Culture

Faster, smaller, smarter and more energy-efficient chips for everything from consumer electronics to big data to brain-inspired computing could soon be on the way after engineers at The University of Texas at Austin created the smallest memory device yet. And in the process, they figured out the physics dynamic that unlocks dense memory storage capabilities for these tiny devices.

The research published recently in Nature Nanotechnology builds on a discovery from two years ago, when the researchers created what was then the thinnest memory storage device. In this new work, the researchers reduced the size even further, shrinking the cross section area down to just a single square nanometer.

Getting a handle on the physics that pack dense memory storage capability into these devices enabled the ability to make them much smaller. Defects, or holes in the material, provide the key to unlocking the high-density memory storage capability.

"When a single additional metal atom goes into that nanoscale hole and fills it, it confers some of its conductivity into the material, and this leads to a change or memory effect," said Deji Akinwande, professor in the Department of Electrical and Computer Engineering.

Though they used molybdenum disulfide - also known as MoS2 - as the primary nanomaterial in their study, the researchers think the discovery could apply to hundreds of related atomically thin materials.

The race to make smaller chips and components is all about power and convenience. With smaller processors, you can make more compact computers and phones. But shrinking down chips also decreases their energy demands and increases capacity, which means faster, smarter devices that take less power to operate.

"The results obtained in this work pave the way for developing future generation applications that are of interest to the Department of Defense, such as ultra-dense storage, neuromorphic computing systems, radio-frequency communication systems and more," said Pani Varanasi, program manager for the U.S. Army Research Office, which funded the research.

The original device - dubbed "atomristor" by the research team - was at the time the thinnest memory storage device ever recorded, with a single atomic layer of thickness. But shrinking a memory device is not just about making it thinner but also building it with a smaller cross-sectional area.

"The scientific holy grail for scaling is going down to a level where a single atom controls the memory function, and this is what we accomplished in the new study," Akinwande said.

Akinwande's device falls under the category of memristors, a popular area of memory research, centered around electrical components with the ability to modify resistance between its two terminals without a need for a third terminal in the middle known as the gate. That means they can be smaller than today's memory devices and boast more storage capacity.

This version of the memristor - developed using the advanced facilities at the Oak Ridge National Laboratory - promises capacity of about 25 terabits per square centimeter. That is 100 times higher memory density per layer compared with commercially available flash memory devices.

A gene known for helping facilitate communication between neurons in the nervous system has been discovered to be connected with Alzheimer's dementia and cognitive decline, according to a national research team led by The Jackson Laboratory and University of Maine.

Catherine Kaczorowski, associate professor and Evnin family chair in Alzheimer's research at The Jackson Laboratory (JAX), and adjunct professor with the UMaine Graduate School of Biomedical Science and Engineering (GSBSE), spearheaded a study to pinpoint the genetic mechanisms that affect resistance or vulnerability to weakening cognition and dementias, such as Alzheimer's.

Andrew Ouellette, a Ph.D student at JAX and a GSBSE NIH T32 predoctoral awardee, led the project, along with his mentor Kaczorowski and scientists from across the U.S.

By studying the memory and brain tissue from a large group of genetically diverse mice, the team found that the expression of the gene Dlgap2 is associated with the degree of memory loss in mice and risk for Alzheimer's dementia in humans. Further research will ascertain how the gene influences dementia and mental function.

Dlgap2, located in the synapses of neurons, serves to anchor critical receptors for signals between neurons required for learning and memory. When studying post-mortem human brain tissue, the team discovered low levels of Dlgap2 in people experiencing "poorer cognitive health" and "faster cognitive decline" prior to death, according to researchers.

The team's findings were published in the journal Cell Reports.

"The reason why this is so important is because a lot of research around cognitive aging and Alzheimer's has been hyper-focused on well-known risk genes like APOE and brain pathologies," Kaczorowski says. "We wanted to give ourselves the option of looking at new things people keep ignoring because they've never heard about a gene before."

Researchers found that Dlgap2 influences the formation of dendritic spines on neurons, which can affect cognitive function. Longer, thinner spines shaped like mushrooms demonstrate higher mental performance than stubbier spines in mice, Ouellette says, and decreased cognition correlates with a loss in dendritic spines.

