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  • richardmitnick 3:06 pm on December 19, 2014 Permalink | Reply
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    From Brown: “New technique reveals immune cell motion through variety of tissues” 

    Brown University
    Brown University

    December 18, 2014
    Kevin Stacey 401-863-3766

    Neutrophils, a type of white blood cell, are the immune system’s all-terrain vehicles. The cells are recruited to fight infections or injury in any tissue or organ in the body despite differences in the cellular and biochemical composition. Researchers from Brown University’s School of Engineering and the Department of Surgery in the Warren Alpert Medical School collaborated to devise a new technique for understanding how neutrophils move in these confined spaces.

    1
    Cell movement in 3-D tissue By placing neutrophils between two hydrogel sacks, researchers can mimic cell movement through 3-D tissue. Digital micrometers can change the characteristics — density, stiffness — of the medium through which the cells move. Frank lab/Brown University

    The technique involves two hydrogel sacks sandwiched together with a miniscule space in between. Neutrophils could be placed in that space, mimicking the confinement they experience within tissue. Time-lapse cameras measure how fast the cells move, and traction force microscopes determine the forces the cells exert on the surrounding gel.

    In a paper published in the Journal of Biological Chemistry, the researchers used the device to reveal new details about the motion of neutrophils. Bodily tissues are highly confined, densely packed, three-dimensional spaces that can vary widely in physical shape and elasticity. The researchers showed that neutrophils are sensitive to the physical aspects of their environment: They behave differently on flat surfaces than in confined three-dimensional space. Ultimately, the team hopes the system can be useful in screening drugs aimed at optimizing neutrophils to fight infection in specific tissue types.

    Traditionally, research on neutrophil motion in the lab is often done on two-dimensional, inflexible surfaces composed of plastic or glass. Those studies showed that neutrophils move using arm-like appendages called integrins. The cell extends the integrins, which grab onto to flat surfaces like tiny grappling hooks. By reeling those integrins back in, the cell is able to crawl along.

    Scientists thought that by inhibiting integrins, they could greatly reduce the cells’ ability to move through tissue. That, they thought, could be a good strategy for fighting autoimmune diseases in which neutrophils attack and damage healthy tissue.

    But in 2008, a landmark paper showed that neutrophils have a second mode of motion. The work showed that cells in which integrins had been disabled were still able to move through dense tissue.

    Christian Franck, assistant professor of engineering at Brown, and his colleagues wanted to learn more about this second mode of motion.

    “On flat 2-D surfaces there’s integrin-dependent motion, but in complicated 3-D materials there’s integrin-independent motion,” Franck said. “The question we were asking is can we find an in-vitro system that can recreate that integrin-independent motion, because you can’t get it in a regular petri dish.”

    Using their gel system and the traction force microscopes, Franck and his colleagues showed that, when confined, neutrophils exert force in several distinct spots. On the bottom of the cell, forces were generated in a way that was consistent with previous imaging of integrin engagement. But on the top of the cell, there was another source of force. The cell pushed on the upper gel surface with its nuclear lobe, the area of the cell where DNA resides.

    “It’s like a rock climber pushing against the walls of a canyon,” Franck said.

    To see if the force generated by the nuclear lobe was responsible for the cells’ ability to move without integrins, the researchers repeated the experiment with cells in which integrins were chemically inhibited. Sure enough, the cells were still able to move when confined between the gels. In fact, they were able to move faster.

    “We showed that physical confinement is the key feature to reproduce integrin-independent motion in a relatively simple setting,” Franck said. “That wasn’t possible previously on a flat surface.”

    The fact that confined cells actually move faster without their integrin suggests that even though integrins aren’t essential for the cells motion, they still play a regulatory role.

    “What we showed was that [use of integrins] is not black and white,” Franck said. “Even in this integrin-independent motion, integrins remain to regulate motion and force generation.”

    Now that they have a means of recreating how neutrophils travel through confined spaces in the lab, Franck and his team plan to do further experiments aimed at fine-tuning that motion. The system they’ve developed enables them to control the stiffness of the gel surfaces between which the cells travel, mimicking the varying stiffness of tissue in the body.

    “If motility is specific to a neutrophil being in a specific tissue, maybe we could attenuate its response,” Franck said. “Maybe we could make it move faster in the muscle and slower everywhere else, for example.”

    This new system enables testing of drugs aimed at doing just that. Such drugs could be of great benefit to people who have disorders of the immune system.

    Franck’s co-authors on the study were Jennet Toyjanova, Estefany Flores-Cortez, and Jonathan S. Reichner. The research was supported by the National Institutes of Health (grants GM066194 and AI101469), and by a Brown University seed grant.

    See the full article here.

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    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

     
  • richardmitnick 4:34 pm on November 12, 2014 Permalink | Reply
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    From Brown: ” Questions for Peter Schultz – What can we learn by landing on a comet?” 

    Brown University
    Brown University

    November 12, 2014
    Contact: Kevin Stacey 401-863-3766

    ps
    Critical moment Peter Schultz and colleagues react to news that the ESA’s Philae Lander has reached the surface of the comet. Photo: Mike Cohea/Brown University

    On Wednesday, Nov. 12, 2014, the European Space Agency landed a spacecraft on the surface of a comet for the first time. Scientists hope data returned from the Rosetta spacecraft’s Philae Lander might not only offer a new perspective on the nature of comets, but also shed light the evolution of the solar system.

    ESA Rosetta spacecraft
    ESA/Rosetta

    ESA Rosetta Philae Lander
    Philae Lander

    Brown geoscientist Peter Schultz, who was not involved in the ESA mission, is a veteran of three prior missions to comets and asteroids (NASA’s Deep Impact, Stardust-NExT, and EPOXI missions). He spoke with science writer Kevin Stacey about Rosetta.

    Can you give us a bit of background on this comet?

