy format” genie can never be put back into the bottle. Pandemic Legacy followed, lodging itself firmly at the top of the BoardGameGeek charts. Seafall is the third legacy game, and the first wholly designed by Rob Daviau. Sailing Towards The New World Advertisement Seafall’s a 4X game, channeling the spirit of Civilization or, more appropriately, Sid Meier’s Colonization. We set our soundtrack accordingly, and prepared ourselves to follow the footsteps of Messrs Columbus and Cook, de Gama and Cortez. For there is a sea to be sailed, islands to explore, goods to trade, and natives to mistreat. Doing all of the above gains you glory, and glory wins you the game. Not unlike real life, glory is fickle and fleeting, because glory also resets each game. However in due course, the game will reveal how lasting glory can be gained and kept, and the most glorious player will be ultimately victorious at the end of the campaign. Seafall itself is sumptuous. There are miniature ships (one powerful warship, one fast clipper), custom dice, the usual plethora of cardboard, and pre-assembled treasure chests. Each player gets a chest to store their loot, but there are other treasure chests. Sealed ones, and multiple warnings to not open them. Intriguing. Advertisement The mechanics are complex enough to present multiple strategies (should I play the short term game, raid the island villages, and build lasting enmity, or play a longer, gentler game of trading and building?). Future games promise possession of islands (there’s a place to write my name, but no instruction to just yet), and growing warfare between players. But the first game starts as a gentle race to explore. Every time a new island was explored, we open the Captain’s Booke. The permanent marker comes out to mark off the areas we’ve explored, and like a Choose Your Own Adventure book, you are presented with an option: steal from the natives or spend time honouring their ways? Let your sailors rest, or encourage them to gather wood quickly? In so doing, we permanently unlock spaces on the board: spice farms, markets and harbours and other intriguing mysteries. Advertisement One person at the table has been playing Civ 6 hard — he told me he clocked up 22 hours over the weekend. By the end he proclaimed, satisfied: “this scratches my Civ urges.” That’s the game — the prologue game, at least. But the real game, the real joy is the name game. You get to name your leader, your port, your province, and your ships. When you hire advisors, they are yours to name. When you reach the target glory points, you get to name an island. Naming things in perpetuity is a daunting prospect. Should your names be whimsical or referential, geeky or mythical or serious? And the glory of our evolving game is that now it is ours. Advertisement Your copy of Seafall will be different to mine. Only here, with these cards, can Captain Fluffy hire Francis Drake the explorer. Only here can Lara (Croft) guide you to buried treasure, and Dupre (from Ultima) lead your military raids, or risk your lot with that madman, Ham Sandwich. I own a lot of games — a lot of games — but this game is now truly mine. How The Beginning Ends Minor spoilers follow. Advertisement The great preacher, CH Spurgeon, was exceedingly fond of cigars. One vigilant congregation member accused him of turning his cigars into an idol, a false god. The quick-witted Spurgeon replied, “Madam, I burn my idols every day.” The end of the first game ends up by directing you to rip up cards. Not just any old card, but your character card. My character card, which I’d painstakingly named Athena. But as it turns out, gods can die after all. Other cards had been ripped up in the course if this game, but this one was the hardest. One player flat-out refused to destroy his card, and left it at the bottom of his chest for next week. As you can see, when I tried to tear up the card, I could only get halfway. Actually burning the card was excruciating. Turns out, destroying what you love is hard. I love this game already.

Updated: 2012-11-02 13:59 By Lan Lan ( China Daily) A shopper inspects energy-efficient refrigerators at a department store in Zaozhuang, Shandong province. According to a survey, 87 percent of Chinese respondents said they would be willing to pay more for greener products. [Photo/China Daily] Majority of Chinese willing to pay more for greener goods, poll shows The vast majority of Chinese believe climate change is taking place and most consumers are willing to pay more for eco-friendly products to reduce its effects, a survey has found. Some 93 percent of respondents said climate change is under way, while about three out of five respondents feel they have been directly affected by it. The study of 4,169 Chinese adults was carried out from July to September by the Center for China Climate Change Communication, jointly established by Renmin University of China and non-governmental organization Oxfam. About 68.4 percent of respondents said they thought China has already suffered from the effects of climate change, while about half of respondents said it will affect people in rural areas more. About 90 percent of respondents said the government should have prime responsibility for dealing with climate change, followed by the public, media, companies and NGOs. Zheng Baowei, director of Renmin University's Research Center of Journalism and Social Development, said the government should play a dominant role in adopting measures and designing policies in line with the public's expectations and interests. However, implementation of the policies will eventually rely on public participation. More than 93.4 percent of respondents felt they have knowledge of climate change, while just 6.6 percent said they had never heard of it. About 60 percent thought climate change is mainly caused by human activities, while 33 percent considered it to be mainly caused by the environment. Sun Zhen, deputy director of the Department of Climate Change at the National Development and Reform Commission, said the data might sound satisfactory, but climate change is placing increasing pressure on China. As the world is facing more extreme weather-related events, such as hurricanes, drought and floods, the government has an obligation to clarify to what extent climate change has contributed to these, Sun said. Wang Binbin, executive director of the Center for China Climate Change Communication, said addressing climate change also calls for the public to practise low-carbon ways of living and consumption, while the good news is that more Chinese consumers are willing to pay more for a greener life. Some 87 percent of those surveyed said they were willing to pay more for greener products, while more than 34 percent said they would accept a 30 percent price rise to buy such products. The survey also showed that people aged between 18 and 24 were willing to pay more for environmentally-friendly products. More than four out of five respondents said they supported the government in setting standards for mandatory garbage separation and waste recycling, adopting greener materials for construction, and producing greener cars, even if it means higher costs. Only 34 percent of respondents said they separated their garbage. lanlan@chinadaily.com.cn

Toto Wolff thinks drivers would "lose every single race" if they were allowed to call their own strategies from the cockpit. After the Brazilian Grand Prix Lewis Hamilton said he would have liked to try a different strategy to Mercedes team-mate Nico Rosberg to try and unlock some of the pace he felt he was losing in the dirty air behind. Mercedes did not let Hamilton deviate from the three-stop strategy it put both its drivers on once Sebastian Vettel had pitted earlier than expected in the race. Mercedes boss Wolff has no problem with Hamilton questioning the team's strategy during the heat of a grand prix. "The driver in the car being emotional is understandable," Wolff said. "We hired guard dogs and we don't want to have any puppies - and we want them to be guard dogs. Sometimes it is a bit more intense but it is okay." However, he thinks the emotional state drivers find themselves in during a race is one reason strategy must always be dictated from the pit wall. "We are going to keep one strategist. If the driver in the car starts to determine strategy then he is going to lose every single race because that is not an instinct-driven decision. Your instinct might be right sometimes but if you are not having the full set of data you are going to get the majority of your races wrong so that is why we are going to keep it why it is. Not switching Hamilton's strategy nullified his challenge for victory, meaning the only real action came lower down the order. Responding to the charge Mercedes' strategy made for a boring spectacle for fans, Wolff pointed out how the team has resisted implementing team orders. "As a fan I can understand that absolutely. But there are various escalations. We could have done it like some teams have in the past of having a clear number one and a clearn number two, and the number two wouldn't come close to the other one. So we have changed that and sometimes it is difficult for us to manage letting the two fight each other and now you can even say, let's take it one step further and let the strategists play against each other but this is not where we want to go to. "Controversy within the team is detrimental and we have kept the team together, not only the drivers, the travelling team in Brackley and Brixworth because the team comes first. From a fan stand point, I can understand, and from a team standpoint I will give a boring answer that we are not going to change it."

MARK KARLIN, EDITOR OF BUZZFLASH AT TRUTHOUT As Think Progress noted, Elizabeth Warren, Democratic Party senatorial candidate in Massachusetts (for the seat once held by Ted Kennedy), got to the heart of the matter about the difference between people and corporations. Warren admonished the one-time governor of her state, Mitt Romney, that: No, Governor Romney, corporations are not people. People have hearts. They have kids. They get jobs. They get sick. They thrive. They dance. They live. They love. And they die. And that matters. That matters. That matters because we don’t run this country for corporations, we run it for people. That's cutting to the chase. It's not easy sharing the one prime time hour of a convention night with the master of crowd seduction, Bill Clinton, but Warren wooed the delegates and guests with words that spoke to the importance of individual lives over corporate institutions. She rebutted the deification of companies -- the bestowal of a corporate divinity that is at the epicenter of the Republican ticket -- over the value of hearts that beat in human souls. Ironically, the only lives that merit protection in the GOP platform are the unborn, not those who come into this world and are in need. It has become a cliché to appeal to the travails of the working family, but Warren lit a spark of truth to the reality of living on the “ragged edge” of surviving: I’m here tonight to talk about hard-working people: people who get up early, stay up late, cook dinner and help out with homework; people who can be counted on to help their kids, their parents, their neighbors, and the lady down the street whose car broke down; people who work their hearts out but are up against a hard truth--the game is rigged against them. The game is rigged by institutions that profit off the work of those who are barely able to get by. When life is monetized, when the value of an individual with a beating heart is valued as nothing more than dollar signs in the eyes of vulture capitalism, then we have lost our values. Not leaving the playing field of God to the GOP, Warren recalled: I grew up in the Methodist Church and taught Sunday school. One of my favorite passages of scripture is: “Inasmuch as ye have done it unto one of the least of these my brethren, ye have done it unto me.” Matthew 25:40. The passage teaches about God in each of us, that we are bound to each other and called to act. Not to sit, not to wait, but to act--all of us together. No, corporations don't have hearts. They should be at the service of people who do. Call it a divine spark or just the radiant human soul, Elizabeth Warren spoke to the heart of the matter: the blood and spirit of life run through the veins of people, not corporations.

Intel became the world's largest semiconductor company by revenue in 1992 when is surpassed NEC. It has held the top spot ever since, but 25 years later and as predicted Intel is now just like NEC, being replaced. The new world's largest semiconductor company is Samsung. According to the Associated Press, for the April-June quarter, Samsung earned $7.2 billion on sales of $15.8 billion. Intel earned $2.8 billion on sales of $14.8 billion, pushing it into second place overall. However, Patrick Moorhead, principal analyst with Moor Insights & Strategy, said we will likely see the two companies swapping position a few times. For example, Intel could claim back the top spot in six months as it ramps up memory production to full capacity. Samsung's rise to the top is thanks to mobile devices and memory. Consumers can't get enough of mobile gadgets, which are typically full of Samsung parts. We also all want more and more memory, so Samsung's flash memory business is looking very healthy. And it doesn't look like that demand is going to drop off anytime soon. So while we all continue to buy lots of mobile gadgets, the PC market continues its five year slump. That certainly poses a problem for Intel going forward. Even so, the former world's largest semiconductor company is still on course to post $60 billion in annual sales for the year.

Scarcely 24 hours after being fired as manager of Toronto FC, Preki insists he has no regrets about the job he did in Toronto, and that he doesn't intend to alter his highly demanding style of coaching. With Toronto languishing five points outside of the playoffs, the former U.S. international star was relieved of his duties Tuesday, along with team director of soccer Mo Johnston. Former assistant and one-time Canadian U-23 head coach Nick Dasovic was tabbed to replace Preki on an interim basis. Preki was hired last November after a successful three-year stint with Chivas USA that saw him reach the playoffs every year, yet was unable to replicate that success with Toronto. "I'm [leaving] the job with my head held high," Preki said in a telephone interview. "I had all the best of intentions and the job that I did over the past six, seven months, I really have no regrets." When asked what went wrong during his tenure, Preki hinted at a lack of support from owners Maple Leaf Sports & Entertainment, although he refused to get specific. "The last two to three months there were some really challenging and difficult circumstances," he said. "At some point down the line, I'll say more." Preki long has had a reputation as a strict disciplinarian, and with the team struggling through a 1-6-3 stretch, it was widely reported that a player mutiny had ensued. Toronto FC captain Dwayne De Rosario admitted that Preki's style grated on many players, and midfielder Julian De Guzman even went so far as to question Preki's tactical acumen. "I couldn't put my finger on the type of system or my role, what we were trying to do, it was like freestyle," de Guzman told The Toronto Sun. "We play against Cruz Azul and we're amazing, and then against D.C. [United] you're the worst thing out there. It's like a gamble going into a lot of the games." When asked to respond to the comments of his former charges, Preki said: "I don't need to elaborate on the things that De Rosario and De Guzman said. You can see the work I've done with Chivas USA. It's a couple of Canadian guys making those comments. That's all I have to say about that." There were widespread reports that Preki also had a falling out with Dasovic, with the assistant conspicuously absent from the bench the last few games. When asked if he believed he was undermined by Dasovic, Preki said: "He's in charge now. It's up to you to guess." Preki added that he plans to spend the coming weeks trying to collect his thoughts. But he also indicated that he sees no reason to change his approach to coaching, one that worked well while he was with Chivas USA. "I just think that if you come in every day and you ask for commitment and hard work, that's not too much to ask for," he said. "That's the bottom line." Jeff Carlisle covers MLS and the U.S. national team for ESPNsoccernet.

At long last, AMD has launched the second of its so-called Fusion "APUs," where APU stands for "accelerated processing unit" and refers to a single chip that hosts both a Central Processing Unit (CPU) and a Graphics Processing Unit (GPU). Anandtech is first out of the gate with benchmarks for AMD's Llano testbed notebook, and the results show that the new chip is a win for AMD in a two departments. Llano's battery life is excellent, besting nearly all comers in terms of efficiency—only AMD's "Brazos" platform, with its simple Bobcat core, beats Llano in this department. This is the first time in a long time that AMD has been competitive with Intel in mobile power draw. Llano's other big win is in graphics, about which we'll talk more in a moment. But before jumping into that discussion, we should briefly mention where Llano lags behind: the CPU. The 32nm "Stars" cores that form the CPU side of Llano are a straightforward shrink of AMD's existing and venerable Phenom architecture, with a few minor updates. As such, these cores are significantly underpowered compared to Intel's Sandy Bridge cores, and the benchmarks show it. On CPU-bound workloads, Llano gets a sound drubbing from Intel's Sandy Bridge. So the CPU side of Llano is its Achilles heel, a fact that will keep Llano confined to the role of a budget alternative to Sandy Bridge, and not a competitor. Surprises from Llano's GPU The GPU is where Llano gets interesting. In both its mobile and desktop incarnations, Llano's GPU is a DX11-class, +400-shader GPU that takes up almost half of the processor die. Given that this GPU is a real, general-purpose graphics coprocessor, this makes Llano equal parts GPU and CPU. (Compare to Intel's Sandy Bridge, where the GPU is quite a bit smaller than the CPU region.) The fact that Llano's GPU is so beefy is both a blessing and a curse. Unlike Sandy Bridge's relatively anemic GPU (which gets a huge performance boost from moving onto the processor die), Llano's GPU has so much horsepower that it's severely memory-bottlenecked in the on-die configuration. If the desktop Llano's 6550D GPU were put on a discrete graphics card with its own pool of fast GDDR, it would actually out-perform the integrated configuration. This is not something that I expected or predicted, but it makes sense. To see what I mean, check out Anand's benchmarks of Llano in a desktop configuration. When used with an overclocked memory bus (DDR-1866), Llano leaps up in the rankings and lands squarely in budget discrete GPU territory. Clearly Llano's GPU is massively memory-bound, and CPU and GPU together are suffering from a lack of memory bandwidth in the APU socket. This fact has a few interesting implications. First, it means that AMD can boost Llano's performance significantly in future versions simply by adding another dual-channel DDR3 controller and introducing a new socket. Or AMD could also push the more widespread use of higher-clocked DDR. By far the most interesting implication of the Llano results, however, is that this is a chip that would benefit massively from the addition of some kind of IBM-style pool of on-die DRAM (i.e., PS2-style scratchpad RAM). Right now, Llano's CPU and GPU are connected via an internal bus, which is great as far as it goes. But if Llano had a large enough pool of on-die memory on the same bus, it would put it into a whole new performance league. (See below.) Ultimately, Llano as it currently exists is in fine shape in the notebook segment, where it handily beats Intel's Sandy Bridge in almost every gaming benchmark (the exceptions are one or two CPU-bound titles). Despite the memory bottleneck, the GPU in Llano really delivers the gaming goods, and on a price/performance basis it sets a new standard for budget mobile gaming. Llano is so capable that it's able to compete with midrange discrete mobile graphics solutions, a fact that reinforces just how much trouble NVIDIA is in with this particular market. In Anand's desktop preview, the desktop version of Llano puts up a solid showing against Intel's Sandy Bridge, where, again, it easily bests its opponent in all but a few CPU-bound benchmarks. All told, Llano is a solid entry into the mobile market that will make a worthy budget alternative to Intel's mobile Sandy Bridge. On the desktop, Llano looks to be similarly positioned, but given that testing at most sites is still ongoing, we'll have to reserve judgment until the official launch. Postscript: possible futures for Fusion The Llano + eDRAM idea mentioned above is obviously not going to happen with Llano—the current design is transitional, and will live out its life as a budget part. But who's to say that AMD won't do something like this in a future APU? AMD has been made it clear that Llano is just a bridge design—halfway between the integrated graphics of the previous generation and the type of true heterogeneous multiprocessing that will characterize future Fusion efforts. AMD hasn't really let on what it the ultimate Fusion part will look like architecturally, but the endgame for Fusion is probably a giant pool of shader cores, a small number of CPU cores, and a big enough pool of shared, on-die memory that the CPU and GPU can cut way down on the amount of memory traffic that goes off-die. This pool of shared memory could be a wired-down section of L3 cache (IBM does this with its game console chips), or it could be a separate pool of "scratchpad memory" that the CPU and GPU have access to (IBM did this with the PS2's Emotion Engine). From the perspective of boosting graphics performance, the latter seems preferable to me, but my knowledge in this area is spotty, so more informed readers should feel free to correct me in the comments. About four years ago, when IBM first began making waves with its eDRAM efforts, the idea that Big Blue's eDRAM cells might show up on an AMD processor was commonly floated. IBM and AMD have collaborated in the past on fab technology (prior to the Globalfoundries spinoff), so the idea is by no means out of the question. IBM's POWER7 chip, a derivative of which will probably show up under the hood of the Wii U, sports a giant 32MB pool of on-die eDRAM in the form of an L3 cache. Even a fraction of that amount of memory added to Llano could cut back on a lot of off-die memory traffic and give a major leap in graphics performance.

