Tech

Peatlands with their huge diversity of peat moss species store about 30 percent of the earth's soil carbon. This means they store roughly twice as much carbon as all the world's forests combined. However, peat harvesting and climate change are threatening these long-term carbon stores because there is not enough founder material for cultivating peat mosses on a large scale. In collaboration with researchers from the University of Greifswald, a team of scientists led by plant biotechnologist Professor Ralf Reski from the Faculty of Biology of the University of Freiburg in Germany has established the world's largest laboratory collection of mosses of the genus Sphagnum. With this as a foundation, peat mosses can be grown in a sustainable and economic way. The scientists have published their research in the scientific journal New Phytologist. Melanie Heck, a PhD student, is the first author.

For their project - called MOOSzucht - the scientists collected sporophytes, the spore capsules of mosses, of 19 Sphagnum species in Austria, Germany, Latvia, Russia, Sweden, and the Netherlands. The world's largest collection of Sphagnum cultures is now housed in the International Moss Stock Center (IMSC), a resource center founded in 2010 at the University of Freiburg. Scientists use the spores to create pure peat moss cultures in a laboratory environment that are not contaminated by bacteria, fungi, algae, or suchlike. Some species grow at a rate 50 to 100 times faster in the laboratory than in a moor landscape. The researchers measured the growth of the mosses in liquid mediums containing nutrients, also known as suspension cultures. They also determined how many sets of chromosomes could be found in the cell nuclei in the cultures and compared this to the genome size of the already established model moss Physcomitrella patens. In this way they were able to identify haploid and diploid Sphagnum species - in other words, species with single or double sets of chromosomes, respectively. However, they could not find a correlation between the number of sets of chromosomes and moss growth, meaning it is still unclear why diploid mosses exist in nature.

Peat is harvested on a large scale for growing vegetables and ornamental plants in greenhouses and home gardens. Due to climate change and the resulting droughts and higher temperatures, peat mosses are showing poorer growth, deteriorating more quickly, and binding less carbon. The researchers from the University of Freiburg want to replace this dire need for peat with renewable biomass. However, the large amount of founder material that would be needed for this can only be produced in bioreactors. That is why Reski and his team at the IMSC are distributing lab strains of peat mosses to various research institutes and companies who are active in basic research, biotechnology, or in sustainable bioeconomy.

Patients who suffer an intracerebral hemorrhage (ICH) face an increased risk of acute kidney injury (AKI) during their hospitalization. AKI can lead to sudden kidney failure, kidney damage or even death. Researchers from the University of Missouri School of Medicine and MU Health Care have determined which ICH patients are at the highest risk for this kidney injury so doctors can take precautions to prevent it. They also examined how the commonly-used blood pressure lowering drug nicardipine contributes to AKI.

"Over the past five years, clinicians have been concerned about AKI as they see patients who present with ICH, then develop kidney failure and require dialysis," said lead researcher Adnan I. Qureshi, MD, a professor of clinical neurology at the MU School of Medicine. "What we need is a more global body approach to improve the outcome of patients with ICH, rather than just focusing on the brain."

Qureshi's team analyzed data from a multicenter trial in which 1,000 ICH patients with systolic blood pressure above 180 to either intensive (110-139 mm Hg) blood pressure reduction or standard (140-179 mm Hg) reduction within 4.5 hours after symptoms started. Researchers identified AKI by taking creatinine blood samples -- which show how well the kidneys are functioning -- from each patient for three days. They found 15% of all patients developed AKI, higher doses of nicardipine were linked to an increased risk for AKI, and a higher baseline serum creatinine level was associated with a greater risk for AKI. In addition, those with AKI were nearly three times more likely to die within three months of diagnosis.

"Even the initial set of labs seem to have predictive value in who will develop AKI, and I think this study highlights the values doctors can use to actually determine who may be at risk," Qureshi said. "What we thought was an isolated brain disease, is not necessarily the case."

Qureshi believes the next step in preventing AKI after ICH is to use serum creatinine and other markers to identify high-risk patients, then use proactive measures to carefully manage intravenous fluids and avoid medications that are more likely to cause or worsen AKI.

Led by the Department of Energy's Oak Ridge National Laboratory and the University of Tennessee, Knoxville, a study of a solar-energy material with a bright future revealed a way to slow phonons, the waves that transport heat. The discovery could improve novel hot-carrier solar cells, which convert sunlight to electricity more efficiently than conventional solar cells by harnessing photogenerated charge carriers before they lose energy to heat.

"We showed that the thermal transport and charge-carrier cooling time can be manipulated by changing the mass of hydrogen atoms in a photovoltaic material," said ORNL's Michael Manley. "This route for extending the lifetime of charge carriers bares new strategies for achieving record solar-to-electric conversion efficiency in novel hot-carrier solar cells."

UT's Mahshid Ahmadi noted, "Tuning the organic-molecule dynamics can enable control of phonons important to thermal conductivity in organometallic perovskites." These semiconducting materials are promising for photovoltaic applications.

Manley and Ahmadi designed and managed the study, published in Science Advances. Experts in materials synthesis, neutron scattering, laser spectroscopy and condensed matter theory discovered a way to inhibit wasteful charge cooling by swapping a lighter isotope for a heavier one in an organometallic perovskite.

When sunlight strikes a solar cell, photons create charge carriers -- electrons and holes -- in an absorber material. Hot-carrier solar cells quickly convert the energy of the charge carriers to electricity before it is lost as waste heat. Preventing heat loss is a grand challenge for these solar cells, which have the potential to be twice as efficient as conventional solar cells.

The conversion efficiency of conventional perovskite solar cells has improved from 3% in 2009 to more than 25% in 2020. A well-designed hot-carrier device could achieve a theoretical conversion efficiency approaching 66%.

The researchers studied methylammonium lead iodide, a perovskite absorber material. In its lattice, collective excitations of atoms create vibrations. Vibrations moving in sync with each other are acoustic phonons, whereas those moving out of sync are optical phonons.