    This particular comet (officially, 67P/Churyumov-Gerasimenko) goes around the sun about every 6.5 years and was discovered by two Ukranian astronomers (Klim Churyumov and Svetlana Gerasimenko) in 1969.

    comet
    67P/Churyumov-Gerasimenko

    As happens to many short-period comets, it was tugged by Jupiter’s gravity during a close encounter early in 1959. This tug changed its orbit, reducing its closest approach to the sun from 2.7 times the distance from the Earth (an astronomical unit, AU) to the sun to only 1.3 AU. The nucleus rotates on its axis every 12.4 hours but has changed due to jets of gas and dust that are released every time it gets close to the sun. As we now are finding out, cometary nuclei come in all shapes and sizes. This particular nucleus has two large lobes. One is about 2.5 miles across; the other is about 1.5 miles.

    Why was this comet chosen as a target for Rosetta and Philae?

    This comet was not the first choice for the mission, but the rocket that was to carry the spacecraft failed in 2002, which caused a delay. The orbit of this particular comet, however, allowed doing the same mission design, with a few tweaks. The key was to identify a comet that would allow a slow approach to the nucleus so that the spacecraft could rendezvous and then orbit.

    Could you talk about some of the technical challenges involved in landing on a comet?

    ESA scientists and engineers knew that it would be difficult to land on a cometary nucleus, especially because nothing was known about its surface. In fact, the mission was launched in 2002, before NASA’s Deep Impact mission saw the nucleus of 9P/Tempel 1 close-up for the first time, and before we knew anything about the density of a cometary nucleus. As Rosetta first captured its close-up view, it was clear that this nucleus was very different: patches of smooth surfaces, irregular depressions with steep-sided cliffs, and block fields. The Philae Lander will touch down in one of the smooth patches, approaching the surface at around two miles per hour (a slow walking pace). Certain areas look like soft snow while others regions are filled with blocks. As a result, it may be difficult to grab hold or stay put. Engineers designed “harpoons” that should have grabbed on while the lander’s legs are designed to keep the Lander from bouncing off. That’s critical because the escape speed is only about 1 mile per hour.

    What kinds of experiments will Philae be carrying out on the surface?

    Experiments on the lander make a wide range of measurements including the composition at the comet’s surface, the strength and density of the surface, temperature, the nature of compounds from about nine inches below the surface (using drills and instruments), isotopic ratios, magnetic field measurements. One instrument will probe the interior of a nucleus for the first time by sending radio waves from Philae to the orbiting Rosetta. Another will listen to the inside of the nucleus as it cracks and creeks when gas is released. This is like geophysicists and geochemists exploring a field site on Earth, but millions of miles away.

    What, ultimately, do scientists hope to learn by actually landing on a comet?

    In 2005, Deep Impact slammed into the nucleus of a comet in order to expose and measure ices and dust below. This time, Philae provides a softer touch. There’s much to be learned by landing on the surface. One of the key measurements is the relative abundance of heavy and light hydrogen, which may be a key to understanding the source of water on Earth. In addition, a lander is the only way to understand more about the strength of the surface and to understand how its atmosphere (the coma) changes as the comet goes around the sun. If successful, scientists will have a better understanding of how comets work.

    See the full article here.

    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

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  • richardmitnick 9:03 pm on November 3, 2014 Permalink | Reply
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    From Brown: “How a giant impact formed asteroid Vesta’s ‘belt’” 

    Brown University
    Brown University

    November 3, 2014
    Kevin Stacey

    Collisions of heavenly bodies generate almost unimaginable levels of energy. Researchers at Brown used NASA’s ultra-high-speed cannon and computer models to simulate such a collision on Vesta, the second-largest object in the asteroid belt. Their analysis of the images — taken at a million frames per second — shows how Vesta may have gotten the deep grooves that encircle its midsection.

    bunch
    A massive collision A high-speed camera recorded a laboratory simulation of colliding heavenly bodies. An analysis of shock propagation suggests what may have caused the tilted canyon-like grooves around the equator of the asteroid Vesta. Image: Angela Stickle and Peter Schultz

    When NASA’s Dawn spacecraft visited the asteroid Vesta in 2011, it showed that deep grooves that circle the asteroid’s equator like a cosmic belt were probably caused by a massive impact on Vesta’s south pole. Now, using a super high-speed cannon at NASA’s Ames Research Center, Brown University researchers have shed new light on the violent chain of events deep in Vesta’s interior that formed those surface grooves, some of which are wider than the Grand Canyon.

    NASA Dawn Spacecraft
    NASA Dawn schematic
    NASA/Dawn

    “Vesta got hammered,” said Peter Schultz, professor of earth, environmental, and planetary sciences at Brown and the paper’s senior author. “The whole interior was reverberating, and what we see on the surface is the manifestation of what happened in the interior.”

    The research suggests that the Rheasilvia basin on Vesta’s south pole was created by an impactor that came in at an angle, rather than straight on. But that glancing blow still did an almost unimaginable amount of damage. The study shows that just seconds after the collision, rocks deep inside the asteroid began to crack and crumble under the stress. Within two minutes major faults reached near the surface, forming deep the canyons seen today near Vesta’s equator, far from the impact point.

    The research, led by Angela Stickle, a former graduate student at Brown and now a researcher at the Johns Hopkins University Applied Physics Laboratory, will appear in the February issue of the journal Icarus and is now available online.

    “As soon as Pete and I saw the images coming down from the Dawn mission at Vesta, we were really excited,” Stickle said. “The large fractures looked just like things we saw in our experiments. So we decided to look into them in more detail, and run the models, and we found really interesting relationships.”

    For the study, the researchers used the Ames Vertical Gun Range, a cannon with a 14-foot barrel used to simulate collisions on celestial bodies. The gun uses gunpowder and compressed hydrogen gas to launch projectiles at blinding speed, up to 16,000 miles per hour. For this latest research, Schultz and his colleagues launched small projectiles at softball-sized spheres made of an acrylic material called PMMA. When struck, the normally clear material turns opaque at points of high stress. By watching the impact with high-speed cameras that take a million shots per second, the researchers can see how these stresses propagate through the material.

    The experiments showed that that damage from the impact starts where one would expect: at the impact point. But shortly after, failure patterns begin to form inside the sphere, opposite the point of impact. Those failures grow inward toward the sphere’s center and then propagate outward toward the edges of the sphere like a blooming flower.

