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  • richardmitnick 1:34 pm on October 19, 2017 Permalink | Reply
    Tags: , Brown, , LTEM-Laser terahertz emission microscopy, , , This new technique enables measurements down to a resolution of 20 nanometers   

    From Brown: “Terahertz spectroscopy goes nano” 

    Brown University

    [THIS POST ID DEDICATED TO E.B.M. WHO MAY ACTUALLY GET TO USE THIS NEW MICROSCOPY]

    Brown University

    1
    Going nano
    Researchers have improved the resolution of terahertz spectroscopy by 1,000 times, making the technique useful at the nanoscale.
    Mittleman Lab / Brown University

    Brown University researchers have demonstrated a way to bring a powerful form of spectroscopy — a technique used to study a wide variety of materials — into the nano-world.

    Laser terahertz emission microscopy (LTEM) is a burgeoning means of characterizing the performance of solar cells, integrated circuits and other systems and materials. Laser pulses illuminating a sample material cause the emission of terahertz radiation, which carries important information about the sample’s electrical properties.

    “This is a well-known tool for studying essentially any material that absorbs light, but it’s never been possible to use it at the nanoscale,” said Daniel Mittleman, a professor in Brown’s School of Engineering and corresponding author of a paper describing the work. “Our work has improved the resolution of the technique so it can be used to characterize individual nanostructures.”

    Typically, LTEM measurements are performed with resolution of a few tens of microns, but this new technique enables measurements down to a resolution of 20 nanometers, roughly 1,000 times the resolution previously possible using traditional LTEM techniques.

    The research, published in the journal ACS Photonics, was led by Pernille Klarskov, a postdoctoral researcher in Mittleman’s lab, with Hyewon Kim and Vicki Colvin from Brown’s Department of Chemistry.

    For their research, the team adapted for terahertz radiation a technique already used to improve the resolution of infrared microscopes. The technique uses a metal pin, tapered down to a sharpened tip only a few tens of nanometers across, that hovers just above a sample to be imaged. When the sample is illuminated, a tiny portion of the light is captured directly beneath the tip, which enables imaging resolution roughly equal to the size of the tip. By moving the tip around, it’s possible to create ultra-high resolution images of an entire sample.

    Klarskov was able to show that the same technique could be used to increase the resolution of terahertz emission as well. For their study, she and her colleagues were able to image an individual gold nanorod with 20-nanometer resolution using terahertz emission.

    The researchers believe their new technique could be broadly useful in characterizing the electrical properties of materials in unprecedented detail.

    “Terahertz emission has been used to study lots of different materials — semiconductors, superconductors, wide-band-gap insulators, integrated circuits and others,” Mittleman said. “Being able to do this down to the level of individual nanostructures is a big deal.”

    One example of a research area that could benefit from the technique, Mittleman says, is the characterization of perovskite solar cells, an emerging solar technology studied extensively by Mittleman’s colleagues at Brown.

    “One of the issues with perovskites is that they’re made of multi-crystalline grains, and the grain boundaries are what limits the transport of charge across a cell,” Mittleman said. “With the resolution we can achieve, we can map out each grain to see if different arrangements or orientations have an influence on charge mobility, which could help in optimizing the cells.”

    That’s one example of where this could be useful, Mittleman said, but it’s certainly not limited to that.

    “This could have fairly broad applications,” he noted.

    The research was supported by the National Science Foundation, the Danish Council for Independent Research and by Honeywell Federal Manufacturing & Technologies.

    See the full article here .

    Please help promote STEM in your local schools.

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    Stem Education Coalition
    Welcome to Brown

    Brown U Robinson Hall
    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 12:19 pm on June 19, 2017 Permalink | Reply
    Tags: , , , Brown, , Hot rocks not warm atmosphere led to relatively recent water-carved valleys on Mars, Lyot impact crater,   

    From Brown: “Hot rocks, not warm atmosphere, led to relatively recent water-carved valleys on Mars” 

    Brown University
    Brown University

    June 13, 2017
    Kevin Stacey
    kevin_stacey@brown.edu
    401-863-3766

    1
    Valley Networks.Lyot Crater, rendered here with elevations exaggerated, is home to relatively recent water-carved valleys (white streaks). New research suggests the water came from melting snow and ice present at the time of the crater-forming impact.
    David Weiss/NASA/Brown University

    New research shows that water from melted snow and ice likely carved valley networks around Lyot crater on Mars.

    Present-day Mars is a frozen desert, colder and more arid than Antarctica, and scientists are fairly sure it’s been that way for at least the last 3 billion years. That makes a vast network of water-carved valleys on the flanks of an impact crater called Lyot — which formed somewhere between 1.5 billion and 3 billion years ago — something of a Martian mystery. It’s not clear where the water came from.

    Now, a team of researchers from Brown University has offered what they see as the most plausible explanation for how the Lyot valley networks formed. They conclude that at the time of the Lyot impact, the region was likely covered by a thick layer of ice. The giant impact that formed the 225-kilometer crater blasted tons of blazing hot rock onto that ice layer, melting enough of it to carve the shallow valleys.

    “Based on the likely location of ice deposits during this period of Mars’ history, and the amount of meltwater that could have been produced by Lyot ejecta landing on an ice sheet, we think this is the most plausible scenario for the formation of these valleys” said David Weiss, a recent Ph.D. graduate from Brown and the study’s lead author.

    Weiss co-authored the study, which is published in Geophysical Research Letters, with advisor and Brown planetary science professor Jim Head, along with fellow graduate students Ashley Palumbo and James Cassanelli.

    There’s plenty of evidence that water once flowed on the Martian surface. Water-carved valley networks similar to those at Lyot have been found in several locations. There’s also evidence for ancient lake systems, like those at Gale Crater where NASA’s Curiosity rover is currently exploring and at Jezero Crater where the next rover may land.

    Most of these water-related surface features, however, date back to very early in Mars’ history — the epochs known as the Noachian and the Hesperian, which ended about 4 billion and 3 billion years ago respectively. From about 3 billion years ago to the present, Mars has been in a bone-dry period called the Amazonian.