"Typically, charge carriers first lose their heat to optical phonons, which propagate slower than acoustic phonons," explained ORNL co-author Raphael Hermann. "Later, optical phonons interact with acoustic phonons that carry away this energy."

However, in a region called the "hot phonon bottleneck," exotic physics prevent electrons from losing their energy to collective vibrations that transport heat. To enhance this effect in a photovoltaic perovskite, the researchers used inertia, the tendency of an object to keep doing what it's doing, be that resting or moving.

"We basically slowed down how fast the molecules can sway, similar to slowing a spinning ice skater by putting weights in her hands," Hermann said.

To do that in an orderly atomic lattice, Ahmadi and ORNL's Kunlun Hong led the synthesis of crystals of methylammonium lead iodide at the Center for Nanophase Materials Sciences, a DOE Office of Science User Facility at ORNL. They substituted a lighter isotope of hydrogen, normally occurring protium, which has no neutrons, with a heavier one, deuterium, which has one neutron, in the perovskite's central organic molecule, methylammonium, or MA. Isotopes are chemically identical atoms that differ only in mass owing to the difference in neutron number.

Next, Manley and Hermann together with ORNL's Songxue Chi conducted triple-axis neutron scattering experiments at the High Flux Isotope Reactor, a DOE Office of Science User Facility at ORNL, to map the phonon dispersion in protonated and deuterated crystals. Because they saw a disagreement between their measurements and published data from inelastic X-ray measurements, they made additional measurements at the Spallation Neutron Source, another DOE Office of Science User Facility at ORNL. There, Luke Daemen of ORNL used the VISION vibrational spectrometer to reveal all possible vibrational energies. The combined results indicated that longitudinal acoustic modes with short wavelengths propagate more slowly in the deuterated sample, suggesting thermal conductivity may be reduced.

Hsin Wang of ORNL performed thermal diffusivity measurements to investigate how heat moved in the crystals. "Those measurements told us that deuteration decreased the already-low thermal conductivity by 50%," Manley said. "We realized then that maybe this finding affects things that builders of solar devices care about -- specifically, keeping charge carriers hot."

The study provided unprecedented understanding of the effect of atomic mass increase on heat transfer.

"A lot of vibrations, like stretching modes for the hydrogen atoms, have such high frequencies that they don't normally interact with the lower-energy vibrations of the crystal," Daemen said. The lower-energy modes include swaying of molecules.

The swaying frequency of the organic molecule MA is a little higher than the frequency of the collective vibrations. However, when a deuterium atom substitutes for a lighter hydrogen isotope, its greater mass slows the swaying of MA. It sways at a frequency closer to that of the collective vibrations, and the two start to interact and then strongly couple. The synced phonons slow, becoming less effective at removing heat.

Hermann compared the influence of frequency to a boy's different actions when his father pushes him on a swing. "The protonated case is like the boy moving his legs too fast to be in sync with the dad pushing. He's not going to go higher. But if he starts moving his legs at about the same frequency as the swinging, that's like the deuterated case. The kid has slowed down his legs just enough so that he's starting to get in sync with the pushed swing, adding momentum. He is able to swing higher because the two motions are coupled."

The ORNL measurements revealed an effect that far exceeded what was expected from changing the mass of the hydrogen: Deuteration slowed heat transport so much that the charge-carrier cooling time doubled.

To confirm this finding, ORNL co-author Chengyun Hua used pump-probe laser experiments to measure the electrons' energy dissipation in the deuterated and protonated perovskites over tiny timescales, quadrillionths of a second.

"These measurements confirmed that the giant changes in phonons and thermal conductivity that the heavy isotope induced translate into a slower relaxation time for photo-excited electrons," Hua said. "This is an important factor in improving photovoltaic properties."

University of California, Berkeley, co-authors Yao Cai and Mark Asta, who is also with DOE's Lawrence Berkeley National Laboratory, performed theory-based calculations to provide insight into complexities of phonon behavior.

The discovery made in the ORNL-UT-led study may provide a bright spot for future manufacturers of hot-carrier solar cells.

"Phonons look like a pretty effective knob to turn, and we know how to turn the knob," Manley said. "When you want to improve the materials, you can add a molecule, methylammonium or something else. The finding can inform developers' decisions about how they grow their crystals."

Added Ahmadi, "This knowledge can be used to guide materials design for applications beyond photovoltaics, such as optical sensors and communication devices."

HOUSTON - (Oct. 5, 2020) - When you take a medication, you want to know precisely what it does. Pharmaceutical companies go through extensive testing to ensure that you do.

With a new deep learning-based technique created at Rice University's Brown School of Engineering, they may soon get a better handle on how drugs in development will perform in the human body.

The Rice lab of computer scientist Lydia Kavraki has introduced Metabolite Translator, a computational tool that predicts metabolites, the products of interactions between small molecules like drugs and enzymes.

The Rice researchers take advantage of deep-learning methods and the availability of massive reaction datasets to give developers a broad picture of what a drug will do. The method is unconstrained by rules that companies use to determine metabolic reactions, opening a path to novel discoveries.

"When you're trying to determine if a compound is a potential drug, you have to check for toxicity," Kavraki said. "You want to confirm that it does what it should, but you also want to know what else might happen."

The research by Kavraki, lead author and graduate student Eleni Litsa and Rice alumna Payel Das of IBM's Thomas J. Watson Research Center, is detailed in the Royal Society of Chemistry journal Chemical Science.

The researchers trained Metabolite Translator to predict metabolites through any enzyme, but measured its success against the existing rules-based methods that are focused on the enzymes in the liver. These enzymes are responsible for detoxifying and eliminating xenobiotics, like drugs, pesticides and pollutants. However, metabolites can be formed through other enzymes as well.