Effect of time of eCG administration on the fate of ovarian follicle in Holstein heifers. The objective of this study was to investigate the effect of equine chorionic gonadotropin (eCG) on ovarian follicles at three stages of development (emergence, dominance and early static phases) during the first follicular wave (FFW) in Holstein heifers. Heifers (n=20) were randomly assigned into four experimental groups (n=5 in each group). Heifers received eCG (500 IU; Folligon®; Intervet, Holland; i.m) a) on the day of follicle emergence (day of ovulation; group 1), b) on the dominant phase (dominant follicle (DF): the first day in which follicle was observed at ≥10 mm; group 2, and c) on the early static phase (group 3) of the FFW. Control group heifers did not receive any treatment. Daily ultrasonography was conducted to monitor ovarian structure throughout estrous cycle. All treatment group heifers, regardless of the stage of follicle development, displayed follicle growth after eCG injection. Administration of eCG, in group 1, hastened DF detection and induced co-dominant follicles; whereas, in groups 2 and 3, it delayed DF regression, and increased cycle length compared to control. In all treatment group heifers, DF was present 84 h after eCG injection. Maximum diameter of corpus luteum was larger in eCG treated groups compared to control (P<0.05). In conclusion, depending on the time of eCG administration throughout the FFW (emergence, dominant and early static phases), co-dominancy, maintenance of DF, enhancement of follicle and corpus luteum growth and increase in estrous cycle length could be observed in Holstein heifers.

Neuroprotective Effects of Calmodulin Peptide 76‐121aa: Disruption of Calmodulin Binding to Mutant Huntingtin Abstract Huntington's disease (HD) is a neurodegenerative disease caused by mutant huntingtin protein containing an expanded polyglutamine tract, which may cause abnormal protein–protein interactions such as increased association with calmodulin (CaM). We previously demonstrated in HEK293 cells that a peptide containing amino acids 76‐121 of CaM (CaM‐peptide) interrupted the interaction between CaM and mutant huntingtin, reduced mutant huntingtin‐induced cytotoxicity and reduced transglutaminase (TG)‐modified mutant huntingtin. We now report that adeno‐associated virus (AAV)‐mediated expression of CaM‐peptide in differentiated neuroblastoma SH‐SY5Y cells, stably expressing an N‐terminal fragment of huntingtin containing 148 glutamine repeats, significantly decreases the amount of TG‐modified huntingtin and attenuates cytotoxicity. Importantly, the effect of the CaM‐peptide shows selectivity, such that total TG activity is not significantly altered by expression of CaM‐peptide nor is the activity of another CaM‐dependent enzyme, CaM kinase II. In vitro, recombinant exon 1 of huntingtin with 44 glutamines (htt‐exon1‐44Q) binds to CaM‐agarose; the addition of 10 µM of CaM‐peptide significantly decreases the interaction of htt‐exon1‐44Q and CaM but not the binding between CaM and calcineurin, another CaM‐binding protein. These data support the hypothesis that CaM regulates TG‐catalyzed modifications of mutant huntingtin and that specific and selective disruption of the CaM‐huntingtin interaction is potentially a new target for therapeutic intervention in HD. INTRODUCTION Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by chorea and cognitive disturbances (27). The gene involved in HD, interesting transcript 15 (IT15), encodes for the protein huntingtin (1). In HD, IT15 has an expanded CAG trinucleotide repeat in its first exon, resulting in a mutated form of the huntingtin protein containing an expanded polyglutamine tract in its N-terminus (34). Medium spiny neurons in the striatum are selectively vulnerable to neurodegeneration in HD (47). In HD brains, insoluble deposits that contain aminoterminal fragments of huntingtin with an expanded glutamine repeat are found in neurons (12). Huntingtin is a substrate of transglutaminase (TG), and, as the length of the glutamine repeat is increased, the protein becomes a better substrate (7,16,21,23). It has been hypothesized that TG modifies huntingtin, thereby aiding in the stabilization of monomeric huntingtin (48), and the formation and stabilization of huntingtin containing aggregates (7,17). Huntingtin has been shown to interact with many proteins, including cyclic adenosine monophosphate (cAMP) responseelement binding protein (CREB)-binding protein (CBP) (26), huntingtin-interacting protein 1 (HIP1), the spliceosome protein HYPA (18), and calmodulin (CaM) (3). It has also been reported that mutant huntingtin containing an expanded glutamine repeat interacts with CaM with a higher affinity than wild-type huntingtin (3). Interestingly, CaM, a calcium (Ca 2+ ) binding protein that activates many enzymes, also interacts with TG and increases TG activity (36). We previously demonstrated that CaM colocalizes with TG2 and huntingtin protein in intranuclear inclusions in the HD cortex (49). Furthermore, inhibition of CaM results in decreased TG-catalyzed modifications of huntingtin in cells expressing mutant huntingtin and TG2 (49). TGs (EC2.3.2.13) are a family of enzymes that catalyze a calcium-dependent acyl-transfer reaction between the g-carboxy group of a protein-bound glutamine and either the e-amino group of a protein-bound lysine or a primary amine, resulting in the formation of an e-(g-glutamyl) lysine bond (15). TG mRNA, protein levels and activity are all elevated in an HD brain (23,25,50). TG-catalyzed e-(g-glutamyl) lysine bonds and TG2 both colocalize with huntingtin in intranuclear inclusions in HD brain (48). Treatment of HD-transgenic mice with cystamine, a TG inhibitor, or knocking out TG2 increases survival (2,11,28,46). Similarly, treating cells that express N-terminal mutant huntingtin and TG2 with cystamine increases cell survival and decreases the amount of TG-catalyzed modifications of huntingtin (50). In HD, mutant huntingtin may alter the normal interaction between CaM and TG. One result could be an increased interaction between CaM and huntingtin resulting in a subsequent increase in TG activity. Another possible result could be sequestration of CaM, thereby inhibiting its biochemical functions such as activation of nitric oxide synthase (NOS), an enzyme which has been shown to have decreased activity in an HD mouse model (8). Previously, in HEK-293 cells transiently expressing N-terminal huntingtin with an expanded polyglutamine repeat and TG2, we found that a peptide containing amino acids 76-121 of CaM (CaM-peptide) and encoded by a fragment of exons 4 and 5 of the CaM gene was able to decrease the TG-catalyzed modifications of mutant huntingtin, the cytotoxicity induced by mutant huntingtin and the binding of mutant huntingtin to CaM (13). The goal of the current study was to examine the effect of adeno-associated viral (AAV) mediatedexpression of that peptide (CaM-peptide) in differentiated neuroblastoma SH-SY5Y cells that stably express an N-terminal (63 amino acids in length) fragment of huntingtin containing 148 glutamines (SH-SY5Y-htt-N63-148Q cells). Previous studies demonstrated that a fragment of CaM from amino acid 78 to 148 was able to inhibit CaM-induced stimulation of phosphodiesterase and myosin light chain kinase (MLCK) (29,30). Therefore, we hypothesized that CaM-peptide would compete with endogenous fulllength CaM for binding to mutant huntingtin, resulting in inhibition of the endogenous CaM-mutant huntingtin interaction. We examined the effects that CaM-peptide had on TG-catalyzed modifications of mutant huntingtin, cytotoxicity associated with mutant huntingtin, total TG activity and binding of CaM to exon 1 of mutant huntingtin. AAV vector construction A fragment of exons 4 and 5 of the CaM gene, encoding amino acids 76-121 of CaM . Cell lysates were mixed with (g-32 P) adenosine triphosphate (ATP) (at 3000 Ci/mmol, 10 mCi/mL), activation buffer containing 5 mM CaCl2 and 5 mM calmodulin or control buffer containing 5 mM EGTA, with and without biotinylated CaM kinase II substrate. After incubation at 30°C for 2 minutes, the reaction was terminated by adding 7.5 M guanidine hydrochloride and spotted to a streptavidin-impregnated membrane. Membranes were washed and retained radioactivity was quantitated by liquid scintillation counting (Beckman, Fullerton, CA, USA). Radioactive counts were converted to endogenous CaM kinase II activity in the sample by the following formula: Enzyme activity in pmol min g of protein After addition of the lysate supernatant, the column was then washed with 12 column volumes of PBS pH 7.4, followed by elution of the fusion protein with two column volumes of PBS with 10 mM maltose. The fusion protein was further purified by incubating with Ni-NTA agarose (Qiagen, Valencia, CA, USA) in PBS supplemented with 10 mM imidazole with rocking for 2 h at 4°C. The resin was then washed three times with PBS supplemented with 20 mM imidazole, and fusion protein was eluted with six resin volumes of PBS supplemented with 250 mM imidazole. Purified fusion protein was analyzed by SDS-polyacrylamide gel electrophoresis (PAGE) and visualized by Coomassie staining. In vitro mutant huntingtin-CaM binding Binding of purified mutant huntingtin to calmodulin was studied Statistics All statistical analyses were performed using GB Stat software (Dynamic Microsystems, Inc., Silver Spring, MD, USA). Data are expressed as means Ϯ standard error of the mean (SEM). Analysis of Variance (ANOVA) or a two-tailed Student's t-test was used to analyze the data. Post-hoc comparisons were conducted using a Newman-Keuls test. Figure 2B). However, these values were lower than previously measured for this MOI, perhaps caused by conditions associated with neuronal differentiation. AAV-mediated expression of CaM-peptide decreases TG-catalyzed modifications of mutant huntingtin in SH-SY5Y-htt-N63-148Q cells With the cell and viral system now defined, we determined the effect of viral-mediated expression of CaM-peptide in differentiated SHSY5Y-htt-N63-148Q cells on TG-catalyzed modifications of N-terminal mutant huntingtin. Cells were differentiated, infected with either AAV-CaM-peptide + GFP, AAV-scram-CaM-peptide + GFP or AAV-GFP (MOI = 50), and forty-eight hours post-infection cells were assayed for TG-modified N-terminal mutant huntingtin. SHSY5Y-htt-N63-148Q cells expressing CaM-peptide had a significantly lower amount of TG-modified N-terminal huntingtin compared with cells expressing scram-CaM-peptide or only GFP (Figure 3). Effect of AAV-mediated expression of CaM-peptide on total TG activity in neuroblastoma cell lines that stably express N-terminal mutant huntingtin Next, we examined the effect of expression of the CaM-peptide on total TG activity in differentiated non-htt-SHSY5Y and SHSY5Yhtt-N63-148Q cells. Cells were infected with either AAV-CaMpeptide + GFP, AAV-scram-CaM-peptide + GFP or AAV-GFP (MOI = 50), and harvested forty-eight hours post-infection. TG activity was measured ex vivo based on the incorporation of 5-(biotinamido)pentylamine into the N,N′-dimethylcasein substrate coated onto micro-plates. There were no significant differences in total TG activity between the different infections in either non-htt-SHSY5Y cells or SHSY5Yhtt-N63-148Q cells ( Figure 5A). There were small but insignificant increases in total TG activity in SHSY5Y-htt-N63-148Q cells expressing scram-CaM-peptide or only GFP, compared with nonhtt-SHSY5Y cells expressing either GFP only, scram-CaM-peptide or CaM-peptide ( Figure 5A). To determine whether cell lysis had an effect on enzyme activity, we measured total TG activity in situ. Non-htt-SHSY5Y and SHSY5Y-htt-N63-148Q cells were infected with one of the various AAV, and 42 h post-infection, were treated with 5-(biotinamido)pentylamine. Six hours later, cells were harvested and the cell lysates were applied to micro-plates coated with anti-e-(g-glutamyl) lysine (81D4) antibody in order to capture ᭤ proteins that were modified by TG in situ. TG-catalyzed incorporation of 5-(biotinamido)pentylamine into cellular proteins was then determined by incubation with streptavidin-HRP. Similar to the ex vivo assay, there was no significant difference in total TG activity between the various infections in SHSY5Y-htt-N63-148Q cells ( Figure 5B). Similarly, there also was no difference in total TG activity in the various infections in non-htt-SHSY5Y cells. However, there was a significant decrease in total TG activity in non-htt-SHSY5Y cells compared with SHSY5Y-htt-N63-148Q cells expressing scram-CaM-peptide or only GFP. Total TG activity in non-htt-SHSY5Y cells was not significantly different from total TG activity in SHSY5Y-htt-N63-148Q cells expressing CaM-peptide ( Figure 5B). CaM-peptide does not significantly affect CaM kinase II activity To determine if expression of CaM-peptide has effects on the activity of other CaM-dependent enzymes, we examined whether expression of CaM-peptide affects CaM-dependent protein kinase II (CaM kinase II) activity. SH-SY5Y cells were transfected with vector, htt-N63-148Q, CaM-peptide or a combination of htt-N63-148Q and CaM-peptide. We found no significant differences in CaM kinase II activity among the various transfections ( Figure 6). Interestingly, expression of CaM-peptide alone resulted in a small but insignificant increase in CaM kinase II activity compared with all other transfections. We also examined the activity of CaM kinase II without the addition of exogenous CaM (addition of exogenous CaM is recommended, as described in the manufacturer's protocol). There was no significant effect of CaM-peptide under these assay conditions either ( Figure 6). CaM-peptide inhibits binding of N-terminal mutant huntingtin with an expanded polyglutamine repeat and CaM Thus far, all the experiments performed to examine the effects of CaM-peptide were done in cells where other endogenous proteins could play a role in mediating the action of CaM-peptide. Therefore, an in vitro assay was used to determine if CaM-peptide could directly interfere with the interaction of N-terminal mutant huntingtin and CaM. CaM-agarose was used to immunoprecipitate There was a small but insignificant increase in total ex vivo TG activity in SHSY5Y-htt-N63-148Q cells expressing scram-CaM-peptide or GFP compared with non-htt-SHSY5Y cells and SHSY5Y-htt-N63-148Q cells expressing CaM-peptide. B. Similarly there were no significant differences in total in situ TG activity in non-htt-SHSY5Y cells expressing CaM-peptide, scram-CaM-peptide or GFP. However, total in situ TG activity was significantly less in non-htt-SHSY5Y cells compared with SHSY5Y-N63-htt-148Q cells expressing scram-CaM-peptide or GFP. But, total in situ TG activity in non-htt-SH-SY5Y cells was not significantly different from total TG activity in SH-SY5Y-htt-N63-148Q cells expressing recombinant purified huntingtin exon 1 with an expanded polyglutamine repeat (htt-exon1-44Q) in the absence and presence of varying concentrations of CaM-peptide. The amount of CaMbound htt-exon1-44Q was significantly lower when 10 mM of CaM-peptide was present than when CaM-peptide was absent ( Figure 7A,B). To determine if CaM-peptide would nonspecifically inhibit the interaction of CaM with any CaM-binding protein, we incubated calcineurin with CaM-agarose in the absence and presence of 10 mM of CaM-peptide. The presence of 10 mM of CaM-peptide did not affect the binding of CaM with calcineurin ( Figure 7C,D). Next, to investigate the potential site of interaction of CaM-peptide, the CaM antagonist, W-5, was used along with CaM-peptide. W-5 alone did not affect the amount of CaM-bound htt-exon1-44Q, but once again the amount of CaM-bound htt-exon1-44Q was significantly lower when 10 mM of CaM-peptide was present. However, the amount of CaM-bound htt-exon1-44Q was significantly increased when 664 mM W-5 is present along with 10 mM of CaM-peptide (Figure 8). DISCUSSION The disease-causing mutation in HD is an expanded polyglutamine repeat in huntingtin protein. This mutant form of huntingtin becomes a better substrate for TG (6,16,21,23,50) and has increased interaction with CaM (3,49). Interestingly, TG is positively regulated by CaM (5,36,49). Therefore, we hypothesized that the interactions between mutant huntingtin, CaM and TG may be deleterious. Previously, we found in HEK-293 cells transiently expressing N-terminal mutant huntingtin, TG2 and a peptide containing amino acids 76-121 of CaM CaM-peptide that TG-catalyzed modifications of mutant huntingtin were reduced, cytotoxicity associated with mutant huntingtin protein was reduced and carbacol-stimulated calcium release was normalized (13). In order to test the effects of CaM-peptide in an HD transgenic mouse model, we created an AAV which mediates the expression of CaMpeptide. Before proceeding to an HD animal model, we first tested the effects of AAV-mediated expression of CaM-peptide in a neuronal HD cell model as neurons are affected in HD and the effects of CaM-peptide have only been tested in kidney cells. We created neuroblastoma SH-SY5Y cells which stably express N-terminal mutant huntingtin and endogenously express TG 2 (SHSY5Y-htt-N63-148-Q cells; Figure 2A) and examined the effect of AAVmediated expression of CaM-peptide on TG-activity and mutant huntingtin-associated neurotoxicity. Furthermore, we induced differentiation of SHSY5Y cells prior to testing the effects of the CaM peptide to increase the levels of TG expressed in the cells and to acquire a neuronal phenotype, both effects producing a model more closely resembling cells that degenerate in HD. AAV-mediated expression of CaM-peptide was sufficient to result in effects in SHSY5Y-htt-N63-148-Q cells similar to effects previously seen in HEK-293 cells. TG-catalyzed modifications of mutant huntingtin and cytotoxicity were attenuated in SHSY5Yhtt-N63-148Q cells expressing CaM-peptide compared with SHSY5Y-htt-N63-148Q cells expressing scram-CaM-peptide or GFP. These findings make it plausible that AAV-mediated expression of CaM-peptide could potentially have beneficial effects in an HD transgenic mouse model. CaM-peptide was able to attenuate TG-catalyzed modifications to mutant huntingtin, but it was unclear whether this effect was specific to TG-catalyzed modifications of mutant huntingtin or if it was a non-specific effect on TG-catalyzed modifications of all TG substrates. We used two different approaches to measure total TG activity, an ex vivo approach in which total TG activity is measured in lysed cells, and an in situ approach in which an exogenous substrate is added to the media, taken up by cells and then modified by TG in situ. Using both the ex vivo and the in situ approach, TG activity was not significantly affected by expression of CaM-peptide in either SHSY5Y cells not expressing mutant huntingtin (non-htt-SHSY5Y) or in SHSY5Y-htt-N63-148Q cells. TG activity was significantly increased in SHSY5Yhtt-N63-148Q cells expressing scram-CaM-peptide or GFP compared with non-htt-SHSY5Y cells as measured with the in situ assay. This is similar to the disease state in which there is elevated TG activity in the brains of HD patients compared with control subjects (23,25). However, TG activity in SHSY5Y-htt-N63-148Q cells expressing CaM-peptide was not significantly different from non-htt-SHSY5Y cells or from SHSY5Yhtt-N63-148Q cells expressing scram-CaM-peptide or GFP. The results suggest that CaM-peptide does not affect TG activity in cells without mutant huntingtin expression, further indicating that the effects of CaM-peptide are restricted to the site of interaction between TG and mutant huntingtin and therefore does not significantly affect total TG activity. Based on the total TG activity assays, it appeared as though CaM-peptide specifically alters TG activity associated with mutant huntingtin but not total TG activity. However, it was unclear whether CaM-peptide also alters the activity of other CaMdependent enzymes. This was important to investigate as not all CaM-dependent enzymes may have increased activity in HD like TG, or may not even be altered or involved in HD. TG protein levels and activity are elevated in human HD brains (24,25) and there is increased TG activity as well as immunoreactivity in R6/2 HD transgenic mouse brains (11). In contrast to TG, CaM kinase II protein levels are decreased in R6/2 HD transgenic mouse brains (10), suggesting that there may be a subsequent decrease in CaM kinase II activity. However, we found that in SHSY5Y cells trans-fected with mutant huntingtin, there were no significant differences in CaM kinase II activity compared with control cells transfected with vector. This suggests that CaM kinase II activity may not be altered in HD as TG activity is. It is also important to determine whether expression of CaM-peptide would alter CaM kinase II activity. We found that expression of CaM-peptide did not significantly alter CaM kinase II activity in the HD-model cells or in control cells compared with cells not expressing CaM-peptide, suggesting that CaM-peptide does not alter the activity of other CaM-dependent enzymes. Collectively, these data suggest that CaM-peptide may specifically affect the CaM-mutant huntingtin interaction, thereby primarily altering TG-catalyzed modifications of mutant huntingtin. As all of the previously observed effects of CaM-peptide have been in HD cell models, we used a cell-free in vitro assay to determine if there is a direct interaction between mutant huntingtin and CaM, and whether the CaM-peptide could interrupt the interaction. When purified recombinant huntingtin exon 1 with an expanded polyglutamine repeat was incubated with CaM-agarose, we were able to detect a direct interaction between the two proteins. This result differs from previous work in which an 125 I-CaM overlay experiment was performed with purified rat huntingtin and 125 I-CaM failed to bind huntingtin, suggesting that huntingtin and CaM did not bind directly (3). Differences in experimental design could account for the different outcomes. In comparison to the previous study that used full-length, wild-type huntingtin purified from rat brain, we used recombinant huntingtin consisting of exon 1 and having an expanded polyglutamine repeat containing 44 glutamines (htt-exon1-44Q). One possibility is that the polyglutamine expansion in the mutant form of huntingtin increases its affinity for CaM, allowing huntingtin to interact with CaM directly. Another possibility is that the exon 1 fragment of huntingtin has an altered conformation in which the CaM-binding region may be exposed, where otherwise it is masked in the full-length huntingtin structure. Furthermore, the wild-type huntingtin protein sample was resolved by SDS-PAGE and transferred to a membrane which was incubated with 125 I-CaM. It has been shown that some proteins are unable to renature upon transfer to a membrane (4). Possibly, the CaM-binding domains of the 350 kDa huntingtin protein failed to renature on the membrane. We performed our CaM-binding experiments by incubating the htt-exon1-44Q protein sample with CaM-agarose, allowing huntingtin to be in a native state. Lastly, the relative protein concentrations used in the previous experiments may be problematic. In the previous 125 I-CaM overlay experiments, 125 I-CaM failed to bind purified rat huntingtin but bound the positive control, calcineurin. However, only 150 ng (0.43 pmoles) of purified rat huntingtin was used but 500 ng (6.25 pmoles) of calcineurin was used. Calcineurin is one of the highest affinity CaMbinding proteins examined to date (having a Kd = 28 pmols for binding of calcineurin to calcium-saturated CaM) (37). Therefore, it is likely that huntingtin has a lower affinity for CaM compared with calcineurin. In the previous study, an interaction between huntingtin and CaM may not have been detected simply because of the problem that there was not enough huntingtin present. In this study, After a direct interaction between htt-exon1-44Q and CaM was established, we found that 10 mM of CaM-peptide was able to significantly inhibit the interaction between CaM and htt-exon1-44Q. The peptide concentration of 10 mM that was needed to inhibit CaM-mutant huntingtin binding is similar to concentrations required for other synthetic peptides to inhibit protein-protein interactions (14). The presence of W-5 did not affect the interaction between htt-exon1-44Q and CaM. These data suggest that in our previous study, the decreased TG-catalyzed modifications of huntingtin we observed when inhibiting CaM with W-5 (49) was most likely caused by inhibition of CaM activity and not caused by inhibiting the binding of CaM to mutant huntingtin. Furthermore, the presence of 664 mM W-5, but not lower concentrations (66 mM, 210 mM), attenuated the effect of 10 mM CaM-peptide, i.e. to inhibit CaM-mutant huntingtin binding. However, the amount of CaM-bound htt-exon1-44Q was still significantly less than when CaM-peptide was not present. This suggests that CaM-peptide may bind CaM at the site of interaction of W-5, but that CaM-peptide has a higher affinity necessitating a high concentration of W-5 (half a log more than the IC 50 of 210 mM) (20,40) to inhibit binding of CaM-peptide to CaM. Lastly, the lack of an effect of CaM-peptide on the interaction of CaM and calcineurin suggests that CaMpeptide may act directly on CaM and mutant huntingtin and not on other proteins that interact with CaM. As calcineurin has such a high affinity for CaM, the effect of CaM-peptide on the interactions of CaM and other CaM-binding proteins should be examined. However, the expression of the CaM-peptide reduced cytotoxicity in both the neuronal cell model and in a kidney cell model, which suggest that the CaM-peptide is not likely to interfere with crucial interactions of CaM with other proteins. We previously demonstrated that CaM is associated with the aggregates of mutant huntingtin protein (49). Other lines of evidence also support a role for CaM in HD. The CaM binding protein, PEP-19, which inhibits calcium-CaM signaling (38,39), has been shown to be decreased in HD brain regions that are vulnerable to degeneration (45). This decreased the inhibition of CaM, combined with the close proximity of TG and CaM (caused by the interaction of mutant huntingtin with both proteins) may contribute to CaMmediated over-stimulation of TG. It has been shown that TG activity is increased in HD brains (23,25). Increased TG activity can result in increased modifications and stabilization of aggregated and monomeric mutant huntingtin as well as oligomers of mutant huntingtin fragments. The binding of CaM to exon 1 of mutant huntingtin may result in the inhibition of the normal biochemical functions of CaM such as activating NOS. It has been shown that in R6/2 HD transgenic mice, NOS activity is reduced and NOS inhibition accelerates behavioral deficits (9). There are abnormally high levels of cytosolic calcium in HD transgenic mice (43), and mitochondria from HD patients display abnormal calcium homeostasis (33). Furthermore, huntingtin with an expanded glutamine repeat increases inositol 1,4,5-trisphosphate receptor-mediated calcium release (41)(42)(43). These deleterious effects on calcium homeostasis suggest that returning the functioning of CaM toward normal would be beneficial. The ability of the CaM peptide to inhibit the binding of CaM and N-terminal mutant huntingtin could result in increased functioning of CaM, assuaging the disturbed calcium homeostasis as previously shown in HEK-293 cells (13). Our current findings illustrate that the expression of CaMpeptide in a neuronal HD cell model results in decreased TG-modifications of mutant huntingtin and decreased cytotoxicity. Our in vitro findings support the hypothesis that expression of a small fragment of CaM can regulate the binding of CaM and mutant huntingtin, and taken together with the cell culture data, suggest that interrupting this binding provides neuroprotective effects against the detrimental consequences associated with mutant huntingtin expression. Importantly, the CaM-peptide shows selective effects on TG-mediated modifications to mutant huntingtin and do not affect any other CaM-regulated enzymes or TG activity in general. The AAV-expressed CaM-peptide will next be tested in an HD transgenic mouse model. Inhibiting the interaction of CaM with mutant huntingtin protein is a potential target for therapeutic intervention in HD.