    The valley networks at Lyot therefore are a rare example of more recent surface water activity. Scientists have dated the crater itself to the Amazonian, and the valley networks appear to have been formed around the same time or shortly after the impact. So the question is: Where did all that water come from during the arid Amazonian?

    Scientists have posited a number of potential explanations, and the Brown researchers set out to investigate several of the major ones.

    One of those potential explanations, for example, is that there might have been a vast reservoir of groundwater when the Lyot impact occurred. That water, liberated by impact, could have flowed onto the surface along the periphery of the crater and carved the valleys. But based on geological evidence, the researchers say, that scenario is unlikely

    “If these were formed by deep groundwater discharge, that water would have also flowed into the crater itself,” Weiss said. “We don’t see any evidence that there was water present inside the crater.”

    The researchers also looked at the possibility of transient atmospheric effects following the Lyot impact. A collision of this size would have vaporized tons of rock, sending a plume of vapor into the air. As that hot plume interacted with the cold atmosphere, it could have produced rainfall that some scientists think might have carved the valleys.

    But that, too, appears unlikely, the researchers concluded. Any rain related to the plume would have fallen after the rocky impact ejecta had been deposited outside the crater. So if rainwater carved the valleys, one would expect to see valleys cutting through the ejecta layer. But there are almost no valleys directly on the Lyot ejecta. Rather, Palumbo said, “The vast majority of the valleys seem to emerge from beneath the ejecta on its outer periphery, which casts serious doubt on the rainwater scenario.”

    That left the researchers with the idea that meltwater, produced when hot ejecta interacted with an icy surface, carved the Lyot valleys.

    According to models of Mars’ climate history, ice now trapped mainly at the planet’s poles often migrated into the mid-latitude regions where Lyot is located. And there’s evidence to suggest that an ice sheet was indeed present in the region at the time of the impact.

    Some of that evidence comes from the scarcity of secondary craters at Lyot. Secondary craters form when big chunks of rock blasted into the air during a large impact fall back to the surface, leaving a smattering of small craters surrounding the main crater. At Lyot, there far fewer secondary craters than one would expect, the researchers say. The reason for that, they suggest, is that instead of landing directly on the surface, ejecta from Lyot landed on a thick layer of ice, which prevented it from gouging the surface beneath the ice. Based on the terrain on the northern side of Lyot, the team estimates that the ice layer could have been anywhere from 20 to 300 meters thick.

    The Lyot impact would have spat tons of rock onto that ice layer, some of which would have been heated to 250 degrees Fahrenheit or more. Using a thermal model of that process, the researchers estimate that the interaction between those hot rocks and a surface ice sheet would have produced thousands of cubic kilometers of meltwater — easily enough to carve the valley seen at Lyot.

    “What this shows is a way to get large amounts of liquid water on Mars without the need for a warming of the atmosphere and any liquid groundwater,” Cassanelli said. “So we think this is a good explanation for how you get these channels forming in the Amazonian.”

    And it’s possible, Head says, that this same mechanism could have been important before the Amazonian. Some scientists think that even in the early Noachian and Hesperian epochs, Mars was still quite cold and icy. If that was the case, then this meltwater mechanism might have also been responsible for at least some of the more ancient valley networks on Mars.

    “It’s certainly a possibility worth investigating,” Head said.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition
    Welcome to Brown

    Brown U Robinson Hall
    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 8:22 pm on June 6, 2017 Permalink | Reply
    Tags: , Brown, Nanofiber ceramics, , New ceramic nanofiber ‘sponges’ could be used for flexible insulation and water purification,   

    From Brown: “New ceramic nanofiber ‘sponges’ could be used for flexible insulation, water purification” 

    Brown University
    Brown University

    [THIS POST IS DEDICATED TO E.B.M., about to commence his college adventures at Brown University]

    June 2, 2017
    Kevin Stacey
    kevin_stacey@brown.edu
    401-863-3766

    1
    Nanofiber ceramics. Researchers from Brown and Tsinghua Universities have developed sponge-like materials made from ceramic nanofibers. The materials could be useful in a variety of applications, from insulation to water purification. Gao/Li/Wu/Brown/Tsinghua

    Researchers have found a way to make ultralight sponge-like materials from nanoscale ceramic fibers. The highly porous, compressible and heat-resistant sponges could have numerous uses, from water purification devices to flexible insulating materials.

    “The basic science question we tried to answer is how can we make a material that’s highly deformable but resistant to high temperature,” said Huajian Gao, a professor in Brown University’s School of Engineering and a corresponding author of the research. “This paper demonstrates that we can do that by tangling ceramic nanofibers into a sponge, and the method we use for doing it is inexpensive and scalable to make these in large quantities.”

    The work, a collaboration between Gao’s lab at Brown and the labs of Hui Wu and Xiaoyan Li at Tsinghua University in China, is described in the journal Science Advances.

    As anyone who has ever dropped a flower vase knows well, ceramics are brittle materials. Cracks in ceramics tend to propagate quickly, leading to catastrophic failure with even the slightest deformation. While that’s true for all traditional ceramics, things are different at the nanoscale.

    “At the nanoscale, cracks and flaws become so small that it takes much more energy to activate them and cause them to propagate,” Gao said. “Nanoscale fibers also promote deformation mechanisms such as what is known as creep, where atoms can diffuse along grain boundaries, enabling the material to deform without breaking.”

    Because of those nanoscale dynamics, materials made from ceramic nanofibers have the potential to be deformable and flexible, while maintaining the heat resistance that make ceramics useful in high-temperature applications. The problem is that such materials aren’t easy to make. One often-used method of making nanofibers, known as electrospinning, doesn’t work well with ceramics. Another potential option, 3-D laser printing, is expensive and time-consuming.

    So the researchers used a method called solution blow-spinning, which had been developed previously by Wu in his lab at Tsinghua. The process uses air pressure to drive a liquid solution containing ceramic material through a tiny syringe aperture. As the liquid emerges, it quickly solidifies into nanoscale fibers that are collected in a spinning cage. The collected material is then heated, which burns away the solvent material leaving a mass of tangled ceramic nanofibers that looks a bit like a cotton ball.

    The researchers used the method to create sponges made from a variety of different types of ceramics and showed that the materials had some remarkable properties.