The study serves as a springboard for additional research into Dlgap2. Ouellette will explore how it influences cognition and how it can be used in therapeutic treatment for memory loss, in part by manipulating the gene with the editing tool CRISPR. Other members of the Kaczorowski lab are studying how to regulate Dlgap2 with pharmaceuticals to help prevent cognitive decline with age.

Scientists relied on Diversity Outbred mice, a population from eight parents created by The Jackson Laboratory to better reflect genetic diversity in humans. The Dlgap2 study involved 437 mice, each one either six, 12 or 18 months old.

"It's great because you can harness the best parts of a mouse study and human society," Ouellette says. "Historically, research has been done with inbred mice with similar genetic makeups; same, similar genetic models. But clinically, humans don't work like that because they're not genetically identical."

The team performed quantitative trait loci mapping on the mouse population, examining entire genome sequences to identify genes responsible for varying cognitive function and where they occurred in the sequences. After pinpointing the connection between Dlgap2 and memory decline in mice, researchers evaluated its significance in human mental functionality using genomewide association studies for Alzheimer's dementia and studying samples of post-mortem brain tissue using imaging, microscopy and other methods.

Kaczorowski says the project relied on information and expertise from all 25 co-authors. For example, Gary Churchill, professor and Karl Gunnar Johansson chair at JAX, Elissa Chesler, professor at JAX, and postdoctoral fellow Niran Hadad provided their expertise in utilizing diversity outbred models and cross-species genomic data integration to the project. Their efforts, she says, emphasizes the importance of teamwork in advancing medical research.

"We're going to be able to contribute a lot more to human health with team science," she says.

The GSBSE and The Jackson Laboratory partner to provide cooperative Ph.D. programs that include on-site training at the laboratory in Bar Harbor. The school also partners with other academic and research institutions to provide similar learning experiences. UMaine grants the degrees for these programs.

Kaczorowski says the GSBSE's biomedical science Ph.D. program gives students hands-on learning opportunities that, like with Ouellette, can help them realize their passion and talents. Researching Dlgap2 with Kaczorowski influenced Ouellette's Ph.D. dissertation further exploring how the Dlgap2 influences cognition in animals.

"I really like this study because it's very interdisciplinary," Ouellette says, adding that it harmonizes biological and computational science. "This study set me on a path that makes me want to be a more interdisciplinary scientist."

ITHACA, N.Y. - A multi-institution team co-led by a Cornell University researcher has identified the genetic mechanisms that enable the production of a deadly toxin called Victorin - the causal agent for Victoria blight of oats, a disease that wiped out oat crops in the U.S. in the 1940s.

Victoria blight is caused by the fungus Cochliobolus victoriae, which produces the Victorin toxin, but until now no one has uncovered the genes and mechanisms involved.

"The oat varieties favored by farmers in the 1940s were resistant to Crown Rust disease, but scientists later discovered this was the very trait that made those oat varieties susceptible to Victoria blight because the Victorin toxin was targeting that specific plant protein," said co-senior author Gillian Turgeon, professor and chair of the Plant Pathology and Plant-Microbe Biology Section of the School of Integrative Plant Science, in Cornell's College of Agriculture and Life Sciences (CALS). "Unearthing the molecules involved in this fungus-plant interaction is fundamental to our understanding of how plants respond to attack by diverse microbes."

Most fungal toxins are synthesized by large, multi-functional enzymes, and the small peptides created by these enzymes include both toxins and medicines, such as the antibiotic penicillin. But Turgeon and co-author Heng Chooi, a researcher at the University of Western Australia, discovered the Victorin toxin is actually synthesized directly in the ribosome, which is an organelle in cells that makes most proteins. These small molecules produced in ribosomes are known as ribosomally synthesized and post-translationally modified peptides, or RiPPs.

This alternate mechanism for producing small peptides like Victorin - coupled with the fact that fungal genomes likely contain many RiPP-associated genes - could lead to the discovery of additional small molecules, including both new toxins and beneficial compounds.

