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  • richardmitnick 2:44 pm on December 14, 2016 Permalink | Reply
    Tags: , , , Big Bang or Big Bounce, , NOVA   

    From NOVA: “Did the Universe Start with a Bounce Instead of a Bang?” 



    14 Dec 2016
    Marcus Woo

    Big Bounce could have happened, scientists say. Istock

    For a few physicists, the Big Bang wasn’t the beginning of the universe.

    Rather, they say, the universe existed before that point, stretching forever into the past as well as the future. While the universe is expanding today, it was contracting in the time before the Big Bang. In this picture, the Big Bang isn’t so much a bang but a bounce, a moment when a shrinking universe reversed course and began to grow.

    And according to their theory, the universe could bounce again. Today’s expansion could be followed by collapse in the far future, followed by another bounce. Some physicists have suggested this bouncing could be infinite, reviving a cyclic cosmology first proposed in the 1930s.

    But how that infinitesimally hot and dense point came to be remains an unanswered question. Bouncing theories could promise to explain the origin of the cosmos. Whether a single bounce or endless bounces, a handful of cosmologists have spent the last couple decades tinkering with these ideas. But to others, bounce theories are simply speculative and controversial, and to some, they’re discredited and wrong.

    Much of the debate between Big Bang and Big Bounce proponents revolves around the viability of inflation, the mainstream view of how the universe has come to be the way it is today.

    Inflationary Universe. NASA/WMAP
    Inflationary Universe. NASA/WMAP

    And although any cosmologist would agree that inflation is, at the very least, incomplete, the vast majority considers it the best model yet. Still, bounce proponents see fundamental flaws in this model.

    “Inflation’s not doing too well,” says Neil Turok, director of the Perimeter Institute for Theoretical Physics. “It’s had its day. It was useful when it was invented in the early 1980s.” But now, he says, we need a new theory, and that theory could be a bouncing universe.

    A Cosmic Growth Spurt

    The standard story of inflation goes like this: shortly after the Big Bang, the universe ballooned rapidly—much faster than its normal expansion. This sudden growth was necessary to create the smooth, flat, and uniform universe that scientists see today.

    Cosmologists first developed inflation in the early 1980s, before balloon-borne experiments and satellites returned increasingly precise data on the state of the early universe. These observations measured the leftover radiation from the Big Bang, a ubiquitous glow called the cosmic microwave background [CMB].

    CMB per ESA/Planck
    CMB per ESA/Planck

    The radiation is patchily distributed, with some spots hotter and cooler than others, an auspicious result since the exact nature of this patchiness was precisely what inflation predicted.

    Inflation also predicted the mass density of the universe, also measured from the cosmic microwave background. “We’ve measured the mass density to better than a half percent accuracy, and it agrees perfectly with what inflation predicts—which is just gorgeous,” says Alan Guth, a physicist at MIT and the first who proposed inflation in 1980.

    “It’s really remarkable how much this simple idea of inflation has done,” says Robert Brandenberger, a physicist at McGill University. Although he’s exploring alternatives to inflation, the theory is the most self-consistent one out there, he says. “It’s successful because it predicted many things—and I emphasize predicted. Early in my career, we didn’t have the data. I saw inflation pass many more tests.”

    Still, while these successes have been more than encouraging for inflation, the evidence has yet to convince everyone. One prediction that might quell some dissent would be the detection of primordial gravitational waves, ripples in the fabric of space and time that originated from fluctuations of the gravity field in the early universe. It almost happened: In March 2014, the BICEP2 experiment at the South Pole claimed to have seen these gravitational waves. But that heralded discovery vanished when astronomers realized the signal could have been entirely due to dust in the galaxy.

    Gravitational Wave Background from BICEP 2
    Gravitational Wave Background from BICEP 2, quickly discredited.

    Inflation is not without its theoretical issues either. Some critics say that inflation requires initial conditions that are too specialized and contrived to be realistic. To get inflation started, the early universe had to be just right.

    Another point of contention is that inflation could imply the existence of an infinite number of universes. In the early 1980s, physicists discovered that inflation goes on forever, stopping only in some regions of space. But in between these pockets, inflation continues, expanding faster than the speed of light. These bubbles are thus closed off from each other, effectively becoming isolated universes with their own laws of physics. According to this theory, we live in one of these bubbles.

    While inflation proponents embrace this so-called multiverse, detractors say it’s absurd. If anything can happen in these bubble universes, then scientific predictions become meaningless. “If you have a theory that can’t be disproved, you should be dissatisfied with that,” Turok says. “That’s the state with inflation and the multiverse, so I would say this is not a scientific theory.”

    Even ardent supporters of inflation would agree the theory is incomplete. It doesn’t say anything about the moment of the Big Bang itself, for example, when the known laws of physics break down at what’s called a singularity.

    What inflation still lacks is a deeper foundation. Physicists have tried connecting inflation with string theory—the best candidate for a so-called theory of everything. But it’s still a work in progress. “With inflation, we basically add something by hand and we say it works, but we don’t have a more theoretical understanding of where it could come from,” says Steffen Gielen of the Perimeter Institute, who works with Turok on bouncing models.

    Bouncing Ideas

    The suggestion that the Big Bang wasn’t the absolute beginning originates from the first half of the 20th century, when physicists proposed a cyclic universe. But at the time, no one understood the details for how the universe could enter and emerge from each bounce.

    Todays’ physicists still have their work cut out for them, but now they have all the tools of modern particle physics and string theory. In 1992, Maurizio Gasperini and Gabriele Veneziano first used these modern ideas to revisit a pre-Big-Bang universe. Ten years later, Turok and Paul Steinhardt, a physicist at Princeton University and one of inflation’s pioneers turned critic, expanded on that work. They have since become two of the most outspoken detractors of inflation and proponents of a bouncing universe.

    A bouncing universe, they argue, could produce the cosmos we see today—but without inflation. The universe doesn’t need a period of super-expansion to reach the smooth, flat state we see today; it can do so while contracting. And because every corner of a shrinking universe would have been in contact with one another, the whole cosmos could settle into a uniform temperature—again, just as we see it today.

    Because so much of the early universe is unknown, theories of cosmology can vary widely. Inflation, for instance, isn’t one particular theory but a class of models, each a bit different in detail. Likewise, physicists have theorized many ways for how a universe can bounce.

    In one case, dubbed a matter bounce, the universe only bounces once. The collapse into the bounce is like a reverse-order Big Bang. Another version, called an ekpyrotic model, can be cyclical, with contraction followed by expansion followed by contraction, and so on. The anamorphic universe might be similarly cyclical.

    Pretty much all models require some sort of new physics. The differences between these models depend on the details, whether it’s new theories or exotic types of matter that halt the inertia of collapse and guide the universe through the bounce. Figuring out what happens at the bounce poses a big challenge, because that point is where the laws of physics fail, just as they do at the start of an inflationary universe.

    At the bounce, the universe collapses into a singularity, in which Einstein’s theory of gravity, general relativity, breaks down. Relativity isn’t currently compatible with quantum mechanics, which is needed at the small scales of the singularity. To unite the two, physicists have been searching for a theory of quantum gravity, which doesn’t yet exist.

    Over the past year, though, physicists have claimed modest progress on how to handle the singularity. Turok and Gielen have outlined how a simplified, toy model of a universe could undergo a quantum bounce. A bouncing universe containing only radiation—not unlike the radiation-dominated cosmos at the Big Bang—could cross the singularity in a way like quantum tunneling: According to quantum mechanics, a particle can spontaneously appear on the other side of a barrier that would otherwise be impenetrable in non-quantum physics. A collapsing universe can act like a particle and tunnel through the barrier-like singularity, appearing on the other side as the expanding universe we know today—and evading the singularity’s problems.

    Meanwhile, Steinhardt and Anna Ijjas of Princeton University have proposed a way the universe could bounce without evoking quantum mechanics. They’ve shown that some exotic, negative energy could prevent a universe from collapsing into a singularity in the first place. By avoiding a singularity, the universe never gets small enough for quantum mechanics to come into play, so you don’t need quantum gravity. The universe then proceeds to expand.

    But while these two proposals might be a small advance, neither marks a radical leap from what’s been done before, Brandenberger says. We’re still far from solving the problem of the singularity. “If we solve the singularity problem by evoking exotic matter, the question is just twisted,” he says. In other words, instead of explaining the singularity, you now have to explain the exotic matter.

    Without new physics, a bounce doesn’t seem likely, according to Guth. “One has to adopt rather special features that one would have to assume in the underlying laws of physics to make the bounce possible,” he says. “To me, that doesn’t seem like a good bet.”

    But it’s still too early to judge, Turok says. The theories aren’t mature enough to be testable yet. Eventually, though, models could start making predictions. Future, more detailed measurements of the cosmic microwave background might support a particular model of inflation or a bouncing universe. Perhaps the most promising evidence would come in the form of primordial gravitational waves, which are about the best indicators of what happened in the moments after the Big Bang (or bounce).

