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  • richardmitnick 9:15 am on July 29, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , , CRISPR/Cas   

    From The Conversation: “CRISPR/Cas gene-editing technique holds great promise, but research moratorium makes sense pending further study “ 

    The Conversation
    The Conversation

    July 29, 2015
    No Writer Credit

    1

    CRISPR/Cas is a new technology that allows unprecedented control over the DNA code. It’s sparked a revolution in the fields of genetics and cell biology, becoming the scientific equivalent of a household name by raising hopes about new ways to cure diseases including cancer and to unlock the remaining mysteries of our cells.

    The gene editing technique also raises concerns. Could the new tools allow parents to order “designer babies”? Could premature use in patients lead to unforeseen and potentially dangerous consequences? This potential for abuse or misuse led prominent scientists to call for a halt on some types of new research until ethical issues can be discussed – a voluntary ban that was swiftly ignored in some quarters.

    The moratorium is a positive step toward preserving the public’s trust and safety, while the promising new technology can be further studied.

    Editing DNA to cure disease

    While most human diseases are caused, at least partially, by mutations in our DNA, current therapies treat the symptoms of these mutations but not the genetic root cause. For example, cystic fibrosis, which causes the lungs to fill with excess mucus, is caused by a single DNA mutation. However, cystic fibrosis treatments focus on the symptoms – working to reduce mucus in the lungs and fight off infections – rather than correcting the mutation itself. That’s because making precise changes to the three-billion-letter DNA code remains a challenge even in a Petri dish, and it is unprecedented in living patients. (The only current example of gene therapy, called Glybera, does not involve modifying the patient’s DNA, and has been approved for limited use in Europe to treat patients with a digestive disorder.)

    That all changed in 2012, when several research groups demonstrated that a DNA-cutting technology called CRISPR/Cas could operate on human DNA. Compared to previous, inefficient methods for editing DNA, CRISPR/Cas offers a shortcut. It acts like a pair of DNA scissors that cut where prompted by a special strand of RNA (a close chemical relative of DNA). Snipping DNA turns on the cell’s DNA repair process, which can be hijacked to either disable a gene – say, one that allows tumor cells to grow uncontrollably – or to fix a broken gene, such as the mutation that causes cystic fibrosis. The advantages of the Cas9 system over its predecessor genome-editing technologies – its high specificity and the ease of navigating to a specific DNA sequence with the “guide RNA” – have contributed to its rapid adoption in the scientific community.

    The barrier to fixing the DNA of diseased cells appears to have evaporated.

    Playing with fire

    With the advance of this technique, the obstacles to altering genes in embryos are falling away, opening the door to so-called “designer babies” with altered appearance or intelligence. Ethicists have long feared the consequences of allowing parents to choose the traits of their babies. Further, there is a wide gap between our understanding of disease and the genes that might cause them. Even if we were capable of performing flawless genetic surgery, we don’t yet know how specific changes to the DNA will manifest in a living human. Finally, the editing of germ line cells such as embryos could permanently introduce altered DNA into the gene pool to be inherited by descendants.

    And making cuts in one’s DNA is not without risks. Cas9 – the scissor protein – is known to cleave DNA at unintended or “off-target” sites in the genome. Were Cas9 to inappropriately chop an important gene and inactivate it, the therapy could cause cancer instead of curing it.

    Take it slow

    All the concerns around Cas9 triggered a very unusual event: a call from prominent scientists to halt some of this research. In March of 2015, a group of researchers and lawyers called for a voluntary pause on further using CRISPR technology in germ line cells until ethical guidelines could be decided.

    Writing in the journal Science, the group – including two Nobel laureates and the inventors of the CRISPR technology – noted that we don’t yet understand enough about the link between our health and our DNA sequence. Even if a perfectly accurate DNA-editing system existed – and Cas9 surely doesn’t yet qualify – it would still be premature to treat patients with genetic surgery. The authors disavowed genome editing only in specific cell types such as embryos, while encouraging the basic research that would put future therapeutic editing on a firmer foundation of evidence.

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    The basic research isn’t ready for deployment in human embryos yet. Petri dishes image via http://www.shutterstock.com

    Pushing ahead

    Despite this call for CRISPR/Cas research to be halted, a Chinese research group reported on their attempts at editing human embryos only two months later. Described in the journal Protein & Cell, the authors treated nonviable embryos to fix a gene mutation that causes a blood disease called β-thalassemia.

    The study results proved the concerns of the Science group to be well-founded. The treatment killed nearly one in five embryos, and only half of the surviving cells had their DNA modified. Of the cells that were even modified, only a fraction had the disease mutation repaired. The study also revealed off-target DNA cutting and incomplete editing among all the cells of a single embryo. Obviously these kinds of errors are problematic in embryos meant to mature into fully grown human beings.

    George Daley, a Harvard biologist and member of the group that called for the moratorium, concluded that “their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes.”

    In the enthusiasm and hype surrounding Cas9, it is easy to forget that the technology has been in wide use for barely three years.

    Role of a moratorium

    Despite the publication of the Protein & Cell study – whose experiments likely took place at least months earlier – the Science plea for a moratorium can already be considered a success. The request from such a respected group has brought visibility to the topic and put pressure on universities, regulatory boards and the editors of scientific journals to discourage such research. (As evidence of this pressure, the Chinese authors were rejected from at least two top science journals before getting their paper accepted.) And the response to the voluntary ban has thus far not included accusations of “stifling academic freedom,” possibly due to the scientific credibility of the organizers.

    While rare, the call for a moratorium on research for ethical reasons can be traced to an earlier controversy over DNA technology. In 1975, a group that came to be known as the Asilomar Conference called for caution with an emerging technology called recombinant DNA until its safety could be evaluated and ethical guidelines could be published. The similarity between the two approaches is no coincidence: several authors of the Science essay were also members of the Asilomar team.

    The Asilomar guidelines are now widely viewed as having been a proportionate and responsible measure, placing the right emphasis on safety and ethics without hampering research progress. It turns out recombinant DNA technology was much less dangerous than originally feared; existing evidence already shows that we might not be so lucky with Cas9. Another important legacy of the Asilomar conference was the promotion of an open discussion involving experts as well as the general public. By heeding the lessons of caution and public engagement, hopefully the saga of CRISPR/Cas will unfold in a similarly responsible – yet exciting – way.

    See the full article here.

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  • richardmitnick 7:34 am on July 29, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , ,   

    From Princeton: “New chemistry makes strong bonds weak” 

    Princeton University
    Princeton University

    July 28 2015
    Tien Nguyen

    Researchers at Princeton have developed a new chemical reaction that breaks the strongest bond in a molecule instead of the weakest, completely reversing the norm for reactions in which bonds are evenly split to form reactive intermediates.

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    Catalytic alkene carboamination enabled by oxidative proton-coupled electron transfer

    Published on July 13 in the Journal of the American Chemical Society, the non-conventional reaction is a proof of concept that will allow chemists to access compounds that are normally off-limits to this pathway. The team used a two-component catalyst system that works in tandem to selectively activate the strongest bond in the molecule, a nitrogen-hydrogen (N-H) bond, through a process known as proton-coupled electron transfer (PCET).

    “This PCET chemistry was really interesting to us. In particular, the idea that you can use catalysts to modulate an intrinsic property of a molecule allows you to access chemical space that you couldn’t otherwise,” said Robert Knowles, an assistant professor of chemistry who led the research.

    Using PCET as a way to break strong bonds is seen in many essential biological systems, including photosynthesis and respiration, he said. Though this phenomenon is known in biological and inorganic chemistry settings, it hasn’t been widely applied to making new molecules—something Knowles hopes to change.

    Given the unexplored state of PCET catalysis, Knowles decided to turn to theory instead of the trial and error approach usually taken by synthetic chemists in the initial stages of reaction development. Using a simple mathematical formula, the researchers calculated, for any pair of catalysts, the pair’s combined “effective bond strength,” which is the strength of the strongest bond they could break. Because both molecules independently contribute to this value, the research team had a high degree of flexibility in designing the catalyst system.

    When they tested the catalyst pairs in the lab, the researchers observed a striking correlation between the “effective bond strength” and the reaction efficiency. While effective bond strengths that were lower or higher than the target N-H bond strength gave low reaction yields, the researchers found that matching the strengths promoted the reaction in very high yield.

    “To see this formula actually working was really inspiring,” said Gilbert Choi, a graduate student in the Knowles lab and lead author on the work. Once he identified a successful catalyst system, he explored the scope of the reaction and its mechanism.

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    Proposed catalytic cycle

    The researchers think that the reaction starts with one of the catalysts, a compound called dibutylphosphate, tugging on a hydrogen atom, which lengthens and weakens the N-H bond. At the same time, the other catalyst, known as a light-activated iridium complex, targets the weakened bond and plucks off one electron from the two-electron bond, slicing it down the middle.