Further, first author Simon Kessler, a doctoral student at the University of Western Australia, confirmed the enzymatic function of several Victorin genes, including a novel enzyme that converts the Victorin peptide to its active form. Surprisingly, the research team found that the Victorin genes encoding these enzymes are scattered across repetitive regions in the pathogen genome - a stark contrast to genes for most known small molecules which are typically found in compact clusters on the fungal chromosomes.

The finding could help researchers better understand the evolutionary origins of molecules like the Victorin peptides, what determines the virulence of emerging crop diseases and how to better prevent them in the future.

Turgeon notes that Victorin peptides have also been shown to interact with targets in plant cells called thioredoxins, which are also found in humans, and have potential as a site for cancer therapies.

"The discovery that these genes are not found in closely related fungi gives us insight into how virulence factors are acquired and transmitted," Turgeon said. "Our findings from this study vastly expand the potential for small molecule discovery in fungal organisms, which will increase our repertoire of knowledge about both their beneficial and harmful activities."

Humans have a longstanding relationship with the sea that spans nearly 200,000 years. Researchers have long hypothesized that places like coastlines helped people mediate global shifts between glacial and interglacial conditions and the impact that these changes had on local environments and resources needed for their survival. Coastlines were so important to early humans that they may have even provided key routes for the dispersal of people out of Africa and across the world.

Two new multidisciplinary studies published in the journals Quaternary Science Reviews and Quaternary Research document persistent human occupation along the South African eastern seaboard from 35,000 years ago to 10,000 years ago. In this remote, and largely unstudied, location -- known as the "Wild Coast" -- researchers have used a suite of cutting-edge techniques to reconstruct what life was like during this inclement time and how people survived it.

The research is being conducted by an international and interdisciplinary collaboration of scientists studying coastal adaptations, diets and mobility of hunter-gatherers across glacial and interglacial phases of the Quaternary in coastal South Africa. The research team is led by Erich Fisher, Institute of Human Origins at Arizona State University; Hayley Cawthra with the South Africa Council for Geoscience and Nelson Mandela University; Irene Esteban, University of the Witwatersrand; and Justin Pargeter, New York University.

Together, these scientists have been leading excavations at the Mpondoland coastal rock shelter site known as Waterfall Bluff for the last five years. These excavations have uncovered evidence of human occupations from the end of the last ice age, approximately 35,000 years ago, through the complex transition to the modern time, known as the Holocene. Importantly, these researchers also found human occupations from the Last Glacial Maximum, which lasted from 26,000 to 19,000 years ago.

The Last Glacial Maximum was the period of maximum global ice volume, and it affected people and places around the world. It led to the formation of the Sahara desert and caused major reductions in Amazonian rainforest. In Siberia, the expansion of polar ice caps led to drops in global sea levels, creating a land bridge that allowed people to cross in to North America.

In southern Africa, archaeological records from this globally cold and dry time are rare because there were widespread movements of people as they abandoned increasingly inhospitable regions. Yet records of coastal occupation and foraging in southern Africa are even rarer. The drops in sea level during the Last Glacial Maximum and earlier glacial periods exposed an area on the continental shelf across southern Africa nearly as large as the island of Ireland. Hunter-gatherers wanting to remain near coastlines during these times had to trek out onto the exposed continental shelf. Yet these records are gone now, either destroyed by rising sea levels during warmer interglacial periods or submerged under the sea.

The research team -- the Mpondoland Paleoclimate, Paleoenvironment, Paleoecology, and Paleoanthropology Project (P5 Project) -- has hypothesized that places with narrow continental shelfs may preserve these missing records of glacial coastal occupation and foraging.

"The narrow shelf in Mpondoland was carved when the supercontinent Gondwana broke up and the Indian Ocean opened. When this happened, places with narrow continental shelfs restricted how far and how much the coastline would have changed over time," said Hayley Cawthra.

In Mpondoland, a short section of the continental shelf is only 10 kilometers wide.

"That distance is less than how far we know past people often traveled in a day to get sea foods, meaning that no matter how much the sea levels dropped anytime in the past, the coastline was always accessible from the archaeological sites we have found on the modern Mpondoland coastline. It means that past people always had access to the sea, and we can see what they were doing because the evidence is still preserved today," said Erich Fisher.

The oldest record of coastal foraging, which has also been found in southern Africa, shows that people relied on coastlines for food, water and move favorable living conditions over tens of thousands of years.