The president of Checker Yellow Cabs says he’s pleased police appear to be paying closer attention to incidents of abuse against cabbies after a woman was charged with assault for allegedly throwing a bag of vomit on one of his drivers. Kurt Enders said he believes drivers are now also bringing these issues “to the forefront, because things are starting to get done and charges are being laid.” He added passengers do get sick in cars, probably every weekend, but this is the first time he’s heard of a bag of vomit being thrown at one of his drivers, calling this “an extreme case.” The assault charge was laid after the driver came forward at an open house attended by taxi drivers and police officers. Police learned the incident took place around 3:20 a.m. on Aug. 23, when the taxi went to pick up a woman near 1st Street and 4th Avenue S.E. in downtown Calgary, and drove her to a home in the northwest Sandstone Valley area. On the way there, the passenger threw up in the vehicle. The cabbie gave her a bag, then continued driving. Once they arrived at the home, the passenger continued vomiting on the exterior of the vehicle. When the driver requested a cleanup fee, the passenger became abusive and threw the bag of vomit on him, covering his clothes, phone, car seat and floor mats, police said. “She became upset and agitated,” said Det. Matt Baker. “She was intoxicated by alcohol and wasn’t prepared to pay the cleanup fee.” The passenger’s family later paid both the cleanup fee and fare. Selena Narayan-Lachapelle, 33, of Calgary, was charged with one count of common assault, and is expected to appear in court on Oct. 14. Baker said the driver reported the incident to police at an Aug. 25 open house, which was held in response to the incidents of abuse against taxi drivers, including one in which a passenger was reportedly caught on camera screaming racial slurs and profanities at a taxi driver and a similar case in which a woman was charged with uttering threats to cause death or bodily harm against a driver that have recently been made public. “The difference with this (most recent) one and the others is the assault is minor in nature and not racially motivated,” he added. Police also recently charged a man in connection with two taxi carjacking incidents and charged a man after he allegedly slapped a taxi driver’s face and tore off the vehicle’s dashboard camera. Baker said he hopes to hold another similar open house where cabbies can open up about their concerns, adding he encourages drivers to reports all incidents of abuse or assault to police. Enders said sometimes it comes down to the public being respectful of drivers and their workplaces. “I think people have to realize this is the driver’s office,” he said. “You wouldn’t want me coming to your office disrespecting you in your office.”

DALLAS -- Dallas Mavericks owner Mark Cuban lambasted the NBA on Wednesday for allowing the league-owned New Orleans Hornets to complete a trade with the Sacramento Kings in which the financially troubled franchise will absorb salary and send an undisclosed amount of cash to the Kings. New Orleans sent guard Marcus Thornton, who is earning $762,195, plus cash to Sacramento for forward Carl Landry, who is earning $3 million. The Hornets, who are over the salary cap, were able to fit Landry into a trade exception. The difference in salary is $2.24 million, of which the Hornets will be responsible for the prorated amount for the remainder of the season. "If New Orleans is taking back $2 million and the team is losing money and I own 1/29th of it, I'm going to go against the grain and say that's just wrong," Cuban said prior to the Mavericks' home game against the Utah Jazz. "There's no way, with their payroll, having to dump salary before they were sold to us [NBA owners]; now they can take on more salary while they're losing money. That's just wrong every which way." The NBA -- Cuban and 28 other owners -- took over ownership of the Hornets from George Shinn on Dec. 6. The league funds the organization and set an operating budget. Cuban said he never anticipated the Hornets to be in a position of taking on salary. "I don't have a problem if they go dollar-for-dollar, great, more power to them," Cuban said. "You could see if it was like a marquee guy and he's going to bring in lots of dollars. No disrespect to Carl Landry, but I don't see that's the way it works. It's just wrong. I'm one of the owners. The league is supposed to just give them a budget and it never dawned on me that the budget would say you can spend more money to bring in players." The Mavs and Hornets are Southwest Division rivals and split two heated games earlier in the season. It is possible they could meet in the first round of the playoffs. Cuban wouldn't acknowledge if the Mavs had interest in acquiring the 6-foot-8 power forward, who is in the final year of his contract. Cuban said plenty of teams did have interest in Landry, though few are willing to take back salary, making the Hornets' deal the sweetest for a struggling Sacramento franchise. "That's the whole point," Cuban said. "Other teams have interest in him, but not a lot of teams are going to take back money. If it's a better deal, great. But the dollars should add up." Cuban launched the most pointed criticism toward the league since it took over ownership. Los Angeles Lakers coach Phil Jackson has publicly questioned the wisdom of the league's owning the Hornets, but has not criticized the league as firmly. "All I know is if most of the owners in this league can't take back salary in a deal," Cuban said, "the Hornets shouldn't be allowed to either." Jeff Caplan covers the Mavericks for ESPNDallas.com.

CANBERRA (Reuters) - It seemed unbelievable when bids to buy a heartbroken man’s life in Australia reached A$2.2 million (US$2.1 million) — and it was, with the bemused seller aware his life was only worth a quarter of that amount. Ian Usher poses on a beach at Lancelin, about 130 km (81 miles) north of Perth in this undated handout photo made available to Reuters June 18, 2008. When Usher's partner of 12 years left him broken-hearted, he knew he needed a drastic change so decided to auction his life on eBay with the package including his house, job, car, motorbike, clothes and even friends. REUTERS/Handout Ian Usher, 44, announced in March he was auctioning his life on eBay with the package including his A$420,000 three-bedroom house in Perth, Western Australia, a trial for his job at a rug store, his car, motorbike, clothes and even friends. His decision to sell his life followed the break-up of his five-year marriage and 12-year relationship with Laura with whom he had built the house. Usher, originally from County Durham in Britain before moving to Perth in 2001, said he hoped to raise up to A$500,000 to fund a new life but on the first day of the week-long auction, bids skyrocketed to A$2.2 million. But Usher knew his life was not worth that and was quick to realize there was a glitch in the system with auction Web site eBay allowing offers from non-registered bidders which took a day to sort out. “Apologies to all, but I guess there are a lot of bored idiots out there,” Usher said in a statement e-mailed to Reuters that was to be posted on his website www.alife4sale.com. “Anyway after a long day on the computer, I have decided to pull all bids back as far as the first registered bidder, and the price is back to A$155,000 as I write this ... we are back in the land of common sense and reality, so it’s over to you.” After 21 bids the amount had risen to A$245,100. A spokeswoman for eBay, Sian Kennedy, said Usher had to verify all the bidders before the auction to check they were genuine buyers and he could delete any he believed were hoaxes. She said this was his responsibility as the bids were not binding. Usher’s life has come under the real estate section on eBay as his house is the main asset in the sale. “The real estate category on eBay is a non-binding section because of the real estate laws in Australia. You need a special license to sell real estate,” said Kennedy. “You need to get in contact with him and he has to verify you are a genuine bidder before you can bid. If he doesn’t think you are genuine he can remove your bid.” Kennedy said Usher is not the first person to put his life up for sale but could be the first to offer it in this package. Australian philosophy student Nicael Holt, 24, offered his life to the highest bidder last year in a protest about mass consumerism. Slideshow (2 Images) American John Freyer started All My Life For Sale (www.allmylifeforsale.com) in 2001 and sold everything he owned on eBay, later visiting the people who bought his things. Adam Burtle, a 20-year-old U.S. university student, offered his soul for sale on eBay in 2001, with bidding hitting $400 before eBay called it off, saying there had to be something tangible to sell. Burtle later admitted he was a bored geek. Usher’s auction closes at noon on June 29.

Distribution, diversity and functional dissociation of the mac genes in marine biofilms Abstract Bacteria produce metamorphosis-associated contractile (MAC) structures to induce larval metamorphosis in Hydroides elegans. The distribution and diversity of mac gene homologs in marine environments are largely unexplored. In the present study mac genes were examined in marine environments by analyzing 101 biofilm and 91 seawater metagenomes. There were more mac genes in biofilms than in seawater, and substratum type, location, or sampling time did not affect the mac genes in biofilms. The mac gene clusters were highly diverse and often incomplete while the three MAC components co-occurred with other genes of different functions. Genomic analysis of four Pseudoalteromonas and two Streptomyces strains revealed the mac genes transfers among different microbial taxa. It is proposed that mac genes are more specific to biofilms; gene transfer among different microbial taxa has led to highly diverse mac gene clusters; and in most cases, the three MAC components function individually rather than forming a complex.

One question more than a few people have asked me is if Luke Kuechly could possibly play OLB, specifically SAM. Initially I wasn’t so sure. His Combine workout opened a lot of eyes so I went back to the tape to see if my take on this had changed. I popped in the BC/Miami game. Here are some notes I took: Kuechly — Read end around to Miller and got him for loss. Took a good angle on the play. When Miller tried to put on a move, Luke was able to react and still make the stop. Smart, patient player. Moves well laterally. Attacks upfield when he sees the ball and can get to it. Sometimes was lined up toward the outside. Will fight to shed blocks. Tackled RB after short catch over the middle. Great vision. Plays under control so that when he finds the football he can go get it. Flew out to the flat and slammed the FB down hard after a short catch. Almost picked off pass to Streeter on a deep seam route. PBU. Slammed down TE after short catch over the middle. Showed good closing speed when flying over to slam down a RB after short catch. Deflected a pass over the middle by skying for the ball. Deflected pass over the middle going to Streeter. Tommy was able to catch the deflection and got 8 yds on the play. The Streeter PBU was really impressive. Kuechly ran downfield 30 or so yards with the WR and was in perfect position. The ball was underthrown and he made a good stab at picking it off, but just couldn’t hold on. Streeter ran well at the Combine so this isn’t a case of Luke staying with a lumbering player. He had to go all out to be in the right position on that play. I do think Kuechly could play SAM in our system. The key to that is alignment. The Wide 9 has the DEs out wide and the OLBs off the ball and more to the middle of the field. The SAM is in the RG/RT area, but a couple of yards back. In the old system, the SAM would be up on the LOS and over the TE. He would be more of an edge player. The x-factor here is what Juan Castillo wants to do with SAM. Last year he hoped Jamar Chaney would be a really coverage coverage LB who could handle RBs and TEs out in space. When Chaney moved to the middle, Juan switched up what he wanted out of Moise Fokou and Akeem Jordan. They were more focused on run defense. If Juan wants to go back to a coverage guy, Kuechly would not fit as well. He’s good in zone and when sitting back and reading plays in front of him. Kuechly isn’t nearly as effective at running with a RB or TE out in the flat and reacting to the moves put on by the player. I would certainly prefer Luke to stay at MLB, but it is interesting to at least consider the option of playing him at SAM. There is no prospect in this draft or in FA that is a perfect SAM target for us. The most intriguing scenario is for the Eagles to sign David Hawthorne and then draft Luke Kuechly and put one at MLB and the other at SAM. You could figure out which combination worked best and then go with that. Hawthorne played WLB in Seattle in the 2010 season. He’s got starting experience at OLB. Kuechly has the better SAM frame at 6’3, 242. He was mostly a MLB in college, but did play WLB for part of his Freshman season. Kuechly played Safety back in HS. I truly doubt the Eagles go this way at LB. Adding a key FA LB and then using a Top 15 pick on a LB would be a huge change for them. Expect one or the other. If they did want to be aggressive, the team could add both guys and I think they could make it work. * * * * * Today the Eagles added LB Monte Simmons, a Practice Squad player from SF. This isn’t a move to get excited about, but Simmons is an interesting guy. At Kent State he racked up 21.5 sacks and 6 FFs. He is only 6’1, 234 so that sure doesn’t sound like DE size, even in the Wide 9. Most likely he’s here to compete at SAM. Simmons had a strong showing at his Pro Day last spring and has the athleticism to play in the NFL. I’ll have to go back and find some Kent State tape to watch and get a feel for his game. Not a big deal, but with our LB situation, all competition is welcome. * * * * * NFL Gimpy has up his new MAQB column. The Saints could be in for a big tumble. They have several key FAs who could leave and will likely lose at least one draft pick this year. They don’t have the cap space to just sign replacements. And losing Sean Payton for a month or two (or more?) could really hurt them. Ouch. For those interested in hearing Adam Caplan’s show from Saturday, WCHE has a podcast up. Adam moves at a quick pace and covers a lot of NFL ground. * * * * * Tags and new deals flying around the NFL today. I’ll take all of this in and then address it after coming up with a genius conclusion.