    Depending on what these waves look like, researchers can start ruling out models of both bouncing universes and inflation. While the BICEP2 findings in 2014 were a false alarm, researchers hope other instruments will succeed, including its successor, BICEP3. The Atacama B-mode Search is now operating in the Atacama Desert in Chile, and researchers are planning future experiments with names such as the Primordial Inflation Polarization Explorer, Qubic, and Polarbear.

    The Right Path

    In the end, however, it may not simply come down to an either-or choice between bouncing models or inflation, even though proponents of bouncing models sell their idea as an alternative. “What they’re doing is much more closely allied to inflation than they would have you think,” says Andrew Liddle, a cosmologist at the University of Edinburgh. “I don’t think it’s that radical of a departure.” Many of the mathematical tools used in bouncing models are similar to those used for inflation, he says. And when you apply observations like the cosmic microwave background, both bouncing models and inflation give similar results.

    You can even have both a bounce and inflation. “Now, sociologically, many people who study bounce cosmologies do so because they’re interested in finding an alternative to inflation,” says Sean Carroll, a physicist at the California Institute of Technology. “That’s fine, but if you just said, without any preexisting agendas, does the universe have a bounce, and if so, could it also involve inflation? I think you’d say sure.”

    Still, the debates between bounce proponents and the most outspoken inflation supporters can get contentious, each somewhat dismissive of the other side. The conflict is a reminder that science—and perhaps theoretical physics, in particular—is ultimately a human endeavor, filled with egos and subjectivity. Legacies and Nobel Prizes could be at stake.

    “In the absence of data, you’re welcome to your opinion—opinion is all you have,” Carroll says. “All of these ideas have significant challenges and question marks next to them.” While a problem may be a deal-breaker for one person, it’s only a minor stumbling block to another. When blazing a new trail, the right path is often subjective.

    See the full article here .

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    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.

  • richardmitnick 9:04 am on October 6, 2016 Permalink | Reply
    Tags: , Australia Is Moving Itself 1.8 Meters North on Maps, NOVA   

    From NOVA: “Australia Is Moving Itself 1.8 Meters North on Maps” 



    01 Aug 2016 [Just appeared in social media.]
    Tim De Chant

    Australia is drifting north, necessitating a change in its coordinate system.

    Time to update your maps—Australia’s moving.

    Since 1994, when the country last updated its coordinates, Australia has drifted 1.5 meters north (about 5 feet). In an effort to stay ahead of the Earth’s tectonic plates, the country is moving itself 1.8 meters north (about 6 feet).

    The shift will future proof the continent as it prepares for more autonomous vehicles, from farm tractors to cars.

    While a few feet here or there is within the limits of accuracy for many GPS systems, future systems will be accurate to within inches. Here’s Chris Foxx, reporting for BBC News:

    “If you want to start using driverless cars, accurate map information is fundamental,” said [project head Dan] Jaksa.

    “We have tractors in Australia starting to go around farms without a driver, and if the information about the farm doesn’t line up with the co-ordinates coming out of the navigation system there will be problems.”

    Australia, like most regions, has its own coordinate system, also known as a geodetic datum. There are the several global coordinate systems that are perfectly serviceable, but local versions do a better job at minimizing the distortion occurs when transferring the true shape of the Earth onto a flat coordinate plane.

    Because the Earth isn’t a perfect sphere, no datum is perfect. But by limiting the amount of the Earth’s surface that needs to be pulled and stretched when flattened, datums that cover smaller areas can more closely approximate the real thing.

    Australia’s new datum is expected to align with reality sometime in 2020.

    See the full article here .

    Please help promote STEM in your local schools.

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    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.

  • richardmitnick 12:22 pm on September 13, 2016 Permalink | Reply
    Tags: , NOVA, Triple-Alpha Process Shows That Other Universes Might Be Better Suited to Life Than Ours   

    From NOVA: “Triple-Alpha Process Shows That Other Universes Might Be Better Suited to Life Than Ours” 



    02 Sep 2016
    Allison Eck

    If life is rare in our universe, it might be more common in alternate ones.

    According to scientists, life is possible because a triad of alpha particles unite to fuse into carbon. But there are some problems with that theory—fusing two alpha particles leads to a very unstable isotope (beryllium-8), which makes the abundance of carbon in the universe seem odd and improbable.

    In the 1950s, astronomer Fred Hoyle suggested that to resolve this problem, the fusion of three alpha particles must create carbon-12 with more energy than it needs. This “resonance” between the collective alpha particle energies and the excited state of carbon-12, which later decays to a ground state, is very sensitive—if you change it just slightly, the creation of carbon isn’t possible. Some experts insist that this fact is evidence of the multiverse’s existence: since the chances of this critical value arising are so low, other universes with other such fundamental constants must exist, too. Only those universes that are appropriately fined-tuned would give birth to life.

    Now, cosmologists are taking this idea to the next level.

    Here’s Jacob Aron, reporting for New Scientist:

    “But now Adams and his colleague Evan Grohs have argued that if other universes have different fundamental constants anyway, it’s possible to create a universe in which beryllium-8 is stable, thus making it easy to form carbon and the heavier elements.

    For this to happen would require a change in the binding energy of beryllium-8 of less than 0.1 MeV – something that the pair’s calculations show should be possible by slightly altering the strength of the strong force, which is responsible for holding nuclei together.

    Simulating how stars might burn in such a universe, they found that the stable beryllium-8 would produce an abundance of carbon, meaning life as we know it could potentially arise. ‘There are many more working universes than most people realise,’ says Adams.”

    See the full article here .

    Please help promote STEM in your local schools.

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    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.

  • richardmitnick 3:29 pm on August 25, 2016 Permalink | Reply
    Tags: , , NOVA   

    From NOVA: “The ‘Quantum Theory’ of Cancer Treatment” 



    20 Jul 2016 [This just appeared in social media.]
    Amanda B. Keener

    In April 2011, Christopher Barker, a radiation oncologist at Memorial Sloan Kettering Cancer Center in New York, received some unusual news about a participant in a clinical trial. The patient was battling a second recurrence of melanoma that had spread to several areas of her body. After more than a year on the experimental drug, her tumors had only gotten bigger, and after one near her spine started causing back pain, her doctors arranged for local radiation therapy to shrink the tumor and give her some relief.

    But the tumor near her spine was not the only one that shrank. “From one set of images to another, the radiologist noticed that there was a dramatic change in the extent of the melanoma,” Barker says. Although only one tumor was exposed to radiation, two others had started shrinking, too.

    The striking regression was a very rare effect of radiation therapy, Barker and his colleagues concluded, called an abscopal response. “It’s not common,” says Barker. “But we see it, and it’s pretty remarkable when it happens.”

    A woman prepares to receive radiation treatment for cancer. Photo credit: Mark Kostich/iStockphoto.

    Although the abscopal response was first recognized back in 1953, and a smattering of case reports similar to Barker’s appeared in the literature throughout the 1960s, ’70s, and ’80s, the mystery behind the abscopal response largely went unsolved until a medical student named Silvia Formenti dusted it off.

    While studying radiation therapy in Milan during the 1980s, Formenti couldn’t shake the idea that local radiotherapy must have some effect on the rest of the body. “When you burn yourself, the burn is very localized, yet you can get really systemic effects,” says Formenti, now chair of the department of radiation oncology at Weill Cornell Medical College in New York. “It seemed that applying radiotherapy to one part of the body should be sensed by the rest of the body as well.”

    The primary goal of therapy with ionizing radiation—the type used to shrink tumors—is to damage the DNA of fast-growing cancer cells so they self-destruct. But like burns, radiation also causes inflammation, a sign of the immune system preparing for action. For a long time, it was unclear what effect inflammation might have on the success of radiation therapy, though there were some hints buried in the scientific literature. For example, a 1979 study showed that mice lacking immune cells called T cells had poorer responses to radiation therapy than normal mice. But exactly what those T cells had to do with radiation therapy was anyone’s guess.

    Better Together

    In 2001, shortly after arriving in New York, Formenti attended a talk by Sandra Demaria, a pathologist also at Weill Cornell. Demaria was studying slivers of breast tumors removed from patients who had received chemotherapy and had found that in some patients, chemotherapy caused immune cells to flood the tumors. This made Formenti wonder if the same thing could happen after radiation therapy.

    In addition to fighting off illness-causing pathogens, part of the immune system’s job is to keep tabs on cells that could become cancerous. For example, cytotoxic T cells kill off any cells that display signs of cancer-related mutations. Cancer cells become troublesome when they find ways to hide these signs or release proteins that dull T cells’ senses. “Cancer is really a failure of the immune system to reject [cancer-forming] cells,” Formenti says.