    Once the bond is split, the reactive nitrogen intermediate goes on to form a new carbon-nitrogen bond, giving rise to structurally complex products. This finding builds on work the Knowles lab published earlier this year also in the Journal of the American Chemical Society on a similar reaction that used a more sensitive catalyst system.

    Their research has laid a solid foundation for PCET catalysis as a platform for developing new reactions. “My sincere view is that ideas are a lot more valuable than reactions,” Knowles said. “I’m optimistic that people can use these ideas and do things that we hadn’t even considered.”

    See the full article here.

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    As a world-renowned research university, Princeton seeks to achieve the highest levels of distinction in the discovery and transmission of knowledge and understanding. At the same time, Princeton is distinctive among research universities in its commitment to undergraduate teaching.

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  • richardmitnick 4:42 pm on July 28, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , ,   

    From NYT: “The Singular Mind of Terry Tao’ 

    New York Times

    The New York Times

    JULY 24, 2015
    GARETH COOK

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    A prodigy grows up to become one of the greatest mathematicians in the world.

    This April, as undergraduates strolled along the street outside his modest office on the campus of the University of California, Los Angeles, the mathematician Terence Tao mused about the possibility that water could spontaneously explode. A widely used set of equations describes the behavior of fluids like water, but there seems to be nothing in those equations, he told me, that prevents a wayward eddy from suddenly turning in on itself, tightening into an angry gyre, until the density of the energy at its core becomes infinite: a catastrophic ‘‘singularity.’’ Someone tossing a penny into the fountain by the faculty center or skipping a stone at the Santa Monica beach could apparently set off a chain reaction that would take out Southern California.

    This doesn’t tend to happen. And yet, Tao explained, nobody can say precisely why. It’s a decades-­old conundrum, and Tao has recently been working on an approach to a solution — one part fanciful, one part outright absurd, like some lost passage from ‘‘Alice’s Adventures in Wonderland.’’

    Imagine, he said, that someone awfully clever could construct a machine out of pure water. It would be built not of rods and gears but from a pattern of interacting currents. As he talked, Tao carved shapes in the air with his hands, like a magician. Now imagine, he went on, that this machine were able to make a smaller, faster copy of itself, which could then make another, and so on, until one ‘‘has infinite speed in a tiny space and blows up.’’ Tao was not proposing constructing such a machine — ‘‘I don’t know how!’’ he said, laughing. It was merely a thought experiment, of the sort that [Albert] Einstein used to develop the theory of special relativity. But, Tao explained, if he can show mathematically that there is nothing, in principle, preventing such a fiendish contraption from operating, then it would mean that water can, in fact, explode. And in the process, he will have also solved the Navier-­Stokes global regularity problem, which has become, since it emerged more than a century ago, one of the most important in all of mathematics.

    Tao, who is 40, sat at a desk by the window, papers lying in drifts at the margins. Thin and unassuming, he was dressed in Birkenstocks, a rumpled blue-gray polo shirt and jeans with the cuffs turned up. Behind him, a small almond couch faced a glyph-­covered blackboard running the length of the room. The couch had been pulled away from the wall to accommodate the beat-up Trek bike he rides to work. At the room’s other end stood a fiberboard bookcase haphazardly piled with books, including ‘‘Compactness and Contradiction’’ and ‘‘Poincaré’s Legacies, Part I,’’ two of the 16 volumes Tao has written since he was a teenager.

    Fame came early for Tao, who was born in South Australia. An old headline in his hometown paper, The Advertiser, reads: ‘‘TINY TERENCE, 7, IS HIGH-SCHOOL WHIZ.’’ The clipping includes a photo of a diminutive Tao in 11th-grade math class, wearing a V-neck sweater over a white turtleneck, kneeling on his chair so he can reach a desk he is sharing with a girl more than twice his age. His teacher told the reporter that he hardly taught Tao anything, because Tao was always working two lessons ahead of the others. (Tao taught himself to read at age 2.)

    A few months later, halfway through the school year, Tao was moved up to 12th-grade math. Three years later, at age 10, Tao became the youngest person in history to win a medal in the International Mathematical Olympiad. He has since won many other prizes, including a MacArthur ‘‘genius’’ grant and the Fields Medal, considered the Nobel Prize for mathematicians. Today, many regard Tao as the finest mathematician of his generation.

    That spring day in his office, reflecting on his career so far, Tao told me that his view of mathematics has utterly changed since childhood. ‘‘When I was growing up, I knew I wanted to be a mathematician, but I had no idea what that entailed,’’ he said in a lilting Australian accent. ‘‘I sort of imagined a committee would hand me problems to solve or something.’’ But it turned out that the work of real mathematicians bears little resemblance to the manipulations and memorization of the math student. Even those who experience great success through their college years may turn out not to have what it takes. The ancient art of mathematics, Tao has discovered, does not reward speed so much as patience, cunning and, perhaps most surprising of all, the sort of gift for collaboration and improvisation that characterizes the best jazz musicians. Tao now believes that his younger self, the prodigy who wowed the math world, wasn’t truly doing math at all. ‘‘It’s as if your only experience with music were practicing scales or learning music theory,’’ he said, looking into light pouring from his window. ‘‘I didn’t learn the deeper meaning of the subject until much later.’’

    Possibly the greatest mathematician since antiquity was Carl Friedrich Gauss, a dour German born in the late 18th century. He did not get along with his own children and kept important results to himself, seeing them as unsuitable for public view. They were discovered among his papers after his death. Before and since, the annals of the field have teemed with variations on this misfit theme, from Isaac Newton, the loner with a savage temper; to John Nash, the ‘‘beautiful mind’’ whose work shaped economics and even political science, but who was racked by paranoid delusions; to, more recently, ­Grigory Perelman, the Russian who conquered the Poincaré conjecture alone, then refused the Fields Medal, and who also allowed his fingernails to grow until they curled.

    Tao, by contrast, is, as one colleague put it, ‘‘super-normal.’’ He has a gentle, self-­deprecating manner. He eschews job offers from prestigious East Coast institutions in favor of a relaxed, no-drama department in a place where he can enjoy the weather. In class, he conveys a sense that mathematics is fun. One of his students told me that he had recently joked with another about the many ways Tao defies all the Hollywood mad-­genius tropes. ‘‘They will never make a movie about him,’’ he said. ‘‘He doesn’t have a troubled life. He has a family, and they seem happy, and he’s usually smiling.’’

    This can be traced to his own childhood, which he experienced as super-normal, even if, to outside eyes, it was anything but. Tao’s family spent most of his early years living in the foothills south of Adelaide, in a brick split-­level with views of Gulf St. Vincent. The home was designed by his father, Billy, a pediatrician who immigrated with Tao’s mother, Grace, from Hong Kong in 1972, three years before Tao, the eldest of three, was born in 1975. The three boys — Nigel, Trevor and ‘‘Terry,’’ as everyone calls him — often played together, and a favorite pastime was inventing board games. They typically appropriated a Scrabble board for a basic grid, then brought in Scrabble tiles, chess pieces, Chinese checkers, mah-jongg tiles and Dungeons & Dragons dice, according to Nigel, who now works for Google. For story lines, they frequently drew from video games coming out at the time, like Super Mario Bros., then added layers of complex, whimsical rules. (Trevor, a junior chess champion, was too good to beat, so the boys created a variation on that game as well: Each turn began with a die roll to determine which piece could be moved.) Tao was a voracious consumer of fantasy books like Terry Pratchett’s Discworld series. When a class was boring, he doodled intricate maps of imaginary lands.

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    Terry Tao, age 7, in an 11th-grade math class. Credit Photograph by The Advertiser, from the Tao family

    By the spring of 1985, with a 9-year-old Tao splitting time between high school and nearby Flinders University, Billy and Grace took him on a three-week American tour to seek advice from top mathematicians and education experts. On the Baltimore campus of Johns Hopkins, they met with Julian Stanley, a Georgia-­born psychologist who founded the Center for Talented Youth there. Tao was one of the most talented math students Stanley ever tested — at 8 years old, Tao scored a 760 on the math portion of the SAT — but Stanley urged the couple to keep taking things slow and give their son’s emotional and social skills time to develop.

    Even at a relatively deliberate pace, by age 17, Tao had finished a master’s thesis (‘‘Convolution Operators Generated by Right-­Monogenic and Harmonic Kernels’’) and moved to Princeton University to start on his Ph.D. Tao’s application to the university included a letter from Paul Erdos, the revered Hungarian mathematician. ‘‘I am sure he will develop into a first-rate mathematician and perhaps into a really great one,’’ read Erdos’s brief, typewritten note. ‘‘I recommend him in the highest possible terms.’’ Yet on arrival, it was Tao, the teenage prodigy, who was intimidated. During Tao’s first year, Andrew Wiles, then a Princeton professor, announced that he proved Fermat’s Last Theorem, a legendary problem that had gone unsolved for more than three centuries. Tao’s fellow graduate students spoke eloquently about mathematical fields of which he had barely heard.