A Hybrid Asymmetric Integer-Only Quantization Method of Neural Networks for Efficient Inference The demand for adopting neural networks in resource-constrained embedded devices is continuously increasing. Quantization is one of the most promising solutions to reduce computational cost and memory storage on embedded devices. In order to reduce the complexity of deploying neural networks on Integer-only hardware, most of the current quantization methods use a symmetric quantization mapping strategy. However, the robustness and generalization of this quantization mapping strategy are poor. It is difficult for the quantized model to meet the accuracy requirements, especially for complicated tasks with higher accuracy requirements. In this paper, an efficient hybrid asymmetric Integer-only quantization method for different types of neural network layers is proposed. The proposed method can resolve the contradiction between the quantization accuracy and the ease of implementation, and balance the trade-off between clipping range and quantization resolution, and thus improve the accuracy of the quantized neural network. The results show that compared with the traditional symmetric quantization method, the accuracy of the proposed method can be improved up to 2.02% for classification models and up to 5.52% for the Yolo-v3 tiny target detection model, enabling the neural network to be easily deployed and implemented on embedded devices.

PHILADELPHIA (Reuters) - A U.S. judge on Monday sentenced an American woman who called herself Jihad Jane to 10 years in prison - at least a decade less than prosecutors had sought for her role in a failed plot to kill a Swedish artist who had depicted the head of the Muslim Prophet Mohammad on a dog. Colleen R. LaRose, 50, who converted to Islam online and has maintained her faith, was given credit for the four years she has already served. LaRose, who pleaded guilty to following orders in 2009 from alleged al Qaeda operatives, could have received a life sentence. “It’s a just and reasonable sentence,” her attorney, Mark Wilson, told reporters after the hearing. “She’s pleased. Ten years is about what we were hoping for all along.” U.S. District Judge Petrese Tucker called LaRose’s crimes “gravely serious,” adding: “The court has no doubt that, given the opportunity, Ms. LaRose would have completed the mission.” Tucker also cited the significant cooperation LaRose has given the Federal Bureau of Investigation in other terrorism cases since her 2009 arrest, as well as the sexual and other abuse she suffered as a child. That abuse was chronicled in a 2011 Reuters investigative series. LaRose, who used the name Jihad Jane as she became involved in the Muslim online community, traveled to Europe in 2009 intending to participate in a militant plot to shoot artist Lars Vilks in the chest six times. But LaRose became impatient with the men who lured her to Europe and she gave up after six weeks and returned to Philadelphia, where she was arrested. At Monday’s hearing, LaRose apologized for blindly following the instructions of her handlers. “I was in a trance and I couldn’t see anything else,” she said. “I don’t want to be in jihad no more.” Assistant U.S. Attorney Jennifer Arbittier Williams had sought “decades behind bars” for LaRose, arguing that despite her extensive cooperation, she still was a danger to society. Prosecutors also had pointed out that LaRose - a blond, green-eyed, white American - did not fit the stereotype of an Islamic militant. “This is a sentencing that people are watching,” Williams said on Monday. “Ms. LaRose had such a big impact in the public and press because she really did change the face of what the world thought of as a violent jihadist. It was scary for people to hear that Ms. LaRose could have been radicalized simply online in the U.S.” CHILDHOOD SCARS Wilson told the court that the plot to kill Vilks was “more aspirational than operational” and that LaRose had never even fired a gun. He had described LaRose as a lonely and vulnerable woman easily manipulated by others online. Her behavior, while not excusable, can be explained in part by deep psychological scars from her childhood, he said. LaRose’s biological father repeatedly raped her from about age 7 to 13, when she ran away and became a prostitute, according to court documents. At age 16, LaRose married a man twice her age and later became a heavy drug user. “I survived a lot of things that should have rightfully have killed me,” LaRose told Reuters in a 2012 interview. While LaRose was in contact with an al Qaeda operative in Pakistan, her conspirators repeatedly bungled a plot that never moved much past the planning stages. Vilks, the artist, had told Reuters that he believes LaRose has spent enough time in prison and should be freed. “That’s a pretty tough sentence,” Vilks told the Swedish news agency TT on Monday. Under U.S. sentencing rules, LaRose likely will serve 90 percent of her sentence, which means she will be eligible for release around 2020. She has requested imprisonment near her sister, Pam LaRose, in the Fort Worth, Texas, area, but a final decision will be up to the Bureau of Prisons. LaRose was in solitary confinement for four years but recently moved to the general population at a Philadelphia jail. Colleen LaRose, known by the self-created pseudonym of "Jihad Jane", is pictured in this photo released by Site Intelligence Group on March 10, 2010. REUTERS/Site Intelligence Group/Handout Ali Damache, LaRose’s alleged handler in Ireland, remains jailed there, fighting extradition to the United States on terrorism charges. Jamie Paulin Ramirez, who flew from Colorado to marry Damache in Ireland, has pleaded guilty to related terrorism charges and is scheduled to be sentenced on Wednesday. The sentencing for another co-conspirator who has pleaded guilty, Mohammad Hassan Khalid, has delayed in order to complete psychological evaluations. Khalid, who grew up in Pakistan and was an honor student in suburban Baltimore, committed his crimes when he was 15 and 16. He is the youngest person ever charged with terrorism inside the United States. According to a November report in the Guardian newspaper, documents leaked by Edward Snowden, a former contractor for the U.S. National Security Agency, to the British newspaper show that the FBI became involved in the Jihad Jane case after the NSA intercepted communications.

Accurate Analytical Solution for Free Vibration of the Simply Supported Triangular Plate Exploiting the superposition method developed earlier by the author, a highly accurate analytical-type solution is obtained for the free vibration of the general simply supported triangular plate. A new technique is introduced for the orderly storage of eigenvalues. It is shown how advantage can be taken of the more easily obtained isosceles triangular plate solutions. Accurate eigenvalues are tabulated for a wide range of plate geometries. This represents the first accurate and comprehensive treatment of this problem to appear in the literature. a b D E h K K* M W

President Obama campaigned on behalf of Democratic presidential nominee Hillary Clinton Hillary Diane Rodham ClintonSanders: 'I fully expect' fair treatment by DNC in 2020 after 'not quite even handed' 2016 primary Sanders: 'Damn right' I'll make the large corporations pay 'fair share of taxes' Former Sanders campaign spokesman: Clinton staff are 'biggest a--holes in American politics' MORE in Nevada on Sunday, also pushing those gathered to vote for Democrats running down ballot. “Nevada’s always close,” he told the crowd in North Las Vegas, “but that’s what makes it exciting.” ADVERTISEMENT After thanking the state for helping to elect him, praising retiring Sen. Harry Reid Harry Mason ReidBottom Line Brennan fires back at 'selfish' Trump over Harry Reid criticism Trump rips Harry Reid for 'failed career' after ex-Dem leader slams him in interview MORE and touting the progress made during his eight years in office, Obama launched into an attack on GOP nominee Donald Trump Donald John TrumpHouse committee believes it has evidence Trump requested putting ally in charge of Cohen probe: report Vietnamese airline takes steps to open flights to US on sidelines of Trump-Kim summit Manafort's attorneys say he should get less than 10 years in prison MORE. “You’ve got a guy who proves himself unfit for this office every single day in every single way,” he said. He also criticized Trump for claiming the election process is rigged, saying: “If this was rigged, boy it would be a really big conspiracy." “The Republican governor is not going to rig an election for Hillary Clinton or rig an election for Catherine [Cortez Masto],” he added, referring to the Democrat running for Reid’s seat. “We’ve got to have a Congress that is willing to make progress on the issues Americans care about,” he said, before launching an extended attack on Rep. Joe Heck, the Republican facing off against Masto. He said Heck supported Trump when it was “politically convenient” and asked “What the heck took you so long?” to denounce the nominee. Heck dropped his support for Trump earlier this month after The Washington Post uncovered a 2005 “Access Hollywood” tape in which Trump boasts of kissing and groping women without consent. “Too late,” Obama said. “You don’t get credit for that.” As he criticized Heck, he asked “Nevada, what the heck?” and then led the crowd in chants of “Heck no!” Polls show a tight race between Heck and Cortez Masto, the former Nevada attorney general in a race that Heck had been narrowly leading for months. Clinton is ahead of Trump by nearly 5 points in the RealClearPolitics average, and the latest average for the Senate race shows Cortez Masto up by 2 points. Heck revoking his support of Trump has set off a backlash against from Trump supporters, and he’s privately acknowledged he’s in a “very difficult situation” for no longer supporting his party’s standard-bearer.

JOSEPHINE COUNTY, Ore. - The human remains found by hikers on February 7 have been identified as that of Chase Cook, 22. News10 first reported on this story . The remains were found in a wooded area near Williams Highway. Josephine County authorities responded to the scene and they determined that the remains were believed to have been there for an extended period of time. OSP were requested to assist with the investigation. Cook had been reported missing in 2012 and was believed to be driving in the area of Williams highway when he went missing. Cook's remains were discovered less than a mile from where the vehicle he was reportedly driving at the time of his disappearance. Evidence located at the scene supports that he died of self-inflicted gunshot wound.

Both the Yvan Muller Racing Norma M30 and #26 United Autosports Ligier JSP3 will take no further part in this week’s ELMS Prologue test at Monza after sizeable incidents in this afternoon’s on-track action. The YMR Norma M30 came off worse of the two after Bronze driver Gwenaël Delomier rolled the car at Ascari, leaving the team in a race against time to get the car to the season opener at Silverstone. Che paura in Ascari per una LMP3 della @EuropeanLMS durante i test di oggi a Monza! 😱 #ELMS #officialtest2017 foto @marcofossen pic.twitter.com/bYDUclPpXr — Autodromo Naz. Monza (@Autodromo_Monza) March 28, 2017 Team principal Yvan Muller has confirmed to DSC that after looking at the onboard footage of the incident, no other cars were involved. Since the crash, Delomier has gone for mandatory medical checks after complaining of pain in his knees. At United Autosports meanwhile, its Gulf-liveried JSP3 of Richard Meins and Shaun Lynn will not take to the track again after Meins significantly damaged the front-end of the the car after an off which has damaged the tub. Unfortunately a crash at the end of the day for Richard Meins in the Gulf Ligier means it won’t take any further part in testing…. — United Autosports (@UnitedAutosport) March 28, 2017 Meins has been reported as ok by a United team spokesperson.

The Legislature in its closing hours voted to legalize medical marijuana and to deliver a second round of tax cuts to Minnesotans, with property refund checks going to nearly a million homeowners, renters and farmers. Finishing ahead of the mandated Monday adjournment, lawmakers wrapped up Friday night by passing a handful of major bills. “History might look at it as the most productive legislative biennium in a generation,” said Senate Majority Leader Tom Bakk, DFL-Cook. The medical marijuana bill was one of the final votes, passing the Senate and House 89-40 with significant bipartisan support. “It is nice when Republicans and Democrats work together to help people by expanding their personal freedoms, rather than limiting them,” said Rep. Pat Garofalo, R-Farmington. The House and Senate also gave final votes to adopt $1 billion in state-backed construction projects. Lawmakers also voted by wide margins to ban vaping of e-cigarettes in some public places and prohibited the sale of such devices to minors. The House passed the tax bill unanimously, and the medical marijuana bill and construction package both drew DFL and GOP support. Earlier this year the Legislature had passed a minimum-wage increase, income tax cuts, a long-sought antibullying bill for schoolchildren and a Women’s Economic Security Act designed to improve pay and conditions for female workers. “I think we did have an incredibly productive two years, I think there’s no doubt about that,” said House Speaker Paul Thissen, DFL-Minneapolis. Medical marijuana bill authors Sen. Scott Dibble and Rep. Carly Melin were congratulated after the bill passed the House on a bipartisan vote. DFL Gov. Mark Dayton praised the results. “Two years ago, when I was asked what Minnesotans could expect from a DFL governor and a DFL Legislature, I said: Progress,” he said in a statement. “That is exactly what we delivered again this session.” Senate Minority Leader David Hann, R-Eden Prairie, decried the emphasis on spending. “Spending money and having good intentions is not enough,” he said. “There are too many kids in this state who are left behind. Spending money hasn’t helped them.” Deals yield bipartisanship While this year’s session ended with a number of bipartisan coalitions on major bills, it required a flurry of last-minute deal-making and vote-trading to make it happen. That came into play most visibly with the construction bill, which the House passed about 3 a.m. Friday. The Senate followed suit about nine hours later, sending Dayton a package of bond- and cash-backed projects that includes the State Capitol restoration, affordable housing upgrades, campus buildings, roads and bridges, local economic development projects, the Lewis and Clark water pipeline, a new Senate office building and other ventures. “It’s going to be a really bright star in terms of helping our economic development,” said Sen. LeRoy Stumpf, DFL-Plummer, who helped assemble the package. The construction measure required Republican votes in order to authorize the required bond sales, which gave the minority party rare leverage. They exercised it by demanding House Democrats scrap a DFL bill, the so-called Toxic Free Kids Act, which would have required manufacturers to notify consumers of the presence of toxic chemicals in toys, school supplies and personal care products. “We were able to stop that from proceeding and we think that’s good,” House Minority Leader Kurt Daudt said. Republicans called it an overly burdensome regulation for businesses. Dayton also jumped into the deal-making fray. Legislative leaders trying to hold together the fragile coalition around the construction bill asked the governor to promise he wouldn’t use his veto pen to delete specific projects from the final package. Dayton responded with his own printed list of demands, which administration staffers circulated to reporters in the wee hours of Friday morning. Lawmakers delivered most of the governor’s demands, which included oil pipeline safety requirements, a veterans hiring measure, money for a sober schools program, tougher regulations for commercial breeding facilities, and a demand that lawmakers give up their attempts to repeal sprinkler requirements for new larger homes. Dayton also demanded the Toxic Free Kids proposal, which he did not get. The governor declined to make any promises about construction bill vetoes; he has 14 days from the end of the session to sign or veto bills passed on the last day. Democrats and Republicans also agreed on $103 million in new tax breaks, with more than half of that devoted to direct relief for about 940,000 homeowners, farmers and renters. The measure passed unanimously in the House on Friday, and with just one vote against it in the Senate. Under the measure, the average homeowner would see direct property tax relief of more than $800, with more than $600 for renters and an average of $410 for farmers. Individual amounts will vary. That was the second tax relief measure of the session. In March, Dayton signed a bill providing $444 million in relief that reached about a million taxpayers. “Between this bill and the last one, we will have delivered $550 million in tax cuts for Minnesotans this year,” said Rep. Ann Lenczewski, DFL-Bloomington. Limits for medical marijuana The medical marijuana proposal prompted the most high profile policy debate of the session. Lawmakers and the Dayton administration had struck a final deal on the proposal just a day earlier. They agreed to a limited system of production and distribution that is considered the most restrictive among the 21 states that currently authorize access to medical marijuana. The new medical marijuana law, which Dayton has promised to sign, authorizes access to the drug for about 5,000 Minnesotans with conditions including cancer, epilepsy, HIV/AIDS and a handful of others. With a health care provider’s permission, those patients will enroll in a patient registry that will allow the state Department of Health to monitor their progress. Rep. Kurt Zellers hugged fellow Rep. Mary Liz Holberg, both of whom plan to retire. The drug will be available only in pill or oil forms, with smoking not allowed and access to the drug in its original plant form forbidden. That was not enough to mollify some skeptics. “It will change the face of Minnesota, folks, and don’t think it won’t,” said Sen. Carrie Ruud, R-Breezy Point. “We’re legalizing a drug.” Others said the move was premature. “We don’t have any studies, or proven methods of knowing what works for who, and at what level,” said Rep. Kathy Lohmer, R-Stillwater. “We’re basically just saying, we’re going to try this and see how this works. I think that is the opposite of compassion.” Bakk noted the proposal was stalled for much of the session and revived only with the persistent lobbying of a small group of families of children with epilepsy who want to treat their kids’ seizures with a marijuana-based oil. “This was not on the legislative agenda of most of us in this room,” Bakk said. “What that tells me is this is a wonderful example of how representative democracy works. A small group of families with their hurting children came to the Capitol, and they changed the law.”

Melting behavior of H2O at high pressures and temperatures Water plays an important role in the physics and chemistry of planetary interiors. In situ high pressure‐temperature Raman spectroscopy and synchrotron x‐ray diffraction have been used to examine the phase diagram of H2O. A discontinuous change in the melting curve of H2O is observed at approximately 35 GPa and 1040 K, indicating a triple point on the melting line. The melting curve of H2O increases significantly above the triple point and may intersect the isentropes of Neptune and Uranus. Solid ice could therefore form in stratified layers at depth within these icy planets. The extrapolated melting curve may also intersect with the geotherm of Earth's lower mantle above 60 GPa. The presence of solid H2O would result in a jump in the viscosity of the mid‐lower mantle and provides an additional explanation for the observed higher viscosity of the mid‐lower mantle.

Instinct and the Origins of Mind and Behavior Instinct has been one of the more contentious concepts throughout the history of psychology and social psychology. Broadly defined, instinct is considered innate, patterned behavior for living organisms that does not require learning or experience. Almost all early psychologists engaged in the study of instincts, and many attempted to classify them. One of the debates that emerged was whether there is a simple dichotomy between instinct and reason, with animals endowed with instinct for survival but only humans with the ability to rely on reason. With more influence from Darwin’s evolutionary theory, however, the idea that instincts were modifiable and a common trait for humans and animals became accepted. This also led to the idea that human instincts could be understood by examining the instincts of animals and the mental development of children. With the arrival of behaviorism, the concept of instinct began to fall out of favor altogether, and all behaviors were attributed to learning or conditioning. More recently, evolutionary psychologists have reclaimed the notion of instinct, although the understanding of this concept still varies and has an uncertain fate in the discipline.