"Our bodies are networks of chemical reactions," Litsa said. "They have enzymes that act upon chemicals and may break or form bonds that change their structures into something that could be toxic, or cause other complications. Existing methodologies focus on the liver because most xenobiotic compounds are metabolized there. With our work, we're trying to capture human metabolism in general.

"The safety of a drug does not depend only on the drug itself but also on the metabolites that can be formed when the drug is processed in the body," Litsa said.

The rise of machine learning architectures that operate on structured data, such as chemical molecules, make the work possible, she said. Transformer was introduced in 2017 as a sequence translation method that has found wide use in language translation.

Metabolite Translator is based on SMILES (for "simplified molecular-input line-entry system"), a notation method that uses plain text rather than diagrams to represent chemical molecules.

"What we're doing is exactly the same as translating a language, like English to German," Litsa said.

Due to the lack of experimental data, the lab used transfer learning to develop Metabolite Translator. They first pre-trained a Transformer model on 900,000 known chemical reactions and then fine-tuned it with data on human metabolic transformations.

The researchers compared Metabolite Translator results with those from several other predictive techniques by analyzing known SMILES sequences of 65 drugs and 179 metabolizing enzymes. Though Metabolite Translator was trained on a general dataset not specific to drugs, it performed as well as commonly used rule-based methods that have been specifically developed for drugs. But it also identified enzymes that are not commonly involved in drug metabolism and were not found by existing methods.

"We have a system that can predict equally well with rule-based systems, and we didn't put any rules in our system that require manual work and expert knowledge," Kavraki said. "Using a machine learning-based method, we are training a system to understand human metabolism without the need for explicitly encoding this knowledge in the form of rules. This work would not have been possible two years ago."

Kavraki is the Noah Harding Professor of Computer Science, a professor of bioengineering, mechanical engineering and electrical and computer engineering and director of Rice's Ken Kennedy Institute. Rice University and the Cancer Prevention and Research Institute of Texas supported the research.

WESTMINSTER, Colorado - October 5, 2020 - Horseweed is considered one of the most troublesome weeds in the United States and Canada - able to produce devastating losses in both corn and soybean yields when left uncontrolled. Populations of herbicide-resistant horseweed are now found in 18 countries, and many are resistant to multiple herbicide sites of action.

Two recent studies - one published by the journal Weed Science and the other by the journal Weed Technology - provide insights on the role cover crops might play in controlling horseweed and reducing the need for herbicides.

Cover Crops Alone Are Not Enough

Researchers from The Ohio State University conducted recent field studies to understand the role a rye cover crop might play in the suppression of glyphosate-resistant horseweed in no-till soybean crops. They explored the impact of cover crop planting date and seeding rate on the need for herbicide treatments that are typically applied in the fall and spring.

The team compared cover crops planted in late September to those planted in late October. Some were seeded at 50 kg ha-1, while others were seeded at double that rate. The reduction in horseweed density produced by the cover crop was found to be similar, regardless of the planting time or the seeding density. The earlier planted rye at the higher seeding rate produced the most biomass, though, which researchers say may result in more effective, season-long control of summer annual weeds.

In all instances, horseweed was best controlled with the addition of a comprehensive herbicide treatment program.

"Our studies suggest that a cereal rye cover crop planted at a density of just 50 kg ha-1 may be sufficient to reduce glyphosate-resistant horseweed density, but it cannot be relied upon to reduce the need for fall herbicide treatments or spring residual programs," said Alyssa Essman of The Ohio State University.

"Planting Green" Reduces Horseweed Density

A team of scientists from Michigan State University conducted field tests in Midwest soybean fields where horseweed had escaped treatment during the previous season. Test plots were planted in cereal rye or in winter wheat cover crops using two seeding densities.

Some of the cover crops were terminated a week before planting with a treatment of glyphosate. Others were left in place until one week after soybean crops were planted, which is a technique called "planting green."

The team found planting green resulted in a cover crop biomass that was 212 to 272 percent greater than those on plots terminated before soybeans were planted. Soybean yields were 30 to 108 percent greater. Planting green reduced the biomass of glyphosate-resistant horseweed by 46 to 93 percent compared to plots with no cover crop. Early termination plots provided a less consistent horseweed suppression.

"We found that planting green increased the carbon to nitrogen ratio of the cover crop residue, which improved its ability to suppress glyphosate-resistant horseweed until the time of a postemergence herbicide application five weeks after planting," said John Schramski, a graduate student at Michigan State University and lead researcher for the study. "Cover crops alone, though, were unable to suppress glyphosate-resistant horseweed throughout the entire growing season to harvest time."

HOUSTON -- A new study from researchers at The University of Texas MD Anderson Cancer Center has discovered that mutations found in cancers do not accumulate randomly, but are found in distinct patterns that vary based on the three-dimensional organization of the genome in the cell as well as the underlying factors causing the mutations.

Mutations caused by external factors, such as ultraviolet light or tobacco smoke, led to mutations in different regions than internal factors, such as defects in DNA damage repair or proofreading machinery. The findings, published today in Nature Genetics, are important for understanding what factors may be driving mutations in a given cancer and may point to new therapeutic targets.

"DNA is not randomly organized within the nucleus, and we found that this structure is strongly correlated with how cancer cells accumulate mutations," said lead author Kadir Akdemir, Ph.D., instructor of Genomic Medicine. "We know there are certain processes causing mutations in cancer cells, but we don't always understand the underlying causes. These findings should give us a clue as to how cancer accumulates mutations, and perhaps we can target and kill cancer cells by leveraging the mutations they accumulate."

Within the nucleus of the cell, DNA is packaged with proteins into chromatin, a highly organized and compacted structure that makes up our chromosomes. Within this structure, genes that are frequently used in the cells are organized together in "active domains," which are more readily accessible. Those genes used less often are similarly organized together in "inactive domains."

The researchers analyzed whether mutations are distributed more frequently in these active or inactive domains in cancer by studying publicly available whole-genome sequencing data of 3,000 paired samples of normal tissue and tumor tissue across 42 cancer types.