    Using numerical models to scale the lab collision up to the size of Vesta, the second-largest object in the asteroid belt, the researchers showed that the outward-blooming “rosette” of damage extending to the surface is responsible for the troughs that form a belt around Vesta’s equator.

    The results answer some questions about Vesta’s belt that had long been puzzling. Chief among them is the orientation of the belt with respect to the crater. The belt’s angle isn’t exactly what would be expected if it were caused by the Rheasilvia impact.

    “The belt is askew,” Schultz said, “as if Vesta were making a fashion statement.”

    These new experiments suggest that the crooked belt is the result of the angle of impact. An oblique impact causes the damage plane to be tilted with respect the crater. The orientation of Vesta’s belt sheds light on the nature of the impact. The researchers conclude that the object that created Rheasilvia came in at an angle less than 40 degrees, traveling at about 11,000 miles per hour.

    “Vesta was lucky,” Schultz said. “If this collision had been straight on, there would have been one less large asteroid and only a family of fragments left behind.”

    The research shows that even a glancing blow can have tremendous consequences.

    “When big things happen to small bodies,” Schultz said, “it shakes them to the core.”

    See the full article, with video, here.

    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

    ScienceSprings relies on technology from

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  • richardmitnick 6:18 pm on October 28, 2014 Permalink | Reply
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    From Brown: “Can the wave function of an electron be divided and trapped?” 

    Brown University
    Brown University

    October 28, 2014
    Kevin Stacey 401-863-3766

    Electrons are elementary particles — indivisible, unbreakable. But new research suggests the electron’s quantum state — the electron wave function — can be separated into many parts. That has some strange implications for the theory of quantum mechanics.

    New research by physicists from Brown University puts the profound strangeness of quantum mechanics in a nutshell — or, more accurately, in a helium bubble.

    Experiments led by Humphrey Maris, professor of physics at Brown, suggest that the quantum state of an electron — the electron’s wave function — can be shattered into pieces and those pieces can be trapped in tiny bubbles of liquid helium. To be clear, the researchers are not saying that the electron can be broken apart. Electrons are elementary particles, indivisible and unbreakable. But what the researchers are saying is in some ways more bizarre.

    tank
    The electron wave function A canister of liquid helium inside the blue cylinder allowed researchers to experiment with tiny electron bubbles only 3.6 nanometers in diameter. The work suggests that the wave function of an electron can be split and parts of it trapped in smaller bubbles. Photo: Mike Cohea/Brown University

    In quantum mechanics, particles do not have a distinct position in space. Instead, they exist as a wave function, a probability distribution that includes all the possible locations where a particle might be found. Maris and his colleagues are suggesting that parts of that distribution can be separated and cordoned off from each other.

    “We are trapping the chance of finding the electron, not pieces of the electron,” Maris said. “It’s a little like a lottery. When lottery tickets are sold, everyone who buys a ticket gets a piece of paper. So all these people are holding a chance and you can consider that the chances are spread all over the place. But there is only one prize — one electron — and where that prize will go is determined later.”

    If Maris’s interpretation of his experimental findings is correct, it raises profound questions about the measurement process in quantum mechanics. In the traditional formulation of quantum mechanics, when a particle is measured — meaning it is found to be in one particular location — the wave function is said to collapse.

    “The experiments we have performed indicate that the mere interaction of an electron with some larger physical system, such as a bath of liquid helium, does not constitute a measurement,” Maris said. “The question then is: What does?”

    And the fact that the wave function can be split into two or more bubbles is strange as well. If a detector finds the electron in one bubble, what happens to the other bubble?

    “It really raises all kinds of interesting questions,” Maris said.

    The new research is published in the Journal of Low Temperature Physics.

    Electron bubbles

    Scientists have wondered for years about the strange behavior of electrons in liquid helium cooled to near absolute zero. When an electron enters the liquid, it repels surrounding helium atoms, forming a bubble in the liquid about 3.6 nanometers across. The size of the bubble is determined by the pressure of the electron pushing against the surface tension of the helium. The strangeness, however, arises in experiments dating back to the 1960s looking at how the bubbles move.

    In the experiments, a pulse of electrons enters the top of a helium-filled tube, and a detector registers the electric charge delivered when electron bubbles reach the bottom of the tube. Because the bubbles have a well-defined size, they should all experience the same amount of drag as they move, and should therefore arrive at the detector at the same time. But that’s not what happens. Experiments have detected unidentified objects that reach the detector before the normal electron bubbles. Over the years, scientists have cataloged 14 distinct objects of different sizes, all of which seem to move faster than an electron bubble would be expected to move.

    “They’ve been a mystery ever since they were first detected,” Maris said. “Nobody has a good explanation.”

    Several possibilities have been proposed. The unknown objects could be impurities in the helium—charged particles knocked free from the walls of the container. Another possibility is that the objects could be helium ions — helium atoms that have picked up one or more extra electrons, which produce a negative charge at the detector.

    But Maris and his colleagues, including Nobel laureate and Brown physicist Leon Cooper, believe a new set of experiments puts those explanations to rest.

    New experiments

    The researchers performed a series of electron bubble mobility experiments with much greater sensitivity than previous efforts. They were able to detect all 14 of the objects from previous work, plus four additional objects that appeared frequently over the course of the experiments. But in addition to those 18 objects that showed up frequently, the study revealed countless additional objects that appeared more rarely.

    In effect, Maris says, it appears there aren’t just 18 objects, but an effectively infinite number of them, with a “continuous distribution of sizes” up to the size of the normal electron bubble.

    “That puts a dagger in the idea that these are impurities or helium ions,” Maris said. “It would be hard to imagine that there would be that many impurities, or that many previously unknown helium ions.”

    The only way the researchers can think of to explain the results is through “fission” of the wave function. In certain situations, the researchers surmise, electron wave functions break apart upon entering the liquid, and pieces of the wave function are caught in separate bubbles. Because the bubbles contain less than the full wave function, they’re smaller than normal electron bubbles and therefore move faster.