    Tao became notorious for his nights haunting the graduate computer room to play the historical-­simulation game Civilization. (He now avoids computer games, he told me, because of what he calls a ‘‘completist streak’’ that makes it hard to stop playing.) At a local comic-book store, Tao met a circle of friends who played ‘‘Magic: The Gathering,’’ the intricate fantasy card game. This was Tao’s first real experience hanging out with people his age, but there was also an element, he admitted, of escaping the pressures of Princeton. Gifted children often avoid challenges at which they might not excel. Before Tao went to Princeton, his grades had flagged at Flinders. In a course on quantum physics, the instructor told the class that the final would include an essay on the history of the field. Tao, then 12, blew off studying, and when he sat down for the exam, he was stunned to discover that the essay would count for half the grade. ‘‘I remember crying,’’ Tao said, ‘‘and the proctor had to escort me out.’’ He failed.

    At Princeton, crisis came in the form of the ‘‘generals,’’ a wide-­ranging, arduous oral examination administered by three professors. While other students spent months working through problem sets and giving one another mock exams, Tao settled on his usual test-prep strategy: last-­minute cramming. ‘‘I went in and very quickly got out of my depth,’’ he said. ‘‘They were asking questions which I had no ability to answer.’’ Immediately after, Tao sat with his adviser, Elias Stein, and felt that he had let him down. Tao wasn’t really trying, and the hardest part was yet to come.

    The true work of the mathematician is not experienced until the later parts of graduate school, when the student is challenged to create knowledge in the form of a novel proof. It is common to fill page after page with an attempt, the seasons turning, only to arrive precisely where you began, empty-handed — or to realize that a subtle flaw of logic doomed the whole enterprise from its outset. The steady state of mathematical research is to be completely stuck. It is a process that Charles Fefferman of Princeton, himself a onetime math prodigy turned Fields medalist, likens to ‘‘playing chess with the devil.’’ The rules of the devil’s game are special, though: The devil is vastly superior at chess, but, Fefferman explained, you may take back as many moves as you like, and the devil may not. You play a first game, and, of course, ‘‘he crushes you.’’ So you take back moves and try something different, and he crushes you again, ‘‘in much the same way.’’ If you are sufficiently wily, you will eventually discover a move that forces the devil to shift strategy; you still lose, but — aha! — you have your first clue.

    As a group, the people drawn to mathematics tend to value certainty and logic and a neatness of outcome, so this game becomes a special kind of torture. And yet this is what any ­would-be mathematician must summon the courage to face down: weeks, months, years on a problem that may or may not even be possible to unlock. You find yourself sitting in a room without doors or windows, and you can shout and carry on all you want, but no one is listening.

    Within his field, Tao is best known for a proof about a remarkable set of numbers known as the primes. The primes are the whole numbers larger than 1 that can be divided evenly by only themselves and 1. Thus, the first few primes are 2, 3, 5, 7 and 11. The number 4 is not a prime because it divides evenly by 2; the number 9 fails because it can be divided by 3. Prime numbers are fundamental building blocks in mathematics. Like the chemical elements, they combine to form a universe. To a chemist, water is two atoms of hydrogen and one of oxygen. Similarly, in mathematics, the number 12 is composed of two ‘‘atoms’’ of 2 and one ‘‘atom’’ of 3 (12 = 2 x 2 x 3).

    The primes are elementary and, at the same time, mysterious. They are a result of simple logic, yet they seem to appear at random on the number line; you never know when the next one will occur. They are at once orderly and disorderly. They have been incorporated into mysticism and religious ritual and have inspired works of music and even an Italian novel, ‘‘The Solitude of Prime Numbers.’’ It is easy to see why mathematicians consider the primes to be one of the universe’s foundations. From counting, you can develop the concept of number, and then, quite naturally, the basic operations of arithmetic: addition, subtraction, multiplication and division. That is all you need to spot the primes — though, eerily, scientists have uncovered deep connections between primes and quantum mechanics that remain unexplained. Imagine that there is an advanced civilization of aliens around some distant star: They surely do not speak English, they may or may not have developed television, but we can be almost certain that their mathematicians have discovered the primes and puzzled over them.

    Tao’s work is related to the twin-prime conjecture, which the French mathematician Alphonse de Polignac suggested in 1849. Go up the number line, circling the primes, and you may notice that sometimes a pair of primes is separated by just 2: 5 and 7, 11 and 13, 17 and 19. These are the ‘‘twin primes,’’ and as the journey along the number line continues, they occur less frequently: 2,237 and 2,239 are followed by 2,267 and 2,269; after 31,391 and 31,393, there isn’t another pair until you reach 31,511 and 31,513. Euclid devised a simple, beautiful proof showing that there is an infinite number of primes. But what of the twin primes? As far as you go on the number line, will there always be another set of twins? The conjecture has roundly defeated all attempts at proving it.

    When mathematicians face a question they cannot answer, they sometimes devise a less stringent question, in the hope that solving it will provide insights. This is the path that Tao took in 2004, in collaboration with Ben Green of Oxford. Twins are two primes that are separated by exactly 2, but Green and Tao considered a looser definition, strings of primes separated by a constant, be it 2 or any other number. (For example, the primes 3, 7 and 11 are separated by the constant 4.) They sought to prove that no matter how long a string someone found, there would always be another longer string with a constant gap between its primes. That February, after some initial conversations, Green came to visit Tao at U.C.L.A., and in just two exhilarating months, they completed what is now known as the Green-Tao theorem. It could be a way point on the path to the twin-prime conjecture, and it forged deep connections between disparate areas of math, helping establish an interdisciplinary area called additive combinatorics. ‘‘It opened a lot of new directions in research,’’ says Izabella Laba, a University of British Columbia mathematician who has worked with Tao. ‘‘It gave a lot of people a lot of things to do.’’

    This sort of collaboration has been a hallmark of Tao’s career. Most mathematicians tend to specialize, but Tao ranges widely, learning from others and then working with them to make discoveries. Markus Keel, a longtime collaborator and close friend, reaches to science fiction to explain Tao’s ability to rapidly digest and employ mathematical ideas: Seeing Tao in action, Keel told me, reminds him of the scene in ‘‘The Matrix’’ when Neo has martial arts downloaded into his brain and then, opening his eyes, declares, ‘‘I know kung fu.’’ The citation for Tao’s Fields Medal, awarded in 2006, is a litany of boundary hopping and notes particularly ‘‘beautiful work’’ on Horn’s conjecture, which Tao completed with a friend he had played foosball with in graduate school. It was a new area of mathematics for Tao, at a great remove from his known stamping grounds. ‘‘This is akin,’’ the citation read, ‘‘to a leading English-­language novelist suddenly producing the definitive Russian novel.’’

    The Green-Tao theorem on primes was a similar collaboration. Green is a specialist in an area called number theory, and Tao originally trained in an area called harmonic analysis. Yet, as they told me, the proof depended on the insights of many other mathematicians. In the game of devil’s chess, players have no real hope if they haven’t studied the winning games of the masters. A proof establishes facts that can be used in subsequent proofs, but it also offers a set of moves and strategies that forced the devil to submit — a devious way to pin one of his pieces or shut down a counterattack, or an endgame move that sacrifices a bishop to gain a winning position. Just as a chess player might examine variations of the Ruy Lopez and King’s Indian Defense, a mathematician might study particularly clever applications of the Chinese remainder theorem or the sieve of Eratosthenes. The wise player has a vast repertoire to draw on, and the crafty player intuits the move that suits the moment.

    For their work, Tao and Green salvaged a crucial bit from an earlier proof done by others, which had been discarded as incorrect, and aimed at a different goal. Other maneuvers came from masterful proofs by Timothy Gowers of England and Endre Szemeredi of Hungary. Their work, in turn, relied on contributions from Erdos, Klaus Roth and Frank Ramsey, an Englishman who died at age 26 in 1930, and on and on, into history. Ask mathematicians about their experience of the craft, and most will talk about an intense feeling of intellectual camaraderie. ‘‘A very central part of any mathematician’s life is this sense of connection to other minds, alive today and going back to Pythagoras,’’ said Steven Strogatz, a professor of mathematics at Cornell University. ‘‘We are having this conversation with each other going over the millennia.’’