    Formenti and Demaria, a fellow Italian native, quickly joined forces to determine whether the immune system was driving the abscopal response. To test their idea, their team injected breast cancer cells into mice at two separate locations, causing individual tumors to grow on either side of the animals’ bodies. Then they irradiated just one of the tumors on each mouse. Radiation alone prevented the primary tumor from growing, but didn’t do much else. Yet when the researchers also injected a protein called GM-CSF into the mice, the size of the second tumor was also controlled.

    GM-CSF expands the numbers of dendritic cells, which act as T cells’ commanding officers, providing instructions about where to attack. But the attack couldn’t happen unless one of the tumors was irradiated. “Somehow radiation inflames the tumor and makes it interesting to the immune system,” Formenti says.

    Formenti and Demaria knew that if their findings held up in human studies, then it could be possible to harness the abscopal effect to treat cancer that has metastasized throughout the body.

    Although radiation therapy is great at shrinking primary tumors, once a cancer has spread, the treatment is typically reserved for tumors that are causing patients pain. “Radiation is considered local therapy,” says Michael Lim, a neurosurgeon at Johns Hopkins University in Baltimore who is studying ways to combine radiotherapy with immunotherapy to treat brain tumors. But, he adds, “if you could use radiation to kindle a systemic response, it becomes a whole different paradigm.”

    When Demaria and Formenti first published their results in 2004, the concept of using radiation to activate immunity was a hard sell. At the time, research into how radiation affected the immune system focused on using high doses of whole-body irradiation to knock out the immune systems of animal models. It was counterintuitive to think the same treatment used locally could activate immunity throughout the body.

    That perspective, however, would soon change. In 2003 and 2004, James Hodge, an immunologist at the National Cancer Institute and his colleagues published two mouse studies showing that after radiation, tumor cells displayed higher levels of proteins that attract and activate cancer-killing T cells. It was clear radiation doesn’t just kill cancer cells, it can also make those that don’t die more attractive to immune attack, Hodge says.

    This idea received another boost in 2007 when a research team from Gustave Roussy Institute of Oncology near Paris reported that damage from radiation caused mouse and human cancer cells to release a protein that activates dendritic cells called HMGB1. They additionally found that women with breast cancer who also carried a mutation preventing their dendritic cells from sensing HMGB1 were more likely to have metastases in the two years following radiotherapy. In addition to making tumors more attractive to the immune system, Hodge says, the damage caused by radiation also releases bits of cancer cells called antigens, which then prime immune cells against the cancer, much like a vaccine.

    In some ways, Barker says, oncologists have always sensed that radiation works hand-in-hand with the immune system. For example, when his patients ask him where their tumors go after they’ve been irradiated, he tells them that immune cells mop up the dead cell debris. “The immune system acts like the garbage man,” he says.

    Now, immunologists had evidence that the garbage men do more than clean up debris: they are also part of the demolition team, and if they could coordinate at different worksites, they could generate abscopal responses. With radiation alone, this only happened very rarely. “Radiation does some of this trick,” Formenti says. “But you really need to help radiation a bit.”

    Formenti and Demaria had already shown in mice that such assistance could come in the form of immunotherapy with GM-CSF, and in 2003 they set out to test their theory in patients. They treated 26 metastatic cancer patients who were undergoing radiation treatment with GM-CSF. The researchers then used CT scans to track the sizes of non-irradiated tumors over time. Last June, they reported that the treatment generated abscopal responses in 20% of the patients. Patients with abscopal responses tended to survive longer, though none of the patients were completely cured.

    As the Weill Cornell team was conducting their GM-CSF study, a new generation of immunotherapeutic drugs arrived on the scene. Some, like imiquimod, activate dendritic cells in a more targeted way than GM-CSF does. Another group, the checkpoint inhibitors, release the brakes on the immune system and T cells in particular, freeing the T cells to attack tumors.

    In 2005, Formenti and her team found that a particular checkpoint inhibitor worked better with radiotherapy than alone and later reported that the same combination produces abscopal responses in a mouse model of breast cancer.

    Off-target, Spot-on

    In 2012, Formenti had an unexpected chance to test this treatment in the clinic when one of her patients who had read about her research requested that she try the combination on him. The patient had run out of options, so Formenti’s team obtained an exception to use the immunotherapy ipilimumab, which she had used in her 2005 study and had only been approved for melanoma, and proceeded to irradiate tumors in the patient’s liver. After five months, all but one of his tumors had disappeared. “We were ecstatic,” Formenti says. “He’s still alive and well.”

    The availability of checkpoint inhibitors seems to have opened the floodgates. Since the US Food and Drug Administration approved ipilimumab in 2011, there have been at least seven reports of suspected or confirmed abscopal responses in patients on checkpoint inhibitors, including the one Barker witnessed. Contrast that with the previous three decades, where less than one per year was reported, according to one review. Almost all of the recent cases involving checkpoint inhibitors have been in patients with melanoma, since that’s where the drugs have mainly been tested. But, abscopal responses with or without immunotherapy have been reported in patients with cancers of the liver, kidney, blood, and lung.

    There are now dozens of clinical trials combining radiation with a range of immunotherapies, including cancer vaccines and oncolytic viruses. “There’s quite a nice critical mass of people working on this,” Formenti says. She and Demaria are now finishing up a clinical trial in lung cancer patients using a protocol similar to the one that worked so well in their original patient.

    “I think we know that people who respond to checkpoint inhibitors already have more immune-activating tumors,” Demaria says. The question now, she says, is whether radiation can expand the 20% of people who respond to the combination therapy.

    One solution might be to match combinations to particular patients or tumor types. Demaria’s team is collecting blood and tissue samples from patients in a Weill Cornell lung cancer trial to look for differences in the immune responses of those who do and don’t generate abscopal responses. Such changes in the number or status of a cell type associated with particular outcomes are known as biomarkers.

    So far, there is little data about how the two types of responses differ. Barker and his team did publish measurements of a broad range of immune markers from their patient who experienced an abscopal response. “We didn’t really have a lot of clues in terms of what we should look at,” he says. They observed a bump in activated T cells and antibodies specific to tumor proteins following radiation, followed by steady declines of both as the tumors regressed. But, he says, there was no “smoking gun” that could explain why this particular patient responded the way she did.

    Understanding how the immune system responds to immunotherapy and radiation will be key to optimizing the combination of the two. “One needs to do these combinations to try and improve the outcome on both sides of the equation,” says William McBride, a radiation oncologist at the University of California, Los Angeles. There’s still controversy, for example, over whether the immune system responds better to high doses of radiation over short periods or low doses over longer periods. “We think we know the best sequence of therapy based on the pre-clinical studies, but that hasn’t been confirmed in clinical studies yet,” Barker says. “If we had a biomarker that would tell us in what way you should give the radiation, that would be enormously valuable.”

    Demaria says her research suggests that more tumor damage is not always better and that high radiation doses may be counterproductive, activating feedback responses that suppress immunity. She’s currently comparing immune signatures of different radiation regimens in mice. So far she says regimens that make the cancer look and act like virally-infected cells tend to elicit the best immune responses, but there is a long way to go in translating that work into humans.

    “Things are moving faster than they have for a long time, but at this point there are still a lot of unanswered questions,” she says.

    Fortunately, she and Formenti have plenty of motivation to work on those questions. Demaria says she still remembers examining a bit of tumor that was left behind after that first lung cancer patient received treatment. It was full of T cells which had presumably destroyed the cancer. “It’s the picture you never forget,” she says. “It is probably the biggest satisfaction to see somebody’s fate turned around by what you can do.”

    See the full article here .

    Please help promote STEM in your local schools.

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    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.

  • richardmitnick 2:13 pm on August 11, 2016 Permalink | Reply
    Tags: and Scientists Don’t Know Why, , , NOVA, There’s an Abundance of Lithium-6 in the Universe   

    From NOVA: “There’s an Abundance of Lithium-6 in the Universe, and Scientists Don’t Know Why” 



    11 Aug 2016
    Kelsey Houston-Edwards

    The difference between Lithium-6 and Lithium-7 might not seem like much, but it is poking holes in our understanding of how atoms formed during the Big Bang.

    Technically, they’re off by a single neutron: 6Li contains three neutron and 7Li contains four. Compared to theoretical calculations, experiments show that the universe contains way too much 6Li and too little 7Li. Using basic principles of physics, scientists can compute how much of each type of lithium should have been created during the Big Bang. But, the theory doesn’t match the data—each time they look to the sky, physicists observe a different balance of lithium than expected.

    Cosmologists have looked to the small and large Magellanic Clouds, shown here, for measurements of 6Li and 7Li to compare against theoretical models. European Southern Observatory / Wikimedia Commons (CC BY 4.0)

    Scientists have good reason to believe their calculations are correct. They accurately predict the observed quantities of many other elements with startling accuracy.

    A recent experiment published in Physical Review Letters tried to replicate the conditions of the Big Bang to prove that more lithium was produced than scientists originally calculated. The lithium would come from a fusion of a tritium atom and helium ion, which could only be replicated with a giant laser.