Species differences in cardiac energetics. The energy flux of rat, guinea pig, and cat papillary muscles was measured myothermically under resting, isometric, and isotonic conditions at 27 degrees C. Resting heat rate was highest in the smallest species and declined with body size. The slope of the isometric heat-stress relationship was constant across species, whereas the stress-independent heat component was least for rat muscles. The shape of the load enthalpy relationship was similar across species. Maximum mechanical efficiency, work-enthalpy, occurred with lighter loads than for skeletal muscle (approximately 0.2 Po). Rat muscle had the smallest enthalpy per beat and the highest active mechanical efficiency, but this advantage was nullified by the higher basal heat rate. The myothermic data are compared with cardiac oxygen consumption values in the literature and it is concluded, contrary to the deductions of common dimensional arguments, that cardiac energy expenditure across species is not directly proportional to heart rate. Reasons for this discrepancy are considered together with the likely contribution of cardiac metabolism (EH) to total body metabolism (EB). It seems likely that smaller species have lower EH/EB.

Aging in enumerated spin glass state spaces Aging phenomena are observed in many spin class experiments. Heuristic state space models were presented in the past to reproduce these effects. We here start the investigation by considering the real state space of an Ising spin glass Hamiltonian. A branch-and-bound algorithm is used to find the low-energy part of the state space. We solve the problem of the still huge size of the state space by employing a special coarse-graining algorithm. The system can be reduced to a computational treatable size. We demonstrate that these systems still contain all properties necessary for aging effects.

Cannabis leaf (Photo: Boltenkoff, Getty Images/iStockphoto) COLUMBUS – After years of stonewalling efforts to legalize medical marijuana in Ohio, state lawmakers announced a plan to provide patients with medical marijuana by 2018. The proposal, which will be introduced this week, would allow Ohioans older than 18 to buy edible marijuana, patches, plant material and oils with their doctors' recommendation. Who would grow it? That's to be determined. Within a year, a new commission would create rules on how to grow, distribute and sell medical marijuana. That means patients could have access medical marijuana within two years, maybe less, said Rep. Kirk Schuring, R-Canton, who led a several-week task force looking into the benefits of medical marijuana. Lawmakers hope to have the bill on Gov. John Kasich's desk by the summer. Kasich, who is running for the GOP presidential nomination, has said he would be open to "something" on medical marijuana, especially if it helps patients. If approved, Ohio would join 24 states, and likely Pennsylvania soon, that allow medical marijuana. Among the proposed changes: Children, younger than 18, could use medical marijuana with their parent's permission and doctor's recommendation. Patients would not be able to grow marijuana at home, and it's not clear whether they could smoke it. A nine-member medical marijuana control commission would be created under the Ohio Department of Health. Members would include a representative from physicians, pharmacists, law enforcement, mental health, alcohol and drug addiction treatment, employers, labor unions, marijuana proponents and the general public. The commission would have one year to write rules to regulate those who grow, sell and recommend medical marijuana. Only physicians licensed by the state medical board and certified by the medical marijuana commission could recommend medical marijuana to their patients. However, lawmakers would not limit the list of conditions. Physicians would need to report the number of medical marijuana patients, list their patients' conditions and explain why they recommended medical marijuana over other medication every 90 days. Lawmakers would determine how medical marijuana would be taxed before passing a law. Dispensaries that sell medical marijuana would be regulated much like liquor shops, and local communities could vote to ban medical marijuana dispensaries from their cities and villages. Financial institutions that collect money from medical marijuana sales would be granted safe harbor from prosecution. State lawmakers would recommend federal authorities reduce marijuana from a Schedule I drug, the most dangerous classification, to Schedule II. Lawmakers would encourage research into medical marijuana with funding. Employers could still ban employees from using medical marijuana in their employee handbooks, even if employees get approval from doctors. "The workplace can still be drug-free," Schuring said. "Employers do not have to make accommodations for employees being recommended medical marijuana." How we got here After Ohioans soundly defeated a ballot initiative to legalize all marijuana, House and Senate lawmakers took different approaches to investigating the benefits of medical marijuana, which polls show is more popular among Ohioans than recreational marijuana. Sen. Dave Burke, R-Marysville, and Sen. Kenny Yuko, D-Richmond Heights, visited three cities, including Cincinnati, to listen to marijuana activists and opponents. House lawmakers created a task force, led by Schuring, which held multiple meetings in Columbus. The task force included former ResponsibleOhio leaders Jimmy Gould and Chris Stock, who authored Issue 3 to legalize all marijuana. Some in the Senate questioned whether the group's motives were pure with Issue 3 proponents on the panel. Senators, who have been working on their own medical marijuana bill, don't plan to introduce it. Instead, they will follow the House version, Yuko said. Senate President Keith Faber, who had not seen the House version, wants the final version to address his list of concerns. "Does it include smokeable or not? Are we creating a database, just like we do with opiates? How are we going to allow the prescription? How many dispensaries are we going to have? Are we going to limit the production side? How are we going to award the licenses? Is it going to be a monopoly? All of those are questions that we have concerns about," Faber said. NEWSLETTERS Get the News Alerts newsletter delivered to your inbox We're sorry, but something went wrong Be the first to be informed of important news as it happens in Greater Cincinnati. Please try again soon, or contact Customer Service at 1-800-876-4500. Delivery: Varies Invalid email address Thank you! You're almost signed up for News Alerts Keep an eye out for an email to confirm your newsletter registration. More newsletters The Ohio State Medical Association already opposes the House proposal, saying "it draws conclusions about the medicinal benefits of marijuana absent conclusive clinical research." Still, Yuko, a longtime proponent of medical marijuana, said he's confident patients will be able to access medical marijuana sooner once lawmakers hear stories about patients who need help. "I think it'll be a lot shorter than two years," Yuko said. 'Irresponsible' ballot initiatives? Lawmakers are under a time crunch because two groups are working to place medical marijuana before voters in November. But House Speaker Cliff Rosenberger, R-Clarksville, essentially told them to knock it off. Lawmakers haven't been stalling, and they are taking medical marijuana seriously, he said Wednesday. "To those that are operating outside the scope of this process, it is extremely irresponsible to continue without coming forward and participating with us in this process," Rosenberger said Wednesday. Rep. Wes Retherford, R-Hamilton, who introduced a bill last year to allow children with seizures to access cannabis oil, agreed that lawmakers, not outside groups, should drive changes on medical marijuana. The state constitution is much harder to amend than laws. "Anytime things need to be changed, it has to go back on the ballot again," Retherford said. The two ballot initiatives are from Marijuana Policy Project and its Ohio operation, Ohioans for Medical Marijuana, and Grassroots Ohio, a group of Ohio marijuana activists not thrilled about the Marijuana Policy Project's plan. - Marijuana Policy Project's proposal would allow adults older than 21 to grow up to six marijuana plants with a recommendation from their doctor. Those younger than 18 could use marijuana with a parent's permission and physician's recommendation. - Grassroots Ohio plans to legalize medical marijuana for those older than 18 and allow farmers to grow industrial hemp through a constitutional amendment. Then, they would send lawmakers a proposal to regulate the industry and determine how medical marijuana is distributed to patients. Marijuana Policy Project spokesman Mason Tvert wasn't impressed by Rosenberger's language about "irresponsible" ballot initiatives, calling the speaker's speech "arrogant." "Lawmakers often dislike initiatives and assume they could draft better laws. With all due respect, they have spent a couple months looking at this issue and we’ve been working on it for a couple decades," Tvert said. Marijuana Policy Project won't halt its ballot initiative unless lawmakers pass a quality law, said Tvert, adding that he was concerned that the proposal would take two years to implement and physicians would need to report patient information every 90 days. Read or Share this story: http://cin.ci/1N8HMrG

Unlike commercial airliners, modern military aircraft are subjected to ever-changing flying conditions—from high-thrust takeoffs to flying at altitude to combat maneuvers. So why are they outfitted with engines that perform optimally in only one of those flight envelopes? For the next iteration of the F-35 Lightning II, Pratt and Whitney is developing an engine that performs at its best no matter what's required of it. Turbofan technology is the backbone of modern aviation, using a pair of air streams to propel everything from commercial airliners to jet fighters far faster than any propeller could. The problem is that the dual air stream design limits the engine's efficiency to a single speed point. That's why commuter jets can't go supersonic, and fighter jets are terrible at low-speed cruising. Advertisement Turbofans are air-breathing jet engines that use a large fan at the front of the engine with a smaller gas turbine engine core behind. The fan pushes air both into the core as well as a bypass duct that surrounds it. There are some variations to the basic design, of course, as military jets use more and smaller fans while commercial airliners use a single larger fan. "You can design turbofan engines off of that single design point but you are not operating at your best performance and typically what you end up giving up is efficiency," Jimmy Kenyon, Pratt & Whitney's Next Generation Fighter Engine General Manager, explained to Gizmodo. He continued: If you look at the evolution of the turbine engine over time, we started out with turbo jets, and they had what we call a single stream. So the air flowed into the compressor, then went into a combuster, burned, and then exited out the turbine. The turbine actually drives the compressor so it’s something that can keep itself sustained and going. And at the time it was considered a very efficient way of doing business. Later on, we introduced what we called the turbofan. And what the turbofan did was it added an extra turbine on the back end of that turbojet (now called the core), but it added a turbine on the back end of that, and added a big fan up in front. That extra turbine drives that extra fan, but what that allows you to do is, part of the air that comes in the front goes through the core just like it did before, but a part of the air goes through the fan and then passes by the rest of the engine. Advertisement The super-hot compressed exhaust coming from the core then pushes this cooler, denser bypass air to generate the thrust. The ratio of the two streams is called the bypass ratio and it's this ratio that determines the engine's efficiency envelope. For high-performance engines like the Pratt & Whitney F135 powering the F-35 Lightning, the bypass ratio is very low—that is, it uses mostly jet thrust from the core in relation to the bypass stream—hence the term, low-bypass turbofan. Long-haul engines, such as the GE-90 that powers the 787 Dreamliner and military cargo jets, instead utilize more fan thrust from the bypass than jet thrust from the core and are referred to as a high-bypass turbofan. Advertisement But what if you could make an engine that performs equally well at both low- and high-bypass ratios? That's exactly what Pratt & Whitney is attempting with its Adaptive Engine Development Program for the upcoming sixth-generation F135 turbofan. "What we are looking at with adaptive engines are engines that can operate at multiple design points across a range of flight envelopes while maintaining optimal operating efficiency," Kenyon said. Advertisement This adaptive cycle engine will utilize a secondary bypass stream (three air streams in total) to act much like the gearing on a car's transmission, allowing the F135 engine to adjust and match its bypass ratio at will, whether it's high-thrust takeoffs or high-efficiency cruising at altitude. "That third stream is something that we have the ability to modulate, to change the conditions of that flow," Kenyon told Gizmodo. "How much flow, and flow characteristics so that we can kind of optimize the bypass ratio over the flight envelope." Kenyon further explained: On top of that adaptive fan we’re also making improvements, tremendous improvements in the core system as well. We’re putting in a higher pressure ratio, higher efficiency compressor, leveraging a lot of our advanced commercially-derived, 3D aerodynamic design capability...We’re looking at increasing the temperature capability and the efficiency of the turbine stages, and then we’re also looking at the exhaust system. Having that adaptive third stream allows us to work with that stuff as well...we’re making improvements to the efficiency of the core engine, but we’re also using the adaptive architecture to give us a lot more design options in terms of how we can manage the engine over the flight envelope. Advertisement These improvements should translate into marked improvements in the engine's overall fuel efficiency on both sides of the sound barrier. What's more, the new system is expected to offer superior heat sinking abilities that will reduce the plane's thermal signature while further improving its stealth capabilities. You know, just in case the F-35 wasn't deadly enough as it is. [Wikipedia - Pratt & Whitney 1, 2, 3]

Deep in the Antelope Valley in northern Los Angeles County, directly off State Route 138, are the forlorn ruins of a sunbaked, desert ghost town. Large stone chimneys, once the focal point of a cozy hotel, rise into the dry, clear blue sky, almost seeming to touch the snow-capped San Gabriel Mountains in the distance. Beige dirt roads lead to crumbling beige walls, cisterns full of trash, and the rough stone foundations of long-gone homes and workshops. There are no people, only the occasional scurrying lizard, whose movements are amplified in the still, silent air. These ruins serve as the collective tombstone of Llano del Rio, the briefly bustling socialist colony founded nearly a hundred years ago. Job Harriman—handsome, earnest and charismatic—was the face of socialism in California around the turn of 20th century. A perpetual candidate, he mounted unsuccessful campaigns for the governorship of California in 1898 and the vice presidency of the United States in 1900. He ran twice for mayor of Los Angeles, and almost certainly would have won in 1911, if the men accused of bombing the Los Angeles Times—who he had supported and represented—had not pleaded guilty days before the election. After another failed mayoral bid in 1913, the 55-year-old Harriman, wearied by politics and the constant harassment he suffered at the hands of powerful enemies (including Harrison Gray Otis, the bombastic and conservative owner of the Los Angeles Times), began to look to a future outside of LA. He dreamed of a socialist colony, where cooperative living could thrive and serve as an example to others while still staying within the bounds of capitalist norms. “It became apparent to me,” he recalled, “that people would never abandon their means of livelihood, good or bad, capitalistic or otherwise, until other methods were developed which would promise advantages at least as good as those by which they were living.” Harriman formed a plan for the colony centered around these beliefs. He would form a corporation with which to buy land for a cooperative settlement. Each new resident of the colony would be required to buy $2,000 worth of shares, and then would be assigned a job that would pay her or him a good living wage. Looking for money, he took this idea to Gentry P. McCorkle, a socialist banker from Corona. “If you will join me and a few other of my friends,” he told McCorkle, “we will build a city and make homes for many a homeless family. We will show the world a trick they do not know, which is how to live without war or interest on money or rent on land or profiteering in any manner.” McCorkle thought Harriman’s vision made sound economic sense and agreed to join him in his venture. The new corporation began to search for an ideal place for the colony. According to McCorkle, they were presented with the perfect location one day at their offices in the Higgins Building in Downtown Los Angeles: Mr. James L. Stanley, the old man of the mountain, came into the office one morning and asked to see the boss. He had gray hair and wore long whiskers. He looked like a ‘possum’ more than a man, but he had a good story for us. We loaded ourselves into an automobile, and, in three hours we were standing beside the Big Rock Creek where the water from it came rushing along by us … The Antelope Valley looked to be as large as the Pacific Ocean … some of this adjacent land was set out to Bartlett pear orchards and a few acres were set out to alfalfa. There were but three dwelling houses in sight. Ten thousand acres had nothing but jack rabbits and stink weeds and could be bought for one dollar an acre … We paid Mr. Stanley $25 for his day’s work and his information and proceeded to buy Llano Del Rio Ranchero. The land, much of which was owned by the Mescal Land and Water Company, had once been the site of a failed temperance colony. It was virtually worthless, and the “starry-eyed” socialist grossly overpaid for the honor of owning around 9,000 acres of boulder-strewn desert landscape. However, included in the purchase were the essential water rights to Big Rock Creek. The Mescal Land and Water Company was officially reorganized into the Llano del Rio Company on October 10, 1913. For good or bad, Llano del Rio was theirs. Harriman and his cohorts, including holdovers from his mayoral campaigns, set about finding settlers for their new colony. Ads were placed in the Western Comrade, LA’s new socialist magazine, which would eventually be printed at Llano. One ad touted a booklet written by Harriman: Are you tired of the competitive world? Do you want to get into a position where every hour’s work will be for yourself and your family? Do you want assurances of employment and provisions for the future? Ask for the booklet entitled Gateway to Freedom. Subscribe to the Western Comrade … and keep posted on the progress of the colony. The widely disseminated Gateway to Freedom promised a wage of $4 a day to new settlers, an impressive salary at the time. Harriman’s adversaries at the Los Angeles Times derided the booklet, “which in flowery language pictures the beauties and blessings on the contemplated colony in Antelope Valley.” They mocked the full-length picture of Harriman on the title page and questioned the socialist bona fides of the colony, since the booklet stated confusingly that “this is not a co-operative colony, but it is a corporation.” Ten thousand acres had nothing but jack rabbits and stink weeds and could be bought for one dollar an acre. Despite the Times’s derision, the colony soon found many willing to buy into the Llano dream. Millie Miller, Harriman’s stenographer, was the first to buy a colony stock certificate, partially with shares earned through her work with the Llano del Rio Company. Others quickly followed, and the hard work of clearing land and laying irrigation ditches began. The work was done by future residents, many exchanging their labor for shares in the corporation. By May 1914, excited colonists began to move to the isolated new settlement, 90 miles from Los Angeles over rough, treacherous roads. From all over the country and all walks of life, they were tied together by the dream of a better, more equal society. “We felt happy, exhilarated, and confident that the Llano del Rio Co-operative Colony would, indeed, become a paradise on earth,” Miller remembered. The colony grew rapidly. By October 1915, there were 500 people living at Llano, mostly in makeshift tents (in which most would reside until the colony’s demise). When at Llano, Harriman also stayed in a tent, which he scandalously shared with colonist Mildred Buxton, while his wife Theo stayed in Los Angeles. Construction of more permanent structures began in earnest during the summer of 1915. The colonists often used local resources: The local adobe clay formed the basic building block of Llano’s earliest residential architecture. A lime kiln was built on the side of a bluff in a canyon south of the colony, and utilized native rock to make cement for construction purposes … The Llano site was remarkably stony. This detriment was turned around by the colonists who built many foundations of stone, since it could be used at no further cost on the site. Circumstance also aided in the construction needs. One day a man was accepted into the colony despite his lack of cash. But he did have a complete sawmill outfit, which was pulled by four yokes of oxen. His equipment, set up in the San Gabriel Mountains above Llano, started producing lumber for the colony’s construction. In early 1915, the hotel, which would become the focal point of social life at Llano, was completed. “The first community building, the hotel, combined cobblestone foundations with native boulders and frame walls,” the authors of Bread and Hyacinths: The Rise and Fall of Utopian Los Angeles write. “This structure, in addition to living quarters for bachelors and arriving members, contained a large dining room assembly hall with fireplaces. Colonists gathered around these hearths on cool winter evenings before blazing juniper fires.” The assembly room became a beehive of activity and intrigue. Curious tourists and weekend visitors from progressive organizations like the Young People’s Socialist League would file in for meals and lectures. The General Assembly, Llano’s nominal governing body, would meet in the large room, practicing “democracy rampant, belligerent, unrestricted.” Life was proving to be hard at Llano. Fresh fruits and vegetables were often scarce, and the long work hours were punishing in the relentless desert sun. A rival faction—known as the “brush gang” for their clandestine outdoor meetings—began to call for the ouster of Harriman as de facto leader. Lawsuits against the colony were filed by some early defectors, and dissatisfied colonists began to go to the press. Neighboring ranchers also began to sue the upstart colony over their alleged water rights to Big Rock Creek. All this noise caught the attention of the state Commissioner of Corporations. As early as the spring of 1915, representatives of the anti-socialist commission, including Deputy Commissioner H.W. Bowman, began to visit Llano. In December 1915, Bowman issued a scathing report on the less-than-year-old settlement. He claimed that there was not enough food at the colony, and that “although it is assumed that supplies are furnished to the colonists at cost, such is not always the fact.” He derided Llano’s hygiene, stating, “the only bathtubs or sanitary toilet appliances in the colony are those which still lie crated among the debris in the scrap pile behind the carpenter and machine shop.” He reserved his most biting commentary for Harriman himself, which the Los Angeles Times reported with glee: The general statements usually made by the colony’s promoters cannot safely be accepted without qualifications and explanations. The same is true of much of the company’s literature … There is a studied effort to induce the belief that the influence of each stockholding colonist in the control of the colony’s affairs is equal to that of any other. The fact is that the colony is almost autocratically dominated and controlled by one man, Mr. Harriman. However, the commission gave the Llano del Rio Company the right to keep functioning, provided “a true copy of the permit shall be exhibited and delivered to each prospective subscriber for or purchaser of said securities.” Harriman’s enemies didn’t care. “The Modern Moses,” the “Oligarch of Misrule” was continually taunted in the Times, with headlines celebrating every defection and lawsuit. However, to the close to 800 colonists living at Llano, all of this turmoil didn’t really matter. Over 1916 and early 1917, through backbreaking work and sacrifice, the colony began to coalesce into a seemingly fully functioning village. According to Bread and Hyacinths: By 1917, over 60 departments functioned under division managers. A representative list of economic activities included: agriculture, architecture and surveying, art studio, bakery, barber shop, bee-keeping, cabinet shop, cannery, cleaning and pressing, clearing, fencing and grading land, dairy, fish hatchery, general store, hay and grain, hogs, horses and teaming, the hotel, irrigation, laundry, lime kiln, library, machine shop, medical department, poultry, printing, post office, rabbits, rugs, sawmill, sanitation, shoe shop, soap factory, tannery, tractors, transportation, tin shop, wood and fuel. The inventive elementary school was led by Prudence Stokes Brown, who had studied under education pioneer Maria Montessori. Secondary education was supplied in the form of an industrial school, where teenage girls and boys were taught skills seen at the time as appropriate to their sex. “The boys have their managers of departments, make their own laws, try their own culprits and acquire a sense of responsibility,” an in-house publication reported. “Boys, who have seemed to be incorrigible, have transformed into loveable, tractable, good natured workers.” Beige dirt roads lead to crumbling beige walls, cisterns full of trash, and the rough stone foundations of long-gone homes and workshops. Adults also partook in continuing education classes and joined social and craft clubs. Writer Aldous Huxley, who lived near the colony in the 1940s, wrote that former colonists “had often talked to me nostalgically of that brass band, those mandolins and barber-shop ensembles” that made Llano life unique. There were also plenty of eccentric personalities to entertain, like the Zorne brothers, who built an airplane around an old Model T motor to the fascination of their fellow colonists—only for it to mysteriously burn to the ground after a failed test run. Llano chronicler Robert Hine described one of the colony’s largest scale celebrations, presided over by a seemingly confident and jubilant Harriman: The May Day festivities of 1917 commenced at nine o'clock in the morning with intra-community athletic events, including a Fat Women's Race. The entire group of colonists then formed a Grand Parade and marched to the hotel where the Literary Program followed. The band played from a bunting-draped grandstand, the choral society sang appropriate revolutionary anthems like the `Marseillaise', then moved into the Almond Grove for a barbecue dinner. After supper, a group of young girls injected the English into the radical tradition by dancing about the May Pole. At 7:30 the dramatic club presented ‘Mishaps of Minerva' with newly decorated scenery in the Assembly Hall. Dancing consumed the remainder of the evening. Sadly, by that May 1917—though most residents didn’t know it—Llano had been a dead colony walking for almost a year. Although Harriman was often accused of being the colony’s virtual “czar,” the rigidly democratic nature of the General Assembly also led to dysfunction. The 1917 crop of alfalfa was lost, because the General Assembly had failed to authorize its harvest. The continuing lawsuits from disgruntled shareholders and alleged mismanagement by McCorkle also took a toll on the colony’s finances. But Llano’s real death knell had actually come in July 1916, when the colony’s application to secure their water rights and build a dam to help irrigate their fields was denied by California Commissioner of Corporations H.L. Carnahan. “Your people do not seem to have the necessary amount of experience and maybe the sums of money it will involve,” he wrote. “The application is denied.” After the ruling, Harriman and his remaining partners began quietly looking for a new home for the colony. By fall of 1917, they had found a suitable new homestead—an old mill town in Louisiana they named New Llano. By early 1918, Llano del Rio had been involuntarily forced into bankruptcy and most of its colonists had begun to leave, some for New Llano. On March 30, 1918, the Los Angeles Times, hypocritically waxing poetic about its failed nemesis, reported that the last community meal was being served in the hotel that evening: At sundown tonight, Llano del Rio, which in its heyday had nearly 1000 souls, will simmer down to a deserted village containing just sixteen men … The town itself begins with a pretentious cobblestone hotel and men’s dormitory, a large bath-house for men and the administration building and post office. It moves on, across the street, to the industrial center, where there is a machine shop, a blacksmith shop and a sawmill … All over this portion of the townsite are the remains of what were homes, wrecked buildings, and the frames that once supported canvass that provided shelters for colonists. At the upper end of the town stands the temple of weaving arts. A weather-beaten loom stands outside in the burning sun. The temple was to send Llano weaves to the socialist world far and wide. Just now it houses an old bed, a couple of broken chairs and a pine table. Job Harriman moved to New Llano (which lingered until the 1930s) before returning to Los Angeles in ill health. He died virtually penniless in 1925, his dream for a better socialist future still improbably intact. Aldous Huxley, speaking of the Llano colonists he knew who had remained in the Antelope Valley decades later, poignantly described them as:

April 23--CHESAPEAKE -- When it comes to marijuana, the nose knows. Even in a moving car. Even with the windows up. Police officers in Chesapeake have been pulling over cars on the grounds that they smelled marijuana while cruising down local roadways, defense attorneys say. And according to the testimony of one officer, it's become common practice to try to sniff out pot from behind the wheel. "We drive our patrol car with the vents on, pulling air from the outside in, directly into our faces," Officer Barrett C. Ring said late last year in court during a preliminary hearing, according to a transcript of the proceedings. "Commonly, we'll be behind vehicles that somebody in the vehicle is smoking marijuana, and we can smell it clear as day." Before officers pull over a car to search it, he said, they will follow it until there are no other cars in the area and they are certain about the source of the odor. Assistant Public Defender Matthew Taylor and several other defense attorneys question the officers' "supernatural" sense of smell. "The idea that police can drive behind a car and smell marijuana is preposterous," said Taylor, who tried unsuccessfully last week to get Ring's search of his client's car thrown out of court. "What do we need drug dogs for if (people) can drive behind cars and smell marijuana?" Kent Willis, executive director of the ACLU in Virginia, agreed with Taylor, saying, "It stretches the imagination that the police can drive down the road and home in on a car." He predicted that traffic stops based only on an officer's sense of smell will draw more legal challenges in the future. "Experts will have to tangle over this and decide," he said. Officials with the Chesapeake Police Department declined to comment. So far, the officers' behavior appears to have withstood legal review. No defense attorney contacted by The Virginian-Pilot had seen any such searches overturned. Attorney Robert L. Wegman said he has handled two cases involving pot-sniffing police on patrol but did not challenge the searches because the officers had other reasons to conduct the traffic stops. On Thursday, Judge V. Thomas Forehand Jr. ruled in Chesapeake Circuit Court that the search of Deon Crudup's car was lawful, but he didn't specifically address the officers' ability to detect pot while in their moving car. Rather, he noted that Ring and his partner, Officer James H. Rich, never initiated a traffic stop based on smelling pot. After smelling the marijuana on April 10, 2011, while driving about 35 miles per hour on Battlefield Boulevard, they followed Crudup's car into the parking lot of Blakely's night club, walked up to the parked vehicle and searched it without needing permission, according to court testimony. The officers found some dried marijuana in a bag along with what authorities said was heroin. "None of this argument about what the officer could smell in his car... has any import," said Forehand, adding that the only thing that mattered was that the police smelled marijuana as they approached the parked car on foot. Crudup, 29, was convicted in October on one count of misdemeanor possession of marijuana and is scheduled to stand trial May 8 on one count of felony possession of heroin. The air-vent technique hasn't been adopted on any large scale in South Hampton Roads outside Chesapeake, according to officials in Portsmouth, Suffolk and Virginia Beach. Suffolk Commonwealth's Attorney C. Phillips Ferguson said he hadn't heard of the practice but expects it to catch on as more officers learn about it. "It's very creative policing," he said. Ferguson saw no problem with police officers using their noses to identify suspicious vehicles, follow them and then find another reason to pull them over -- such as a broken taillight. He said officers are allowed to search a vehicle when they smell marijuana during a routine traffic stop. If an officer used the odor of marijuana he sensed while driving down a highway as the sole basis to justify a traffic stop, Ferguson could see a defense attorney having more success persuading a judge to throw out the vehicle search. "I'm not saying they wouldn't have been justified (to stop the car), but it's pushing the line," Ferguson said. Taylor said he decided to challenge the search of Crudup's car partly with the hope that he could prevent the technique from becoming common. "If cops can get away with this, they will have total authority," he said. Scott Daugherty, 757-222-5221, scott.daugherty@pilotonline.com Copyright 2012 - The Virginian-Pilot, Norfolk, Va.

Dr. Marshall A. Lichtman: The Wit and Wisdom of One of Stem Cells' Founding Fathers introduce the STEM CELLS audience once more to the remarkable wit, and wisdom, of Dr. Marshall A. Lichtman. As Curt Civin and I recently reminded our readers, Marshall was one of the “Founding Fathers” of STEM CELLS. It was his idea, among others, to include a “Concise Reviews” section in the journal and it has proven to be one of its most successful features as judged by download activity from our Web site. Marshall is truly one of the giants of modern hematology. A prodigious intellect with a wide variety of interests, he has authored well in excess of 230 research articles dealing with virtually every hematopoietic lineage (so we have to love him at STEM CELLS!), as well as the origins of clonal myeloid malignancies. Career benchmarks include serving as Dean of the University of Rochester School of Medicine and Dentistry (where he is still Professor of Medicine, Biochemistry and Biophysics), the Board of Governors of the American Red Cross, and one of the highest honors in the world of hematology, being elected President of the American Society of Hematology. I came to know Marshall personally as a result of my association with the Leukemia and Lymphoma Society, where Marshall also serves as its Executive Vice President for Research and Medical Programs. During my tenure as Chair of the Society’s Medical and Scientific Affairs Committee, Marshall was a constant source of support, inspiration, and the most helpful commodity of all, good advice served up with a sense of humor. The little ditty we publish is an excellent example of this. So what does one call a scholar who is a real gentleman in the truest sense of the word? If one is lucky, as I am, “Friend” is the word that rises to the top. We at STEM CELLS are proud of this friendship and Marshall’s many contributions to the field and to the journal.

Identification of transcription factor binding sites from ChIP-seq data at high resolution MOTIVATION Chromatin immunoprecipitation coupled to next-generation sequencing (ChIP-seq) is widely used to study the in vivo binding sites of transcription factors (TFs) and their regulatory targets. Recent improvements to ChIP-seq, such as increased resolution, promise deeper insights into transcriptional regulation, yet require novel computational tools to fully leverage their advantages. RESULTS To this aim, we have developed peakzilla, which can identify closely spaced TF binding sites at high resolution (i.e. resolves individual binding sites even if spaced closely), as we demonstrate using semisynthetic datasets, performing ChIP-seq for the TF Twist in Drosophila embryos with different experimental fragment sizes, and analyzing ChIP-exo datasets. We show that the increased resolution reached by peakzilla is highly relevant, as closely spaced Twist binding sites are strongly enriched in transcriptional enhancers, suggesting a signature to discriminate functional from abundant non-functional or neutral TF binding. Peakzilla is easy to use, as it estimates all the necessary parameters from the data and is freely available. AVAILABILITY AND IMPLEMENTATION The peakzilla program is available from https://github.com/steinmann/peakzilla or http://www.starklab.org/data/peakzilla/. CONTACT stark@starklab.org. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

For too long, anarchist projects have been mismanaged by arrogant fantasies of mass. We have unconsciously adopted the Statist, Capitalist and Authoritarian belief that “bigger equalsbetter” and that we must tailor our actions and groups towards this end. Despite our intuitive understandings that large organizations rarely accomplish more than small, tight groups working together, the desire for mass remains strong. We must re-examine how we organize projects in order to awake from the nightmare of over-structure that inevitably leads to bureaucracy, centralization and ineffective anarchist work. This article suggests a few ideas on how anarchists can reject the trap of mass and reinvent ourselves, our groups and our work: from local community activities to large revolutionary mobilizations. The rejection of mass organizations as the be-all, end-all of organizing is vital for the creation and rediscovery of possibilities for empowerment and effective anarchist work. The Tyranny of Structure Most mass structures are a result of habit, inertia and the lack of creative critique. Desire for mass is accepted as common sense in the same way it is ‘common sense’ that groups must have leaders, or that that they must make decisions by voting. Even anarchists have been tricked into accepting the necessity of super structures and large organizations for the sake of efficiency, mass, or unity. These super structures have become a badge of legitimacy and they are often the only conduits by which outsiders, whether the media, the police or other leftists, can understand us. The result is an alphabet soup of mega-groups which largely exist to propagate themselves and, sadly, do little else. Unfortunately, we haven’t just been tricked into accepting superstructures as the overriding venue of our work: many of us have gone along willingly, because the promise of mass is a seductive one. Large coalitions and super-structures have become the coin of the realm not only for leftist groups in general but also for anarchist enterprises. They appeal to activists’ arrogant fantasies of mass: the authoritarian impulse to be leading (or at least be part of) a large group of people that reinforce and legitimize our deeply held ideologies and beliefs. Even our best intentions and wildest dreams are often crowded out by visions of the black clad mob storming the Bastille or the IMF headquarters. The price of the arrogant dream of mass is appallingly high and the promised returns never come. Super-structures, which include federations, centralized networks and mass organizations, demand energy and resources to survive. They are not perpetual motion machines which produce more energy than what is poured into them. In a community of limited resources and energy like ours, a super-structure can consume most of these available resources and energies, rendering the group ineffective. Mainstream non-profits have recently illustrated this tendency. Large organizations like the Salvation Army commonly spend 2/3 of their monies (and even larger amounts of its labor) on simply maintaining its existence: officers, outreach, meetings and public appearance. At best, only 1/3 of their output actually goes to their stated goals. The same trend is replicated in our political organizations. We all know that most large coalitions and super-structures have exceedingly long meetings. Here’s a valuable exercise: The next time you find yourself bored by an overlong meeting, count the number of people in attendance. Then multiply that number by how long the meeting lasts: this will give you the number of person-hours devoted to keeping the organization alive. Factor in travel time, outreach time and the propaganda involved in promoting the meeting and that will give you a rough estimate of the amount of activist hours consumed by greedy maw of the superstructure. After that nightmarish vision, stop and visualize how much actual work could be accomplished if this immense amount of time and energy were actually spent on the project at hand instead of what is so innocently referred to as ‘organizing’. Affinity or Bust Not only are super-structures wasteful and inefficient, but they also require that we mortgage our ideals and affinities. By definition, coalitions seek to create and enforce agendas. These are not merely agendas for a particular meeting but larger priorities for what type of work is important. Within non-anarchist groups, this prioritization often leads to an organizational hierarchy to ensure that all members of the group promote the overall agenda. A common example is the role of the media person or ‘spokesman’ (and it is almost always a man) whose comments are accepted as the opinion for dozens, hundreds or sometimes thousands of people. In groups without a party line or platform, we certainly shouldn’t accept any other person speaking for us — as individuals, affinity groups or collectives. While the delusions of media stars and spokespeople are merely annoying, superstructures can lead to scenarios with much graver consequences. In mass mobilizations or actions, the tactics of an entire coalition are often decided by a handful of people. Many of the disasters of particular recent mobilizations can be squarely blamed on the centralization of information and tactical decisions on a tiny cadre of individuals within the larger coalition/organization (which might include dozens of collectives and affinity groups). For anarchists, such a concentration of influence and power in the hands of a few is simply unacceptable. It has long been a guiding principle of anarchist philosophy that people should engage in activities based on their affinities and that our work should be meaningful, productive and enjoyable. This is the hidden benefit of voluntary association. It is arrogant to believe that members in a large structure, which again can number in the hundreds or thousands of people, should all have identical affinities and ideals. It is arrogant to believe that through discussion and debate, any one group should convince all the others that their particular agenda will be meaningful, productive and enjoyable for all. Due to this nearly impossible situation, organizations rely on coercion to get their agendas accepted by their membership. The coercion is not necessarily physical (like the State) or based on deprivation (like Capitalism) but based on some sense of loyalty or solidarity or unity. This type of coercion is the stock and trade of the vanguard. Organizations spend a significant amount of their time at meetings trying to convince you that your affinities are disloyal to the greater organization and that your desires and interests obstruct or remove you from solidarity with some group or another. When these appeals fail, the organization will label your differences as obstructionist or breaking ‘unity’ — the hobgoblin of efficiency. Unity is an arrogant ideal which is too often used against groups who refuse to cede their autonomy to a larger super-structure. Many anarchists whose primary work is done in large organizations often never develop their own affinities or skills and instead, do work based on the needs of super-structures. Without affinity groups or collective work of their own, activists become tied to the mass abstract political goals of the organization, which leads to even greater inefficiency and the ever present “burn-out” that is so epidemic in large coalitions and super-structures. Liberty, Trust and True Solidarity “All Liberty is based on Mutual Trust” — Sam Adams If we seek a truly liberated society in which to flourish, we must also create a trusting society. Cops, armies, laws, governments, religious specialists and all other hierarchies are essentially based on mistrust. Super-structures and coalitions mimic this basic distrust that is so rampant and detrimental in the wider society. In the grand tradition of the Left, large organizations today feel that due to their size or mission, they have a right to micromanage the decisions and actions of all its members. For many activists, this feeling of being something larger that themselves fosters an allegiance to the organization above all. These are the same principles that foster nationalism and patriotism. Instead of working through and building initiatives and groups that we ourselves have created and are based in our own communities, we work for a larger organization with diluted goals, hoping to convince others to join us. This is the trap of the Party, the three letter acronym group and the large coalition. In large groups, power is centralized, controlled by officers (or certain working groups) and divvied out, as it would be done by any bureaucratic organization. In fact a great deal of its energies are devoted to guarding this power from others in the coalition. In groups which attempt to attract anarchists (such as anti-globalization coalitions) this centralization of power is transferred to certain high profile working groups such as ‘media’ or ‘tactical’. Regardless of how it appears on the outside, superstructures foster a climate in which tiny minorities have disproportionate influence over others in the organization. As anarchists, we should reject all notions of centralized power and power hoarding. We should be critical of anything that demands the realignment of our affinities and passions for the good of an organization or abstract principle. We should guard our autonomy with the same ferocity with which the super-structure wishes to strip us of it. Mutual aid has long been the guiding principle by which anarchists work together. The paradox of mutual aid is that we can only protect our own autonomy by trusting others to be autonomous. Super-structures do the opposite and seek to limit autonomy and work based on affinity in exchange for playing on our arrogant fantasies and the doling out power. Decentralization is the basis of not only autonomy (which is the hallmark of liberty), but also of trust. To have genuine freedom, we have to allow others to engage in their work based on their desires and skills while we do the same. We can hold no power from them or try to coerce them into accepting our agenda. The successes that we have in the streets and in our local communities almost always come from groups working together: not because they are coerced and feel duty-bound, but out of genuine mutual aid and solidarity. We should continue to encourage others to do their work in coordination with ours. In our anarchist work, we should come together as equals: deciding for ourselves with whom we wish to form affinity groups or collectives. In accordance with that principle, each affinity group would be able to work individually with other groups. These alliances might last for weeks or for years, for a single action or for a sustained campaign, with two groups or two hundred. Our downfall is when the larger organization becomes our focus, not the work which it was created for. We should work together, but only with equal status and with no outside force, neither the state, god nor some coalition, determining the direction or shape of the work we do. Mutual trust allows us to be generous with mutual aid. Trust promotes relationships where bureaucracies, formal procedures and large meetings promote alienation and atomization. We can afford to be generous with our limited energies and resources while working with others because these relationships are voluntary and based on a principle of equality. No group should sacrifice their affinity, autonomy or passions for the privilege to work with others. Just as we are very careful with whom we would work within affinity group, we should not offer to join in coalition with groups with whom we do not share mutual trust. We can and should work with other groups and collectives, but only on the basis of autonomy and trust. It is unwise and undesirable to demand that particular group must agree with the decisions of every other group. During demonstrations, this principle is the foundation of the philosophy of “diversity of tactics”. It is bizarre that anarchists demand diversity of tactics in the streets but then are coerced by calls for ‘unity’ in these large coalitions. Can’t we do better? Fortunately, we can. Radical Decentralization: A New Beginning So let us begin our work not in large coalitions and super structures but in small affinity groups. Within the context of our communities, the radical decentralization of work, projects and responsibility strengthens the ability of anarchist groups to thrive and do work which best suits them. We must reject the default of ineffective, tyrannical super structures as the only means to get work done and must strengthen and support existing affinity groups and collectives. Let us be as critical of the need for large federations, coalitions and other super-structures as we are of the State, religion, bureaucracies and corporations. Our recent successes have defied the belief that we must be part of some giant organization “to get anything done”. We should take to heart the thousands of anarchist DIY projects being done around the world outside super structures. Let us come to meetings as equals and work based on our passions and ideals, and then find others with whom we share these ideals. Let us protect our autonomy and continue to fight for liberty, trust and true solidarity.