    The Green-Tao theorem caught the mathematical community by surprise, because that problem was thought to be many years from succumbing to proof. On the day I visited Tao, we ate lunch on the outdoor patio of the midcentury-­modern faculty center. Working on a modest plate of sushi, Tao told me that he and Green have continued to work around the margins of the twin-prime conjecture, as have others, with a lot of success recently. It is his sense, he said, that a proof is close at hand, more than a century and half after it was first articulated. ‘‘Maybe 10 years,’’ he said.

    It was dinnertime when I headed to Tao’s home, a white-and-tan five-­bedroom on the western edge of campus. Tao was originally going to take his 12-year-old son, William, to a piano lesson, but William had received a callback for a Go-Gurt commercial. (He has already been in a Honda ad, in which he played the role of ‘‘boy who sleeps contentedly in the back seat.’’) While Tao’s wife, Laura, ferried William home, their daughter, Maddy, 4, finished her meal at an island in their spacious kitchen. She took a bite of her dessert — a cronut — and then clambered down her stool and began running from room to room, arms raised, squealing with delight.

    Tao has emerged as one of the field’s great bridge-­builders. At the time of his Fields Medal, he had already made discoveries with more than 30 different collaborators. Since then, he has also become a prolific math blogger with a decidedly non-­Gaussian ebullience: He celebrates the work of others, shares favorite tricks, documents his progress and delights at any corrections that follow in the comments. He has organized cooperative online efforts to work on problems. ‘‘Terry is what a great 21st-­century mathematician looks like,’’ Jordan Ellenberg, a mathematician at the University of Wisconsin, Madison, who has collaborated with Tao, told me. He is ‘‘part of a network, always communicating, always connecting what he is doing with what other people are doing.’’

    In my visit with Tao, I noticed only one way in which he conforms to the math-­professor stereotype: an absent-mindedness that dates to his childhood. When he was a boy, he constantly lost books, even his book bag; he put clothes on backward or inside out, or he neglected to put on both socks. (This is why he wears Birkenstocks now. ‘‘One less step,’’ he explained.) As he showed me around the house, his gait was a bit awkward, as if, at some level, he was just not that interested in walking. I asked to see his office, and he pointed out an unremarkable chamber off a back hallway. He doesn’t get as much done there as he used to, he said; recently, he has been most productive on flights, when he has a block of hours away from email and all the people who hope for an audience with him.

    After William arrived home, with Laura trailing behind, we sat down for dinner: pork chops in tomato sauce, a recipe taken from a handwritten collection, its notebook cover emblazoned with a teddy bear, that Laura received as a gift from Tao’s mother. William was gregarious. The Go-Gurt callback went well. (He eventually got the part.) William has some of his father’s natural facility for mathematics — as a sixth grader, he took an online course in precalculus — but his real passions at the moment are writing, particularly fantasy, and acting, particularly improv. He was also heavy into Minecraft, though he was annoyed because he was having trouble updating his hacks. Once, he said, he and a friend tried to hack math itself by proving that 1 equals 0, but then realized that it is forbidden to divide by 0. Tao rolled his eyes.

    An effort to prove that 1 equals 0 is not likely to yield much fruit, it’s true, but the hacker’s mind-set can be extremely useful when doing math. Long ago, mathematicians invented a number that when multiplied by itself equals negative 1, an idea that seemed to break the basic rules of multiplication. It was so far outside what mathematicians were doing at the time that they called it ‘‘imaginary.’’ Yet imaginary numbers proved a powerful invention, and modern physics and engineering could not function without them.

    Early encounters with math can be misleading. The subject seems to be about learning rules — how and when to apply ancient tricks to arrive at an answer. Four cookies remain in the cookie jar; the ball moves at 12.5 feet per second. Really, though, to be a mathematician is to experiment. Mathematical research is a fundamentally creative act. Lore has it that when David Hilbert, arguably the most influential mathematician of fin de siècle Europe, heard that a colleague had left to pursue fiction, he quipped: ‘‘He did not have enough imagination for mathematics.’’

    Math traffics in abstractions — the idea, for example, that two apples and two oranges have something in common — but much of Tao’s work has a tangible aspect. He is drawn to waves of fluid or light, or things that can be counted, or geometries that you might hold in your mind. When a question does not initially appear in such a way, he strives to transform it. Early in his career, he struggled with a problem that involved waves rotating on top of one another. He wanted to come up with a moving coordinate system that would make things easier to see, something like a virtual Steadi­cam. So he lay down on the floor and rolled back and forth, trying to see it in his mind’s eye. ‘‘My aunt caught me doing this,’’ Tao told me, laughing, ‘‘and I couldn’t explain what I was doing.’’

    Tao’s most recent work in exploding water began when a professor from Kazakhstan claimed to have completed a Navier-­Stokes proof. After looking at it, Tao felt sure that the proof was incorrect, but he decided to take this intuition a step further and show that any proof using the professor’s approach was sure to fail. While he was wading through the proof, asking colleagues for help in translating the explanatory text from the original Russian, he struck upon the notion of his imaginary, self-­replicating water contraption — drawing on ideas from engineering to make progress on a question in pure mathematics.

    The feat is as much psychological as mathematical. Many people think that substantial progress on Navier-­Stokes may be impossible, and years ago, Tao told me, he wrote a blog post concurring with this view. Now he has some small bit of hope. The twin-prime conjecture had the same feel, a sense of breaking through the wall of intimidation that has scared off many aspirants. Outside the world of mathematics, both Navier-­Stokes and the twin-prime conjecture are described as problems. But for Tao and others in the field, they are more like opponents. Tao’s opponent has been known to taunt him, convincing him that he is overlooking the obvious, or to fight back, making quick escapes when none should be possible. Now the opponent appears to have revealed a weakness. But Tao said he has been here before, thinking he has found a way through the defenses, when in fact he was being led into an ambush. ‘‘You learn to get suspicious,’’ Tao said. ‘‘You learn to be on the lookout.’’

    This is the thrill of it, and the dread. There is a shifting beneath the ground. The game is afoot.

    See the full article here.

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  • richardmitnick 4:04 pm on July 28, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , , , ,   

    From BNL: “New Computer Model Could Explain how Simple Molecules Took First Step Toward Life” 

    Brookhaven Lab

    July 28, 2015
    Alasdair Wilkins

    Two Brookhaven researchers developed theoretical model to explain the origins of self-replicating molecules

    1
    Brookhaven researchers Sergei Maslov (left) and Alexi Tkachenko developed a theoretical model to explain molecular self-replication.

    Nearly four billion years ago, the earliest precursors of life on Earth emerged. First small, simple molecules, or monomers, banded together to form larger, more complex molecules, or polymers. Then those polymers developed a mechanism that allowed them to self-replicate and pass their structure on to future generations.

    We wouldn’t be here today if molecules had not made that fateful transition to self-replication. Yet despite the fact that biochemists have spent decades searching for the specific chemical process that can explain how simple molecules could make this leap, we still don’t really understand how it happened.

    Now Sergei Maslov, a computational biologist at the U.S. Department of Energy’s Brookhaven National Laboratory and adjunct professor at Stony Brook University, and Alexei Tkachenko, a scientist at Brookhaven’s Center for Functional Nanomaterials (CFN), have taken a different, more conceptual approach. They’ve developed a model that explains how monomers could very rapidly make the jump to more complex polymers. And what their model points to could have intriguing implications for CFN’s work in engineering artificial self-assembly at the nanoscale. Their work is published in the July 28, 2015 issue of The Journal of Chemical Physics.

    To understand their work, let’s consider the most famous organic polymer, and the carrier of life’s genetic code: DNA. This polymer is composed of long chains of specific monomers called nucleotides, of which the four kinds are adenine, thymine, guanine, and cytosine (A, T, G, C). In a DNA double helix, each specific nucleotide pairs with another: A with T, and G with C. Because of this complementary pairing, it would be possible to put a complete piece of DNA back together even if just one of the two strands was intact.

    While DNA has become the molecule of choice for encoding biological information, its close cousin RNA likely played this role at the dawn of life. This is known as the RNA world hypothesis, and it’s the scenario that Maslov and Tkachenko considered in their work.

    The single complete RNA strand is called a template strand, and the use of a template to piece together monomer fragments is what is known as template-assisted ligation. This concept is at the crux of their work. They asked whether that piecing together of complementary monomer chains into more complex polymers could occur not as the healing of a broken polymer, but rather as the formation of something new.

    “Suppose we don’t have any polymers at all, and we start with just monomers in a test tube,” explained Tkachenko. “Will that mixture ever find its way to make those polymers? The answer is rather remarkable: Yes, it will! You would think there is some chicken-and-egg problem—that, in order to make polymers, you already need polymers there to provide the template for their formation. Turns out that you don’t really.”

    Instilling memory

    2
    A schematic drawing of template-assisted ligation, shown in this model to give rise to autocatalytic systems. No image credit.