In the study published in the journal Quaternary Research, led by Erich Fisher, a multidisciplinary team of researchers documents the first direct evidence of coastal foraging in Africa during a glacial maximum and across a glacial/interglacial transition.

According to Fisher, "The work we are doing in Mpondoland is the latest in a long line of international and multidisciplinary research in South Africa revealing fantastic insights into human adaptations that often occurred at or near coastlines. Yet until now, no one had any idea what people were doing at the coast during glacial periods in southern Africa. Our records finally start to fill in these longstanding gaps and reveal a rich, but not exclusive, focus on the sea. Interestingly, we think it may have been the centralized location between land and sea and their plant and animal resources that attracted people and supported them amid repeated climatic and environmental variability."

To date this evidence, P5 researchers collaborated with South Africa's iThemba LABS and researchers at the Centre for Archaeological Science of the University of Wollongong to develop one of the highest-resolution chronologies at a southern Africa Late Pleistocene site, showing persistent human occupation and coastal resource use at Waterfall Bluff from 35,000 years ago to 10,000 years ago. This evidence, in the form of marine fish and shellfish remains, shows that prehistoric people repeatedly sought out dense and predictable seafoods.

This finding complements the results of a companion study published in the journal Quaternary Science Reviews, where paleobotanists and paleoclimatologists, led by Irene Esteban, used different lines of evidence to investigate interactions between prehistoric people's plant-gathering strategies and climate and environmental changes over the last glacial/interglacial phase. This is the first multiproxy study in South Africa that combines preserved plant pollen, plant phytoliths, macro botanical remains (charcoal and plant fragments) and plant wax carbon and hydrogen isotopes from the same archaeological archive.

According to Irene Esteban, "It is not common to find such good preservation of different botanical remains, both of organic and inorganic origin, in the archaeological record."

Each one of these records preserves a slightly different window to the past. It let the researchers compare different records to study how each one formed and what they represented, both individually and together.

"Ultimately," said Esteban, "it allowed us to study interactions between hunter-gatherer plant-gathering strategies and environmental changes across a glacial-interglacial transition."

Today, Mpondoland is characterized by afrotemperate and coastal forests as well as open woodlands that are interspersed with grasslands and wetlands. Each of these vegetation types supports different plant and animal resources. One of the key findings of this study is that these vegetation types persisted across glacial and interglacial periods albeit in varying amounts due to changes in sea levels, rainfall and temperature. The implication is that people living in Mpondoland in the past had access to an ever present and diverse suite of resources that let them survive here when they couldn't in many other places across Africa.

Importantly, this study showed that people who lived at Waterfall Bluff collected wood from coastal vegetation communities during both glacial and interglacial phases. It is another link to the coastline for the people living at Waterfall Bluff during the Last Glacial Maximum. In fact, the exceptional quality of the archaeological and paleoenvironmental records demonstrates that those hunter-gatherers targeted different, but specific, coastal ecological niches all the while collecting terrestrial plant and animal resources from throughout the broader landscape and maintaining links to highland locales inland.

"The rich and diverse resource bases targeted by Mpondoland's prehistoric hunter-gatherers speaks to our species' unique generalist-specialist adaptations," said Justin Pargeter. "These adaptions were key to our species ability to survive wide climate and environmental fluctuations while maintaining long-distance cultural and genetic connections."

Together, these papers enrich our understanding about the adaptive strategies of people facing widespread climatic and environmental changes. They also provide a complementary perspective on hunter-gatherer behavioral responses to environmental shifts that is often biased by ethnographic research on African hunter-gatherers living in more marginal environments. In the case of Mpondoland, it is now evident that at least some people sought out the coast -- probably because it provided centralized access to fresh water as well as both terrestrial and marine plant and animal resources, which supported their daily survival.

According to Esteban and Fisher, "These studies are just a drop in the ocean compared to the richness of the archaeological record we already know is preserved in Mpondoland. We have high expectations about what else we will discover there with our colleagues in South Africa and abroad when we can get back to the field safely in this post-COVID world."