Across every cancer type studied, the inactive domains carried significantly more mutations than the active domains, suggesting that the accumulation of mutations is strongly correlated with the three-dimensional organization of the genome.

As a validation of these findings, the researchers looked specifically at the X chromosome in male and female patients. In females, one of their two X chromosomes is inactivated, so it is essentially itself an inactive domain. When comparing the X chromosome between sexes, females had more mutations than males with a marked distribution difference, largely driven by an abundance of mutations on the inactive chromosome.

Knowing that mutations can be caused by a variety of distinct processes, the researchers also investigated whether external environmental factors resulted in different mutation patterns compared to those caused by internal factors in the cell.

"Interestingly, we found that different causes of mutations resulted in distinct accumulation patterns within the cell," said senior author Andy Futreal, Ph.D., chair of Genomic Medicine. "Extrinsic factors were associated with an enrichment of mutations in inactive domains, whereas intrinsic factors were correlated with enriched mutations in active domains. This provides us an important foundation going forward to understand the root of cancer mutations when we don't otherwise know the cause."

Knowing the causes and distributions of cancer-related mutations may open up potential therapeutic options, explained Akdemir, such as targeted therapies against a specific signaling pathway or combinations with immunotherapy.

For example, immunotherapy may be able to better recognize a cancer cell if more mutations are present. However, if mutations occur primarily in inactive domains, they would rarely be seen by the immune system. Therapeutic agents that restore activity to these domains, used in combination with immune checkpoint inhibitors, could stimulate a stronger anti-tumor immune response.

The researchers hope to investigate strategies such as this in future studies to determine their feasibility as treatment options.

A team of soil scientists from RUDN University organized a summer school to study urban soils in 5 climatic zones. Students from Germany, Russia, China, and the USA spent two weeks analyzing the state of soils and vegetation in cities and towns all the way from the Barents to the Azov Sea. The results of their study confirmed the effect of urbanization on the soil such as decrease of soil acidity, increase of carbon concentrations, and shrinkage of tree trunks by 40% - 60%. The results of the study were published in the Journal of Environmental Quality.

Soil scientists from three countries organized the first international summer school of urban soil studies in the world. Its participants had a chance to work in five different climatic zones in the European part of Russia, from tundra to dry steppes. The organizing team included the RUDN Department of Landscape Planning and Sustainable Ecosystems, International Union of Soil Sciences, and Urban Soils Institute (USA). During the two-week-long school students and postgraduates from Germany, Russia, China, and the USA traveled 3,000 km and studied the effect of urbanization on soils and vegetation. A methodical learning framework developed by the team of the school will be used for future practical courses.

"The idea of our summer school is to teach through practice. The learning framework provides active communication between students and professors and joint projects give the participants many valuable skills, such as data processing, team collaboration, analytical competencies, and the ability to effectively articulate their results. This comprehensive approach is based on the interchange of not only professional but also social and cultural practices, and it is extremely useful for young scientists. The feedback that we received from the participants proves it," says Anastasia Konstantinova, PhD in Social Sciences, and an employee of the Research Laboratory "Smart Technologies for Sustainable Urban Development under Global Change" at RUDN University.

The summer school was the first ever to cover such a vast territory; fieldwork was carried out in 12 cities and towns from the Barents to the Azov Sea. The lecturers included experts in plant science, geochemistry, soil science, ecology, climate studies, and geology. At every stop along the route, the students had a chance to talk to local specialists. The participants learned about different types of soils, from tundra ashen gray to steppe black. In each region, the students evaluated soil composition, the level of CO2 emissions, heavy metal concentrations, soil temperature, and moisture, as well as analyzed the characteristics of trees in urban parks and public gardens.

The data collected during the school confirmed many existing concepts regarding urban soils. In all climatic zones, the so-called heat island effect was observed in the cities (i.e. urban soil temperatures were higher compared to those of virgin land soils). Regardless of the region, urban soils contained pieces of brick, plastic, and other waste, had higher levels of organic carbon because of accumulated waste and contaminated waters, and showed reduced acidity levels due to the constant deposition of construction and industrial dust. The students also collected verifiable data confirming the negative impact of roads and other anthropogenic activities on tree trunk diameters: the trees turned out to be 40% to 60% thinner in crowded parks and on contaminated soils.

"One of the main goals of 3MUGIS was to show our students the diversity and complexity of natural and anthropogenic factors that affect the formation of urban soils in different environments. The school managed to combine teaching and research, fieldwork and expert consultations, guided projects and self-managed teamwork, thus allowing the students to learn many methods and techniques on a profound level," added Viacheslav Vasenev, PhD in Biological Sciences, a coordinator of the project, and a researcher at the Research Laboratory "Smart Technologies for Sustainable Urban Development under Global Change" at RUDN University.

Philadelphia, October 5, 2020 -Researchers from Children's Hospital of Philadelphia (CHOP) and the University of Pennsylvania's Annenberg Public Policy Center have demonstrated the feasibility of incorporating a virtual driving assessment system into the driver's licensing process in Ohio. In a report published today in Health Affairs, the researchers also assessed the validity of the tool in identifying likely on-road test failure while providing personalized feedback regarding skills that need improvement to keep drivers safe.

Adolescents face a variety of health risks, yet motor vehicle crashes remain the leading cause of adolescent mortality and injury in the United States, with the peak risk immediately after obtaining a driver's license. One out of every five deaths between the ages of 16 and 19 in the United States in 2018 was caused by a motor vehicle crash. Therefore, the time when adolescents are getting their driver's licenses is a critical point for a safety intervention aimed at reducing risk and ultimately preventing these crashes.

The new report describes the success of a program implemented by CHOP, the State of Ohio, and Diagnostic Driving, Inc., a CHOP spin-out company utilizing virtual technology to expose drivers to the most common serious potential crash scenarios under safe simulated conditions.