    In their new paper, Maris and his team lay out a mechanism by which fission could happen that is supported by quantum theory and is in good agreement with the experimental results. The mechanism involves a concept in quantum mechanics known as reflection above the barrier.

    In the case of electrons and helium, it works like this: When an electron hits the surface of the liquid helium, there’s some chance that it will cross into the liquid, and some chance that it will bounce off and carom away. In quantum mechanics, those possibilities are expressed as part of the wave function crossing the barrier, and part of it being reflected. Perhaps the small electron bubbles are formed by the portion of the wave function that goes through the surface. The size of the bubble depends on how much wave function goes through, which would explain the continuous distribution of small electron bubble sizes detected in the experiments.

    The idea that part of the wave function is reflected at a barrier is standard quantum mechanics, Cooper said. “I don’t think anyone would argue with that,” he said. “The non-standard part is that the piece of the wave function that goes through can have a physical effect by influencing the size of the bubble. That is what is radically new here.”

    Further, the researchers propose what happens after the wave function enters the liquid. It’s a bit like putting a droplet of oil in a puddle of water. “Sometime your drop of oil forms one bubble,” Maris said, “Sometimes it forms two, sometimes 100.”

    There are elements within quantum theory that suggest a tendency for the wave function to break up into specific sizes. By Maris’s calculations, the specific sizes one might expect to see correspond roughly to the 18 frequently occurring electron bubble sizes.

    “We think this offers the best explanation for what we see in the experiments,” Maris said. We’ve got this body of data that goes back 40 years. The experiments are not wrong; they’ve been done by multiple people. We have a tradition called Occam’s razor, where we try to come up with the simplest explanation. This, so far as we can tell, is it.”

    But it does raise some interesting questions that sit on the border of science and philosophy. For example, it’s necessary to assume that the helium does not make a measurement of the actual position of the electron. If it did, any bubble found not to contain the electron would, in theory, simply disappear. And that, Maris says, points to one of the deepest mysteries of quantum theory.

    “No one is sure what actually constitutes a measurement. Perhaps physicists can agree that someone with a Ph.D. wearing a white coat sitting in the lab of a famous university can make measurements. But what about somebody who really isn’t sure what they are doing? Is consciousness required? We don’t really know.”

    Authors on the paper in addition to Maris were former Brown postdoctoral researcher Wanchun Wei, graduate student Zhuolin Xie, and George Seidel, professor emeritus of physics.

    See the full article here.

    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

    ScienceSprings relies on technology from

    MAINGEAR computers

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  • richardmitnick 3:45 pm on October 2, 2014 Permalink | Reply
    Tags: , , , Brown University,   

    From Brown- “Invasive species: Darwin had it right” 

    Brown University
    Brown University

    October 2, 2014
    David Orenstein 401-863-1862

    Based on insights first articulated by Charles Darwin, professors at Brown University and Syracuse University have developed and tested the “evolutionary imbalance hypothesis [ETH]” to help predict species invasiveness in ecosystems. The results suggest the importance of accounting for the evolutionary histories of the donor and recipient regions in invasions.

    Dov Sax of Brown University and Jason Fridley of Syracuse University aren’t proposing a novel idea to explain species invasiveness. In fact, Charles Darwin articulated it first. What’s new about Sax and Fridley’s “Evolutionary Imbalance Hypothesis” (EIH) is that they’ve tested it using quantifiable evidence and report in Global Ecology and Biogeography that the EIH works well.

    The EIH idea is this: Species from regions with deep and diverse evolutionary histories are more likely to become successful invaders in regions with less deep, less diverse evolutionary histories. To predict the probability of invasiveness, ecologists can quantify the imbalance between the evolutionary histories of “donor” and “recipient” regions as Sax and Fridley demonstrate in several examples.

    dar
    Survival of the fittest: An iceplant, from a region of high diversity in South Africa, is overtopping and killing a native shrub on the New Zealand coast, a region with far less diversity. Plant lines that have had to struggle against robust competition are strong invaders in areas where native plants have had an easier time. Photo: Jason Fridley

    Darwin’s original insight was that the more challenges a region’s species have faced in their evolution, the more robust they’ll be in new environments.

    “As natural selection acts by competition, it adapts the inhabitants of each country only in relation to the degree of perfection of their associates,” Darwin wrote in 1859. Better tested species, such as those from larger regions, he reasoned, have “consequently been advanced through natural selection and competition to a higher stage of perfection or dominating power.”

    To Sax and Fridley the explanatory power of EIH suggests that when analyzing invasiveness, ecologists should add historical evolutionary imbalance to the other factors they consider.

    “Invasion biology is well-studied now, but this is never listed there even though Darwin basically spelled it out,” said Sax, associate of ecology and evolutionary biology. “It certainly hasn’t been tested before. We think this is a really important part of the story.”

    cd
    Charles Darwin

    The theory was correct. What was missing was quantifiable evidence. That evidence has now been collected.

    Evidence for EIH

    Advancing Darwin’s insight from idea to hypothesis required determining a way to test it against measurable evidence. The ideal data would encapsulate a region’s population size and diversity, relative environmental stability and habitat age, and the intensity of competition. Sax and Fridley found a suitable proxy: “phylogenetic diversity (PD)” , an index of how many unique lineages have developed in a region over the time of their evolution.

    “All else equal, our expectation is that biotas represented by lineages of greater number or longer evolutionary history should be more likely to have produced a more optimal solution to a given environmental problem, and it is this regional disparity, approximated by PD, that allows predictions of global invasion patterns,” they wrote.

    With a candidate measure, they put EIH to the test.

    Using detailed databases on plant species in 35 regions of the world, they looked at the relative success of those species’ invasiveness in three well-documented destinations: Eastern North America, the Czech Republic, and New Zealand.

    They found that in all three regions, the higher the PD of a species’ native region, the more likely it was to become invasive in its new home. The size of the effect varied among the three regions, which have different evolutionary histories, but it was statistically clear that plants forged in rough neighborhoods were better able to bully their way into a new region than those from evolutionarily more “naive” areas.