    For example, the sponges were able to rebound after compressive strain up to 50 percent, something that no standard ceramic material can do. And the sponges can maintain that resilience at temperatures up to 800 degrees Celsius.

    The research also showed that the sponges had a remarkable capacity for high-temperature insulation. In one experiment, the researchers placed a flower petal on top of 7-millimeter-thick sponge made from titanium dioxide (a common ceramic material) nanofibers. After heating the bottom of the sponge to 400 degrees Celsius for 10 minutes, the flower on top barely wilted. Meanwhile, petals placed on other types of porous ceramic materials under the same conditions were burnt to a crisp.

    The sponges’ heat resistance and its deformability make them potentially useful as an insulating material where flexibility is important. For example, Gao says, the material could be used as an insulating layer in firefighters’ clothing.

    2
    Ceramic nanofiber sponges retain the heat resistance that makes ceramics useful in high-temperature applications. They even outperform other ceramic materials (Al2O3) in insulating at temperature around 400 degrees C.

    Another potential use could be in water purification. Titanium dioxide is a well-known photocatalyst used to break down organic molecules, which kills bacteria and other microorganisms in water. The researchers showed that a titanium dioxide sponge could absorb 50 times its weight in water containing an organic dye. Within 15 minutes, the sponge was able to degrade the dye under illumination. With the water wrung out, the sponge could then be reused — something that can’t be done with the titanium dioxide powders normally used in water purification.

    In addition to these, there may be other applications for ceramic sponges that the researchers haven’t yet considered.

    “The process we used for making these is extremely versatile; it can be used with a great variety of different types of ceramic starting materials,” said Wu, one of the corresponding authors from Tsinghua. “So we think there’s huge prospect for potential applications.”

    The work was supported by the National Basic Research Program of China, the National Natural Science Foundation of China, the Chinese Program for New Century Excellent Talents in University and the U.S. National Science Foundation (CMMI-1634492).

    See the full article here .

    Please help promote STEM in your local schools.

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    Stem Education Coalition
    Welcome to Brown

    Brown U Robinson Hall
    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 4:33 pm on June 2, 2017 Permalink | Reply
    Tags: , Brown, Magnetocapacitance, ,   

    From Brown: “Researchers flip the script on magnetocapacitance” 

    Brown University
    Brown University

    June 1, 2017
    Kevin Stacey
    kevin_stacey@brown.edu

    1
    A new study shows that anti-parallel electron spins between two electrodes create more capacitance than parallel spins, which is opposite of what is normally observed.

    The study demonstrates for the first time a new type of magnetocapacitance, a phenomenon that could be useful in the next generation of ‘spintronic’ devices.

    Capacitors, electronic components that store and quickly release a charge, play an important role in many types of electrical circuits. They’ll play an equally important role in next-generation spintronic devices, which take advantage of not only electron charge but also spin — the tiny magnetic moment of each electron.

    Two years ago, an international team of researchers showed that by manipulating electron spin at a quantum magnetic tunneling junction — a nanoscale sandwich made of two metal electrodes with an insulator in the middle — they could induce a large increase in the junction’s capacitance.

    Now, that same research team has flipped the script on the phenomenon, known as magnetocapacitance. In a paper published in the journal Scientific Reports, they show that by using different materials to build a quantum tunneling junction, they were able to alter capacitance by manipulating spins in the opposite way from “normal” magnetocapacitance. This inverse effect, the researchers say, adds one more potentially useful phenomenon to the spintronics toolkit.

    “It gives us more parameter space to design devices,” said Gang Xiao, chair of the physics department at Brown and one of the paper’s coauthors. “Sometimes normal capacitance might be better; sometimes the inverse might be better, depending on the application. This gives us a bit more flexibility.”

    Magnetocapacitors could be especially useful, Xiao says, in making magnetic sensors for a range of different spintronic devices, including computer hard drives and next-generation random access memory chips.

    The research was a collaboration between Xiao’s lab at Brown, the lab of Hideo Kaiju and Taro Nagahama at Japan’s Hokkaido University and the lab of Osamu Kitakami at Tohoku University.

    Xiao has been investigating magnetic tunneling junctions for several years. The tiny junctions can work in much the same way as capacitors in standard circuits. The insulator between the two conducting electrodes slows the free flow of current across the junction, creating resistance and another phenomenon, capacitance.

    But what makes tunneling junctions especially interesting is that the amount of capacitance can be changed dynamically by manipulating the spins of the electrons within the two metal electrodes. The electrodes are magnetic, meaning that electrons spinning within each electrode are pointed in one particular direction. The relative spin direction between two electrodes determines how much capacitance is present at the junction.

    In their initial work on this phenomenon, Xiao and the research team showed just how large the change in capacitance could be. Using electrodes made of iron-cobalt-boron, they showed that by flipping spins from anti-parallel to parallel, they could increase capacitance in experiments by 150 percent. Based on those results, the team developed a theory predicting that, under ideal conditions, the change in capacitance could actually go as high as 1,000 percent.

    The theory also suggested that using electrodes made from different types of metals would create an inverse magnetocapacitance effect, one in which anti-parallel spins create more capacitance than parallel spins. That’s exactly what they showed in this latest study.

    “We used iron for one electrode and iron oxide for the other,” Xiao said. “The electrical properties of the two are mirror images of each other, which is why we observed this inverse magnetocapacitance effect.”

    2
    Iron oxide and iron have different cation orientations in their crystalline structure, which causes them to have inverse electrical properties.

    Xiao says the findings not only suggest a larger parameter space for the use of magnetocapacitance in spintronic devices, they also provide important verification for the theory scientists use to explain the phenomenon.

    “Now we see that the theories fit well with the experiment, so we can be confident in using our theoretical models to maximize these effects, either the ‘normal’ effect or the inverse effect that we have demonstrated here,” Xiao said.