    Explaining the experimental set up, here’s Chris Lee writing for Ars Technica:

    “The laser is used to compress a capsule containing tritium (a hydrogen atom with two neutrons couch surfing in the nucleus) and 3He (a helium atom with a missing neutron). The compression and shockwave are so fast that the heavy nuclei have very little time to accelerate, so the result is a cold, dense plasma. This plasma has a temperature and density that is pretty much what cosmologists think was present during Big Bang nucleosynthesis. Thus, tritium and helium ions can fuse to form 6Li at rates that correspond to exactly those that should have been present during the Big Bang.”

    But the experiment didn’t produce enough 6Li to account for all that’s observed—that is, the new results support the existing perplexing calculations. The disconnect between theoretical and experimental values of lithium in the universe cannot be explained, and that’s a big problem for our understanding of basic physics.

    Fortunately, there’s one possible explanation for the discrepancy that hasn’t been ruled out yet—lithium is created and destroyed inside stars. It’s possible that scientists accurately predicted how much 6Li was produced during the Big Bang, and the rest was created later in stars. But for now, lithium is challenging our understanding of the Big Bang, big time.

    See the full article here .

    Please help promote STEM in your local schools.

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    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.

  • richardmitnick 4:41 pm on June 26, 2016 Permalink | Reply
    Tags: , NOVA, The hope of digital reconstruction   

    From NOVA: “The Technology That Will Resurrect ISIS-Destroyed Antiquities” 



    09 Jun 2016
    Evan Hadingham

    On October 5, 2015, the world watched in horror as Islamic State forces blew up the iconic 2,000 year-old Arch of Triumph in the ancient city of Palmyra, Syria. This carefully orchestrated act was the climax of a 10-month rampage of destruction and mass executions perpetrated by ISIS at the UNESCO World Heritage site. With Palmyra secured and a fragile Syrian truce in place, some news stories have given the impression that the worst wave of heritage destruction is over.

    The Arch of Triumph in Palmyra as seen on January 15, 2013.

    In fact, satellite photography is revealing a shocking picture of the ongoing, systematic destruction of churches, mosques, antiquities, and museums throughout Syria and parts of Iraq and threats to heritage sites elsewhere in the Middle East. But that hasn’t stopped courageous local archaeologists and citizens from risking their lives to combat the devastation, aided by specialists outside the war zone who are deploying satellite and 3D imaging to help monitor, record, and replicate ancient sites.

    A digital reconstruction of the Arch of Triumph.

    “It’s the worst cultural heritage crisis since World War II,” says Michael Danti, an archaeologist at Boston University. “And technology can help us keep up with the destruction and expose who’s responsible.”

    Documenting the Destruction

    Danti leads a team that publishes a weekly report documenting attacks on sites in Syria and northern Iraq. Known as ASOR Heritage Cultural Initiatives and funded by the U.S. State Department, the team draws on a wide range of images, from Cold War-era CORONA spy photos to constantly updated, high-resolution coverage provided by the commercial satellite operator DigitalGlobe. Since the full extent of damage to ancient sites is not always visible from space, ASOR’s bulletins are also based on a network of over fifty on-the-ground informants, including local citizens, refugees, Syrian archaeologists, and NGO workers. Some informants report from inside ISIS-controlled areas at great personal risk. (Danti lived in Raqqa, the ISIS “capital,” for 20 years, and many of his contacts spring from personal connections made during that time.) Social media from inside Syria and Iraq is another rich source of tips for the ASOR team; sometimes, they get to know about acts of destruction before ISIS can publicize them.

    In its first year of operation, ASOR recorded 722 heritage attacks in Syria and 90 in Iraq. During that period, ISIS grabbed global headlines with its flagrant acts of demolition at World Heritage sites including the blowing up of Palmyra’s Temple of Bel, the smashing of sculptures in the Mosul Museum, and the destruction of the Assyrian city of Nimrud with sledgehammers, power tools, and finally explosives. But the satellite images reveal a huge increase in less conspicuous acts of destruction: looters’ pits that are visible from space as pockmarks disfiguring sites across the region.

    Looting as Organized Crime

    ASOR’s analysis shows that in the first four years of the Syrian conflict, more than 3,000 sites have been looted, nearly an order of magnitude increase over the pre-war period. The evidence implicates all parties in the Syrian war, including Assad’s military, but the most intensively ransacked sites are clearly the handiwork of ISIS. “Cultural heritage always suffers during conflict,” Danti says, “but what’s new is that ISIS has turned cultural destruction into a systematic business.” For instance, ISIS issues “dig” permits and hires contractors to bulldoze sites, while charging 20% sales tax on looted items.

    “The international community has still not fully woken up to the industrial scale of the looting,” Danti says. “It’s a highly organized trafficking organization that provides a major source of income to ISIS.”

    The entrance to the Temple of Bel is all that remains standing of the ancient building after ISIS forces brought down the rest.

    Beyond the illegal antiquities trade, ISIS engages in “cultural cleansing,” destroying historic and modern churches and mosques to demoralize the Shia, Christian, Yezzidi, and other minorities that their ideology brands as “apostate.” Space imagery has again proven crucial in tracking the destruction. Such images have helped a team of Czech scholars to assess the impact of a demolition campaign targeting sacred structures in Mosul following the city’s capture by ISIS in June 2014.

    “Mosul was a crossroads of culture and peaceful co-existence during medieval times,” says Karl Novacek, an archaeologist at the University of Olomouc in Moravia. “Many different ethnic traditions gave rise to a unique style of sacred architecture that’s barely been studied.” The space images show that 38 monuments—mostly early Islamic mosques—have either been reduced to ruins or completely razed and turned into car parks. The images are part of a database in which the team is assembling all the records, archives, and photos they can find of the lost monuments, many of them scattered among scholars and the collections of local people. “If we succeed, we could create a base for future architectural restoration,” Novacek says.

    The Promise of Digital Restoration

    Besides tracking what’s been lost, digital technology opens up new possibilities for a post-war future that’s faced with the challenge of restoring iconic structures. The Syrian government’s Directorate-General of Antiquities and Museums is already collaborating with ICONEM, a Paris-based architecture firm, to produce “before” and “after” 3D models that anyone can access to zoom in and study wrecked sites in extraordinary, stone-by-stone detail. For example, Krak des Chevaliers, one of Syria’s best known 11th century Crusader castles, was severely damaged when government forces finally drove rebels from the hilltop in 2014. ICONEM programmers designed a “bot” to roam the web and harvest thousands of pre-war photos of the castle, which they then assembled and used to generate a “point cloud” representing a partial 3D model of the Castle. They can superimpose a layer showing recent damage on top of the pre-war model. This may well provide an indispensable visual guide for any eventual attempt to restore the site.

    Tour through ICONEM’s digital reconstruction of Krak des Chevaliers.
    Access mp4 video here .

    The potential of 3D printing to replicate sites generated worldwide headlines in April, when a two-thirds scale model of Palmyra’s Arch of Triumph was erected in London’s Trafalgar Square; the Arch may travel to New York in the Fall. The model was, again, recreated from pre-war photos and was programmed to drive a massive stonecutting machine at a quarry at Carrara in northern Italy, next door to where Michelangelo obtained marble for his statue of David.

    ICONEM used pre-war photographs to build a 3D model of the Temple of Bel.

    The aim of the project was to erect a symbol of cultural resistance in the face of ISIS and to raise public awareness of the heritage threat and was partly the work of an innovative Oxford-based venture known as the Institute for Digital Archaeology. In collaboration with UNESCO and leading universities and foundations, the institute’s major goal is to compile a comprehensive library of 3D imagery of threatened sites across the Middle East that they’re calling the Million Image Database. To create the image bank, the plan is to distribute 5,000 pocket 3D cameras to volunteers and heritage workers across the region. The Institute’s director, Roger Michel, says their ambitious mission is “to rebuild the landscape of the Middle East and the great symbols of our shared cultural heritage that have been destroyed.”

    Can Replicas Replace What’s Lost?

    But when peace finally comes, will the new replication techniques match the quality of what’s been lost? And how will local communities respond to the results? “That’s part of a wider debate about the changing meaning of these places,” says Allison Cuneo, a member of the ASOR team. “Palmyra is no longer simply a tourist site. ISIS child soldiers carried out executions in the amphitheater and left behind a mass grave of civilians. How can clean-up and restoration efforts pay homage to that fact?”

    A satellite image of Palmyra’s amphitheater.

    Meanwhile, ISIS and other extremist groups still pose a dire threat to the Middle East’s ancient cultural treasures. Among the most serious current threats outside Syria, Libya poses the gravest concern. As a shaky coalition government is still taking shape, ISIS forces are converging on coastal Greco-Roman cities such as Cyrene and Leptis Magna that are scarcely less imposing or extensive than Palmyra itself. Meanwhile, in Egypt, security at ancient sites is unraveling. Space archaeologist Sarah Parcak, who used satellite imagery to detect a possible new Norse site in Newfoundland in NOVA’s recent show “Vikings Unearthed“, recently applied the same techniques to study the looting of ancient Egyptian sites. She has documented a 50% jump in looting at four major sites since the 2011 revolution.