A Simple Method For Real-Time Detection Of Voltage Sags and Swells in Practical Loads Abstract This paper presents an algorithm for real time detection of short duration voltage disturbances that occur in single phase power supply systems. The method used involves the use of a sliding, overlapping window of fixed size for measuring the RMS(root mean square) value of the voltage signal. The RMS value of a fixed number of voltage samples, is computed over a cycle, and this value is updated over a sample period by the overlapping window. A trigger signal is generated in response to the comparison of the RMS values between two consecutive cycles of the voltage signal. The trigger thus obtained, can be used to initiate the operation of the main control system of a Dynamic Voltage Restorer (DVR) to be used in conjunction with the detection unit to mitigate the sag or swell, or as a triggering function to a digital recorder to record the occurrence of the disturbance. The modeling of the algorithm and test of its functioning was carried out in Matlab - Simulink environment. Reliability of the functioning of the algorithm under conditions of noise and change in the nature of the sag and swell in the voltage signal was tested on real data acquired during events such as starting of induction motor, intermittent loading of welding transformer, and dynamic loading of a captive diesel generator. TMS320F6713 Digital Signal Processor used for the implementation of the algorithm has been programmed through the Matlab embedded link for code composer studio. The experimental set up consists of a digital signal processor (DSP) TMS320C6713, for generation of trigger, a personal computer for record of the parameters and is successfully tested for real time disturbance detection.

Interstitial Lung Disease in Undifferentiated Forms of Connective Tissue Disease The intersection of interstitial lung disease (ILD) and connective tissue disease (CTD) is complex and commonly includes the scenario whereby ILD is identified in patients with pre-existing, well-characterized forms of CTD, is the presenting manifestation of a well-characterized form of CTD, or arises within the context of a poorly defined, “undifferentiated” form of CTD. Determining that an ILD is CTD associated is important because this knowledge often impacts management and prognosis. Identifying occult CTD in patients with an “idiopathic” ILD can be challenging and requires a comprehensive, often multidisciplinary, evaluation. There is much uncertainty and controversy surrounding undifferentiated forms of CTD-associated ILD and prospective studies are needed to provide a better understanding of the natural history of these cohorts, how to best manage them, and to determine whether they behave similar to definite forms of CTD-associated ILD.

. Electrocardiographic tests in 281 workers of metallurgical industry, exposed for 3-20 years to mechanical and acoustic vibrations exceeding allowable standards, were carried out. The control group consisted of 120 subjects unexposed to physical or chemical hazards. In 82 subjects exposed to vibration and noise, 43 workers exposed to isolated noise and 30 subjects of the control group, the amount of 3 methoxy--4 hydroxymandelic (3M4HM) acid before and after work was determined. Significantly more frequent repolarization disturbances of neurovegetative nature (V-3), particularly in those simultaneously exposed to general and local vibration, were evidenced. In those exposed exclusively to noise no ECG changes were found. In addition, increased 3M4HM secretion, due to both local and whole--body transmitted vibration, was found. Isolated noise does not induce an increase in 3M4HM secretion.

Like the way it expands the cops’ ability to surreptitiously record citizens during the course of an investigation. Instead of having to go to a judge for a warrant, in many cases all the police now need is the permission of a state’s attorney. The prospect of increased eavesdropping without a warrant is serious enough that the ACLU, which initially helped craft the legislation, now opposes the new law. It’s “too great an expansion of police power,” says ACLU spokesman Edwin C. Yohnka. As for conversations between ordinary citizens, the new law makes it illegal to surreptitiously record any communication when one or more parties has a “reasonable expectation” of privacy. What’s a “reasonable” expectation? “Any expectation recognized by law.” If you don’t know what that might cover (and who but a legal expert would?), you’re back to requiring express permission before you hit record if you want to be safe from potential prosecution. And what about the situation that got Chris Drew in trouble? In the era of Ferguson and “I can’t breathe,” can Illinois citizens now record police officers in action? The ACLU says yes: the new law “respects” an appellate court ruling that cops on duty have “no reasonable expectation of privacy in their conversations in public places.” You won’t find that language in the law itself, however. State representative Elaine Nekritz, who sponsored the bill in the house, says that’s no accident. We made a decision “not to specifically state that citizens can record cops,” Nekritz says. “I thought if we tried to describe every instance in which you either were or were not committing eavesdropping, we would run into more trouble than we’ve created by having this more general standard. We just can’t write every circumstance in which someone has a reasonable expectation of privacy.” Like the definition of guilt beyond a reasonable doubt, she says, “we know it when we see it.”

Violation in B → π + π − and the Unitarity Triangle We analyze the extraction of weak phases from CP violation in B → π+π− decays. We propose to determine the unitarity triangle (ρ̄, η̄) by combining the information on mixing induced CP violation in B → π+π−, S, with the precision observable sin 2β obtained from the CP asymmetry in B → ψKS . It is then possible to write down exact analytical expressions for ρ̄ and η̄ as simple functions of the observables S and sin 2β, and of the penguin parameters r and φ. As an application clean lower bounds on η̄ and 1 − ρ̄ can be derived as functions of S and sin 2β, essentially without hadronic uncertainty. Computing r and φ within QCD factorization yields precise determinations of ρ̄ and η̄ since the dependence on r and φ is rather weak. It is emphasized that the sensitivity to the phase φ enters only at second order and is extremely small for moderate values of this phase, predicted in the heavy-quark limit. Transparent analytical formulas are further given and discussed for the parameter C of direct CP violation in B → π+π−. We also discuss alternative ways to analyze S and C that can be useful if new physics affects Bd–B̄d mixing. Predictions and uncertainties for r and φ in QCD factorization are examined in detail. It is pointed out that a simultaneous expansion in 1/mb and 1/N leads to interesting simplifications. At first order infrared divergences are absent, while the most important effects are retained. Independent experimental tests of the factorization framework are briefly discussed. PACS numbers: 11.30.Er, 12.15.Hh, 13.25.Hw buchalla@theorie.physik.uni-muenchen.de safir@theorie.physik.uni-muenchen.de

Children's Original Thinking: An Empirical Examination of Alternative Measures Derived From Divergent Thinking Tasks Abstract Children's creative potential is often assessed using cognitive tests that require divergent thinking, such as the Torrance Tests of Creative Thinking (TTCT; E. P. Torrance, 1974, 1976, 1990). In this study the authors investigated the effect of various scoring systems on the originality index, evaluating the high intercorrelation of fluency and originality measures found in the TTCT scoring system and the applicability of TTCT scoring norms over time and across age groups. In 3 studies, the originality of elementary school children was measured using TTCT norms and various sample-specific scoring methods with the TTCT Unusual Uses of a Box test as well as social-problem-solving tasks. Results revealed an effect of scoring technique on creativity indices as well as on the reliability of originality scores and the relationship between originality and other ability measures. The usefulness of the various measures for understanding children's original thinking are discussed.

Challenges to Preparing and Conducting Christian Worship in Nursing Homes This essay explores and details the various challenges that are faced in the design of Christian worship within the nursing home environment. People in this setting have special needs-physical, mental, social, and spiritual. The physical plant itself demands special considerations when preparing for worship. Difficulties are defined and solutions presented for those who would provide intentional and accessible Christian worship that allows for action and response from the community in these settings. Sources include Christian liturgical reference materials and on-site interviews with chaplains and activity directors at three care facilities in southeast Michigan.

The Susan B. Anthony List is known for misleading ads. So it may come as a small surprise that a recent ad it sponsored featuring the Ryun family doesn't mention the family patriarch's long history as a Republican operative with close links to the Tea Party and the Koch brothers. Ned Ryun, who appears with his wife and daughter in an ad that targets North Carolina's incumbent senator, Democrat Kay Hagan, has a long history as a Republican operative with close links to the Tea Party and the Koch brothers. Women Speak Out PAC via YouTube Ned Ryun and Becca Parker Ryun are a telegenic couple, who star in a heart-wrenching 65-second advertisement that targets North Carolina’s incumbent senator, Democrat Kay Hagan. The Ryuns tell the story of their daughter, Charlotte, who was born severely premature—at 24 weeks gestation—but survived and thrived. “I didn’t think, at 24 weeks, you could have a viable baby,” Becca tells the interviewer. “It’s a human being. It wants to live. It has a soul. It has a will. It has a desire to live,” says her husband, Ned. The emotive video then shows images of the couple’s smiling daughter, as Ned says, “For those that are advocating late-term abortions, look at my daughter.” Get the facts, direct to your inbox. Subscribe to our daily or weekly digest. SUBSCRIBE The ad finishes with the message that Kay Hagan is “too extreme for North Carolina,” due to her support for later abortions. It’s a slick production, and a moving story, paid for by the Susan B. Anthony List, a leading anti-choice group, which announced last month that it was going on another advertising buying spree of up to $100,000, buying ads targeting Hagan, who is facing a tough battle to retain her seat in this year’s midterm elections. The Susan B. Anthony List is known for misleading ads. In fact, earlier this year, it went to the U.S. Supreme Court to defend its right to lie in political advertisements. So it may come as a small surprise that the ad tells only part of the story of the Ryuns, presented as an all-American couple, who could well be from North Carolina. In reality, Ned Ryun has a long history as a Republican operative with close links to the Tea Party and the Koch brothers—context that may well change how viewers see the conclusions he and Becca drew from what was undoubtedly a deeply emotional, personal experience. Neither Ned Ryun nor the Susan B. Anthony List returned Rewire’s requests for comment. Ned and Becca Ryun don’t live in North Carolina. The couple lives in Purcellville, Virginia, with their four children. Ned’s father is Jim Ryun, the former Republican U.S. Representative from Kansas who served ten years in Congress. Jim Ryun is best known for his achievements as an Olympic athlete (he was a Silver Medalist in the 1,500-meter race in the 1968 Mexico City games), and for his consistently conservative views. For instance, Jim Ryun voted against No Child Left Behind, the Bush administration’s marquee education law that was intended to boost poor-performing schools. People of all political persuasions objected to the law, but not for Ryun’s reasons: He voted “no” on the basis that states should have more control over education policy and rejected the need for additional funds. This, despite the fact that Kansas has some of the nation’s lowest performing public schools, and the greatest race-based inequality in educational opportunity. He also voted to ban adoptions by same-sex couples, to ban family planning as part of US foreign aid, and against an array of reproductive rights measures. His voting record earned him a zero rating from NARAL. Jim Ryun now runs Christian running camps, where attendees “learn how to apply racing, training strategies, and as well as hear from top Christian athletes who will share how their faith has helped them reach their fullest potential.” It’s not just Papa Ryun who is immersed in conservative politics. Ned himself is a former speechwriter for George W. Bush, while his twin brother, Drew, was a deputy director at the Republican National Committee. Along with their dad, the Ryun brothers have turned Tea Party politics into a family business. Drew and Jim Ryun are leaders of the ultra-conservative Madison Project, a group whose views of an array of things, including Europe, read more like the satirical news site The Onion. Referring to many European countries’ policies on abortion, the Madison Project’s website says: In Europe, the duly elected representatives in parliament decided the issue. Being that Europe is a morally decedent leftist utopia, they elected politicians who reflect their values. Ned heads up American Majority Inc., a 501(c)(3) nonprofit entity whose goal is to “create a national political training institute dedicated to recruiting, identifying, training and mentoring potential political leaders.” While it claims to be non-partisan, American Majority Inc. says it is committed to promoting “individual freedom through limited government and the free market.” In reality, that has mostly meant the Tea Party. Ned even wrote a monthly column in The Spectator called “With the Tea Partiers.” Like the brothers, American Majority Inc. has a twin—a 501(c)(4) called American Majority Action, which is led by Drew. Together, the American Majority organizations have donated to numerous Tea Party groups across the country, according to the entities’ tax filings. In 2010 the American Majority apparatus gave $520,000 to radical groups, including $22,500 to the St. Louis Tea Party in Missouri; $5,000 to the Jefferson County Tea Party in Missouri; and $275,000 to Grassroots Outreach, a Tempe, Arizona-based firm that has been linked to voter fraud. They have also made multiple donations to so-called 9/12 Project associations. The 9/12 Project is linked to Glenn Beck, and its goals include “tak[ing] over the Republican Party.” The American Majority nonprofits are licensed to do business in at least 34 states, and have drawn controversy for tactics such as paying field staffers in Ohio up to $10 an hour to get out the vote during Mitt Romney’s 2012 campaign. Traditionally, field canvassers have been volunteers. Just as interesting as who gets money from American Majority is who has donated to the Ryuns’ political operations. An analysis by Rewire, based on numbers collected by the Center for Media and Democracy, shows that American Majority received $3.9 million from DonorsTrust and its affiliated entity, the Donors Capital Fund, between 2010 and 2012. That puts American Majority among the top 15 recipients of DonorsTrust funds. DonorsTrust is one of the largest pass-through entities for conservative giving. Essentially a legal form of money laundering, DonorsTrust facilitates contributions from anonymous donors to be channeled toward conservative groups they specify. The Center for Media and Democracy names DonorsTrust as a key component of the Koch brothers’ political web. Between 2010 and 2012, the Donors entities distributed $252 million to a wide range of groups, including the Koch brothers-affiliated Americans for Prosperity Foundation, the Mercatus Center (a bastion of libertarianism, partly founded by the Koch brothers, according to Daniel Schulman’s recently published history of the Koch family, Sons of Wichita), and the right-wing Franklin Center for Government and Public Integrity. And the Ryuns’ connections to the “Kochtopus” don’t end there. According to The American Spectator, the idea for the American Majority groups “was conceived” by the Sam Adams Alliance, an organization that was active from 2007 through 2011, whose mission was to encourage “citizen engagement in politics, with specialties in studying and training citizen activists and bloggers.” The alliance was headed by long-time ultra-conservative and libertarian Eric O’Keefe, who has been close to the Koch brothers for decades. According to his online biography, O’Keefe worked on the Libertarian Party presidential campaign in 1980, in which David Koch was drafted by his older brother, Charles, into running as the vice presidential candidate. O’Keefe became close with another member of the Kochs’ inner circle, Ed Crane, who ran at the top of the Libertarian Party ticket and then spent the next few decades leading the Cato Institute, the extreme “free market” think tank that was almost entirely funded by the Kochs. O’Keefe joined Cato’s board in 1988. According to the Center for Media and Democracy, O’Keefe also worked for a group called Citizens for a Sound Economy, which was the predecessor to the Koch’s new funding vehicle, Americans for Prosperity. Thanks to O’Keefe’s ideas about training citizen activists, the Ryuns are now emerging as potential rivals to Karl Rove, and his enormous political machine, as masters of the “shadow” conservative movement, where power is held not by elected representatives, or even by the Republican National Committee, but by a cadre of highly paid consultants and deep-pocketed donors. In addition to American Majority, the brothers have established at least two other entities that feed into the extreme right’s political infrastructure. In 2012, American Majority reported using nearly $900,000 from its nonprofits to support a new outfit, called Media Trackers, a site that says it is “dedicated to media accountability, government transparency, and quality fact-based journalism.” In reality, Media Trackers has made claims about voter harassment in Wisconsin that PolitiFact later found were “mostly false,” and the group was active in attempting to undermine the Wisconsin effort to recall Gov. Scott Walker. Media Trackers is “a project” of another nonprofit entity with the Orwellian name Greenhouse Solutions. Tax filings show that Ned’s brother, Drew, and their father, Jim, are on the board. (It’s noteworthy that of the three bills noted by American Majority Action in its 2011 tax filings as particular lobbying targets, one was the NATGAS Act, a bipartisan measure intended to support natural gas. The name “Greenhouse Solutions” appears to literally be the opposite of what the Ryuns work toward.) However, perhaps the Ryuns’ most promising new entity is a voter database company known as Gravity. (It goes by iterations of that name—sometimes called Political Gravity, and sometimes, Voter Gravity.) Political parties increasingly rely on sophisticated voter databases to win elections, and they’re willing to pay high premiums for the best data, and those who know how to wield it. In the aftermath of Mitt Romney’s loss in the 2012 presidential race, the relative inferiority of his team’s database—known as Orca—became a key sore point for Republicans. Since then, competing teams in the shadow conservative world have been racing to build new systems to match up with the Democratic Party’s data tools—and with each other. Politico last year reported that the Koch brothers have established a political data company called i360, while Karl Rove’s group, Liberty Works, is also putting together a platform —each attempting to build the dominant conservative data tool. And then there are the Ryun twins, whose Gravity platform was expected to pass 1 million voter contacts by late 2012, propelling them into the financial center of right-wing politics. The company’s website boasts that “while Romney’s ‘Orca’ was going belly-up on Election Day, another group of conservatives were enjoying the fruits of labor that began long before voters headed to the polls.” Increasingly, they are being taken seriously as highly connected conservative heavyweights. While none of this detracts from Ned and Becca Ryun’s experience with the premature birth of their daughter, it does change the way viewers might see the conclusions that the couples drew from that experience. The Ryuns are far from being “everyday” North Carolinians. They are ensconced in the ultra-conservative movement, and their income derives from convincing the public of their very particular worldview. It would be fair to say that, if North Carolina voters knew the reality of who the Ryuns are, they’d be less inclined to see Kay Hagan as an “extremist,” and more likely to look closely at what the Ryuns believe. Moreover, Ned Ryun’s failure to disclose his conflicts of interest raises questions about how much trust can be placed in the views he expresses. Not only did he and the Susan B. Anthony List neglect to mention Ned’s extensive Koch brothers connections, but neither group mentioned that they had worked together in the past, when they both helped to launch Ohio Life and Liberty in October 2012. Nor did Ned disclose that the Susan B. Anthony List had contributed $28,000 to his father’s political campaign. (Koch Industries contributed more than $86,000.) But Ned Ryun’s failure to disclose even extends to his interest in Voter Gravity. On the company’s Facebook page, a reviewer purrs about the quality of Gravity’s service: “It was a bit of a no brainer for me to use Voter Contact: They saved me lots of money and got me a better product.” The reviewer gave Voter Gravity a five-star rating. Political Gravity’s account then replies, “Thank you Mr. Ryun.” That’s right. That reviewer was Ned Ryun, who replies—possibly to himself—“You bet. This is good stuff.” If the Ryuns’ entity, Media Trackers, is intended to police truth in the media, perhaps they should take a look at themselves. Surely they’d see no conflict of interest with that, either. Sofia Resnick contributed research to this report.