    The work was supported by the National Science Foundation (DMR-1307056), the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research (B), 15H03981), the Japanese Ministry of Education, Culture, Sports, Science and Technology (Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials) and the Center for Spintronics Research Network at Tohoku University.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition
    Welcome to Brown

    Brown U Robinson Hall
    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 7:09 am on April 25, 2017 Permalink | Reply
    Tags: 4-in-1 catalyst, , Brown, , Researchers develop eco-friendly   

    From Brown: “Researchers develop eco-friendly, 4-in-1 catalyst” 

    Brown University
    Brown University

    April 24, 2017
    Kevin Stacey
    kevin_stacey@brown.edu
    401-863-3766

    1
    More reactions, less waste. Catalysts like this new one developed at Brown University might help make industrial chemistry more sustainable. Sun lab / Seto lab / Brown University

    Brown University researchers have developed a new composite catalyst that can perform four separate chemical reactions in sequential order and in one container to produce compounds useful in making a wide range of pharmaceutical products.

    “It normally takes multiple catalysts to carry out all of the steps of this reaction,” said Chao Yu, a post-doctoral researcher at Brown who co-led the work with graduate student Xuefeng Guo. “But we found a single nanocatalyst that can perform this multistep reaction by itself.”

    The research, described in the Journal of the American Chemical Society, was a collaboration between the labs of Brown professors Christopher Seto and Shouheng Sun, who are coauthors of the paper.

    The work was done, the researchers said, with an eye toward finding ways of making the chemical industry more environmentally sustainable. Multi-reaction catalysts like this one are a step toward that goal.

    “If you’re running four different reactions separately, then you’ve got four different steps that require solvents and starting materials, and they each leave behind waste contaminated with byproducts from the reaction,” Seto said. “But if you can do it all in one pot, you can use less solvent and reduce waste.”

    The team made their new catalyst by growing silver-palladium nanoparticles on the surface of nanorods made of oxygen-deficient tungsten-oxide (tungsten-oxide with a few of its oxygen atoms missing). The researchers showed that it could catalyze the series of reactions needed to convert common starting materials formic acid, nitrobenzene and an aldehyde into a benzoxazole, which can be used to make antibacterials, antifungals and NSAID painkillers. The researchers showed that the catalyst could also be used to create another compound, quinazoline, which is used in a variety of anti-cancer drugs.

    Experiments showed that the catalyst could perform the four reactions with a nearly quantitative yield — meaning it produces the maximum possible amount of product for a given amount of starting materials. The reactions were performed at a lower temperature, in a shorter amount of time, and using solvents that are more environmentally friendly than those normally used for these reactions.

    “The temperature we used to synthesize this product is around 80 degrees Celsius,” Guo said. “Normally the reaction happens around 130 degrees and you need to run the reaction for one or two days. But we can get a similar yield at 80 degrees in eight hours.”

    The new catalyst also is able to make the benzoxazole compounds using starting materials that are more environmentally benign than those generally used. The reaction chain requires a hydrogen source for its initial step. That source could be pure hydrogen gas, which is difficult to store and transport, or it could be extracted from a chemical compound. A compound called ammonia borane is often used for this purpose, but the new catalyst enables formic acid to be used instead, which is “cheaper, greener and less toxic,” Yu said.

    And while many catalysts tested in these reactions cannot be used more than once without severely damaging their efficiency, the researchers were able to use the new catalyst up to five times with little drop-off in reaction yield.

    Sun says that studies like this one represents an emerging line of research in greener chemistry.

    “Normally in catalysis we’re doing one reaction at a time, with a different catalyst for each reaction” said Shouheng Sun, a professor of chemistry at Brown. “But there’s growing interest in coming up with catalysts that can perform multiple reactions in one pot, and that’s what we’ve done here.”

    The work was supported in part by the U.S. Army Research Laboratory and the U.S. Army Research Office (W911NF-15-1-0147).

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition
    Welcome to Brown

    Brown U Robinson Hall
    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 3:41 pm on February 4, 2017 Permalink | Reply
    Tags: , “Giant acceleration of diffusion” or GAD, , Brown, Brownian motion, , ,   

    From Brown: “Research pushes concept of entropy out of kilter” 

    Brown University
    Brown University

    [THIS POST IS DEDICATED TO EBM, READY TO ROCK THE CAMPUS]

    February 2, 2017
    Kevin Stacey
    kevin_stacey@brown.edu
    401-863-3766

    Entropy, the measure of disorder in a physical system, is something that physicists understand well when systems are at equilibrium, meaning there’s no external force throwing things out of kilter. But new research by Brown University physicists takes the idea of entropy out of its equilibrium comfort zone.

    The research, published in Physical Review Letters, describes an experiment in which the emergence of a non-equilibrium phenomenon actually requires an entropic assist.

    1
    DNA drag race. Fluorescent stained DNA molecules make their way across of fluid channel pocked with tiny pits. The pits act as “entropic barriers.”
    Stein Lab / Brown University

    “It’s not clear what entropy even means when you’re moving away from equilibrium, so to have this interplay between a non-equilibrium phenomenon and an entropic state is surprising,” said Derek Stein, a Brown University physicist and co-author of the work. “It’s the tension between these two fundamental things that is so interesting.”

    The phenomenon the research investigated is known as “giant acceleration of diffusion,” or GAD. Diffusion is the term used to describe the extent to which small, jiggling particles spread out. The jiggling refers to Brownian motion, which describes the random movement of small particles as a result of collisions with surrounding particles. In 2001, a group of researchers developed a theory of how Brownian particles would diffuse in a system that was pushed out of equilibrium.

    Imagine jiggling particles arranged on a surface with undulating bumps like a washboard. Their jiggle isn’t quite big enough to enable the particles to jump over the bumps in the board, so they don’t diffuse much at all. However, if the board were tilted to some degree (in other words, moved out of equilibrium) the bumps would become easier to jump over in the downward-facing direction. As tilt begins to increase, some particles will jiggle free of the washboard barriers and run down the board, while others will stay put. In physics terms, the particles have become more diffusive — more spread-out — as the system is moved out of equilibrium. The GAD theory quantifies this diffusivity effect and predicts that as tilt starts to increase, diffusivity accelerates. When the tilt passes the point where all the particles are able to jiggle free and move down the washboard, then diffusivity decreases again.

    The theory is important, Stein says, because it’s one of only a few attempts to make solid predictions about how systems behave away from equilibrium. It’s been tested in a few other settings and has been found to make accurate predictions.