    With all the human suffering of the Syrian war and the refugee crisis, why should we care about endangered heritage? Michael Danti stresses that the issue goes far beyond the concerns of archaeologists. “ISIS is practicing cultural terrorism,” he says, “as they target and eliminate the identity of entire sections of society in a way that’s directly comparable with Nazi atrocities.” By supporting the efforts of local heritage workers to protect and reclaim sites, scientists can help embattled communities hang on to hope and a sense of community in a time of terror.

    See the full article here .

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    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.

  • richardmitnick 12:03 pm on June 11, 2016 Permalink | Reply
    Tags: , NOVA, , , Sarah Demers   

    From NOVA via FNAL: Women in Science “What Does Beauty Have To Do with Physics?” Sarah Demers 



    FNAL Art Image  by Angela Gonzales
    FNAL Art Image by Angela Gonzales

    31 May 2016 [NOVA did not put this article into social media.]
    Sarah Scoles

    Sarah Demers

    As a Harvard undergraduate, Sarah Demers—now a professor at Yale University—didn’t have the job you would imagine of a young student of particle physics. She wasn’t running code, writing equations on whiteboards, or trawling data for statistically significant signals. Instead, she was sitting in a basement, transforming 10,000 sheets of gold-coated Mylar into an instrument that would go inside the Fermilab particle accelerator.

    FNAL particle accelerator complex

    It was menial, tedious labor, and she was the only woman in the windowless room. Even after the transformation was complete, the work and the instrument itself didn’t scream “glamorous.” In its DIY, basement-built glory, the detector looked less like a sophisticated science instrument and more like someone toppled over a set of cheap garage shelves.

    Before the job started, she thought she would hate it, and—worse—that she wouldn’t understand the underlying physics, that she was just messing around with foil sheets.

    But she found that she did understand, and soon she could comprehend not only how the strange instrument worked, but also how it would help reveal fundamentals of physics. “I gave myself permission to think about underlying questions,” she says.

    The galaxy Messier 104

    Inside the Fermilab particle accelerator, her instrument looked on as protons collided at near light-speed with their opposites—antiprotons—and the resulting particle shards decayed after the cataclysmic blast. By rewinding that action, physicists could dissect it in slow motion. From there, they could pick up its pieces, discover what matter is made of and the forces that hold it together, and pry it apart.

    Despite the foil-wrapped contraption’s messiness, those close observations of the femtoscale explosions are what helped her see she beauty. “A lot of us go into science partly driven by how beautiful the theories are,” Demers says.

    Physicists often describe their earliest experiences with the field as borderline spiritual, moments in which they realized that they—they!—can represent the world with math. They can describe how stars shrink to black holes, how hard you will hit your head if you slip on a banana peel, and how protons fall apart inside particle accelerators. That ability gives them a sense of control in the way that describing something gives humans dominion over it.

    For many physicists, this fosters a desire to get to the very, very bottom of things: the theory of everything. Such a theory, many physicists often believe, should be beautiful, simple, elegant, aesthetically pleasing. All of the forces should fit under one umbrella; all particles need to emerge from a nested set of equations. No ifs, ands, buts, or loopholes. Physicists sometimes use these qualities, and their opposites—ugliness, caveats, asymmetries—as respective hot-and-cold indicators to guide them on the path toward understanding, describing, and conquering the universe.

    The current gold standard for describing the nature of reality, the Standard Model, isn’t physicists’ ideal because, among other blemishes, it isn’t perfectly symmetric, and the way it glues fundamental forces together is a little kludgy.

    The Standard Model of elementary particles (more schematic depiction), with the three generations of matter, gauge bosons in the fourth column, and the Higgs boson in the fifth.
    The Standard Model of elementary particles (more schematic depiction), with the three generations of matter, gauge bosons in the fourth column, and the Higgs boson in the fifth.

    That’s partially why scientists have developed a new idea, called supersymmetry, which smooths and extends the Standard Model, giving each of those old-school particles a new-school “supersymmetric” counterpart.

    Standard model of Supersymmetry DESY
    Standard model of Supersymmetry DESY

    Despite the fact that particle physicists have found no evidence of supersymmetry, they continue hunting for the elusive supersymmetric partners—partly because the theory is more aesthetically appealing than the Standard Model.

    But not all physicists believe that beauty should count as indirect evidence in favor of an idea.

    As Demers dug in to her research, she began to have doubts. Maybe it was okay for the universe to be a little bit ugly. And with that thought, Demers joined a faction of physicists who believe that the pursuit of beauty as truth may be leading the field of particle physics astray.


    Marcelo Gleiser, a professor of physics at Dartmouth College, began his career the same way as Demers: searching for the underlying explanations of why the universe is the way it is. But about a decade ago, he felt Demers’s same uncertainty tugging at him. “You look outside, and what you see in nature is not really perfection and symmetry,” he says. “You see patterns and formats which are not exactly perfect. Animal, tree, cloud, face: They obviously have symmetry but not perfect symmetry. It’s not really perfection, but near perfection.”

    He saw the blemishes in physics, too. There is more matter than antimatter, for example. If the two were perfectly balanced and symmetric, they would have annihilated each other like the particles in Demers’ detector, and the universe would be empty—there’d be no physicists to wonder why, or to high-five each other after the discovery of a beautiful but deadly cosmic balance. “Something happened during the history of the early universe to cause this,” he says. “That got me thinking that perhaps the insistence that we have in search of perfect symmetry is not a physics idea, but a bias.”

    Demers’s epiphany took place as she was composing grant applications to fund her work after graduate school with the Large Hadron Collider, where the so-called “God particle” Higgs boson was discovered. Around 3,000 people worked on the ATLAS instrument team with her—attempting to discover physics that’s beyond the well-established Standard-Model. In the grant application, she also had to justify her experiment and the motivations behind it. Some of the reasons she jotted down, she realized, were purely aesthetic. It made her uncomfortable. “I personally had been sloppier about that than I should have been,” Demers says. “It struck me: You wonder, how equipped are we to be making aesthetic judgments given what we know now?” she adds. “How contrived is too contrived? And how fine-tuned is too fine-tuned?”

    Millennia of Aesthetics

    The human desire for a fine-tuned, aesthetically pleasing cosmos goes much further back than our ability to build particle accelerators. Plato believed the universe was made of geometry: simple, pure shapes that some deus snapped together to form a Lego-like reality. A sufficiently smart person, he reasoned, could unsnap those building blocks to reveal the fundamental forms.

    Early astronomers also believed that planetary orbits were perfect circles. After all, in their view, God wouldn’t have doomed the planets to orbit along an imperfect path. Because every early astronomer started with this belief, it took Johannes Kepler six years to figure out that the evidence pointed to unappealing elliptical orbits instead. But when he allowed the experimental data to lead him toward a conclusion, he discovered a truth about the universe.

    The spiral arms of the galaxy Messier 74

    After Kepler’s data-driven discovery, Isaac Newton created the theories of gravitational force that described how and why orbits actually trace ellipses, though his ideas again reached back toward aesthetic pleasure. The same gravity that makes apples fall onto our heads also makes Earth go around the Sun. One beautiful force to control them both.

    In this kind of thinking, Gleiser sees a different version of the ancients’ god-driven commitment to perfect circles. And in modern scientists’ pursuit of further unification—like making the physics of atoms and subatomic particles work with the classical physics that governs the everyday world—he sees a renewed religious impulse. “The idea that there is a force that describes everything is sort of a monotheistic cultural vice that we have,” he says. “Growing up in a culture for two or three thousand years where there is a god and a central command of things—I think that’s deeply ingrained in people’s heads.” In some sense, physicists have replaced their one true, symmetrically-faced God with one true, symmetric theory.

    Take Einstein, who in the early 1900s said that general relativity was too beautiful to be wrong. Or physicist Paul Dirac, who in the 1960s said that the elegance of an equation outweighed the outcome of an experiment. It’s as though they had both taken to heart what poet John Keats wrote in 1820: “Beauty is truth, truth beauty.”

    For Demers and Gleiser, aesthetics as evidence loses its appeal when it is taken as…well…on par with evidence. For example, when the Large Hadron Collider failed to find any evidence of supersymmetry, many theorists tweaked their ideas about supersymmetry—saying, “Here’s why we don’t see any evidence”—rather than accepting that perhaps the evidence was pointing them elsewhere.

    The Cat’s Eye Nebula

    Demers believes particle physics is in a data-rich era and that physicists should let data lead the way. As the Large Hadron Collider continues its run, it produces more and more evidence for experiments physicists like her to analyze—and then for theorists explain. “I think we may be more likely to win by the data just forcing us in a direction, as opposed to having some great idea that’s aesthetically motivated that pans out to be true,” she says. In other words, it isn’t a physicist’s job to write mathematical poetry expounding upon the platonic “universeness” of the universe. It’s their job to describe the physical reality that we interact with, that we have concrete experimental data about.