Based on 4,643 paired virtual driving assessments and on-road test results conducted by the Ohio Bureau of Motor Vehicles (OBMV), researchers found that the technology was not only valid, feasible and efficient, but also advanced safe driving, with applicants receiving personalized automated feedback to identify their safety-critical skill deficits.

"The success of these partnerships demonstrates the effectiveness of the innovative work being done to keep children safe," said Flaura K. Winston, MD, PhD, founder and scientific director of the Center for Injury Research and Prevention (CIRP) at CHOP, one of the founders of Diagnostic Driving, Inc., and co-author of the analysis. "We believe the work we have done in Ohio could serve as a foundational model for the future of driving safety, where personalized virtual assessments beyond the on-road examinations are a gold standard in preparing adolescents prior to obtaining their licenses."

The report also addresses how the COVID-19 pandemic has emphasized the need for virtual driving assessments going forward. States adopted a variety of strategies to amend the typical licensing process to accommodate social distancing and reduce backlogs. However, many of these strategies involved even less exposure to safety-critical situations during a modified driving exam, potentially licensing a large number of unsafe new drivers.

Additional studies have shown that many parents and guardians are underprepared to offer guidance to adolescent drivers for safe and independent driving. The challenges of 2020 have revealed a critical need to be able to assess new drivers safely without relying on traditional classroom and behind-the-wheel instruction.

"This partnership has shown that implementing a successful intervention for improving driver safety can be widely deployed and remain cost-effective," said Elizabeth Walshe, PhD, a research scientist at CIRP, a fellow at the Annenberg Public Policy Center (APPC) of the University of Pennsylvania, and co-author of the analysis. "Translational research is still needed to improve how we can truly help as many adolescents as possible prepare, but the strength of this program has established a road map for us to know where that research needs to go."

The authors recommend the following immediate, short-term, and longer-term opportunities for virtual driving assessment:

as a complete replacement for or in conjunction with the limited road testing due to contact restrictions during the current or future emergent situations (e.g., COVID-19 pandemic)

as a screening/pre-test model to identify underprepared drivers and to ensure consistency in evaluations (e.g., with 3rd party testing)

as a strategy for providing systematic feedback and coaching regarding safe driving skill deficits to the applicant, the applicant's family and their driving school.

Our thoughts, feelings, and movements are controlled by billions of neurons talking to each other at trillions of specialized communication points called synapses. In an in-depth study of neurons grown in laboratory petri dishes, National Institutes of Health researchers discovered how the chattiest of some synapses find the energy to support intense conversations thought to underlie learning and memory. Their results, published in Nature Metabolism, suggest that a series of chemical reactions control a feedback loop that senses the need for more energy and replenishes it by recruiting cellular powerplants, called mitochondria, to the synapses. The experiments were performed by researchers in a lab led by Zu-Hang Sheng, Ph.D., at the NIH's National Institute of Neurological Disorders and Stroke (NINDS).

The team studied synapses that use the neurotransmitter glutamate to communicate. Communication happens when a packet of glutamate is released from presynaptic boutons which are tiny protrusions that stick out, like beads on a string, of long, wiry parts of neurons called axons. Previously, Dr. Sheng's team showed that synaptic communication is an energy-demanding process and that mitochondria traveling along axons can control signals sent by boutons. Boutons that had mitochondria sent stronger and more consistent signals than those that were missing powerplants. The difference was due to higher energy levels produced by the mitochondria in the form of ATP.

In this study, led by Sunan Li, Ph.D., a post-doctoral fellow at NINDS, the team investigated what happens when boutons undergo intense communication thought to underlie learning and memory. They found that this type of signaling quickly dropped energy levels at boutons. These changes triggered a series of chemical reactions controlled by an energy sensor called AMP-activated protein kinases (AMPK) that ultimately led to the rapid recruitment of mitochondria to the boutons. Genetically blocking or chemically interfering with this feedback loop prevented the delivery of mitochondria to boutons and lowered energy levels. This, in turn, reduced synaptic responses during intense communication more than seen in control cells and slowed the recovery of the responses after the bursts ended. The researchers concluded that this feedback loop may normally play a critical role in providing the energy needed to sustain synaptic communication throughout a healthy nervous system. For example, they cite studies which implied that problems with this system may occur in some cases of Alzheimer's disease and other neurological disorders.

A team of scientists led by the Max Born Institute (MBI), Berlin, Germany, and the Massachusetts Institute of Technology (MIT), Cambridge, USA, has demonstrated how tiny magnetization patterns known as skyrmions can be written into a ferromagnetic material faster than previously thought possible. The researchers have clarified how the topology of the magnetic system changes in this process. As reported in the journal Nature Materials, the findings are relevant for topological phase transitions in general, and may inspire new routes how to use magnetic skyrmions in information technology.

Magnetic skyrmions are tiny swirls in the magnetization of thin magnetic films, where the direction of magnetization points in different directions as shown schematically in the first Figure. It turns out that the particular magnetization pattern can be characterized according to its so-called topology - a mathematical concept to describe the shape or geometry of a body, a set or - as in this case - a physical field (see infobox on topology). Importantly, the topology of skyrmions is different from the simple uniform state where the magnetization points in the same direction everywhere. To change between the two spin patterns, also the topology of the system must be changed. This contributes substantially to the stability of the skyrmions but also makes their fast creation very difficult.

In their work, which employs imaging of nanometer-sized skyrmions with x-rays and electrons, the researchers were first able to show that a single laser pulse of sufficient intensity allows to create skyrmions with a particular topology - that is, the magnetization pattern swirls in a particular fashion only.