    Maslov and Tkachenko’s model imagines some kind of regular cycle in which conditions change in a predictable fashion—say, the transition between night and day. Imagine a world in which complex polymers break apart during the day, then repair themselves at night. The presence of a template strand means that the polymer reassembles itself precisely as it was the night before. That self-replication process means the polymer can transmit information about itself from one generation to the next. That ability to pass information along is a fundamental property of life.

    “The way our system replicates from one day cycle to the next is that it preserves a memory of what was there,” said Maslov. “It’s relatively easy to make lots of long polymers, but they will have no memory. The template provides the memory. Right now, we are solving the problem of how to get long polymer chains capable of memory transmission from one unit to another to select a small subset of polymers out of an astronomically large number of solutions.”

    According to Maslov and Tkachenko’s model, a molecular system only needs a very tiny percentage of more complex molecules—even just dimers, or pairs of identical molecules joined together—to start merging into the longer chains that will eventually become self-replicating polymers. This neatly sidesteps one of the most vexing puzzles of the origins of life: Self-replicating chains likely need to be very specific sequences of at least 100 paired monomers, yet the odds of 100 such pairs randomly assembling themselves in just the right order is practically zero.

    “If conditions are right, there is what we call a first-order transition, where you go from this soup of completely dispersed monomers to this new solution where you have these long chains appearing,” said Tkachenko. “And we now have this mechanism for the emergence of these polymers that can potentially carry information and transmit it downstream. Once this threshold is passed, we expect monomers to be able to form polymers, taking us from the primordial soup to a primordial soufflé.”

    While the model’s concept of template-assisted ligation does describe how DNA—as well as RNA—repairs itself, Maslov and Tkachenko’s work doesn’t require that either of those was the specific polymer for the origin of life.

    “Our model could also describe a proto-RNA molecule. It could be something completely different,” Maslov said.

    Order from disorder

    The fact that Maslov and Tkachenko’s model doesn’t require the presence of a specific molecule speaks to their more theoretical approach.

    “It’s a different mentality from what a biochemist would do,” said Tkachenko. “A biochemist would be fixated on specific molecules. We, being ignorant physicists, tried to work our way from a general conceptual point of view, as there’s a fundamental problem.”

    That fundamental problem is the second law of thermodynamics, which states that systems tend toward increasing disorder and lack of organization. The formation of long polymer chains from monomers is the precise opposite of that.

    “How do you start with the regular laws of physics and get to these laws of biology which makes things run backward, which make things more complex, rather than less complex?” Tkachenko queried. “That’s exactly the jump that we want to understand.”

    Applications in nanoscience

    The work is an outgrowth of efforts at the Center for Functional Nanomaterials, a DOE Office of Science User Facility, to use DNA and other biomolecules to direct the self-assembly of nanoparticles into large, ordered arrays. While CFN doesn’t typically focus on these kinds of primordial biological questions, Maslov and Tkachenko’s modeling work could help CFN scientists engaged in cutting-edge nanoscience research to engineer even larger and more complex assemblies using nanostructured building blocks.

    “There is a huge interest in making engineered self-assembled structures, so we were essentially thinking about two problems at once,” said Tkachenko. “One is relevant to biologists, and second asks whether we can engineer a nanosystem that will do what our model does.”

    The next step will be to determine whether template-aided ligation can allow polymers to begin undergoing the evolutionary changes that characterize life as we know it. While this first round of research involved relatively modest computational resources, that next phase will require far more involved models and simulations.

    Maslov and Tkachenko’s work has solved the problem of how long polymer chains capable of information transmission from one generation to the next could emerge from the world of simple monomers. Now they are turning their attention to how such a system could naturally narrow itself down from exponentially many polymers to only a select few with desirable sequences.

    “What we needed to show here was that this template-based ligation does result in a set of polymer chains, starting just from monomers,” said Tkachenko. “So the next question we will be asking is whether, because of this template-based merger, we will be able to see specific sequences that will be more ‘fit’ than others. So this work sets the stage for the shift to the Darwinian phase.”

    This work was supported by the DOE Office of Science.

    See the full article here.

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    BNL Campus

    One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. The Laboratory’s almost 3,000 scientists, engineers, and support staff are joined each year by more than 5,000 visiting researchers from around the world.Brookhaven is operated and managed for DOE’s Office of Science by Brookhaven Science Associates, a limited-liability company founded by Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.
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  • richardmitnick 1:04 pm on July 28, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , ,   

    From PNNL: “Tiny grains of rice hold big promise for greenhouse gas reductions, bioenergy” 


    PNNL Lab

    July 28, 2015
    Dawn Zimmerman

    Rice serves as the staple food for more than half of the world’s population, but it’s also the one of the largest manmade sources of atmospheric methane, a potent greenhouse gas. Now, with the addition of a single gene, rice can be cultivated to emit virtually no methane from its paddies during growth. It also packs much more of the plant’s desired properties, such as starch for a richer food source and biomass for energy production, according to a study in Nature.

    1
    In addition to a near elimination of greenhouse gases associated with its growth, SUSIBA2 rice produces substantially more grains for a richer food source. The new strain is shown here (right) compared to the study’s control.
    Image courtesy of Swedish University of Agricultural Sciences

    With their warm, waterlogged soils, rice paddies contribute up to 17 percent of global methane emissions, the equivalent of about 100 million tons each year. While this represents a much smaller percentage of overall greenhouse gases than carbon dioxide, methane is about 20 times more effective at trapping heat. SUSIBA2 rice, as the new strain is dubbed, is the first high-starch, low-methane rice that could offer a significant and sustainable solution.

    Researchers created SUSIBA2 rice by introducing a single gene from barley into common rice, resulting in a plant that can better feed its grains, stems and leaves while starving off methane-producing microbes in the soil.

    The results, which appear in the July 30 print edition of Nature and online, represent a culmination of more than a decade of work by researchers in three countries, including Christer Jansson, director of plant sciences at the Department of Energy’s Pacific Northwest National Laboratory and EMSL, DOE’s Environmental Molecular Sciences Laboratory. Jansson and colleagues hypothesized the concept while at the Swedish University of Agricultural Sciences and carried out ongoing studies at the university and with colleagues at China’s Fujian Academy of Agricultural Sciences and Hunan Agricultural University.

    “The need to increase starch content and lower methane emissions from rice production is widely recognized, but the ability to do both simultaneously has eluded researchers,” Jansson said. “As the world’s population grows, so will rice production. And as the Earth warms, so will rice paddies, resulting in even more methane emissions. It’s an issue that must be addressed.”
    Channeling carbon

    During photosynthesis, carbon dioxide is absorbed and converts to sugars to feed or be stored in various parts of the plant. Researchers have long sought to better understand and control this process to coax out desired characteristics of the plant. Funneling more carbon to the seeds in rice results in a plumper, starchier grain. Similarly, carbon and resulting sugars channeled to stems and leaves increases their mass and creates more plant biomass, a bioenergy feedstock.

    In early work in Sweden, Jansson and his team investigated how distribution of sugars in plants could be controlled by a special protein called a transcription factor, which binds to certain genes and turns them on or off.

    “By controlling where the transcription factor is produced, we can then dictate where in a plant the carbon — and resulting sugars — accumulate,” Jansson said.

    To narrow down the mass of gene contenders, the team started with grains of barley that were high in starch, then identified genes within that were highly active. The activity of each gene then was analyzed in an attempt to find the specific transcription factor responsible for regulating the conversion of sugar to starch in the above-ground portions of the plant, primarily the grains.

    The master plan

    Upon discovery of the transcription factor SUSIBA2, for SUgar SIgnaling in BArley 2, further investigation revealed it was a type known as a master regulator. Master regulators control several genes and processes in metabolic or regulatory pathways. As such, SUSIBA2 had the ability to direct the majority of carbon to the grains and leaves, and essentially cut off the supply to the roots and soil where certain microbes consume and convert it to methane.

    Researchers introduced SUSIBA2 into a common variety of rice and tested its performance against a non-modified version of the same strain. Over three years of field studies in China, researchers consistently demonstrated that SUSIBA2 delivered increased crop yields and a near elimination of methane emissions.

    Next steps

    Jansson will continue his work with SUSIBA2 this fall to further investigate the mechanisms involved with the allocation of carbon using mass spectrometry and imaging capabilities at EMSL. Jansson and collaborators also want to analyze how roots and microbial communities interact to gain a more holistic understanding of any impacts a decrease in methane-producing bacteria may have.

    Funding for this research was provided by The Swedish University of Agricultural Sciences, the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, the National Natural Science Foundation of China and the Carl Tryggers Foundation.

    See the full article here.

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    Pacific Northwest National Laboratory (PNNL) is one of the United States Department of Energy National Laboratories, managed by the Department of Energy’s Office of Science. The main campus of the laboratory is in Richland, Washington.