    And so, while beauty may be truth, the science of physics isn’t actually the pursuit of truth, nor the quest for beauty. The universe may be, at its most fundamental, as perfectly balanced as a Shakespearean sonnet. But if the data from experiments suggests not a sonnet but a modern prose poem—which is no less pretty, just different, unconventional, and more complicated—it is still physicists’ duty as scientists to analyze it.

    Agnostic Quests

    In April 2015, after a two-year break for an upgrade, the Large Hadron Collider spooled back up. This summer, the accelerator—including the ATLAS experiment that Demers is part of—will conduct its second data-taking run at these higher energies with more particle collisions. By the end of the season, it will have recorded twice as much information as it did in all of 2015. In that data, says Demers, physicists should still search for evidence of the Standard Model and supersymmetry—she’s not opposed to those theories. But they should also go on “agnostic quests,” she says, where they don’t go looking for something in particular. Instead, they should just look, and see what they find.

    The Veil Nebula is the remains of a massive star that exploded 8,000 years ago.

    But some physicists may be reluctant to give up their beautiful theories, even if the data dictates they should. For example, while the Large Hadron Collider has so far failed to show evidence of supersymmetry, many have essentially said that the collision wasn’t powerful enough or that some small modifications are all that’s needed to fit the theory they love with the data they gathered.

    “Supersymmetry has been around since 1974, for 42 years, and it doesn’t really have any evidence that it’s there. But people really bet their careers on this,” Gleiser explains. “Many physicists have spent 40 years working on this, which is basically their whole professional life.”

    That may change in in ten years or so, he says, when further advances to the LHC could force the hangers-on to let go if the data they need doesn’t materialize. “If we don’t find evidence, people who still stick to it after that are doing it as a philosophical practice,” he says.

    Of course, it’s certainly possible that the answers to life, the universe, and everything will be elegant. To physicists like Demers and Gleiser, that’s not the problem: The problem is the a priori assumption that it is so. And if the foundational principles of the universe turn out to be ugly or tedious, perhaps we can find the beauty beneath the mess.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

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    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.

  • richardmitnick 7:12 pm on May 29, 2016 Permalink | Reply
    Tags: , , NOVA, Perineuronal net   

    From NOVA: “Unlocking the Brain’s Deepest Secrets” 



    25 May 2016
    Teal Burrell

    In neuroscience, neurons get all the glory. Or rather, they used to. Researchers are beginning to discover the importance of something outside the neurons—a structure called the perineuronal net. This net might reveal how memories are stored and how various diseases ravage the brain.

    The realization of important roles for structures outside neurons serves as a reminder that the brain is a lot more complicated than we thought. Or, it’s exactly as complicated as neuroscientists thought it was 130 years ago.

    In 1882, Italian physician and scientist Camillo Golgi described a structure that enveloped cells in the brain in a thin layer. He later named it the pericellular net. His word choice was deliberate; he carefully avoided the word “neuron” since he was engaged in a battle with another neuroscience luminary, Santiago Ramón y Cajal, over whether the nervous system was a continuous meshwork of cells that were fused together—Golgi’s take—or a collection of discrete cells, called neurons—Ramón y Cajal’s view.

    Perineuronal nets, seen here stained red, wrap around neurons from a mouse’s brain. No image credit.

    Ramón y Cajal wasn’t having it. He argued Golgi was wrong about the existence of such a net, blaming the findings on Golgi’s eponymous staining technique, which, incidentally, is still used today.

    Ramón y Cajal’s influence was enough to shut down the debate. While some Golgi supporters labored in vain to prove the nets existed, their findings never took hold. Instead, over the next century, neuroscientists focused exclusively on neurons, the discrete cells of the nervous system that relay information between one another, giving rise to movements, perceptions, and emotions. (The two adversaries would begrudgingly share a Nobel Prize in 1906 for their work describing the nervous system.)

    But it seems the focus on neurons has ignored crucial elements; neurons can’t explain everything about how the brain works, like how memories are stored or how various diseases ravage the brain. Now, neuroscientists are discovering that perineuronal nets may hold the secrets to some of the greatest mysteries of neuroscience.

    Making Memories

    One thing perineronal nets might unlock are the workings of our memories. “Up to this point, we still don’t understand how we maintain memories in our brains for up to our entire lifetimes,” says Sakina Palida, a graduate student in Roger Tsien’s lab at the University of California, San Diego.

    Our current understanding is that memories are formed when the synapses—the spaces between two neurons—in our brain are reconfigured. As we learn, new synapses—new connections between neurons—are forged. If those connections are reinforced, proteins within the neurons are activated to boost the signal at that particular synapse, and what we’ve learned becomes committed to memory.

    But existing theories have a few loose ends. For one, the proteins responsible are replaced too quickly, on a scale of days to weeks. It’s difficult to imagine long-term memories being stored in such a system.

    To Tsien, a modern Nobel laureate, the breakthrough came when he started thinking outside the neuron. Instead of molecules inside neurons retaining memories, molecules outside neurons might be the key. “You need very long lasting molecules to store things and what else is better than just on the other side, the outside of the synapse?” Tsien says. “You have equal access to the information that’s in the synapse, but the proteins and carbohydrates that are on the outside of the synapse can last forever.”

    Which brings us back, 130 years after it was first proposed, to the perineuronal net.

    The perineuronal net is an organized tangle of proteins that helps form the extracellular matrix, a sort of neuron exoskeleton. As our brain matures, from before birth through the teenage years, connections between neurons are refined; unnecessary connections wither away while other, more vital circuits are strengthened. The perineuronal net is the finishing touch: it surrounds neurons, establishing a physical barrier to prevent aberrant connections from forming while leaving holes in the armor to let existing synapses through.

    Tsien thinks that the structure of the net might be what’s holding our long-term memories. A hole in the net represents a memory: a stable, reinforced connection between two neurons. That the perineuronal net is involved in some form of memory isn’t entirely new; Tsien’s hypothesis is that it is the structure for long-term memory, and that is new.

    But first, Tsien and his collaborators had to prove that the nets are long lasting. To test this, Varda Levram-Ellisman, a scientist in Tsien’s lab, gave baby mice food containing nitrogen-15, a rare isotope, some of which would be incorporated into the animal’s developing brain structures. When the mice were six weeks old, after their perineuronal nets were fully developed, they were switched back to normal food. If the nitrogen-15 was still present months later, it would mean those structures had lasted that long. Indeed, nitrogen-15 was still a part of the perineuronal net after 180 days (the equivalent of years in human terms).

    The next step in developing the hypothesis was showing that the nets—and the holes within them—hold lasting memories. Palida likens making holes in the net to carving into stone. “Stone is a stable substrate. You retain the information regardless of what comes and goes over it as long as the substrate remains stable,” she says. Making new synapses requires certain enzymes to chisel through the net. When Levram-Ellisman gave mice a drug that inhibited one of these chiseling enzymes, the mice had poor long-term memory. Their short-term memory remained intact, however, suggesting drilling holes in the net was specific to long-lasting memories. In another experiment, Palida found that she could erode the nets in particular areas of the brain when she introduced a protein known to enhance memory.

    Palida has also developed new ways to visualize the nets, enabling her to detect them even when their composition varies. With these tools, she has discredited the thinking that the nets were specific to certain brain regions or cell types. “These nets are widespread throughout the brain. They surround all neurons,” she says.

    In 2009, perineuronal nets were blamed for the fact that fear memories are nearly impossible to erase in adults. In animal studies, fear memories are created by pairing a noise with a foot shock; mice learn to fear the noise since it means an impending jolt. In young mice, these memories can be completely wiped away by playing the noise over and over again without the foot shock; the mice relearn the noise is innocuous. But adult mice never really forget. Their memories can only be temporarily masked, they still crop up in triggering situations, like when put back in the cage that originally shocked them.

    The maturation of the perineuronal nets marks this transition between child and adult; when adult mice were given a drug that degraded the nets, they were able to completely forget their fear, in the same way young mice do. Understanding this process could help explain post-traumatic stress disorder—in which horrifying memories seem etched in stone—and provide a new target for treatment; perhaps degrading the nets could help release some of the unrelenting memories.

    A New Target

    The prevalence of perineuronal nets suggests that they could be the driving force behind not just long-term memories, but also certain neurological diseases. Sabina Berretta, an associate professor of psychiatry at Harvard Medical School, found that perineuronal nets are decreased in certain brain areas in schizophrenia. Additionally, several genes that have been implicated in schizophrenia code for molecules that make up the net or the enzymes that regulate it. Berretta found evidence that the nets are disrupted in bipolar disorder, too.

    There have been striking results in studies of Alzheimer’s disease, as well; postmortem studies of patients show fewer nets compared to controls. “Once we understand what may be the factors that contribute to these changes, then it may be possible to start understanding how to address them from a therapeutic point of view,” Berretta says.