    But Stein and his team wanted to test the theory in an unfamiliar setting — one that introduces entropy into the mix.

    For the experiment, Stein and his colleagues placed DNA strands into nanofluidic channels — essentially, tiny fluid-filled hallways through which the molecules could travel. The channels were lined however with nanopits — tiny rectangular depressions that create deep spots within the relatively narrower channels. At equilibrium, DNA molecules tend to arrange themselves in disordered, spaghetti-like balls. As a result, when a molecule finds its way into a nanopit where it has more room to form a disordered ball, it tends to stay stuck there. The pits can be seen as being somewhat like the dips between bumps on the theoretical GAD washboard, but with a critical difference: The only thing actually holding the molecule in the pit is entropy.

    “This molecule is randomly jiggling around in the pit — randomly selecting different configurations to be in — and the number of possible configurations is a measure of the molecule’s entropy,” Stein explained. “It could, at some point, land on a configuration that’s thin enough to fit into the channel outside the pit, which would allow it to move from one pit to another. But that’s unlikely because there are so many more shapes that don’t go through than shapes that do. So the pit becomes an ‘entropic barrier.’”

    Stein and his colleagues wanted to see if the non-equilibrium GAD dynamic would still emerge in a system where the barriers were entropic. They used a pump to apply pressure to the nanofluidic channels, pushing them out of equilibrium. They then measured the speeds of each molecule to see if GAD emerged. What they saw was largely in keeping with the GAD theory. As the pressure increased toward a critical point, the diffusivity of the molecules increased — meaning some molecules zipped across the channel while others stayed stuck in their pits.

    “It wasn’t at all clear how this experiment would come out,” Stein said. “This is a non-equilibrium phenomenon that requires barriers, but our barriers are entropic and we don’t understand entropy away from equilibrium.”


    Anastasios Matzavinos, a professor of applied math at Brown, developed computer simulations of the experiment to help understand the forces at play.

    The fact that the barriers remained raises interesting questions about the nature of entropy, Stein says.

    “Non-equilibrium and entropy are two concepts that are kind of at odds, but we show a situation in which one depends on the other,” he said. “So what’s the guiding principle that tells what the tradeoff is between the two? The answer is: We don’t have one, but maybe experiments like this can start to give us a window into that.”

    In addition to the more profound implications, there may also be practical applications for the findings, Stein says. The researchers showed that they could estimate the tiny piconewton forces pushing the DNA forward just by analyzing the molecules’ motion. For reference, one newton of force is roughly the weight of an average apple. A piconewton is one trillionth of that.

    The experiment also showed that, with the right amount of pressure, the diffusivity of the DNA molecules was increased by factor of 15. So a similar technique could be useful in quickly making mixtures. If such a technique were developed to take advantage of GAD, it would be a first, Stein says.

    “No one has ever harnessed a non-equilibrium phenomenon for anything like that,” he said. “So that would certainly be an interesting possibility.”

    The work was led by Stein’s graduate student Daniel Kim. Co-authors were Clark Bowman, Jackson T. Del Bonis-O’Donnell and Anastasios Matzavinos, all from Brown. The work was supported by the National Science Foundation.

    See the full article here .

    Please help promote STEM in your local schools.

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    Welcome to Brown

    Brown U Robinson Hall
    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 11:17 pm on December 23, 2016 Permalink | Reply
    Tags: Brown, , Jon Witman   

    From Brown: “Galápagos waters illustrate ecological drama of climate change” 

    Brown University
    Brown University

    December 21, 2016
    David Orenstein

    1
    Algae cage
    Brown biology graduate student Robbie Lamb cages off an area of algae as part of an experiment to investigate patterns of grazing by herbivorous fish and urchins. Images: Jon Witman

    Brown marine biologist Jon Witman and students have spent much of 2016 in the Galápagos Islands, continuing years of chronicling the complex and dramatic ecological changes wrought by the increasingly volatile El Niño – La Niña cycle.

    When Brown University Professor Jon Witman returned this year to a small patch of coral off the Galápagos Islands that he had first marked off for study in 2000, he saw virtually nothing — and that told him a lot. An underwater ecosystem that had been teeming with diverse life 16 years ago was now a barren patch, an apparent victim of increasingly strong El Niño weather systems amid global climate change.

    “The 2015-16 El Niño was exceptionally strong,” Witman said. “Climatologists predict that the frequency of strong El Niños will increase with climate change.”

    2
    Degraded diversity
    The same patch of coral in 2000 (left) and 2016 (right) shows a severe decline in its biodiversity. Image: Jon Witman

    This year, with funding from the National Science Foundation, Witman has made several expeditions with graduate and undergraduate students to witness the effects of the latest El Niño. He journeyed to the Galápagos in January, March and again last summer, and he’s there again now through February on sabbatical. He celebrated Thanksgiving with graduate student Robert Lamb and colleagues at the Charles Darwin Research Station with a holiday meal of ahi tuna, cornbread, pumpkin soup and baked sweet potato.

    It’s been a busy year.

    “During this past year of fieldwork in Galápagos, there were so many surprises that we could hardly keep up with all the effects of the strong El Niño,” Witman said.

    Amid the warmest water at the beginning of the year, for example, Lamb discovered the emergence of a skin-wasting disease in the reef fishes that he studies.

    “We were surprised to find this novel wildlife disease running rampant in at least 20 different species,” Lamb said. “Such outbreaks of disease are one of the least understood but potentially devastating manifestations of climate change.”

    The disease abated later in the year as the cooler La Niña took over from El Niño. But other changes associated with the warm water were apparent, too: rampant grazing of algae by sea urchins, for example, and the ominous emergence of mats of cyanobacteria.

    “The cyanobacteria is a species that we haven’t seen at these sites in all the time we’ve been working there,” said Fiona Beltram, a Brown junior from Glocester, R.I., who has been a member of the Witman lab for two years. “I’m interested in determining if the cyanobacteria cover leads to bleaching in coralline algae, which are important foundation species on the Galápagos reefs.”

    Among the responsibilities assigned to Beltram, who joined the team in the Galápagos this summer, was to set up experiments to study the cyanobacteria. She also helped to measure what’s been going on at about two dozen specific areas, or “transects,” that Witman has been monitoring for years.