    PNNL scientists conduct basic and applied research and development to strengthen U.S. scientific foundations for fundamental research and innovation; prevent and counter acts of terrorism through applied research in information analysis, cyber security, and the nonproliferation of weapons of mass destruction; increase the U.S. energy capacity and reduce dependence on imported oil; and reduce the effects of human activity on the environment. PNNL has been operated by Battelle Memorial Institute since 1965.

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  • richardmitnick 9:45 am on July 28, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , , Surface-plasmon-polaritons   

    From ETH: “Smaller, faster, cheaper” 

    ETH Zurich bloc

    ETH Zurich

    28.07.2015
    Oliver Morsch

    1
    Colourized electron microscope image of a micro-modulator made of gold. In the slit in the centre of the picture light is converted into plasmon polaritons, modulated and then re-converted into light pulses. (Photo: Haffner et al. Nature Photonics)

    Transmitting large amounts of data, such as those needed to keep the internet running, requires high-performance modulators that turn electric signals into light signals. Researchers at ETH Zurich have now developed a modulator that is a hundred times smaller than conventional models.

    In February 1880 in his laboratory in Washington the American inventor Alexander Graham Bell developed a device which he himself called his greatest achievement, greater even than the telephone: the “photophone”. Bell’s idea to transmit spoken words over large distances using light was the forerunner of a technology without which the modern internet would be unthinkable. Today, huge amounts of data are sent incredibly fast through fibre-optic cables as light pulses. For that purpose they first have to be converted from electrical signals, which are used by computers and telephones, into optical signals. In Bell’s days it was a simple, very thin mirror that turned sound waves into modulated light. Today’s electro-optic modulators are more complicated, but they do have one thing in common with their distant ancestor: at several centimeters they are still rather large, especially when compared with electronic devices that can be as small as a few micrometers.

    In a seminal paper in the scientific journal Nature Photonics, Juerg Leuthold, professor of photonics and communications at ETH Zurich, and his colleagues now present a novel modulator that is a hundred times smaller and that can, therefore, be easily integrated into electronic circuits. Moreover, the new modulator is considerably cheaper and faster than common models, and it uses far less energy.

    The plasmon-trick

    For this sleight of hand the researchers led by Leuthold and his doctoral student Christian Haffner, who contributed to the development of the modulator, use a technical trick. In order to build the smallest possible modulator they first need to focus a light beam whose intensity they want to modulate into a very small volume. The laws of optics, however, dictate that such a volume cannot be smaller than the wavelength of the light itself. Modern telecommunications use laser light with a wavelength of one and a half micrometers, which accordingly is the lower limit for the size of a modulator.

    In order to beat that limit and to make the device even smaller, the light is first turned into so-called surface-plasmon-polaritons. Plasmon-polaritons are a combination of electromagnetic fields and electrons that propagate along a surface of a metal strip. At the end of the strip they are converted back to light once again. The advantage of this detour is that plasmon-polaritons can be confined in a much smaller space than the light they originated from.

    Refractive index changed from the outside

    In order to control the power of the light that exits the device, and thus to create the pulses necessary for data transfer, the researchers use the working principle of an interferometer. For instance, a laser beam can be split onto two arms by a beam-splitter and recombined with beam combiner. The light waves then overlap (they “interfere”) and strengthen or weaken each other, depending on how their relative state of phase in the two arms of the interferometer. A change in phase can result from a difference in the refractive index, which determines the speed of the waves. If one arm contains a material whose refractive index can be changed from the outside, the relative phase of the two waves can be controlled and hence the interferometer can be used as a light modulator.

    In the modulator developed by the ETH researchers it is not light beams, but rather plasmon-polaritons that are sent through an interferometer that is only half a micrometer wide. By applying a voltage the refractive index and hence the velocity of the plasmons in one arm of the interferometer can be varied, which in turn changes their amplitude of oscillation at the exit. After that, the plasmons are re-converted into light, which is fed into a fibre optic cable for further transmission.

    Faster communication with less energy

    Literature reference

    Haffner C et al.: All-plasmonic Mach-Zehnder modulator enabling optical high-speed communication at the microscale. Nature Photonics, 27 July 2015, doi: 10.1038/nphoton.2015.127

    See the full article here.

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    ETH Zurich campus
    ETH Zurich is one of the leading international universities for technology and the natural sciences. It is well known for its excellent education, ground-breaking fundamental research and for implementing its results directly into practice.

    Founded in 1855, ETH Zurich today has more than 18,500 students from over 110 countries, including 4,000 doctoral students. To researchers, it offers an inspiring working environment, to students, a comprehensive education.

    Twenty-one Nobel Laureates have studied, taught or conducted research at ETH Zurich, underlining the excellent reputation of the university.

     
  • richardmitnick 9:31 am on July 28, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , ,   

    From CERN: “A miniature accelerator to treat cancer” 

    CERN New Masthead

    28 Jul 2015
    Matilda Heron

    1
    Serge Mathot with the first of the four modules that will make up the miniature accelerator (Image: Maximilien Brice/CERN)

    CERN, home of the 27-kilometre Large Hadron Collider (LHC), is developing a new particle accelerator. just two metres long.

    The miniature linear accelerator (mini-Linac) is designed for use in hospitals for imaging and the treatment of cancer. It will consist of four modules, each 50cm long, the first of which has already been constructed. “With this first module we have validated all of the stages of construction and the concept in general”, says Serge Mathot of the CERN engineering department.

    Designing an accelerator for medical purposes presented a new technological challenge for the CERN team. “We knew the technology was within our reach after all those years we had spent developing Linac4,” says Maurizio Vretenar, coordinator of the mini-Linac project. Linac4, a larger accelerator designed to boost negative hydrogen ions to high energies, is scheduled to be connected to the CERN accelerator complex in 2020.

    The miniature accelerator is a radiofrequency quadrupole (RFQ), a component found at the start of all proton accelerator chains. RFQs are designed to produce high-intensity beams. The challenge for the mini-Linac was to double the operating frequency of the RFQ in order to shorten its length. This desired high frequency had never before been achieved. “Thanks to new beam dynamics and innovative ideas for the radiofrequency and mechanical aspects, we came up with an accelerator design that was much better adapted to the practical requirements of medical applications,” says Alessandra Lombardi, in charge of the design of the RFQ.

    The “mini-RFQ” can produce low-intensity beams, with no significant losses, of just a few microamps that are grouped at a frequency of 750 MHz. These specifications make the “mini-RFQ” a perfect injector for the new generation of high-frequency, compact linear accelerators used for the treatment of cancer with protons.

    And the potential applications go beyond hadron therapy. The accelerator’s small size and light weight mean that is can be set up in hospitals to produce radioactive isotopes for medical imaging. Producing isotopes on site solves the complicated issue of transporting radioactive materials and means that a wider range of isotopes can be produced.

    The “mini-RFQ” will also be capable of accelerating alpha particles for advanced radiotherapy. As the accelerator can be fairly easily transported, it could also be used for other purposes, such as the analysis of archaeological materials.

    See the full article here.

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    Meet CERN in a variety of places:

    Cern Courier

    THE FOUR MAJOR PROJECT COLLABORATIONS

    ATLAS
    CERN ATLAS New
    ALICE
    CERN ALICE New

    CMS
    CERN CMS New

    LHCb
    CERN LHCb New

    LHC

    CERN LHC New
    CERN LHC Grand Tunnel

    LHC particles

    Quantum Diaries

     
  • richardmitnick 9:08 am on July 28, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , Puppies Go to Prison   

    From NYT: “Puppies Go to Prison to Become Dogs That Save Lives” 

    New York Times

    The New York Times

    JULY 27, 2015
    ETHAN HAUSER

    1
    An inmate and his dog at Coffee Correctional Facility in Nicholls, Ga., where there is a training program for dogs to teach them to sniff out bombs, narcotics or other threats. Credit Bryan Meltz for The New York Times

    All dressed up in a shiny new red shirt, little Opelika could not stand still in the anteroom of the City Council chambers. And who could blame her? In a few minutes she would meet the mayor of this Alabama city for which she is named. Her meltingly calm mother, Lily, ignored her fidgeting.

    They were being honored this day for their community service, and midway through the presentation, as little ones will do, Opelika stole the show from the starchy lawmakers: She barked.

    Opelika and Lily, yellow Labrador retrievers, are part of the Canine Performance Sciences Program at Auburn University, which breeds and trains dogs to use their powerful sense of smell to keep people safe. After a year of preparation, Opelika will probably be placed with a government agency or a private security firm to sniff out bombs, narcotics or other threats.