VIRTUAL MEETING (CST), November 22, 2020 -- Swelling is one of the most dangerous and immediate consequences of a brain injury or stroke. Doctors have long known about the dangers of swelling, which has traditionally been blamed on ruptured blood vessels. New research suggests the brain's other plumbing system, the one that circulates cerebrospinal fluid (CSF), may play an underappreciated role in both good health and response to injury.

Douglas Kelley, a mechanical engineer at the University of Rochester who uses fluid dynamics to probe the inner workings of the brain, teamed up with Rochester neuroscientist Maiken Nedergaard to demonstrate the early swelling immediately after an injury or stroke results not from blood, but from an inrush of CSF. The blood flows in later through tears in the blood-brain barrier.

"There is this whole other fluid transport system beyond blood," said Kelley, who presented the work at the 73rd Annual Meeting of the American Physical Society's Division of Fluid Dynamics. "It matters for disease, and for pathology, and it matters for drug delivery."

Researchers had assumed that CSF only flowed around brain tissue. Then, in 2012, Nedergaard's group published evidence pointing to the existence of CSF pathways through the brain. Their findings suggested that during sleep, CSF flows along these glymphatic pathways and rinses away cellular debris, like the amyloid-beta and tau proteins that accumulate and have been linked to Alzheimer's disease. Since then, research into the fluid dynamics of CSF has emerged as its own subfield that can provide new insights to biologists and neuroscientists.

"Having numbers on things helps you make better predictions," said Kelley. "They let us make predictions about the speed of flow, and when flow is more important, and when diffusion is more important. We can make better predictions now than anybody could three or four years ago."

Saikat Mukherjee, a postdoctoral researcher at the University of Minnesota, Twin Cities, noted that researchers still disagree about whether or not CSF enters brain tissue. If it doesn't, then the brain primarily relies on diffusion to clear toxic proteins. If CSF does seep into the brain tissue, even a little, then advection--the clearing of material by fluid flow--could help significantly with the cleanup.

The difference may be huge. "Toxic proteins get released from the brains and don't just sit there," said Mukherjee. "They aggregate into higher and higher molecular weight proteins." Mukherjee's work suggests that diffusion is not as efficient in clearing larger aggregates, while advection may clear proteins of any size. If advection does turn out to play a role, he said, then perhaps that knowledge could be harnessed to develop new neurodegenerative disease treatments that better clear protein aggregates.

Mukherjee and his colleagues are currently studying clinical data on plaque buildup in the brain to see how well it matches their simulations. They're also reviewing findings from studies investigating the clearance of toxic proteins during the sleep-wake cycle.

Ultimately, said Mukherjee, using fluid dynamics to study brain fluids points opens up two clear pathways of research. First, it can help neuroscientists better understand how the body gets rid of cellular debris--and what happens, from a physics point of view, when that system breaks down. Second, it could lead to insights on more fundamental questions about fluid dynamics and reaction-diffusion transport mechanisms in the brain.

"It lets us look at new physics that no one else has looked at yet," said Mukherjee.

In a recent article in The Quarterly Review of Biology, "Beyond Equilibria: The Neglected Role of History in Ecology and Evolution," author Hamish G. Spencer argues for a revitalized view of history. This historical view is a response to current research in the field of ecology and evolution, which is dominated by an ahistorical view of dynamic systems. In this ahistorical view, mathematical models are extensively used to describe and analyze systems at an equilibrium. Such equilibrium-focused analyses are currently privileged, because they allow researchers to generalize their models of a system: that is, these equilibrium-focused analyses enable researchers "to distill the essence of a system into principles that apply elsewhere." While the article acknowledges the value of equilibrium-focused analyses, such analyses tend to unfairly evaluate biological history as dependent on non-generalizable particularities. As a result, current research in ecology and valuate tends to avoid historical forms of analysis.

In response to this common assumption about history, the article argues that there are at least nine "flavors" or understandings of history. These understandings of history, in turn, allow researchers to generalize their findings and the observe scientific laws at work. These nine understandings of history are as follows: (1) history as contingency, (2) history as chance, (3) history as chaos, (4) history as capriciousness, (5) history as approach, (6) history as constraint, (7) history as construction, (8) history as turnover, and (9) history as template.