Bangkok: The dangerous stand-off over an oil rig in a disputed area of the South China Sea has pushed Vietnamese authorities to crack down on fierce anti-China protests and forcibly break up small demonstrations in two cities. Witnesses in southern Ho Chi Minh City said police dragged away several demonstrators from a park in the city centre. Vietnam’s Prime Minister Nguyen Tan Dung ordered an end to all “illegal protests” amid expectations of more anti-China unrest in Ho Chi Minh City and Hanoi, as Vietnam and China feuded over the placement over a $US1 billion ($1.06 billion) Chinese oil rig in the South China Sea. China, meanwhile, had evacuated more than 3000 of its nationals via flights and was sending five ships to evacuate more, the state-run Xinhua news service reported on Sunday.

ON THE ACCELERATION AND JERK IN MOTION ALONG A SPACE CURVE WITH QUASI-FRAME IN EUCLIDEAN 3-SPACE In this paper, we consider a particle moves on a space curve in the Euclidean 3-space and resolve its acceleration and jerk vectors according to quasi-frame. In this resolution, by appyling Siacci's theorem, we state the acceleration vector as the sum of its tangential and radial components, and obtain the jerk vector along the tangential direction and radial directions in osculating and rectifying planes. On the basis of the jerk vector formula , we give the maximum admissible speed on a space curve at all trajectory points. Furthermore, we present illustrative examples to explain how our results work.

Book Review: Governing Narratives: Symbolic Politics and Policy Change How is public policy implemented, and what informs its implementation by public administrators? Debate in the academic literature over policy development and implementation issues is long standing; a major consensus is that policy making is accomplished rationally, by calculating benefits and risk. In spite of challenges to this consensus, developing a coherent counterapproach has proven extremely difficult. The persistent scholarly search for new explanations of the differences between policy making and implementation processes has recently yielded to what is described in the academic literature as the narrative approach (Lindquist, 2009; Pepper & Wildy, 2009). New books attempt to explain how it can help policy makers, scholars, and students of public policy and administration understand options in the process of policy development and implementation. Sandford Borins, of the University of Toronto, not long ago published his renowned book—Governing Fables: Learning from Public Sector Narratives and Innovating with Integrity—which explains the repercussions of storytelling for the development and implementation of public policy. Partly through expanding the role of narratives, or storytelling, on policy analysis and implementation, Hugh T. Miller’s new book, Governing Narratives: Symbolic Politics and Policy Change, has enhanced our understanding of the importance of policy discourse from a narrative perspective. It has, further, added a significant voice to those speaking for the limitations of rationalism in policy making and implementation. According to Miller, the narrative approach seeks to “get beneath, around, and behind the way the media, society, lobbyists, public relations consultants, and people in government discuss public policy” (p. 18). As Miller himself rightly points out, the essence of the approach, and the purpose of the book, is to cast doubt on the “modern image of a rational, autonomous, intentional actor”: the scientific approach, in other words, to policy analysis that has dominated the field since the era of scientific management government and the emergence of the economic idea propounded by classical policy analysis scholars. Miller replaces that actor with “a decentred subject whose personage is inscribed by childhood experiences, family practices, and educational background, and many other cultural influences (p. xi).” It is a way to understand what and how policy discourses are shaped, and attends to what may be described as the idiosyncrasies of the personalities involved in advancing any course of action. Such a decentered subject, he notes, is not a product of the rational school of thought, but is, rather, “a product of the inscriptions accumulated through socialization and experience, by cultural symbolization, and genetic inheritance” (p. 14). The preface sets the tone of the book. Thereafter, Miller proceeds to demonstrate the importance of narrative’s governing of the policy making and implementation spheres by examining some critical concepts: he describes them in Chapter 1 as Words/Action. Here he draws the attention of the reader to critical issues in narratives, such as symbolic communication (p. 3), 482749 ARP43610.1177/0275074013482749American Review of Public AdministrationBook Review research-article2013

On Episode 28, I bag with one clean shot, a perfectly healthy free-range Honnold. Alex sits down in a clean, well-lit place to expound on his life in the glare of the klieg lights . He tells us what it was like to lock eyes with the beautiful and mysterious Lara Logan, what it was like to lock eyes with the happy-go-lucky Steve Denny on a lonely night on El Cap, and what its like to lock eyes with you, as he blows past on that hanging belay in Yosemite. From shy boy to pro-sesh hero, Alex lets us sit in on his world for an hour. Turns out, its pretty fun and chill in the Republic of Honnoldlandia. Alex on 60 Minutes (if you’re lucky, with a Viagra commercial, or two) Alex on No Way Jose, North Wash, UT vs. Our friend JP Ouellet on No Way Jose Want more Alex Honnold, you freak? Just google him and say goodbye to the afternoon!

Single-shot non-invasive three-dimensional imaging through scattering media We present a method for single-shot three-dimensional imaging through scattering media with a three-dimensional memory effect. In the proposed computational process, a captured speckle image is two-dimensionally correlated with different scales, and the object is three-dimensionally recovered with three-dimensional phase retrieval. Our method was experimentally demonstrated with a lensless setup and was compared with a multi-shot approach used in our previous work . INTRODUCTION Imaging through scattering media has been long studied for biomedical imaging, astronomical imaging, and so on . Recently, optical sensing and control through strongly scattering media, which are difficult to handle in conventional approaches relying on the existence of non-scattered light, have attracted interest in the field of optics and photonics. The rapidly growing computational power and the improved performance of optical elements for light control drive this area, and various methods have been reported. These methods are categorized into three types: feedback-based, inversion-based, and correlationbased . The feedback-based approach utilizes wavefront shaping behind or inside scattering media with an iterative feedback process based on an optimization algorithm . Issues with the feedback-based approach are the large number of feedback loops and the need for a probing process to measure the focusing state in the every loop. The inversion-based approach, including time reversal and phase conjugation, senses and controls the optical distribution through scattering media by taking the inverse of a transmission matrix expressing the scattering process . These methods realize single-shot imaging and focusing without any feedback process. However, they need to probe the whole or part of the transmission matrix before the imaging and focusing stage. The correlation-based approach exploits the shift invariance of speckles, which is called the memory effect . In the correlation-based methods, an autocorrelation process is used for removing speckles and exposing object signals in captured images. An advantage of the correlation-based approach is the lack of a need for the probing process, which is a drawback of the previous two approaches. As a result, the correlation-based approach has realized non-invasive imaging through scattering media. This approach has been recently extended to a threedimensional case . Drawbacks with the methods for correlation-based threedimensional imaging through scattering media include the need for capturing multiple images and/or invasive optical processes. Thus, they are difficult to apply to imaging of dynamical and practical scenes. Here we present a method for tomographic reconstruction of a three-dimensional object from a single speckle image captured through scattering media without any invasive or probing process. We demonstrated the method experimentally with a lensless setup. Our method enhances the possibility and practicability of imaging though scattering media for a wide range of applications, including biomedicine, security, and industry. METHOD The optical setup in the proposed method is shown in Fig. 1. A three-dimensional object o is illuminated with spatially incoherent illumination through a first diffuser, and the light scattered by a second diffuser is captured by a lensless image sensor as i. The relationship between the object and the captured speckle is three-dimensionally shift-invariant, based on the three-dimensional memory effect . Then, the imaging process is written with a scattering impulse response h as where r i = (x i , y i , z i ) are the spatial coordinates in the object space, and r o = (x o , y o , z o ) are the spatial coordinates in the sensor space, respectively. The x-and y-axes are lateral to the image sensor, and the z-axis is axial to the image sensor. The origin of these coordinates is the center of the second diffuser. The impulse response h is laterally random and axially scaled with a scaling factor s, which is written as In our previous work on multi-shot three-dimensional imaging through scattering media , the image sensor is axially scanned to observe the three-dimensional speckle distribution i, which is three-dimensionally autocorrelated to remove the impact of the scattering process h as where ⋆ 3D is the three-dimensional correlation, ⊗ 3D is the threedimensional convolution, F 3D denotes the three-dimensional Fourier transform, and O is the three-dimensional transform of o. Here, h ⋆ 3D h is approximated by the delta function due to the laterally random and axially scaled distribution of h . The object signal o is recovered by a phase retrieval process for |O| 2 . In this study, as shown in Fig. 2, a three-dimensional object is tomographically reconstructed from a single captured speckle image i 2D , which contains differently scaled impulse responses h depending on the object distances z o , using the optical setup in Fig. 1. The captured speckle image is computationally and laterally scaled multiple times, instead of multiple measurements made while axially scanning the image sensor as in the previous work . This computational scaling process mimics the optical scaling process in Eq. (2) by axial scanning, where the scaling factor is monotonically increased or decreased. This process is exploited for searching relative scales of the impulse responses on the original speckle image through the following correlation process, where high correlations appear if the original and scaled impulse responses are coincident, and vice versa. The scaled speckle images are computationally and laterally correlated as follows: where ⋆ 2D is the two-dimensional correlation, the superscript , and the superscript m = 0, 1, · · · , M − 1 denotes the index of the scaling factor. In this study, o ⋆ 3D o in Eq. (5) is approximated by c k . The object o is three-dimensionally reconstructed from the correlation result c k based on three-dimensional phase retrieval. The phase retrieval process in this study follows the previous work on speckle-correlation-based imaging through scattering media . Here two algorithms, which are called the error reduction algorithm and the hybrid input-output algorithm , are sequentially performed, as shown in Fig. 2. The second algorithm is a modified version of the first one, and they use the loop in the iterative processes shown in Fig. 3. The difference between them is the process of constraints. First, the common aspects are described, and then the differences are explained. The iterative process of the error reduction algorithm and the hybrid input-output algorithm is shown in Fig. 3 and is described as follows: 1. The object's Fourier spectrum is initially given with a three-dimensional random phase θ n by O n = (|O| 2 ) (1/2) exp(jθ n ), where j is the imaginary unit, |O| 2 is the three-dimensional Fourier transform of c k in Eq. (7), and the subscript n is the counter of the iteration, which is set to one. 2. O n is three-dimensionally inverse Fourier transformed, and the result is set as the intermediately estimated object o ′ n . 3. o ′ n is rectified with some constraints, which are described in the following paragraphs, and the result is the estimated object o n at the n-th iteration. 4. o n is three-dimensionally Fourier transformed, and the result is set as the intermediately estimated object's Fourier spectrum O ′ n . 5. The argument of O ′ n is extracted, and it is used as a replacement of the argument θ n of the estimated object's Fourier spectrum O n , where the counter n is incremented by one. The rectifying process with constraints at Step 3 is the difference between the error reduction algorithm and the hybrid input-output algorithm . In the error reduction algorithm, the intermediately estimated object o ′ n at the n-th iteration is updated with the following rule: where Γ is the set of all spatial positions r o which violate the constraints. In the hybrid input-output algorithm, the updating rule is as follows: where β is a feedback parameter. In the reconstruction according to the proposed scheme, as shown in Fig. 2, the hybrid input-output algorithm is performed first. In this algorithm, the feedback parameter β is decreased from 2.0 to 0.0 in intervals of 0.05, and the loop of Fig. 3 is iterated ten times for each β. Then, the error reduction algorithm is performed by using the result of the hybrid input-output algorithm as the initial estimate at Step 1, and the loop of Fig. 3 is iterated five hundred times. The constraints used here are realness, non-negativity, and the range of pixel intensities. Realness and non-negativity are introduced by using spatially incoherent illumination, such as a light emitting diode (LED) or fluorescence . The range of pixel intensities suppresses some reconstruction artifacts . This phase retrieval has trivial ambiguities of the spatial shift and the conjugate inversion, which have been studied in the literature on phase retrieval . EXPERIMENTAL DEMONSTRATION The proposed method was demonstrated with threedimensionally arranged point sources fabricated by a 3D printer (M2030TP manufactured by L-DEVO). The object had three levels, where the step height was 0.5 cm, and holes with a diameter of 0.4 mm were located at different positions on each level, as shown in Fig. 4(a). One hole was made on the front level, two diagonally arranged holes were made on the middle level, and two vertically arranged holes were made on the back level, respectively. As shown in Fig. 1, the object was located between two diffusers and it was illuminated with an incoherent LED (M565L3 manufactured by Thorlabs, nominal wavelength: 565 nm, full width at half maximum of spectrum: 103 nm) through a bandpass filter (578NM X 16NM 25MM manufactured by Edmund Optics, central wavelength 578 nm, full width at half maximum of spectrum: 22 nm) and a diffuser (LSD5PC10-5 manufactured by Luminit). The distance between the first diffuser and the object was 75 mm. Light passing through object was scattered by The three-dimensional phase retrieval result with the multi-shot approach in Reference , where the scale bar is 2 mm at the object plane. another diffuser (LSD20PC10-5 manufactured by Luminit) and captured by a monochrome image sensor (hr29050MFLGEA manufactured by SVS-Vistek, pixel count: 4384 × 6576, pixel pitch: 5.5 × 5.5 µm) without any imaging optics. The distance (z o ) between the object and the second diffuser was 92 mm, and the distance (z i ) between the second diffuser and the image sensor was 25 mm, as shown in Fig. 1. The captured speckle image is shown in Fig. 4(b), where the central 600 × 600 pixel area was clipped for visualization purposes. After background compensation, the captured image was scaled with a computational scaling factor s m com based on Eq. (2) as follows: where ∆ z o is the axial resolution of the object space, which was set to 0.5 mm, corresponding to the step height of the object. The number of scaled speckle images (M) was set to six. The scaled speckle images were laterally correlated as in Eq. (7). The central 800 × 800 pixel areas of the correlations were clipped and laterally down-sampled by a factor of four to reduce the computational cost in the next phase retrieval process. Biases of the correlations were equalized with the average values outside the central areas. The result of this correlation process is shown in Fig. 4(c), where the central 150 × 150 pixel areas were clipped, and contrast enhancement was applied for visualization purposes. The three-dimensional phase retrieval process was applied to the correlations, and the results are shown in Fig. 4(d), where the ambiguities of the spatial shift and the conjugate inversion were manually compensated, and the central 150 × 150 pixel areas were clipped for visualization purposes. The holes were three-dimensionally recovered. The reconstruction result of the multi-shot approach with axial scanning of the image sensor in our previous work is shown in Fig. 4(e). These results were comparable, although some interference from other planes in the single-shot approach was stronger than that in the multishot approach. An issue with the single-shot approach compared with the multi-shot one is distortion of the autocorrelation through the scaling process. The distortion should be smaller than the lateral resolution of speckle correlations. The limitation of the scaling factor in Eq. (10) is calculated as where d is the object size on the image sensor and is estimated as half of the correlative area, and δ is the resolution of speckle correlations and is √ 2-times larger than the grain size of the speckles, assuming a Gaussian distribution. In the case of the experiment, d = 300 pixels and δ = √ 2 × 17 pixels , so the above limitation was satisfied. CONCLUSION We proposed single-shot three-dimensional imaging through scattering media based on speckle correlation. An object is three-dimensionally reconstructed from a single speckle image with a scaling process, a correlation process, and a phase retrieval process. The proposed method was experimentally demonstrated with three-dimensionally arranged point sources between diffusers. The result was comparable to the multi-shot case reported previously. Our method simplifies the optical setup for threedimensional imaging through scattering media. It is useful in a wide range of modalities, including lensless imaging, microscope imaging, and telescope imaging, and applications such as looking around corners and reflection-mode scattered imaging. Also, this method may provide interesting insights for three-dimensional imaging without the need to calibrate optical hardware or probe optical phenomena before an imaging stage.