Next, they set out to understand how such a change of topology is mediated by the laser pulse by investigating how this transition from a uniform pattern to skyrmions proceeds in time. Towards that end, they performed x-ray scattering experiments at the x-ray free-electron laser European XFEL in Hamburg, Germany, where the deflection of the x-ray beam by the skyrmions is detected. Hitting the ferromagnetic thin film in its uniform state first with an optical laser pulse followed by an x-ray laser pulse, they could map out how size and spacing of the skyrmions evolve over time. The first surprising result was that the topological change was finished after 300 picoseconds, which is significantly faster than observed for skyrmions in any other ferromagnetic system before. Comparing the experimental data with theoretical simulations, the team could infer how the topological transition comes about. The laser pulse promotes the system in a high-temperature state where the magnetization breaks up in small independently fluctuating regions, rapidly changing their magnetization direction. In this topological fluctuation state, the energy barrier for the nucleation of skyrmions is very much reduced, and they appear and disappear continuously. As the system cools down after laser excitation, some of the small skyrmion nuclei freeze out and subsequently grow to form the larger skyrmions, which have been observed in the initial imaging experiments.

Given that skyrmions can have a size in the range of ten nanometers and yet be very stable at room temperature, these findings may have interesting implications for future concepts of magnetic data processing and storage. Already today, the formation of "ordinary" bits on a magnetic hard drive is limited by the ability to switch very small yet stable bits with a magnetic field. Local heating by a laser is announced to be the next technology step in providing higher storage density, and the topological switching of skyrmions via laser pulses may add a new twist to that.

In a new research paper published in Police Quarterly, University of Colorado Denver School of Public Affairs Assistant Professor Paul Taylor found officers can significantly improve shoot/no-shoot decisions by simply lowering the position of their firearm. In the study, Taylor looked at 313 active law enforcement officers in a randomized controlled experiment that incorporated a police firearms training simulator.

There were three different positions tested during the experiment:

Aiming: The sights of the gun were held in alignment with the of?cer's visual gaze pointed at the projector screen and the index ?nger was to be off the trigger and resting along the slide of the training pistol
High Ready Position: The gun was held at the level of the of?cer's sternum and the index ?nger was to be off the trigger and resting along the slide of the training pistol
Low Ready Position: The gun was held at the level of the of?cer's navel and the index ?nger was to be off the trigger and resting along the slide of the training pistol
After the experiment was complete, it was proven that when officers had firearms at a low ready position, they cut their chance of making misdiagnosis shooting errors by more than half and it only cost them 11/100th of a second. Taylor believes this small amount of time gives the officer a chance to check their swing, enabling them to reassess what they see.

"To put this into context, there is approximately .25 seconds between each trigger pull if an average officer is pulling a trigger as fast as possible," said Taylor. "This means that for the cost of less than half a trigger pull in time, officers can dramatically improve their decision-making."

Training Officers to Shoot from Low Ready Position Could Be a Key to Fewer Shooting Errors
According to The Los Angeles Police Department, of the 211 shooting incidents reported by LAPD between 2013 and 2017, 14% of those were what they call "perception shootings." A perception shooting is when a police officer believes the person in question presented a deadly threat in the moment, when in fact, the threat was proven non-existent in the end. Taylor hopes his research will lead to a lower the number of incidents by pointing out errors in training. Police officers are typically not trained to shoot from the low ready position, and training officers to assume this position could be part of the solution.

Positioning the firearm at a lower angle would also enable the officer to remain safe in unsafe situations. Taylor expresses the importance of resilience engineering, which is to reduce the complexity of the workplace and improve the likelihood for success and safety rather than errors and accidents.

In a study from earlier this year, Taylor examined the effects of dispatched information on the police decision to use deadly force and found that the accuracy of pre-event dispatch information police of?cers received had a signi?cant impact on their subsequent shoot/no shoot decision-making. Taylor's research continues to look at improvements police departments need to make to continue successful policing.

OCTOBER 5, 2020, NEW YORK - A Ludwig Cancer Research study has uncovered a mechanism by which the tumor's harsh internal environment sabotages T lymphocytes, leading cellular agents of the anticancer immune response. Reported in Nature Immunology, the study describes how a variety of stressors prevalent in the tumor microenvironment disrupt the power generators, or mitochondria, of tumor-infiltrating T lymphocytes (TILs), pushing them into a permanently sluggish state known as terminal exhaustion.

The study, led by Ludwig Lausanne Associate Member Ping-Chih Ho, also found that a widely available nutritional supplement--nicotinamide riboside (NR)--helps TILs overcome the mitochondrial dysfunction and preserves their ability to attack tumors in mouse models of melanoma and colon cancer.

"TILs often have a high affinity for antigens expressed by cancer cells," says Ho. "This means that, in principle, they should attack cancer cells vigorously. But we often don't see that. People have always wondered why because it suggests that the best soldiers of the immune system are vulnerable when they enter the battlefield of the tumor. Our study provides a mechanistic understanding of why this happens and suggests a possible strategy for preventing the effect that can be quickly evaluated in clinical trials."

The inner recesses of tumors are often starved of oxygen and essential nutrients, such as the sugar glucose. Cells in these stressful conditions adjust their metabolic processes to compensate--for example, by making more mitochondria and burning their fat reserves for energy.

In tumors, prolonged stimulation by cancer antigens is known to push TILs into an exhausted state marked by the expression of PD-1--a signaling protein that suppresses T cell responses and is targeted by existing "checkpoint blockade" immunotherapies. If sustained, such exhaustion can become permanent, persisting even when the stimulus of cancer antigens is removed.

Ho and his colleagues found that exhausted TILs are packed with damaged--or "depolarized"--mitochondria. Like old batteries, depolarized mitochondria essentially lack the voltage the organelles require to generate energy.

"Our functional analysis revealed that those T cells with the most depolarized mitochondria behaved most like terminally exhausted T cells," said Ho.

Ho and colleagues show that the accumulation of depolarized mitochondria is caused primarily by the TIL's inability to remove and digest damaged ones through a process known as mitophagy. "The TILs can still make new mitochondria but, because they don't remove the old ones, they lack the space to accommodate the new ones," said Ho.

The genomes of these TILs are also reprogrammed by epigenetic modifications--chemical groups added to DNA and its protein packaging--to induce patterns of gene expression associated with terminal exhaustion.