    Perhaps paradoxically, given their role in long-term memory, recent work by Harry Pantazopoulos, a researcher in Berretta’s lab, has suggested that the nets might change over the course of the day. Although the total number of nets remains stable, in both mice and postmortem human brain tissue, the molecules within the nets seem to fluctuate in a rhythmic way; some of the nets’ components are increased during the day in certain brain regions, while others are increased at night. Berretta warns that the data is preliminary, but it suggests that these stable structures are also somehow dynamic. It may be that the composition changes to accommodate learning while we are awake and consolidation of memories while we are asleep.

    Ignored No More

    At the latest Society for Neuroscience meeting in Chicago, it was clear perineuronal nets are not being ignored any longer. “They’re everywhere at this meeting,” says Angela O’Connor, a researcher at the University of Michigan who studies how the nets change when mice are put in stimulating environments.

    Since they were overlooked for so long, perineuronal nets and the extracellular matrix might explain many of neuroscience’s mysteries, from how memories are stored for decades to how certain diseases disrupt the brain. Berretta suspects that there are other, similarly critical components of the extracellular matrix that have been ignored for too long as well. “It is possible from a pathological point of view that we haven’t even begun to understand the extent of these changes not only in schizophrenia, but also their involvement in other brain disorders,” Berretta says.

    “The nets were reported a long time ago by Camillo Golgi. They were drawn, they were described. We simply didn’t know what to do with them, so we kind of ignored them,” she says with a laugh. Those days appear to be over.

    See the full article here .

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    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.

  • richardmitnick 4:09 pm on May 26, 2016 Permalink | Reply
    Tags: , Alzheimer’s Disease May Be Caused By Brain Infections, , NOVA   

    From NOVA: “Alzheimer’s Disease May Be Caused By Brain Infections” 



    26 May 2016
    Allison Eck

    Silent infections earlier in life could be at the root of Alzheimer’s disease.

    Alzheimer’s researchers have long presumed that amyloid beta proteins are the brain’s garbage, accumulating over time but serving no obvious purpose. These plaques trigger the formation of tau proteins (or “tangles”), which proceed to destroy nerve cells.

    Robert D. Moir of Harvard Medical School and Massachusetts General Hospital thought something was missing in this picture—and looked to proteins that live on our innate immune system for answers. Moir and his colleague Rudolph E. Tanzi noticed that amyloid proteins look like these immune system proteins, which trap and then purge harmful viruses, yeast, fungi, and bacteria. The two scientists wanted to see if amyloid plaques serve a similar function in the brain.

    Salmonella bacteria, trapped in amyloid beta plaques.

    In one experiment, Moir and Tanzi subjected young mice’s brains to Salmonella bacteria. They noticed that plaques began to form around single Salmonella bacterium and that in mice without amyloid beta, bacterial infections arose more quickly. The team’s work, published* Wednesday in the journal Science Translational Medicine, suggests that silent, often symptomless infections in the brain could be the precursor to the development of Alzheimer’s disease later in life.

    Here’s Gina Kolata, reporting for The New York Times:

    “The Harvard researchers report a scenario seemingly out of science fiction. A virus, fungus or bacterium gets into the brain, passing through a membrane—the blood-brain barrier—that becomes leaky as people age. The brain’s defense system rushes in to stop the invader by making a sticky cage out of proteins, called beta amyloid. The microbe, like a fly in a spider web, becomes trapped in the cage and dies. What is left behind is the cage—a plaque that is the hallmark of Alzheimer’s.

    So far, the group has confirmed this hypothesis in neurons growing in petri dishes as well as in yeast, roundworms, fruit flies and mice. There is much more work to be done to determine if a similar sequence happens in humans, but plans—and funding—are in place to start those studies, involving a multicenter project that will examine human brains.

    The finding may help explain why some people with Alzheimer’s have exhibited higher levels of herpes antibodies, a sign of previous infection, than others who didn’t have Alzheimer’s.”

    Of course, infection is likely not the only contributing factor. People with the ApoE4 gene aren’t as effective in breaking down beta amyloid, so any potential immune-like response by amyloid proteins could lead to an unhealthy buildup.

    Whatever the complex set of circumstances may be, this finding may fill in some of missing links in Alzheimer’s research.

    *Science paper:
    Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease

    See the full article here .

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  • richardmitnick 11:43 am on May 21, 2016 Permalink | Reply
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    From NOVA: “The Quest for a Simple Cancer Test” 



    19 May 2016
    Jeffrey Perkel

    Embedded in a small translucent wafer measuring just under an inch a side, the spiraling coils—like neatly packed iPod earbuds—aren’t much to look at.

    But judging on appearance alone would sell short the brainchild of Chwee Teck Lim of National University Singapore and Jongyoon Han of the Massachusetts Institute of Technology. Those coils sift through millions upon millions of blood cells for faintly detectable indicators of a solid tumor lurking in a patient’s body—the handful of cancer cells that are often found circulating in the blood. Called circulating tumor cells, these cells may well be the seeds of distant metastases, which are responsible for 90% of all cancer deaths.

    Over the past several years, researchers and clinicians have become increasingly fixated on these circulating cells as cellular canaries-in-the-coalmine, indicators of distant disease. The blood of cancer patients is chock-full of potentially telling molecules, and researchers and clinicians are hotly investigating these materials for their efficacy as indicators and predictors of illness, disease progression, response to treatment, and even relapse.

    Soon, a simple blood test could reveal whether a person has cancer.

    For patients with cancer, such tests could provide a welcome respite from painful, invasive, and sometimes dangerous biopsies that typically are used to track and diagnose disease—a fact reflected in the terminology often used to describe the new assays: liquid biopsy. For researchers and clinicians, they provide a noninvasive and repeatable way to monitor how a disease changes over time, even in cases when the tumor itself is inaccessible.

    And unlike the finger-stick testing used by the embattled company Theranos, which recently voided two years of results from their proprietary blood-testing machines, the liquid biopsy methods being researched and developed by teams of scientists around the world use standard blood-drawing techniques and have been subject to peer review.

    In the short term, researchers hope to use liquid biopsies to monitor tumor relapse, track a tumor’s response to targeted therapies, and match patients with the treatments most likely to be effective—the very essence of “personalized medicine.” But longer term, some envision tapping the blood for early diagnosis to catch tumors long before symptoms start, the time when they’re most responsive to treatment.

    For now, most such promises are just that: promises. With the exception of one FDA-approved test, a handful of lab-developed diagnostics, and a slew of clinical trials, few cancer patients today are benefitting from liquid biopsies. But many are betting they soon will be. Liquid biopsies, says Daniel Haber, director of the Massachusetts General Hospital (MGH) Cancer Center, “currently are aspirational—they don’t yet exist in that they’re not part of routine care. But they have the possibility to become so.”

    Revealing Information

    Despite its name, liquid biopsies are not exactly an alternative to solid tissue biopsies, says Mehmet Toner, a professor of biomedical engineering at MGH who studies circulating tumor cells. Patients who are first diagnosed with cancer via a liquid biopsy would likely still undergo a tissue biopsy, both in order to confirm a diagnosis and to guide treatment.

    But liquid biopsies do provide molecular intel that might otherwise be impossible to obtain—for instance, in the treatment of metastatic disease. Oncologists typically biopsy patients with metastatic disease only once, to confirm the diagnosis, says Keith Flaherty, director of the Henri and Belinda Termeer Center for Targeted Therapies at the MGH Cancer Center. But such a test reveals the genetics of the cancer only at the sampled site. Many patients harbor multiple metastases, some in relatively inaccessible locations like the lungs, brain, or bones, and each may contain cells with different genetic signatures and drug susceptibilities. “Liquid biopsies provide an aggregate assessment of a cancer population,” he says.

    Today, says Max Diehn, an assistant professor of radiation oncology at the Stanford University School of Medicine, oncologists can get a read on how a patient responds to therapy using a handful of protein biomarkers found in blood, urine, or other biofluids, such as prostate-specific antigen (PSA) in the case of prostate cancer, or using noninvasive imaging technologies like magnetic resonance imaging (MRI) or computed tomography (CT). But those tests often fall short. Many biomarkers aren’t specific enough to be useful, and imaging is relatively expensive and insensitive. Also, not everything that appears to be a tumor on a scan actually is. And, Flaherty notes, imaging studies reveal little or no molecular information about the tumor itself, information that’s useful in guiding the treatment.