    “I’ve been really passionate about marine science since I was a kid, so it was incredibly exciting to travel down there and actively contribute to fieldwork,” Beltram said. “It’s also just a beautiful place, especially underwater.”

    A cycle out of balance

    3
    Bleached and barren…
    Warm El Niño waters harm the corals.

    4
    …But barnacles grow in
    The colder La Niña encouranges the growth of barnacles, a major food source, on the corals.

    The question, though, is whether that beautiful place will last. Over the years, Witman said, the El Niño – La Niña cycle has yielded a pattern that alternately seems to destroy, but at other times redeem the subtidal ecosystem’s stunning biodiversity.

    “Corals bleach and sometimes die during the extreme temperature variability from the high temperatures during El Niño and the low temperatures of the ensuing La Niña,” he said. “But as La Niña brings more productive water, barnacles reproduce and settle on the stressed corals and all over the bottom.”

    That deteriorates the corals further, but the barnacles serve as food for many other species, promoting a rebound in the undersea life. But the more Witman and his team dives in — literally and figuratively — the more they see that the long-term trend is worrisome.

    “With continued El Niños, the Galápagos subtidal ecosystem may be shifting to a system with more barnacles and their predators and fewer corals,” he said. “I’m concerned, however, that this may be a lower diversity system, which may make it less resilient to future climate shocks.”

    Who eats whom

    At least for now, the food webs in the area remain full of characters, all of whom have a role to be studied. Lamb and Witman spent November formulating experiments to test hypotheses about what species are grazing on algae and how much. They deployed cages that selectively exclude herbivorous fishes or sea urchins, the two major groups of herbivores in this ecosystem.

    “We want to understand the individual and combined ecological roles of these two important groups,” Lamb said. “Because of their different life histories and feeding strategies, they may be vastly different in how they respond to changes in the environment such as increased wave turbulence from storms generated during El Niño.”

    Because algae serve as the basis of much of an ecosystem’s productivity, the answers to these questions come with profound implications. Too much algae consumption can undermine the food supply for other species and reduce biodiversity.

    5
    Survival rivals
    A triggerfish (top) swims along with its rival the hogfish, which will take urchins out of its mouth.

    The food webs play out in complicated ways, Witman has found, as species fight to survive. As it did for Darwin, the Galápagos still deliver plenty of new lessons about how nature works — the critical role of triggerfish, for example.

    “Our research has discovered that triggerfish are keystone predators,” Witman said. “They prey heavily on sea urchins and consequently increase the productivity of the marine ecosystem by releasing algae from consumption by sea urchins. Sea urchins are like underwater lawnmowers mowing down bottom-dwelling algae; anything that changes their consumption of algae has a dramatic effect on productivity. We found that Spanish hogfish slow the rate of triggerfish predation on sea urchins by trying to take the urchin out of the triggerfish’s mouth.”

    Around the world

    As Witman and his students — over the years he’s trained nine undergraduates, six doctoral students and three postdoctoral scholars in the Galápagos alone — continue to piece together how subtidal life is changing with climate in the islands, he’s also working globally. He took a side trip in early December, for example, to check on another of his regular spots: coral reefs near Easter Island, far off the coast of Chile.

    When he’s home in New England, Witman can often be found in the Gulf of Maine at Cashes Ledge, the largest and deepest offshore kelp forest in the North Atlantic. There, too, climate change may threaten biodiversity.

    “We are studying the resilience of the kelp forest to warming, as it is such an ecologically important species, and also trying to achieve permanent protection for the spectacular marine communities on Cashes Ledge as a U.S. Marine National Monument,” Witman said.

    Lamb is working concurrently to show how the unique kelp forests on Cashes Ledge are home to some of the healthiest populations of cod and pollock in the southern Gulf of Maine.

    Whether in the warm waters of the South Pacific or the much chillier North Atlantic, the goal is to understand how ocean ecosystems work so that people can help them thrive rather than threatening their survival.

    “Sound management of the oceans requires understanding the roles that key species and biodiversity play in ecosystem functioning,” Witman said. “And, of course, how this is being altered by human disturbance.”

    See the full article here .

    Please help promote STEM in your local schools.

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    Welcome to Brown

    Brown U Robinson Hall
    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 10:49 am on December 11, 2016 Permalink | Reply
    Tags: , , Brown, CB chondrites, Grand Tack, , Jupiter would have stirred up the asteroid belt enough to produce the high-impact velocities necessary to form these CB chondrites, NASA's Solar System Exploration Virtual Institute, Southwest Research Institute, Vaporizing iron requires really high-velocity impacts   

    From Brown: “Research offers clues about the timing of Jupiter’s formation” 

    Brown University
    Brown University

    December 9, 2016
    Kevin Stacey
    kevin_stacey@brown.edu
    401-863-3766

    The new study shows that Jupiter had probably reached its present day size by about 5 million years after the first solids in the solar system formed.

    1
    Jupiter is the king of the planets of our solar system. http://cosmobiologist.blogspot.com/2016/02/jupiter-king-of-worlds.html

    A peculiar class of meteorites has offered scientists new clues about when the planet Jupiter took shape and wandered through the solar system.

    Scientists have theorized for years now that Jupiter probably was not always in its current orbit, which is about five astronomical units from the sun (Earth’s distance from the sun is one astronomical unit). One line of evidence suggesting a Jovian migration deals with the size of Mars. Mars is much smaller than planetary accretion models predict. One explanation for that is that Jupiter once orbited much closer to the sun than it does now. During that time, it would have swept up much of the material needed to create supersized Mars.

    But while most scientists agree that giant planets migrate, the timing of Jupiter’s formation and migration has been a mystery. That’s where the meteorites come in.

    Meteorites known as CB chondrites were formed as objects in the early solar system—most likely in the present-day asteroid belt—slammed into each other with incredible speed. This new study, published in the journal Science Advances, used computer simulations to show that Jupiter’s immense gravity would have provided the right conditions for these hypervelocity impacts to occur. That in turn suggests that Jupiter was near its current size and sitting somewhere near the asteroid belt when the CB chondrules were formed, which was about 5 million years after formation of the first solar system solids.