    Sax and Fridley conducted another test of the EIH in animals by looking at cases where marine animals were suddenly able to mix after they became united by canals. The EIH predicts that an imbalance of evolutionary robustness between the sides, would allow a species-rich region to dominate a less diverse one on the other side of the canal by even more than a mere random mixing would suggest.

    The idea has a paleontological precedent. When the Bering land bridge became the Bering Strait, it offered marine mollusks a new polar path between the Atlantic and Pacific Oceans. Previous research has shown that more kinds of mollusks successfully migrated from the diverse Pacific to the less diverse Atlantic than vice-versa, and by more so than by their relative abundance.

    In the new paper, Sax and Fridley examined what has happened since the openings of the Suez Canal in Egypt, the Erie Canal in New York, and the Panama Canal. The vastly greater evolutionary diversity in the Red Sea and Indian Ocean compared to the Mediterranean Sea and the Atlantic led to an overwhelming flow of species north through the Suez.

    But evolutionary imbalances across the Erie and Panama Canals were fairly small (the Panama canal connects freshwater drainages of the Atlantic and Pacific that were much more ecologically similar than the oceans) so as EIH again predicts, there was a more even balance of cross-canal species invasions.

    Applicable predictions

    Sax and Fridley acknowledge in the paper that the EIH does not singlehandedly predict the success of individual species in specific invasions. Instead it allows for ecosystem managers to assess a relative invasiveness risk based on the evolutionary history of their ecosystem and that of other regions. Take, for instance, a wildlife official in a historically isolated ecosystem such as an island.

    “They already know to be worried, but this would suggest they should be more worried about imports from some parts of the world than others,” Sax said.

    Not all invasions are bad, Sax noted. Newcomers can provide some ecosystem services — such as erosion control — more capably if they can become established. The EIH can help in assessments of whether a new wave of potential invasion is likely to change the way an ecosystem will provide its services, for better or worse.

    “It might help to explain why non-natives in some cases might improve ecosystem functioning,” Sax said.

    But perhaps Darwin already knew all that.

    See the full article here.

    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

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  • richardmitnick 2:25 pm on September 2, 2014 Permalink | Reply
    Tags: , Brown University, Extinctions   

    From Brown: “Extinctions during human era worse than thought” 

    Brown University
    Brown University

    September 2, 2014
    David Orenstein 401-863-1862

    It’s hard to comprehend how bad the current rate of species extinction around the world has become without knowing what it was before people came along. The newest estimate is that the pre-human rate was 10 times lower than scientists had thought, which means that the current level is 10 times worse.

    Extinctions are about 1,000 times more frequent now than in the 60 million years before people came along. The explanation from lead author Jurriaan de Vos, a Brown University postdoctoral researcher, senior author Stuart Pimm, a Duke University professor, and their team appears online in the journal Conservation Biology.

    “This reinforces the urgency to conserve what is left and to try to reduce our impacts,” said de Vos, who began the work while at the University of Zurich. “It was very, very different before humans entered the scene.”

    In absolute, albeit rough, terms the paper calculates a “normal background rate” of extinction of 0.1 extinctions per million species per year. That revises the figure of 1 extinction per million species per year that Pimm estimated in prior work in the 1990s. By contrast, the current extinction rate is more on the order of 100 extinctions per million species per year.

    Orders of magnitude, rather than precise numbers are about the best any method can do for a global extinction rate, de Vos said. “That’s just being honest about the uncertainty there is in these type of analyses.”

    jd
    Jurriaan de Vos
    “This reinforces the urgency to conserve what is left and to try to reduce our impacts. It was very, very different before humans entered the scene.” Photo: David Orenstein/Brown University

    From fossils to genetics

    The new estimate improves markedly on prior ones mostly because it goes beyond the fossil record. Fossils are helpful sources of information, but their shortcomings include disproportionate representation of hard-bodied sea animals and the problem that they often only allow identification of the animal or plant’s genus, but not its exact species.

    What the fossils do show clearly is that apart from a few cataclysms over geological periods — such as the one that eliminated the dinosaurs — biodiversity has slowly increased.

    The new study next examined evidence from the evolutionary family trees — phylogenies — of numerous plant and animal species. Phylogenies, constructed by studying DNA, trace how groups of species have changed over time, adding new genetic lineages and losing unsuccessful ones. They provide rich details of how species have diversified over time.

    “The diversification rate is the speciation rate minus the extinction rate,” said co-author Lucas Joppa, a scientist at Microsoft Research in Redmond, Wash. “The total number of species on earth has not been declining in recent geological history. It is either constant or increasing. Therefore, the average rate at which groups grew in their numbers of species must have been similar to or higher than the rate at which other groups lost species through extinction.”

    The work compiled scores of studies of molecular phylogenies on how fast species diversified.

    For a third approach, de Vos noted that the exponential climb of species diversity should take a steeper upward turn in the current era because the newest species haven’t gone extinct yet.

    “It’s rather like your bank account on the day you get paid,” he said. “It gets a burst of funds — akin to new species — that will quickly become extinct as you pay your bills.”

    By comparing that rise of the number of species from the as-yet unchecked speciation rate with the historical trend (it was “log-linear”) evident in the phylogenies, he could therefore create a predictive model of what the counteracting historical extinction rate must have been.

    The researchers honed their models by testing them with simulated data for which they knew an actual extinction rate. The final models yielded accurate results. They tested the models to see how they performed when certain key assumptions were wrong and on average the models remained correct (in the aggregate, if not always for every species group).

    All three data approaches together yielded a normal background extinction rate squarely in the order of 0.1 extinctions per million species per year.

    A human role

    There is little doubt among the scientists that humans are not merely witnesses to the current elevated extinction rate. This paper follows a recent one in Science , authored by Pimm, Joppa, and other colleagues, that tracks where species are threatened or confined to small ranges around the globe. In most cases, the main cause of extinctions is human population growth and per capita consumption, although the paper also notes how humans have been able to promote conservation.