The researchers found that the breakdown in mitophagy stems from a convergence of factors: chronic stimulation by cancer antigens, PD-1 signaling and the metabolic stress of nutrient and oxygen deprivation. They also show that the epigenetic reprograming that fixes TILs in a terminally exhausted state is a consequence, not a cause, of the mitochondrial dysfunction.

Related work done by other researchers--including co-authors in the current study, Ludwig Lausanne Investigator Nicola Vannini and Ludwig Lausanne Branch Director George Coukos--has shown that NR, a chemical analogue of vitamin B3, can boost mitophagy and improve mitochondrial fitness in a variety of other cell types.

With this in mind, the researchers explored whether NR might also prevent TILs from committing to terminal exhaustion. Their cell culture experiments showed that the supplement improved the mitochondrial fitness and function of T cells grown under stressors resembling those of the tumor microenvironment.

More notably, dietary supplementation with NR stimulated the anti-tumor activity of TILs in a mouse model of skin cancer and colon cancer. When combined with anti-PD-1 and another type of checkpoint blockade, anti-CTLA-4 immunotherapy, it significantly inhibited the growth of tumors in the mice.

"We have shown that we may be able to use a nutritional approach to improve checkpoint blockade immunotherapy for cancer," said Ho.

He and his colleagues are now exploring the signals from depolarized mitochondria that epigenetically reprogram TILs for terminal exhaustion--information that could be more generally applied to improve cancer immunotherapy.

Human papillomavirus (HPV) is the most common sexually transmitted disease and the primary cause of several cancers. Recent estimates indicate that 70-90 percent of HPV-related cancers may be prevented through vaccination. Despite widespread scientific agreement on benefits, misleading information about the HPV vaccine and concerns about safety are prevalent on social media.

A new study led by VCU Massey Cancer Center researcher Jeanine Guidry, Ph.D., a member of the Cancer Prevention and Control research program, compared how HPV vaccination was portrayed on Pinterest before and after the social media platform began moderating vaccine-related content. Findings may help public health officials utilize social media to tackle potentially harmful rhetoric and disseminate trustworthy health information.

"Vaccine misinformation is immensely prevalent online and particularly on social media," said Guidry, who is also an assistant professor in the Richard T. Robertson School of Media and Culture in the College of Humanities and Sciences and director of the Media+Health Lab at VCU. "Although the specific influence of social media on medical decision-making remains understudied, research supports an association between online health information searches and medical decisions."

Guidry and her collaborators selected Pinterest for their analysis because the platform has a predominantly female audience and research shows that women tend to make the most health care decisions in families. Additionally, Pinterest joined the fight against vaccine misinformation in 2019 by instituting a policy that only allows public health organizations to generate vaccine-related content.

Guidry's study, published in the American Journal of Public Health, examined the information environment prior to Pinterest's policy decisions and analyzed whether the implementations improved sources and content.

For the study, a quantitative analysis of two samples of 500 HPV vaccine-related Pinterest posts was conducted. The first sample was collected prior to Pinterest's actions to moderate vaccine-related search results; the second was collected following the policy changes. Both were collected via a form of manual systematic random sampling.

Researchers also applied the Health Belief Model to their analyses. In the context of HPV vaccination, the theory posits a person's belief in a personal threat of HPV together with a belief in the effectiveness of the vaccine will predict the likelihood the person will actually receive the vaccine.

The investigation showed that the majority of search results prior to policy changes leaned toward vaccine skepticism, specifically focused on perceived vaccine barriers. These posts were associated with higher levels of engagement and mainly published by unverified individuals. Very little content was generated from official public health or medical accounts.

Post-policy search results showed a significant shift to HPV vaccination benefits and increase in the presence of government or medical accounts. However, the proportion of HPV content of any type in search results was significantly lower.

"It was not surprising that earlier posts were largely anti-vaccine," said Guidry. "What surprised us was that many of the posts were not related to the HPV vaccine or HPV at all, but rather MMR or flu vaccine. The quality of the visuals was also problematic in many cases."

While Pinterest's efforts to moderate vaccination discussions were largely successful, limiting HPV vaccination search results overall may contribute to confusion or an information vacuum. Guidry acknowledges that more strategic efforts to promote vaccine awareness and uptake on Pinterest are needed.

"Pinterest's curation actions are to be commended but the process needs to be improved, and this study can help inform efforts to that end - for the HPV vaccine, but also for other vaccines, including the future COVID-19 vaccine," said Guidry.

This is the first study to examine how the HPV vaccine is portrayed on Pinterest and the first to compare vaccine search results before and after platform policy changes. The research builds on Guidry's analysis of vaccine-focused Pinterest posts that she conducted during her doctoral program at VCU. The findings, published in Vaccine in 2015, were a driving force behind Pinterest's policy change to block vaccine misinformation and provide curated public health information.

"We are in the middle of planning for studies related to the future COVID-19 vaccine," said Guidry. "We also just started a follow-up study analyzing content related to multiple other vaccines on Pinterest after the curation actions."

Guidry's research findings provide formative insights and a foundation for other researchers to build upon, as well as important implications for the development of future social media promotions aimed at reducing cancer risk and promoting survivorship.

COLUMBUS, Ohio - Preliminary results from two independent, phase II clinical trials investigating a new PD-1 (programmed cell death protein 1)-based immune therapy for metastatic cervical cancer suggest potential new treatment options for a disease that currently has limited effective options and disproportionately impacts younger women.

David O'Malley, MD, of The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), presented the preliminary study results at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 on Sept. 18. O'Malley was the lead presenter for both trials, which were sponsored by Agenus Inc.

Each study involved more than 150 patients with recurrent or metastatic cervical cancer from cancer treatment centers across the United States and Europe. All patients were previously treated with platinum-based chemotherapy as a first-line therapy. The two independent but consecutive phase II trials tested a new immune-based agent called balstilimab given alone or in combination with a second monoclonal antibody drug called zalifrelimab.