The first five understandings of history are closely related, because they analyze random co-occurrence and unpredictability. First, in an understanding of history as contingency, researchers can approach a system as an "occurrence of events conditional on a vast array of properties." Second, by incorporating history as contingency, researchers are better equipped in analyzing empirical observation over time, such as how fish of different sizes distribute themselves in an environment with a limited amount of nutrients. This analysis of history of contingency is closely tied to a second understanding of history as chance, or stochasticity, because biological systems are subject to random chance. Subsequently, in understanding history of chaos, researchers can analyze a system as incorporating unexpected deterministic behavior, which can be analyzed by mathematical models. Finally, in an understanding of history as capriciousness, ecologists can analyze a system beyond adherence to principles of statistically reliability. For instance, a larger sample size might not result in a mean that is closer to the true mean of a given distribution - a phenomenon that falls under the category of capriciousness.

The next four conceptualizations of history offer a further critique of equilibrium-focused analyses in ecology and evolution. First, in an understanding of history as an approach, researchers can analyze a system as approaching a state of equilibrium, but not at the state of equilibrium itself. Second, in an understanding of history as constraint, researchers can analyze the dynamics of a system as being constrained by "what has already taken place to build the system," such as the reduction of genome size among a particular species living in a specialized environment. Third, in an understanding of history as construction, researchers can begin by understanding that "equilibrial properties are an incomplete--and sometimes misleading--summary of the way the system behaves." Fourth, in understanding history as turnover, researchers can understand a system as perpetually being influenced by new actors, thereby questioning whether a "biological system is (or can ever be) at equilibrium."

Finally, in understanding history as a template, researchers can understand the historical contingencies of a system for both scientific analysis and modeling: for instance, phylogenetic models can be understood as "providing evolution with a template on which to work."

In conclusion, the article suggests that these "flavors" of history can be simultaneously at work in a given biological system. Rather than treating history in ecology and evolution as a set of non-generalizable particulars, researchers can further their analysis of biological systems by "teasing out the many roles various different flavors of history play in nature."

Bulbs of the plant known as Lu Bei (Fritallaria delavayi) have been used in Chinese medicine for more than two thousand years. Now, researchers reporting November 20 in the journal Current Biology have found that, in places where the herb is harvested more, the plant has evolved to blend in better with the background, making them harder for people to find. As a result, the plant varies in color from brown or grey to green, depending on whether it lives in a place that is frequented by human collectors or not.

"We've found that human harvesting of a traditional medicine plant has led to the evolution of camouflage by the plants, to evade detection by collectors," said Martin Stevens of University of Exeter. "And that camouflage is better in locations where collection intensity has been higher."

First author of the new study Yang Niu, Kunming Institute of Botany, Chinese Academy of Sciences, had been studying the evolution of alpine plants for years. He and his colleagues had noticed that the color of F. delavayi showed obvious variation among populations. They also knew it had a long history of use in traditional medicine. Could human harvesting be responsible for those differences in color they were seeing?

It appears that the answer is yes. The researchers found that the degree to which the plants' color matches its mountainous background is associated with estimates of how heavily they are harvested in particular places. Where they are heavily collected, the plants are camouflaged and therefore more cryptic.

To confirm that the plant colors influenced the ability of people to find them, the researchers developed an online citizen science experiment "Spot the Fritillaria." People were asked to spot the plants as quickly as they could. Not surprisingly, those plants that more closely matched the background took longer for people to find.

While it's possible that other animals could exert similar pressures, the researchers say they don't think that's likely. There's no evidence that the plants are a popular food item for other animals living in the area. The plants also produce chemicals that are known to deter rodents. Ironically, it is those same compounds that make them attractive to people as a medicinal herb.

For the plant, the camouflage may have downsides, which the researchers hope to explore in future studies. "In heavily collected populations, camouflage in flowers may weaken their attractiveness to pollinators such as bumblebees," Niu said. "We aim to find out how the plants deal with this problem."

Stevens says his team is "further exploring how animals and plants are being affected by human actions, including how their defensive behaviors and coloration are being influenced by selection pressure and stresses imposed by humans, from noise pollution to climate change."