    The new study, Pimm said, emphasizes that the current extinction rate is a more severe crisis than previously understood.

    “We’ve known for 20 years that current rates of species extinctions are exceptionally high,” said Pimm, president of the conservation nonprofit organization SavingSpecies. “This new study comes up with a better estimate of the normal background rate — how fast species would go extinct were it not for human actions. It’s lower than we thought, meaning that the current extinction crisis is much worse by comparison.”

    Other authors on the paper are John Gittleman and Patrick Stephens of the University of Georgia.

    See the full article here.

    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

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  • richardmitnick 11:05 am on August 19, 2014 Permalink | Reply
    Tags: , , Brown University,   

    From Brown: “Intimacy a strong motivator for PrEP HIV prevention” 

    Brown University
    Brown University

    August 19, 2014
    David Orenstein

    Men in steady same-sex relationships where both partners are HIV negative will often forgo condoms out of a desire to preserve intimacy, even if they also have sex outside the relationship. But the risk of HIV still lurks. In a new study of gay and bisexual men who reported at least one instance of condomless anal sex in the last 30 days, researchers found that the same desire for intimacy is also a strong predictor of whether men would be willing to take antiretroviral medications to prevent HIV, an emerging practice known as pre-exposure prophylaxis or PrEP.

    Earlier this year the U.S. Public Health Service recommended that people at high risk of getting HIV use PrEP, including gay or bisexual men who have condomless anal sex. But as the recommendation becomes clinical practice, many people are wondering whether men will make PrEP part of their daily lives and what will keep them motivated to adhere to it strictly, which is required if the medication is to have its protective effect.

    The new study, published in the Annals of Behavioral Medicine, suggests that PrEP’s appeal to many men who have sex with men (MSM) in romantic relationships with HIV-negative partners is the perception that it can allow them to remain intimate with their partners while still having some protection from HIV.

    kg
    Kristi Gamarel
    “Sex doesn’t happen in a vacuum — interpersonal and relationship context really matter.”

    “In this sample of men who are in a relationship with a perceived HIV-negative man, we found that intimacy motivation was the strongest predictor [of adopting PrEP],” said Kristi Gamarel, a psychiatry and human behavior postdoctoral researcher in the Warren Alpert Medical School of Brown University. She was at the City University of New York with senior author and principal investigator for the NIH-funded project, Sarit Golub, when she performed the research. “Sex doesn’t happen in a vacuum — interpersonal and relationship context really matter. Many HIV infections are occurring between people who are in a primary relationship.”

    The study is based on extensive interviews with 164 HIV-negative MSMs who were in steady same-sex relationships and who had condomless anal sex at least once in the prior 30 days. The researchers found in a multivariate statistical analysis that those who rated intimacy highly as a reason why they sometimes engage in condomless sex also were 55 percent more likely to say they would adopt PrEP if it were available for free (likely a hypothetical condition for many, but not necessarily all, recipients).

    In basic analyses reported in the paper, there were several other factors in the study that also predicted a greater likelihood of adopting PrEP: older age, higher perception of HIV risk, sex (either protected or not) with partners outside the main relationship, and having less than a bachelor’s degree level of education. But upon controlling for possible overlap among factors, desire for intimacy, low education levels and to a lesser extent older age survived as the strongest predictors of using PrEP.

    Relationships matter

    An important implication of the study’s findings are that as physicians and counselors discuss PrEP with MSM in steady relationships, Gamarel said, they should consider that a desire for intimacy in the relationship appears to be a prime motivation.

    “For people who are disseminating PrEP or talking to patients about PrEP, I think it’s important to think about their relationships,” Gamarel said. “Something that’s being supported and endorsed right now by the World Health Organization is couples voluntary testing and counseling. That may be a way to disseminate PrEP and to allow couples to have a discussion about whether PrEP is good for their relationship and how they can support each other using PrEP.”

    Gamarel cautioned that the study results cannot be taken as evidence that PrEP will reduce condom use. The men in this study were already forgoing condoms at times without being on PrEP, Gamarel notes. The study simply sought to ascertain whether these men would adopt PrEP and to determine why. Condoms remain uniquely important to gay men’s sexual health, she noted, both because they reduce the risk of HIV transmission and because they can block other sexually transmitted infections that PrEP does not.

    The National Institute of Mental Health funded the study (grant: R01MH095565 to Golub).

    See the full article here.

    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

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  • richardmitnick 8:59 am on July 14, 2014 Permalink | Reply
    Tags: , Brown University, ,   

    From Brown: “Researchers discover boron ‘buckyball'” 

    Brown University
    Brown University

    July 9, 2014
    Kevin Stacey

    The discovery 30 years ago of soccer-ball-shaped carbon molecules called buckyballs helped to spur an explosion of nanotechnology research. Now, there appears to be a new ball on the pitch.

    Buckyball
    Typical buckyball configuration

    Researchers from Brown University, Shanxi University and Tsinghua University in China have shown that a cluster of 40 boron atoms forms a hollow molecular cage similar to a carbon buckyball. It’s the first experimental evidence that a boron cage structure — previously only a matter of speculation — does indeed exist.

    “This is the first time that a boron cage has been observed experimentally,” said Lai-Sheng Wang, a professor of chemistry at Brown who led the team that made the discovery. “As a chemist, finding new molecules and structures is always exciting. The fact that boron has the capacity to form this kind of structure is very interesting.”

    Wang and his colleagues describe the molecule, which they’ve dubbed borospherene, in the journal Nature Chemistry.

    Carbon buckyballs are made of 60 carbon atoms arranged in pentagons and hexagons to form a sphere — like a soccer ball. Their discovery in 1985 was soon followed by discoveries of other hollow carbon structures including carbon nanotubes. Another famous carbon nanomaterial — a one-atom-thick sheet called graphene — followed shortly after.

    Graphene sheet
    The carbon buckyball has a boron cousin. A cluster for 40 boron atoms forms a hollow cage-like molecule.