Balstilimab is part of a class of drugs called checkpoint inhibitors. These drugs target the PD-1 protein within cancer cells and act as an "on" switch to help the immune system recognize and destroy cancer cells that would otherwise go undetected. Zalifrelimab is a drug that delivers engineered molecules (monoclonal antibodies) that allow for improved immune response to attack cancer cells.

For the first study, 160 patients were treated with single-agent balstilimab, resulting in a 14% response rate in all treated patients and a 19% response rate in PD-L1 positive patients.

For the second study, 155 patients were treated with balstilimab given in combination with zalifrelimab, resulting in a 22% response rate in all patients and a 27% response rate in PD-L1 positive patients.

"These two studies represent the largest trials of immuno-oncology therapies in relapsed cervical cancer to date and show that balstilimab and zalifrelimab may present meaningful new therapies for patients with cervical cancer," O'Malley says. "Advances in these agents offer renewed hope for patients who have limited treatment options. This is especially important because this disease disproportionately affects younger women."

Long known as the hardest of all natural materials, diamonds are also exceptional thermal conductors and electrical insulators. Now, researchers have discovered a way to tweak tiny needles of diamond in a controlled way to transform their electronic properties, dialing them from insulating, through semiconducting, all the way to highly conductive, or metallic. This can be induced dynamically and reversed at will, with no degradation of the diamond material.

The research, though still at an early proof-of-concept stage, may open up a wide array of potential applications, including new kinds of broadband solar cells, highly efficient LEDs and power electronics, and new optical devices or quantum sensors, the researchers say.

Their findings, which are based on simulations, calculations, and previous experimental results, are reported this week in the Proceedings of the National Academy of Sciences. The paper is by MIT Professor Ju Li and graduate student Zhe Shi; Principal Research Scientist Ming Dao; Professor Subra Suresh, who is president of Nanyang Technological University in Singapore as well as former dean of engineering and Vannevar Bush Professor Emeritus at MIT; and Evgenii Tsymbalov and Alexander Shapeev at the Skolkovo Institute of Science and Technology in Moscow.

The team used a combination of quantum mechanical calculations, analyses of mechanical deformation, and machine learning to demonstrate that the phenomenon, long theorized as a possibility, really can occur in nanosized diamond.

The concept of straining a semiconductor material such as silicon to improve its performance found applications in the microelectronics industry more than two decades ago. However, that approach entailed small strains on the order of about 1 percent. Li and his collaborators have spent years developing the concept of elastic strain engineering. This is based on the ability to cause significant changes in the electrical, optical, thermal, and other properties of materials simply by deforming them -- putting them under moderate to large mechanical strain, enough to alter the geometric arrangement of atoms in the material's crystal lattice, but without disrupting that lattice.

In a major advance in 2018, a team led by Suresh, Dao, and Lu Yang from the Polytechnic University of Hong Kong showed that tiny needles of diamond, just a few hundred nanometers across, could be bent without fracture at room temperature to large strains. They were able to repeatedly bend these nanoneedles to tensile strain as much as 10 percent; the needles can then return intact to their original shape.

Key to this work is a property known as bandgap, which essentially determines how readily electrons can move through a material. This property is thus key to the material's electrical conductivity. Diamond normally has a very wide bandgap of 5.6 electron volts, meaning that it is a strong electrical insulator that electrons do not move through readily. In their latest simulations, the researchers show that diamond's bandgap can be gradually, continuously, and reversibly changed, providing a wide range of electrical properties, from insulator through semiconductor to metal.

"We found that it's possible to reduce the bandgap from 5.6 electron volts all the way to zero," Li says. "The point of this is that if you can change continuously from 5.6 to 0 electron volts, then you cover all the range of bandgaps. Through strain engineering, you can make diamond have the bandgap of silicon, which is most widely used as a semiconductor, or gallium nitride, which is used for LEDs. You can even have it become an infrared detector or detect a whole range of light all the way from the infrared to the ultraviolet part of the spectrum."

"The ability to engineer and design electrical conductivity in diamond without changing its chemical composition and stability offers unprecedented flexibility to custom-design its functions," says Suresh. "The methods demonstrated in this work could be applied to a broad range of other semiconductor materials of technological interest in mechanical, microelectronics, biomedical, energy and photonics applications, through strain engineering."

So, for example, a single tiny piece of diamond, bent so that it has a gradient of strain across it, could become a solar cell capable of capturing all frequencies of light on a single device -- something that currently can only be achieved through tandem devices that couple different kinds of solar cell materials together in layers to combine their different absorption bands. These might someday be used as broad-spectrum photodetectors for industrial or scientific applications.

One constraint, which required not only the right amount of strain but also the right orientation of the diamond's crystalline lattice, was to prevent the strain from causing the atomic configuration to cross a tipping point and turning into graphite, the soft material used in pencils.

The process can also make diamond into two types of semiconductors, either "direct" or "indirect" bandgap semiconductors, depending on the intended application. For solar cells, for example, direct bandgaps provide a much more efficient collection of energy from light, allowing them to be much thinner than materials such as silicon, whose indirect bandgap requires a much longer pathway to collect a photon's energy.

The process could be relevant for a wide variety of potential applications, Li suggests, such as for highly sensitive quantum-based detectors that use defects and dopant atoms in a diamond. "Using strain, we can control the emission and absorption levels of these point defects," he says, allowing novel ways of controlling their electronic and nuclear quantum states.

But given the great variety of conditions made possible by the different dimensions of strain variations, Li says, "if we have a particular application in mind, then we could optimize toward that application target. And what is nice about the elastic straining approach is that it is dynamic," so that it can be continuously varied in real time as needed.

This early-stage proof-of-concept work is not yet at the point where they can begin to design practical devices, the researchers say, but with the ongoing research they expect that practical applications could be possible, partly because of promising work being done around the world on the growth of homogeneous diamond materials.