OAK BROOK, Ill. - In response to the critical shortage of nasopharyngeal (NP) swabs early in the COVID-19 pandemic, the Department of Radiology at University of South Florida (USF) Health in Tampa set out to design, validate and create NP swabs using a point-of-care 3D printer. Results of the first clinical trial of 3D-printed NP swabs for COVID-19 testing are being presented at the annual meeting of the Radiological Society of North America (RSNA).

"To date, USF Health has printed more than 100,000 3D NP swabs, and hospitals around the world have used our 3D files to print tens of millions more swabs for point-of-care use," said Summer Decker, Ph.D., associate professor, vice chair for research, and director of the 3D Clinical Applications for the Department of Radiology in the USF Health Morsani College of Medicine and Tampa General Hospital.

The 3D swab has received national and international recognition as an example of the power of medical 3D printing and quick innovation to provide clinical solutions.

The flocked NP swab, which collects a test sample of nasal secretions from the back of the nose and throat for lab analysis, is the current standard of care for diagnosing COVID-19. It consists of a narrow plastic rod and a tip covered in a flocked polyester material.

"COVID-19 appears first in the nasopharyngeal regions and from there it's inhaled into the respiratory system," Dr. Decker explained.

As the pandemic and demand for COVID-19 testing surged in early March, Dr. Decker and her team immediately began studying how they could develop an alternative to the flocked swab.

"We collaborated with our colleagues in infectious disease, virology, emergency medicine and radiology as well as Todd Goldstein, Ph.D., at Northwell Health System's 3D Design and Innovation Lab in New York City. The city was the U.S. epicenter of virus infection at the time," she said. "In a matter of days, we came up with 12 designs and printed three to test on ourselves."

The final prototype, developed using FormLabs printers and surgical grade resin, was sent to infectious disease specialists at both USF and Northwell for validation testing.

"We needed to determine that the 3D NP swab could gather enough viral cells and hold them for up to three days, and that the resin would not interfere with test results," she said.

To compare the performance of the 3D NP swab with the flocked swab, the USF Health team initiated a clinical trial at numerous sites including Tampa General Hospital, Northwell Hospital and Thomas Jefferson University Hospital in Philadelphia.

At the three trial sites, 291 patients (ages 14-94) who were hospitalized or seen in the emergency room were tested for COVID-19 using both the flocked swab and 3D swab. The 3D swab displayed statistically identical results to the flocked swab in the head-to-head trial.

"The results were overwhelmingly positive," Dr. Decker said. "The clinical trial showed that the 3D nasal swabs performed as well as - or, in some cases, better than - flocked swabs."

Tampa General Hospital adopted the 3D NP swab as its standard of care and began printing more than 300 swabs a day for the hospital and its affiliated care centers. The hospital's six printers continue to print about 9,000 swabs per week.

The 3D printing process takes up to 15 hours depending on the printer. The printed swabs are rinsed in isopropyl alcohol, cured and hand-inspected for defects. Finally, a member of the hospital's infectious disease team examines each swab before it is sterilized in an autoclave and packed in a test kit.

USF filed for a provisional patent on the 3D NP swab and provided the design files and clinical data at no cost to hospitals, clinics and licensed medical device companies around the world.

"We wanted to get this swab in as many hands as possible to help slow the spread of the virus," Dr. Decker said. "This is the result of many people working together to make one device to help others."

Dr. Decker notes that the project was initiated and developed through collaborations established in the RSNA 3D Printing Special Interest group.

"Medical 3D printing is housed in the field of radiology, and RSNA and the 3D Printing Special Interest Group give us a voice," she said. "This project shows novel ways that radiology departments around the world can directly impact hospitals and clinical care during a crisis like COVID-19."

Since methods for genetic paternity analyses were introduced it became clear that many pair-living animal species, including humans, do not take partnership fidelity that seriously. In most species there is some proportion of offspring that is not sired by their social father. Coppery titi monkeys living in the Amazon lowland rainforest seem to be an exception. Scientists from the German Primate Center (DPZ) - Leibniz Institute for Primate Research in Göttingen could not find evidence for extra-pair paternity in their study population in Peru. Mate choice seems to be so successful that a potential genetic advantage does not outweigh the social costs of infidelity (Scientific Reports).