    For about half of that year, she will live in a state prison, where inmates who have earned the right to work with the program’s dogs lavish time and attention on them to hone their detection skills and reinforce basic socialization.

    2
    Bart Rogers, a canine instructor with the Canine Performance Sciences Program at Auburn University, working with Notty, a 10-month-old puppy searching for a hidden target. Credit Bryan Meltz for The New York Times

    It’s a lot for a 6-week-old puppy like Opelika to take on; most dogs spend their early months learning little more than how not to gnaw on the living room furniture. But program organizers say the regimen produces highly disciplined dogs whose abilities rival or surpass cutting-edge technology.

    The dogs, mostly Labradors — a breed chosen for its sociability and physical resilience — emerge from the prisons “more mature mentally,” said Jeanne Brock, a chief instructor at Auburn. “They have more stamina and endurance.” And along the way, moments of startling humanity come to light: One older inmate, Ms. Brock recalled, cried when he met his puppy. “I haven’t touched a dog in 40 years,” he told her.

    A couple of miles from the verdant quadrangles of Auburn’s main campus sits the Canine Performance Sciences building. Its otherwise humdrum conference room is crowned with the skin of a 13.5-foot python caught in the Florida Everglades, where Auburn dogs stalked invasive snakes.

    For many years, dogs here were trained to find improvised explosive devices — homemade bombs — that had been planted in a parked car or stashed in a village bazaar. That focus changed somewhat about eight years ago, when Auburn’s scientists and trainers were approached with a new challenge: how to detect an I.E.D. that is on the move, carried by a would-be bomber.

    “The first application we were pointed towards was mass transit,” said Paul Waggoner, a program co-director. The idea was to preserve crowd flow while identifying suspicious individuals. If you make people walk through checkpoints like the kind in airports, Dr. Waggoner explained, then “mass transit becomes non-mass transit.”

    What was the most effective way, Dr. Waggoner and his colleagues wondered, for dogs to patrol crowded areas? They found their answer in the work of Gary Settles, a mechanical engineering professor at Penn State whose research had shown that humans produce thermal plumes that emanate from our bodies and entrain gaseous particles. Most of these particles, like traces of perspiration or perfume, are benign, but the plume can also betray contact with hazardous materials, like those used in bombs. Instead of screening each person, then, the dogs could inspect the “human aerodynamic wakes” that trail behind people in motion and alert a handler to the presence of explosives.

    If that sounds fairly straightforward, “it’s a bigger challenge than you think,” Dr. Waggoner said. “Dogs naturally want to interrogate things and people, and not open space.”

    Among the first animals trained under the new protocol were dogs deployed by Amtrak in 2007, and the rail service has used more than 70. Dogs schooled in vapor wake detection have also guarded the New York City subway system, presidential inaugurations, and sporting events at Busch Stadium in St. Louis.

    Buoyed by the dogs’ advances in tracking air currents, Dr. Waggoner and Craig Angle, a co-director of the Canine Performance Sciences Program, began experimenting with even more elusive targets, including pathogens. In a video shown to a visitor, a dog named Baxter sniffs at the cabinets in a vacant house used as a research site, alerting when he finds a swab of a nasty cattle virus. Researchers are interested in, among other things, whether dogs can be used to find viruses that affect livestock, in the hope that ranchers would no longer need to destroy entire herds to eliminate a few infected animals.

    No one knows precisely what makes a dog’s sense of smell so sensitive, but Dr. Waggoner and others say olfaction may be “the most ‘preserved’ sense — it’s probably the most ancient one.” Dogs’ eyes and ears remain closed for about 14 days after birth, Dr. Waggoner said, but “pups come out smelling, that’s how they interact and get around the world.” By most estimates, dogs have 40 times as many olfactory receptors as humans do — 220 million versus five million. Studies using rats, another animal with superior smelling abilities, have indicated that even when 95 to 98 percent of the receptors are degraded, a sharp sense of smell remains intact.

    3
    A Belgian Malinois that has been trained to lie motionless while fully awake and unrestrained, is presented odor stimuli while undergoing a functional brain M.R.I. The study is investigating the cognitive processing of odor information by dogs to better understand how to select, train, and employ dogs for detection tasks. Credit Bryan Meltz for The New York Times

    Yet what might be most striking is not that dogs can detect odors at parts per trillion (“like a splash of Kool-Aid in a swimming pool,” Dr. Angle said) but that they can discriminate among so many scents. Arson investigators have witnessed this for years, as dogs sift through smoldering ruins to find accelerants. “Think of it like picking out someone’s voice in a crowded conversation,” Dr. Waggoner said. “Dogs can detect a very small sample amidst a lot of odor noise.”

    A Dog’s Brain

    Since their program’s inception, Auburn’s trainers have known that the dogs must be continually rewarded, primarily through toys and verbal encouragement, when they have given an alert they have found a target odor. Until recently, however, the scientists could only speculate on the brain activity behind the dogs’ extreme drive.

    That picture is becoming clearer now, through a neuroscience project financed by the Defense Advanced Research Projects Agency. In the study, Gopikrishna Deshpande, Dr. Waggoner and their colleagues are using functional magnetic resonance imaging recordings to better understand what happens in a dog’s brain when the animal is presented with odors and with photographs and videos of human faces. (Auburn is one of only a handful of sites studying fully awake, unrestrained animals with M.R.I., largely because it takes months of painstaking training to get the dogs to lie with the stillness the machines require.)

    Dr. Deshpande said early data revealed that dogs presented with a learned odor show increased activity in two brain areas: the hippocampus, where memories are stored, and the caudate nucleus, which is associated with rewarding feelings. “Say you eat something good, or buy something that makes you feel good,” he said. “That part of the brain will show blood flow.”

    They are also focusing on the default mode network. The more integrated the network is with the rest of the brain, the higher the likelihood of “referential thinking,” a foundation necessary for sophisticated emotional states, like empathy.

    Though the research is in its early stages, Dr. Waggoner said it could have implications for identifying which dogs will succeed in detection roles and which will thrive as assistance animals.
    Getting to ‘Left of Boom’

    On a day cold by Alabama standards, a black lab named Gus ignored the biting wind and sprinted through a pavilion in a grassy clearing at a training site to scrutinize half a dozen wooden boxes, each with a hole in the top. One of the boxes hid a powder that mimics explosive chemicals, and when Gus alerted on it, he was given a toy.

    Gus and his sister Gala had returned to Auburn days earlier, after six months with their prison handlers. While Gus had immediately stood out, Gala was tentative, “a little more squirrelly,” said Terry Fischer, a chief instructor. As she hunted targets in the brush and gamy husks of felled trees, she looked to her trainer Bart Rogers for help. “Coyote or whatever else she’s smelling out here, it just shut her down,” he said.

    4
    Floyd, a black lab, working in an olfactory detection study. Credit Bryan Meltz for The New York Times

    In the next few weeks, Mr. Fischer and Mr. Rogers would work with the dogs on increasingly challenging tasks, adding to the number of boxes and then moving on to vehicles and complex settings like warehouses and power plants.

    If one of the Auburn research projects proves viable, dogs like Gala will no longer be able to seek aid from their handlers. Borrowing driverless-car technology, the scientists are exploring ways to set dogs off on their own. The goal, Dr. Waggoner said, is to examine wide areas where bomb-making components are stored “before they’re live.”

    “It’s about getting to what people call ‘left of boom,’ ” he added.

    ‘We Will Find It’

    Among people who work with dogs, it is widely understood that the first year of an animal’s life is vital for imprinting. That is when it learns how to socialize and grows accustomed to the sights and sounds of its environment. For the Auburn dogs, this is when they must grasp the kind of trusting but strict relationship they will have with their eventual handlers.

    Originally, Auburn relied on local families to foster the puppies, said Dr. James Floyd, former director of the Canine Performance Sciences Program. Despite the precise guidelines the volunteer hosts were given to maintain the dogs’ fitness and not spoil them, Dr. Floyd said, “you’d visit to check on them and there they’d be, up on the couch, watching TV, being fed potato chips.”

    About 80 percent would fail to meet the rigorous detector-dog standards: “They had been raised as pets,” said Ms. Brock, the Auburn instructor. “The main problem was lack of structure.” (Dogs that drop out are offered for adoption or retained for noninvasive research.) Knowing that service animals had been successfully trained in prisons, the program leaders decided in 2004 to place dogs at Bay Correctional Facility, in Florida. The failure rate fell quickly with the shift to a more stringent environment, and now Auburn has partnerships with five prisons in Florida and Georgia.

    One of them is Coffee Correctional Facility in Nicholls, Ga., which houses men serving sentences of up to 25 years, for “multiple D.U.I.s to murder, and just about everything in between,” said Grady Perry, a former warden. Mr. Perry and his “hall team” led a visitor past the library and the barbershop to the dog-training room, where, on a Friday morning, 10 inmates in white shirts, white pants and slip-on shoes stood in a line, steely and silent.