    “We show that Jupiter would have stirred up the asteroid belt enough to produce the high-impact velocities necessary to form these CB chondrites,” said Brandon Johnson, a planetary scientist at Brown University who led the research. “These meteorites represent the first time the solar system felt the awesome power of Jupiter.”

    Strange structures

    Chondrites are a class of meteorites made up of chondrules, tiny spheres of previously molten material, and are among the most common meteorites found on Earth. The CB chondrites are a relatively rare subtype that have long fascinated meteoriticists. Part of what makes the CB chondrites so interesting is that their chondrules all date back to a very narrow window of time in the early solar system.

    “The chondrules in other meteorites give us a range of different ages,” Johnson said. “But those in the CB chondrites all date back to this brief period 5 million years after the first solar system solids.”

    2
    Chondrules found in CB chondrites were formed in ultra-high-speed collisions.
    Alexander Krot, University of Hawai’i Manoa

    But to Johnson, who studies impact dynamics, there is something else interesting about CB chondrites: They contain metallic grains that appear to have been condensed directly from vaporized iron. “Vaporizing iron requires really high-velocity impacts,” Johnson said. “You need to have an impact speed of around 20 kilometers per second to even begin to vaporize iron, but traditional computer models of the early solar system only produce impact speeds of around 12 kilometers per second at the time when the CB chondrites were formed.”

    So Johnson worked with Kevin Walsh of the Southwest Research Institute in Boulder to generate new computer models of the chondrule-forming period—models that include the presence of Jupiter near the present day position of the asteroid belt.

    Gravity boost

    Big planets generate lots of gravity, which can slingshot nearby objects at high speeds. NASA often takes advantage of this dynamic, swinging spacecraft around planets to generate velocity. Walsh and Johnson included in their simulations a scenario of Jupiter’s formation and migration considered likely by many planetary scientists.

    The scenario, known as the Grand Tack (a term taken from sailing), suggests that Jupiter formed somewhere in the outer solar system. But as it accreted its thick atmosphere, it changed the distribution of mass in the gassy solar nebula surrounding it. That change in mass density caused the planet to migrate, moving inward toward the sun to about where the asteroid belt is today. Later, the formation of Saturn created a gravitational tug that pulled both planets back out to where they are today.

    “When we include the Grand Tack in our model at the time the CB chondrites formed, we get a huge spike in impact velocities in the asteroid belt,” Walsh said. “The speeds generated in our models are easily fast enough to explain the vaporized iron in CB chondrites.”

    The most extreme collision in the model was an object with a 90-kilometer diameter slamming into a 300-kilometer body at a speed of around 33 kilometers per second. Such a collision would have vaporized 30 to 60 percent of the larger body’s iron core, providing ample material for CB chondrites.

    The models also show that the increase in impact velocities would have been short-lived, lasting only about 500,000 years or so (a blink of an eye on the cosmic timescale). That short timescale allowed the researchers to conclude that Jupiter formed and migrated at roughly the same time the CB chondrites formed.

    The researchers say that while the study is strong evidence for the Grand Tack migration scenario, it doesn’t necessarily preclude other migration scenarios. “It’s possible that Jupiter formed closer to the sun and then migrated outward, rather than the in then out migration of the Grand Tack,” Johnson said.

    Whatever the scenario, the study provides strong constraints on the timing of Jupiter’s presence in the inner solar system.

    “In retrospect, it seems obvious that you would need something like Jupiter to stir the asteroid belt up this much,” Johnson said. “We just needed to create these models and calculate the impact speeds to connect the dots.”

    Other co-authors on the paper were David Minton (Purdue University), Alexander Krot (University of Hawai’i, Mānoa) and Harold Levison (Southwest Research Institute). Funding was provided by NASA’s Solar System Exploration Virtual Institute (NNA14AB03A). Computer simulations were run on the National Science Foundation’s XSEDE computer cluster.

    See the full article here .

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    Welcome to Brown

    Brown U Robinson Hall
    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 6:16 am on December 6, 2016 Permalink | Reply
    Tags: 20S proteasome, , , Brown, New compound targets TB bacterium’s defense against the immune system, Syringolins   

    From Brown: “New compound targets TB bacterium’s defense against the immune system” 

    Brown University
    Brown University

    December 5, 2016
    Kevin Stacey
    401-863-3766

    1
    Rational design
    Researchers have designed a new compound that inhibits a key enzyme in Mycobacterium tuberculosis, which makes the bacterium more susceptible to the human immune system. Sello lab / Brown University

    Developed by chemists at Brown University in conjunction with colleagues at MIT and Cornell, the compound could enable a new drug strategy for treating tuberculosis.

    Part of the reason tuberculosis-causing bacteria are so good at colonizing the human body is that they have defenses against the body’s immune system. A research team led by Brown University chemists has developed a new compound that can take down one of those defenses in Mycobacterium tuberculosis. The researchers are hopeful that the compound could be part of a new drug strategy for treating tuberculosis.

    “Given the increasing resistance of Mycobacterium tuberculosis to drugs, we contemplated the treatment of tuberculosis in a fundamentally different way,” said Jason Sello, associate professor of chemistry at Brown who directed the research. “Instead of seeking conventional drug leads that kill M. tuberculosis directly, we hoped to develop compounds that could render the bacterium susceptible to the immune system. We were successful in designing compounds that make laboratory-grown bacteria sensitive to a chemical produced during the immune response.”

    Kyle Totaro, who recently earned his Ph.D. from Brown, led Sello’s team. They also worked collaboratively with research groups at the Massachusetts Institute of Technology and Weill Cornell Medicine. A paper describing the work is published in the journal ACS Infectious Diseases.

    2
    Jason Sello (left) with Kyle Totaro. No image credit.

    The team’s strategy was to inhibit an enzyme found in M. tuberculosis called the 20S proteasome. It acts like a molecular trash collector, disposing of damaged proteins within the bacterial cell. It specializes in cleaning up proteins damaged by nitric oxide, a chemical produced by the innate immune system to help fight pathogens. The ability of the 20S proteasome to dispose of nitric oxide-damaged proteins helps the bacteria survive within the host.