    After buckyballs, scientists wondered if other elements might form these odd hollow structures. One candidate was boron, carbon’s neighbor on the periodic table. But because boron has one less electron than carbon, it can’t form the same 60-atom structure found in the buckyball. The missing electrons would cause the cluster to collapse on itself. If a boron cage existed, it would have to have a different number of atoms.

    Wang and his research group have been studying boron chemistry for years. In a paper published earlier this year, Wang and his colleagues showed that clusters of 36 boron atoms form one-atom-thick disks, which might be stitched together to form an analog to graphene, dubbed borophene. Wang’s preliminary work suggested that there was also something special about boron clusters with 40 atoms. They seemed to be abnormally stable compared to other boron clusters.

    Figuring out what that 40-atom cluster actually looks like required a combination of experimental work and modeling using high-powered supercomputers.

    On the computer, Wang’s colleagues modeled over 10,000 possible arrangements of 40 boron atoms bonded to each other. The computer simulations estimate not only the shapes of the structures, but also estimate the electron binding energy for each structure — a measure of how tightly a molecule holds its electrons. The spectrum of binding energies serves as a unique fingerprint of each potential structure.

    The next step is to test the actual binding energies of boron clusters in the lab to see if they match any of the theoretical structures generated by the computer. To do that, Wang and his colleagues used a technique called photoelectron spectroscopy.

    Chunks of bulk boron are zapped with a laser to create vapor of boron atoms. A jet of helium then freezes the vapor into tiny clusters of atoms. The clusters of 40 atoms were isolated by weight then zapped with a second laser, which knocks an electron out of the cluster. The ejected electron flies down a long tube Wang calls his “electron racetrack.” The speed at which the electrons fly down the racetrack is used to determine the cluster’s electron binding energy spectrum — its structural fingerprint.

    The experiments showed that 40-atom-clusters form two structures with distinct binding spectra. Those spectra turned out to be a dead-on match with the spectra for two structures generated by the computer models. One was a semi-flat molecule and the other was the buckyball-like spherical cage.

    “The experimental sighting of a binding spectrum that matched our models was of paramount importance,” Wang said. “The experiment gives us these very specific signatures, and those signatures fit our models.”

    The borospherene molecule isn’t quite as spherical as its carbon cousin. Rather than a series of five- and six-membered rings formed by carbon, borospherene consists of 48 triangles, four seven-sided rings and two six-membered rings. Several atoms stick out a bit from the others, making the surface of borospherene somewhat less smooth than a buckyball.

    As for possible uses for borospherene, it’s a little too early to tell, Wang says. One possibility, he points out, could be hydrogen storage. Because of the electron deficiency of boron, borospherene would likely bond well with hydrogen. So tiny boron cages could serve as safe houses for hydrogen molecules.

    But for now, Wang is enjoying the discovery.

    “For us, just to be the first to have observed this, that’s a pretty big deal,” Wang said. “Of course if it turns out to be useful that would be great, but we don’t know yet. Hopefully this initial finding will stimulate further interest in boron clusters and new ideas to synthesize them in bulk quantities.”

    The theoretical modeling was done with a group led by Prof. Si-Dian Li from Shanxi University and a group led by Prof. Jun Li from Tsinghua University. The work was supported by the U.S. National Science Foundation (CHE-1263745) and the National Natural Science Foundation of China.

    See the full article here.

    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.


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  • richardmitnick 5:44 am on July 3, 2014 Permalink | Reply
    Tags: , , Brown University,   

    From Brown: “Stem cell type resists chemo drug” 

    Brown University
    Brown University

    July 2, 2014
    David Orenstein 401-863-1862

    In lab tests, Brown University researchers have found that adipose-derived stem cells, which can generate bone tissue, appear resistant to the toxicity of the chemotherapy drug methotrexate, which degrades bone in patients such as kids suffering from acute lymphoblastic leukemia. The newly published findings are preliminary but more tests are planned.

    A new study shows that adipose-derived human stem cells, which can become vital tissues such as bone, may be highly resistant to the common chemotherapy drug methotrexate (MTX). The preliminary finding from lab testing may prove significant because MTX causes bone tissue damage in many patients.

    MTX is used to treat cancers including acute lymphoblastic leukemia, the most common form of childhood cancer. A major side effect of the therapy, however, is a loss of bone mineral density. Other bone building stem cells, such as bone marrow derived stem cells, have not withstood MTX doses well.

    “Kids undergo chemotherapy at such an important time when they should be growing, but instead they are introduced to this very harsh environment where bone cells are damaged with these drugs,” said Olivia Beane, a Brown University graduate student in the Center for Biomedical Engineering and lead author of the study. “That leads to major long-term side effects including osteoporosis and bone defects. If we found a stem cell that was resistant to the chemotherapeutic agent and could promote bone growth by becoming bone itself, then maybe they wouldn’t have these issues.”

    Stem cell survivors

    Originally Beane was doing much more basic research. She was looking for chemicals that could help purify adipose-derived stem cells (ASCs) from mixed cell cultures to encourage their proliferation. Among other things, she she tried chemotherapy drugs, figuring that maybe the ASCs would withstand a drug that other cells could not. The idea that this could help cancer patients did not come until later.

    In the study published online in the journal Experimental Cell Research, Beane exposed pure human ASC cultures, “stromal vascular fraction” (SVF) tissue samples (which include several cell types including ASCs), and cultures of human fibroblast cells, to medically relevant concentrations of chemotherapy drugs for 24 hours. Then she measured how those cell populations fared over the next 10 days. She also measured the ability of MTX-exposed ASCs, both alone and in SVF, to proliferate and turn into other tissues.

    Beane worked with co-authors fellow center member Eric Darling, the Manning Assistant Professor in the Department of Molecular Pharmacology, Physiology and Biotechnology, and research assistant Vera Fonseca.

    They observed that three chemotherapy drugs — cytarabine, etoposide, and vincristine — decimated all three groups of cells, but in contrast to the fibroblast controls, the ASCs withstood a variety of doses of MTX exceptionally well (they resisted vincristine somewhat, too). MTX had little or no effect on ASC viability, cell division, senescence, or their ability to become bone, fat, or cartilage tissue when induced to do so.