    James Reeves, the co-manager of the prison’s dog program, retrieved a black Lab named Keisha from the dog dormitory. She bounded in, and though she looked alarmed by her audience, she quickly found the target odor. In response, the inmates whooped and hollered and clapped, and one of them tossed her a red ball.

    Next up was her littermate Kevin (litters are named by letter), who sent his reward skittering across the floor toward the warden’s feet. As Mr. Perry bent to pick it up, one of the inmates approached. “I’ll get it, Warden,” said the man, the words “God’s Child” tattooed across his Adam’s apple in gothic letters. “It’s all slimy.”

    Some of the Coffee trainers are old pros — one was working with his 10th dog — while others are new to the program. They live in a dedicated dorm, where the dogs’ crates nestle against the inmates’ bunks.

    Mr. Perry says he is tremendously proud of the Auburn partnership, crediting it with improving inmates’ morale and behavior. “The incident rate in that unit is almost nonexistent,” he said. “That dog program just kind of calms everyone.”

    Not every inmate is eligible. To apply, inmates must have a high school diploma or its equivalent and be free of disciplinary reports for a year — a considerable challenge, Mr. Perry said.

    “These aren’t heinous individuals,” he said. “They’re men who’ve made mistakes, serious ones, and they deserve to be forgiven. And the sooner they can forgive themselves, the sooner we can.”

    Working with the dogs, he said, speeds that process. “A lot of these guys have never been given a lot of responsibility, and this is their chance not only to be a responsible adult but a responsible citizen,” he said.

    That sense of duty is explained in a mantra displayed on a wall:

    You Can Design It

    You Can Make It

    You Can Hide It

    K9

    We Will Find It

    Striding past it, Warden Perry and Ms. Brock, the Auburn instructor, paused at the end of a row of bunks, an empty crate brushing their knees.

    Until a few days before, the crate had housed a dog named Joel, who had graduated and gone back to Auburn. “I know you’re wondering,” Ms. Brock said to his trainer. “Joel is doing great.”

    The inmate gestured at the metal grate, onto which he had taped a photograph of a Lab. It was not Joel but a look-alike from a magazine. Possessions are few here, some flimsy, all of them essential. As was this one, a reminder of a dog trained to protect, who may have already done some of his most wondrous work.

    See the full article here.

    Please help promote STEM in your local schools.

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  • richardmitnick 8:20 am on July 28, 2015 Permalink | Reply
    Tags: Applied Research & Technology, Greenland, ,   

    From Nature: “NASA launches mission to Greenland” 

    Nature Mag
    Nature

    28 July 2015
    Jeff Tollefson

    Ship and planes will probe water–ice interface in fjords.

    1
    The MV Cape Race is using sonar to map the depth of water around Greenland’s west coast.Maria Stenzel/UCI

    When the retired fishing trawler MV Cape Race sets off along Greenland’s west coast this week, it will start hauling in a scientific catch that promises to improve projections of how the ice-covered island will fare in a warming world. The ship’s cruise is the initial phase of a six-year air and sea campaign to probe interactions between Greenland’s glaciers and the deep, narrow fjords where they come to an end.

    1
    Greenland

    Called Oceans Melting Greenland (OMG), the US$30-million NASA project will help scientists to predict the future of the Greenland ice sheet, which holds enough water to boost sea levels by around 6 metres and already seems to be melting more rapidly in response to increasing air temperatures. But it is not clear how much the oceans affect the rate of melting along the island’s edges, which depends on poorly known variables such as how warm, saline water interacts with the glaciers.

    “It should be a powerful constraint on our knowledge and ability to model ice loss there,” says principal investigator Joshua Willis, an oceanographer at NASA’s Jet Propulsion Laboratory in Pasadena, California.

    When simulating glacier dynamics, current global climate models consider only ice’s interactions with the atmosphere, says William Lipscomb, an ice modeller at Los Alamos National Laboratory in New Mexico. He is working to incorporate ice–ocean inter­actions around Antarctica into a climate model being developed by the US Department of Energy. But in Greenland, the intricately carved coastline makes this much more difficult. The department plans to give researchers at the Naval Postgraduate School in Monterey, California, $466,000 over 2 years to build a detailed model that will link the land ice and oceans around Greenland. OMG data will help to validate that model, says project leader Frank Giraldo.

    Work by OMG participant Eric Rignot, a glaciologist at the University of California, Irvine, underscores the importance of detailed data (E. Rignot et al. Geophys. Res. Lett. http://doi.org/6dn; 2015). Using sonar data from one part of western Greenland, Rignot’s team found that existing maps underestimate the depth of three fjords by several hundred metres. It also found that glaciers flowing into all three fjords extended deeper than was thought, far enough below fresh surface waters to reach a warm, salty layer flowing up from the Atlantic Ocean that could accelerate melting and contribute more to sea-level rise than had been believed.

    “With OMG, we are going to reveal the depth of these fjords,” says Rignot.

    The programme will also provide valuable information on the physical characteristics of glacier ice. Last December, geophysicist Beata Csatho of the University at Buffalo in New York and her colleagues reported using surface-elevation data to estimate how much ice mass Greenland had lost between 1993 and 2012 (B. M. Csatho et al. Proc. Natl Acad. Sci. USA 111, 18478–18483; 2014). The data were fairly reliable over the island’s interior, Csatho says, but measurements were more difficult along its edges, where the ice tends to be warmer, thicker and full of crevices. “It’s still a challenge to get the mass of these glaciers,” she says.

    When the aerial phase of OMG begins next year, planes will fly inland from the coast, taking measurements of slight changes in gravitational pull that can be used to produce low-resolution maps of the topography under both water and ice. Planes will also drop more than 200 temperature and salinity probes into fjords and coastal waters, and take radar measurements along the coast to track large-scale ice loss over five years. Analysing that ice loss in light of the new topographical and oceanographic data will help researchers to determine where, and to what extent, deeper saltwater currents affect glaciers.

    Lipscomb says that all these OMG data should help modellers as they incorporate ocean–ice interactions around Greenland into their models. That work is still in its early stages, he says, “but the data that they are getting in this project is exactly what we need”.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.

     
  • richardmitnick 8:04 am on July 28, 2015 Permalink | Reply
    Tags: Applied Research & Technology, ,   

    From NOVA: “Fossil Fuels Are Destroying Our Ability to Study the Past” 

    PBS NOVA

    NOVA

    21 Jul 2015
    Tim De Chant

    It’s been used to date objects tens of thousands of years old, from fossil forests to the Dead Sea Scrolls, but in just a few decades, a tool that revolutionized archaeology could turn into little more than an artifact of a bygone era.

    Radiocarbon dating may be the latest unintended victim of our burning of fossil fuels for energy. By 2020, carbon emissions will start to affect the technique, and by 2050, new organic material could be indistinguishable from artifacts from as far back as AD 1050, according to research by Heather Graven, a lecturer at Imperial College London.

    1
    The Great Isaiah Scroll, one of the seven Dead Sea Scrolls, has been dated using the radiocarbon technique.

    The technique relies on the fraction of radioactive carbon relative to total carbon. Shortly after World War II, Willard Libby discovered that, with knowledge of carbon-14’s predictable decay rate, he could accurately date objects that contained carbon by measuring the ratio of carbon-14 to all carbon in the sample. The less carbon-14 to total carbon, the older the artifact. Since only living plants and animals can incorporate new carbon-14, the technique became a reliable measure for historical artifacts. The problem is, as we’ve pumped more carbon dioxide into the atmosphere, we’ve unwittingly increased the total carbon side of the equation.

    Here’s Matt McGrath, reporting for BBC News:

    At current rates of emissions increase, according to the research, a new piece of clothing in 2050 would have the same carbon date as a robe worn by William the Conqueror 1,000 years earlier.

    “It really depends on how much emissions increase or decrease over the next century, in terms of how strong this dilution effect gets,” said Dr Graven.

    “If we reduce emissions rapidly we might stay around a carbon age of 100 years in the atmosphere but if we strongly increase emissions we could get to an age of 1,000 years by 2050 and around 2,000 years by 2100.”

    Scientists have been anticipating the diminished accuracy of radiocarbon dating as we’ve continued to burn more fossil fuels, but they didn’t have a firm grasp of how quickly it could go south. In the worst case scenario, we would no longer be able date artifacts younger than 2,000 years old. Put another way, by the end of the century, a test of the Shroud of Turn wouldn’t be able to definitively distinguished the famous piece of linen from a forgery made today.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    NOVA is the highest rated science series on television and the most watched documentary series on public television. It is also one of television’s most acclaimed series, having won every major television award, most of them many times over.

     
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