    To inhibit the proteasome, Sello and his team envisioned reactive compounds that mimic key chemical attributes of its substrates — the proteins that the enzyme normally breaks down. They anticipated that the proteasome would bind these compounds as it does any other protein and that their reactivity would disable the enzyme. With the proteasome disabled, proteins damaged by nitric oxide will accumulate inside the bacteria and cause their death.

    But there was a key problem the researchers needed to contend with. Humans have a very similar system for the degradation of damaged proteins, and inhibition of this system is known to be lethal to cells. So any compound Sello and his team developed would have to selectively disrupt that bacterial proteasome, without significantly affecting the human version.

    To do that, the researchers drew inspiration from nature. A bacterium called Pseudomonas syringae, a pathogen that infects plants, is known to produce compounds called syringolins, which are known to inhibit the plant proteasome by mimicking its substrates. The compounds are also known to inhibit the human proteasome and have promise as anticancer agents. Sello and his team used predictions about how the syringolins bind the human proteasome and knowledge about the substrates of the M. tuberculosis proteasome to design selective inhibitors.

    Research had indicated that syringolins bound and inhibited the human proteasome by mimicking a preferred substrate have a specific chemical residue (valine) at two key positions. Research had also indicated that the bacterial proteasome prefers to degrade proteins having two different chemical residues (tryptophan and glycine) at the same two key positions. So, the researchers predicted that a syringolin analog in which the valine residue was swapped for structures resembling the tryptophan and glycine, the compound would selectively inhibit the bacterial proteasome.

    Sello and his students at Brown synthesized the designed compound as well as others that matched or conflicted with their design model. In turn, their collaborators at MIT systematically assessed the capacities of the compounds to inhibit both the human and bacterial proteasomes in a test tube.

    The team found that the natural syringolin product was 160-fold more specific for the human proteasome. One of the engineered syringolin analogs, in contrast, was 74-fold more specific for the bacterial proteasome.

    “Using this rational design approach and chemical synthesis, we were able to generate selective inhibitors of the M. tuberculosis 20S proteaseome,” Sello said. “In the best case, our engineering of the syringolins increased the inhibition of the bacterial enzyme by 220-fold, yet reduced the reaction with the human enzyme by 99.6 percent. Our success validated both the apparent substrate specificity of the M. tuberculosis proteasome and the structural model for proteasome inhibition by the syringolins.”

    The next step was to see whether the engineered compounds could indeed make bacteria more susceptible to nitric oxide, the chemical produced during the immune response. Sello’s collaborators at the Weill Cornell Medicine added the engineered syringolins to cultures of M. tuberculosis in the presence and absence of a source of nitric oxide. As expected, they found that the bacteria treated with the compounds were highly susceptible to nitric oxide. In keeping with their weak inhibition of the human proteasome, the engineered syringolin did not inhibit the growth of human cell models.

    “We were pleased to have engineered out the toxicity of the syringolins to human cells,” Sello said. That suggested that an engineered syringolin could be safe in humans.” Sello and his colleagues are hopeful that this initial round of testing could lay the groundwork for developing new drugs to treat tuberculosis. “We’ve only modified the syringolins in two ways,” Sello said. “There are many other possibilities for structural modification that could improve potency and other pharmacological properties of the molecules. We can now see a long but feasible pathway towards the development of a novel therapeutic agent for tuberculosis.”

    Sello says it’s plausible that a drug strategy like this one could be used alongside traditional antibiotics.

    “One of the things that’s clear in the treatment of tuberculosis is that combining drugs can be effective,” he said. “So combining a blocker of the bacterium’s defense against the immune system with a traditional antibiotic could be kind of a one-two punch.”

    Other authors on the paper were Dominik Barthelme (MIT), Peter T. Simpson (a Brown Class of 2014 graduate), Xiujiu Jiang, Gang Lin, Carl Nathan (Weill Cornell Medicine) and Robert Sauer (MIT). The work was supported by the Brown University and its Undergraduate Teaching and Research Award program, the Lura Cook Hull Trust, the National Institutes of Health (AI-16892, 1R21 AI101393, U19 AI111143) and Deutsche Forschungsgemeinschaft (BA 4890/1-1, BA 4890/3-1).

    See the full article here .

    Please help promote STEM in your local schools.

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    Welcome to Brown

    Brown U Robinson Hall
    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 10:46 am on October 1, 2016 Permalink | Reply
    Tags: , , Brown   

    From Brown: “BRAIN grant of $1.6 million powers study of neural signals” 

    Brown University
    Brown University

    September 29, 2016
    David Orenstein
    david_orenstein@brown.edu

    Three-year project will develop a software tool to help scientists and doctors understand how recorded brainwaves emerge from underlying neural activity.

    1
    Thinking cap. An array of electroencephalography sensors allows detailed sensing of neural signals. New software will help researchers understand that data better. Michael Cohea/Brown University

    In her research at Brown University, Stephanie Jones, research associate professor of neuroscience, has led the development of a unique computational model that explains how individual neurons and circuits of them produce the signals detected by external brainwave measurements, such as EEG or MEG sensors. Now, with a three-year, $1.6 million grant from the federal government’s BRAIN Initiative, she hopes to share her innovation with other scientists.

    “The aim of the grant is to turn the model into a user-friendly software tool that researchers and clinicians can use to test hypotheses about the neural origin of their MEG/EEG or electrocorticography data,” said Jones, a member of the Brown Institute for Brain Science. “We are calling this tool the ‘Human Neocortical Neurosolver.'”

    Jones leads the research, which officially starts Sept. 30 in collaboration with Dr. Matti Hamalainen at Massachusetts General Hospital and Dr. Michael Hines at Yale University.

    The team will also “integrate the neural model into existing source localization software so that researchers can study the location, time course and neural mechanisms of their human brain imaging data all in one software package,” Jones added.

    She said the software will not only aid neuroscience, but also future patient care.

    “While there are numerous studies connecting human MEG/EEG data to healthy and abnormal functions, the circuit level interpretation of the underlying neural dynamics is lacking,” she said. “This tool will foster the translational relevance of these technologies by allowing researchers to generate testable hypotheses that can guide further studies and ultimately novel therapeutics.”

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition
    Welcome to Brown

    Brown U Robinson Hall
    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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