    The SVF tissue samples also withstood MTX doses well. That turns out to be significant, Darling said, because that’s the kind of tissue that would actually be clinically useful if an ASC-based therapy were ever developed for cancer patients. Hypothetically, fresh SVF could be harvested from the fat of a donor, as it was for the study, and injected into bone tissue, delivering ASCs to the site.

    To understand why the ASCs resist MTX, the researchers conducted further tests. MTX shuts down DNA biosynthesis by binding the protein dihydrofolate reductase so that it is unavailable to assist in that essential task. The testing showed that ASCs ramped up dihydrofolate reductase levels upon exposure to the drug, meaning they produced enough to overcome a clinically relevant dose of MTX.

    Toward a therapy?

    Now that the researchers are aware of ASC’s ability to resist MTX, they are eager to see if they can make progress toward delivering a medical benefit for cancer patients. They plan several more experiments.

    One is to test ASC survival and performance after 48- and 72-hour exposures to MTX. Another is to begin examining how the cells fare in mouse models of chemotherapy. They also plan to directly compare ASCs and bone marrow-derived stem cells amid various chemotherapies.

    Darling said his team hopes it can make a contribution by helping patients heal from chemotherapy, which does what it must, but at a cost.

    “The first step is to save a life,” he said. “Chemotherapies do a great job of killing cells and killing the cancer, and that’s what you want. But then there is a stage after that where you need to do recovery and regeneration.”

    Further research will reveal whether stem cells can be part of that process.

    The National Institutes of Health (grants R01AR063642, P20GM104937) and the National Science Foundation (CBET1253189) supported the research.

    cells
    Cellular survivor Ten days after treatment with a medically appropriate dose of the chemotherapy drug MTX, adipose-derived stem cells, left, survive while normal human fibroblasts, right, are impaired. Insets show untreated control cells. Darling lab/Brown University

    See the full article here.

    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.


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  • richardmitnick 5:06 am on June 24, 2014 Permalink | Reply
    Tags: , , Brown University,   

    From Brown University: “Emergence of bacterial vortex explained” 

    Brown University
    Brown University

    June 20, 2014
    Kevin Stacey

    When a bunch of B. subtilis bacteria are confined within a droplet of water, a very strange thing happens. The chaotic motion of all those individual swimmers spontaneously organizes into a swirling vortex, with bacteria on the outer edge of the droplet moving in one direction while those on the inside move the opposite direction.

    image
    A mysterious vortex in theory and observation Dyes of different colors on the bodies and flagella of bacteria allowed researchers to determine the direction of their swimming. Direct observation confirmed a computer simulation of bacteria swimming in opposite directions within a water drop. Credit: Brown University and Cambridge University

    Researchers from Brown University and the University of Cambridge have explained for the first time how that dual-motion vortex is generated. Using computer modeling and a clever experiment, the researchers show that the fluid flow generated by all those tiny swimmers explains that strange two-way motion.

    The research is published in Proceedings of the National Academy of Sciences.

    Hugo Wioland and and others in the lab of Raymond Goldstein at Cambridge first demonstrated the phenomenon experimentally in 2013. But at that time, the dynamics of the system — especially the two-directional motion — weren’t fully understood. Enkeleida Lushi, now a postdoctoral researcher in Brown’s School of Engineering and an expert in theoretical modeling, started thinking about this problem while at Cambridge on a fellowship last year.

    “These are very simple organisms,” Lushi said. “They do not consciously decide where to go and how to organize. Most of the dynamics occur just due to physical mechanisms, like collisions with each other and the boundary. But there was no intuitive way to explain what was happening with the dual-motion vortex. It was very puzzling.”

    The initial model attempting to reproduce the phenomenon focused on the mechanical interactions between individual bacteria. Those simulations showed that when individuals swimming in random trajectories start bumping into each other in a confined circular space, they tend to orient each other to the same angle relative to the circular boundary. That helps explain how a coordinated motion starts, but can’t explain why individuals toward the outside of the circle move in the opposite direction from those on the inside.

    That part of the phenomenon, it turns out, is a matter of fluid flow.

    “These bacteria are only a few micrometers long,” Lushi said. “At that scale, the fluid flow to them feels very viscous — very different from what we experience in air or even in water. The effect is that any movement that the bacteria make causes disturbances in the flow that will be felt strongly by their neighbors.”

    So Lushi and her colleagues developed a computer simulation, right, that included the fluid flows created when the bacteria swim. B. subtilis swim by turning tiny corkscrew-like appendages called flagella. The flagellar bundle pushes against the fluid, which propels the bacteria forward and pushes the fluid in the opposite direction.

    When Lushi included those dynamics in her simulation, the source of the two-way motion became clear. The bacteria all tend to align themselves facing in the same direction, the simulation showed. But individuals swimming along the outside of the circle created a flow in the fluid in the opposite direction from the direction they’re swimming. Bacteria toward the inside of the circle are forced to swim against that flow, but can’t quite keep up. They end up moving in the same direction as the flow — the opposite direction of the swimmers on the outside.

    To confirm the model, the researchers set up an experiment with real bacteria, right, using colored dyes on the bacterium body and flagella to determine which direction the bacteria were facing. The experiment showed that all the bacteria were indeed attempting to swim in the same direction. But those in the middle were swept backward, apparently by the fluid flow created along the outside. It was just as the model had predicted.

    “It’s a very basic model,” Lushi said, “but in the end it captures this phenomenon very well. It showed that any study of microbes suspended in a liquid should not ignore the motion of that liquid – it could have important repercussions on the microbes.”

    So why study the strange motion of bacteria in a water drop?

    “We want to understand nature where there are many incidences of independent individual units organizing collectively — this bacterial vortex is but one example,” Lushi said. “But also, we might want to eventually control bacterial colonies, for example to limit their spread. The more we understand how they interact and how they move collectively, the better we can devise ways to control their motion.”

    See the full article here.

    Welcome to Brown

    Rhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interiorRhode Island Hall: Rhode Island Hall’s classical exterior was recently renovated with a modern interior

    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.


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