    In contrast, liquid biopsies can reveal not only whether patients are responding to treatment, but also catch game-changing genetic alterations in real time. In one recent study, Nicholas Turner of the Institute for Cancer Research in London and his colleagues examined cell-free tumor DNA (ctDNA), or tumor DNA that’s floating free in the bloodstream, in women with metastatic breast cancer. They were looking for for the presence of mutations in the estrogen receptor gene, ESR1. Breast cancer patients previously treated with so-called aromatase inhibitors often develop ESR1 mutations that render their tumors resistant to two potential treatments, hormonal therapies that target the estrogen receptor and further use of aromatase inhibitors that block the production of estrogen. Turner’s team detected ESR1 mutant ctDNA in 18 of 171 women tested (10.5%), and those women’s tumors tended to progress more rapidly when treated with aromatase inhibitors than did women who lacked such mutations. Those findings had no impact on the patients in the study—the women were analyzed retrospectively—but they suggest that prospective use of ctDNA analysis might be used to shift treatment toward different therapeutic strategies.

    Viktor Adalsteinsson of the Broad Institute of MIT and Harvard, whose group has sequenced more than a thousand liquid biopsy genomes, calls the ESR1 study “promising and illuminating.” At the moment, he says, such data are not being actively used to influence patient treatment, at least not in the Boston area. But Jesse Boehm, associate director of the Broad Cancer Program, says he thinks it could take as little as two years for that to change. “I’ve been here at the Broad for ten years, and I don’t think I’ve ever seen another project grow from scientific concept to potentially game-changing so quickly,” he says.

    Varied Approaches

    Liquid biopsies generally come in one of three forms. One, ctDNA—Adalsteinsson’s material of choice—is the easiest to study, but also the most limited as it relies on probing short snippets of DNA in the bloodstream for a collection of known mutations. The blood is full of DNA, as all cells jettison their nuclear material when they die, so researchers must identify those fragments that are specifically diagnostic of disease. While the genetic mutations behind some prominent cancers have been identified, many more have not. Also, not all genetic changes are revealed in the DNA itself, says Klaus Pantel, director of the Institute of Tumor Biology at the University Medical Center Hamburg-Eppendorf.

    A second class of liquid biopsy focuses on tiny membrane-encapsulated packages of RNA and protein called exosomes. Exosomes provide researchers a glimpse of cancer cells’ gene expression patterns, meaning they can reveal differences that are invisible at the DNA level. But, because both normal and cancerous cells release exosomes, the trick, as with ctDNA, is to isolate and characterize those few particles that stem from the tumor itself.

    The third counts circulating tumor cells, or CTCs. They are not found in healthy individuals, but neither are they prevalent even in very advanced cases, accounting for perhaps one to 100 per billion blood cells, according to Lim. Researchers can simply count the cells, as CTC abundances tend to scale with prognosis.

    But there’s much more that CTCs can do, Pantel says. “You can analyze the DNA, the RNA, and the protein, and you can put the cells in culture, so you can get some information on responsiveness to drugs.” Stefanie Jeffrey, a professor of surgery at Stanford University School of Medicine, has purified CTCs and demonstrated that individual breast cancer CTCs express different genes than the immortalized breast cancer cells typically used in drug development. That, she says, “raises questions” about the way potential drugs are currently evaluated in the early stages of development.

    Similarly, Toner and Haber have developed a device called the CTC-iChip to count and enrich CTCs from whole blood. The size of a CD—indeed, the chips are fabricated using high-throughput CD manufacturing technology—these devices take whole blood, filter out the red cells, platelets, and white blood cells, and keep what’s left, including CTCs. The team has used this device to evaluate hundreds of individual CTCs from breast, pancreatic, and prostate tumor patients to identify possible ways to selectively kill those cells.

    Elsewhere, Caroline Dive, a researcher at the University of Manchester, has even injected CTCs isolated from patients with small-cell lung cancer into mice. The resulting tumors exhibit the same drug sensitivities as the starting human tumors, providing a platform that could be used to better identify treatment options.

    A Range of Uses

    According to Lim, liquid biopsies have five potential applications: early disease detection, cancer staging, treatment monitoring, personalized treatment, and post-cancer surveillance. Of those, most agree, the likely near-term applications are personalized treatment and treatment monitoring. The most difficult is early detection.

    Among other things, early detection requires testing thousands of early-stage patients and healthy volunteers to demonstrate that the tests are sufficiently sensitive to detect cancer early yet specific enough to avoid false positives. A widely adopted assay that was, say, 90% specific could yield perhaps millions of false positives, Pantel says. “I’m sure that’s fantastic for the lawyers, but not for the patients.”

    Still, researchers have begun demonstrating the possibility. In one 2014 study describing a new method for analyzing ctDNA, Diehn, the Stanford radiation oncologist, and his colleague, Ash Alizadeh, an assistant professor of medical oncology also at Stanford, showed that they could detect half of the stage I non-small-cell lung cancer samples it was confronted with, and 100% of tumors stage II and above. That’s despite the fact that ctDNA fragments are only about 170 bases long—a very short amount—and disappear from the blood within about 30 minutes. “There’s constant cell turnover in tumors,” Diehn says. “There’s always some cells dying, and that’s what lets you detect it.”

    In another study, Nickolas Papadopoulos, a professor of oncology and pathology at the Johns Hopkins School of Medicine, and his colleagues surveyed the ctDNA content of 185 individuals across 15 different types of advanced cancer. For some tumor types, including bladder, colorectal, and ovarian, they found ctDNA in every patient tested; other tumors, such as glioblastomas, were more difficult to pick up. “It made sense,” Papadopoulos says. “These tumors are beyond the blood-brain barrier…and they do not shed DNA into the circulation.” In later studies, the team demonstrated that some tumors are more easily found in bodily fluids other than blood. Certain head and neck cancers are readily detected in saliva, for example, and some urogenital cancers can be detected in urine. But in their initial survey, Papadopoulos and his colleagues also tested blood plasma for the ability to detect localized (that is, non-metastatic) tumors, identifying disease in between about half and three-fourths of individuals.

    Though 50% sensitivity isn’t perfect, it’s better than nothing, Papadopoulos says, especially for cancers of the ovaries and pancreas. “Right now, we get 0% of them because there’s no screening test for these cancers.”

    In the meantime, researchers are focusing on personalized therapy. Alizadeh and Diehn, for instance, have tested patients with stage IV metastatic non-small cell lung cancer, a grave diagnosis, who had been taking erlotinib, a drug that targets specific mutations in the EGFR gene. Over time, all patients develop resistance to these drugs, half of them via a new mutation, Diehn says. Diehn and Alizadeh have begun looking for that mutation in the ctDNA of patients whose disease progresses, or returns, as such tumors can be specifically targeted by a new drug, osimertinib. “It’s been shown in a couple of studies that such patients then have a good response rate,” Diehn says, with the median “progression-free survival” doubling from about ten months to 20.

    Toward the Clinic

    Most scientists working on liquid biopsies agree that the technology itself is mature. What’s needed to make a difference in patients’ lives is clinical evidence of sensitivity, selectivity, and efficacy.

    Fortunately, they’re working on it. According to the National Institutes of Health’s clinical trials database, clinicaltrials.gov, over 350 trials are currently studying the use of liquid biopsies in cancer detection, identification, or treatment.

    One recent trial, published in April in JAMA Oncology, examined the ability of ctDNA analysis to detect key mutations in two genes associated with treatment decision, response, and resistance in non-small cell lung cancer. The 180-patient prospective trial determined that the method used could detect the majority (64% –86%) of the tested mutations with no false-positive readings in most cases. Results were returned on average within three days, compared to 12 to 27 days for solid-tissue biopsy. The technique is ready for clinical use, the authors concluded.

    In an ongoing trial, Pantel and his colleagues are focusing on a breast cancer-associated protein called HER2. Several anticancer therapies specifically target HER2-positive tumors, including trastuzumab and lapatinib. The trial is looking for instances of HER2-expressing CTCs in patients with metastatic breast cancer whose original tumor did not express HER2. About 20% of HER2-negative tumors meet that criterion, Pantel says, but before liquid biopsies became an option, there was really no way to find them. Now, his team is testing “whether the change to HER2-positive CTCs is a good predictor for response to HER2-targeted therapy.” If it is, it could unlock potential treatments for patients.

    In another trial, Flaherty, the center director at MGH, and his colleagues are using a series of liquid biopsies in several hundred patients with metastatic melanoma to determine if they could retrospectively predict drug resistance by monitoring for mutations in a particular gene.

    In the meantime, diagnostics firms are developing assays of their own. Currently, there is only one FDA-approved liquid biopsy test on the market in the United States. But there also are a growing handful of lab-developed assays for specific genetic mutations available and several more in development.

    Early cancer screening is farther out, and while many researchers still express skepticism, the application received a high-profile boost in January when sequencing firm Illumina announced it was launching a spinoff company called Grail. The company, which has already raised some $100 million in funding, will leverage “very deep sequencing” to identify rare ctDNA mutations, and plans to launch a “pan-cancer” screening test by 2019.

    Only time will tell, though, whether Grail or any other company is able to fundamentally alter how patients are treated for cancer. But one thing is certain, Flaherty says: Genetic testing, however it is done, only addresses the diagnostics side of the personalized medicine challenge; progress is also required on the drug development side. After all, what good is a test if there’s no way to act on it?

    See the full article here .

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