Offspring resulting from extra-pair copulations but raised by the social partner are surprisingly common in pair-living species. Various reasons are discussed for this behavior. For instance, mate choice is often limited and sometimes it only turns out later that the chosen partner is not the genetically best one. In order to ensure the best possible genes for your own children, you may use the genes of a neighbor or a floating male without giving up the security of your own territory and the caring social father.

Coppery titi monkeys live in small family-groups, consisting of male, female and offspring, who defend a territory. Usually, a single infant is born per year, that leaves the group when it reaches sexual maturity or shortly after and searches a partner, with whom it occupies an own territory. The pair-partners maintain a strong relationship, spend day and night in close proximity and groom each other. Fourteen groups of coppery titi monkeys were studied at the field station of the German Primate Center "Estación Biológica Quebrada Blanco" and its surroundings in northeastern Peru. Forty-one individuals could be genotyped using faecal samples from which DNA was extracted and sequenced at the Genetics Laboratory of the German Primate Center in Göttingen. None of the 18 offspring examined were not sired by the social father, i.e. genetic monogamy could be confirmed. In addition, it turned out that the adult animals showed a high genetic diversity and that the mating partners were on average unrelated. "Extra-pair breeding would therefore not have provided a genetic advantage for the animals studied, so that they presumably rather avoided the risks of 'infidelity'," says Sofya Dolotovskaya, who studied the animals and their behavior for 14 months of field research as a doctoral student of the German Primate Center.

"In an undisturbed ecosystem, as at our field station, young coppery titi monkeys obviously migrate far enough from their natal group to find a suitable partner without incurring the risk of inbreeding," Eckhard W. Heymann, scientist at the German Primate Center and head of the field station in Peru, concludes from the study. "Further studies must show whether genetic monogamy also prevails in other populations of coppery titi monkeys, especially in fragmented habitats".

Japanese scientists have stumbled onto a simple method for controlling the introduction of defects, called 'vacancy layers', into perovskite oxynitrides, leading to changes in their physical properties. The approach, published in the journal Nature Communications, could help in the development of photocatalysts.

Oxynitrides are inorganic compounds formed of oxygen, nitrogen and other chemical elements. They have gained much attention in recent years because of their interesting properties, with applications in optical and memory devices, and in photocatalytic reactions, for example.

In 2015, solid state chemist Hiroshi Kageyama of Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) and his team reported that they found a way to fabricate oxynitrides using a lower temperature ammonia treatment process than the conventional method that requires more than 1,000°C). The new process produced a polycrystalline powder with layers of missing oxygen atoms, known as oxygen-vacancy planes.

The team wanted to examine the physical properties of this oxynitride, so they grew it as a single crystal thin film on a substrate. "But the oxygen-vacancy layers in the resulting film were in a different plane than the original powder," Kageyama says. They wondered if the underlying substrate influenced the orientation of the oxygen vacancy layers.

The team grew a film of strontium vanadium oxide (SrVO3) on different substrates and treated it in ammonia at a low temperature of 600°C. The plane of the oxygen vacancy layers and their periodicity--how frequently they appear within the film's other layers--changed depending on the degree of mismatch between the 'lattice strains' in the substrate and the overlying film. Lattice strain is a force applied by the substrate that causes the atoms in a material to be slightly displaced relative to their normal position.

"Even though solid state chemists have known that oxygen-defect planes play an important role in changing the properties of oxides, such as inducing superconductivity, we haven't been able to control their formation before," Kageyama says.

Oxides are typically synthesized using high temperature reactions, making it difficult to control their crystal structures. Using a lower temperature and strain in this experiment was key for success.

"Our team developed a method to create and control the direction and periodicity of the oxygen-vacancy layers in thin film oxides simply by applying strain," Kageyama says. "Since the strain energy is enormously large, as large as thousands of degrees Celsius, we're able to use it to stabilize novel structures that don't otherwise form."

Kageyama says it would be interesting to investigate how changes to the thickness of the oxide film, or the reaction temperature and time, could also affect the orientation and periodicity of the oxygen-vacancy layers.

Scientists have discovered how drug-like small molecules can regulate the activity of therapeutically relevant ion channels - and their findings could transform ongoing drug development efforts.

A major mechanism by which cells communicate with their environment is the movement of metal ions through channels located within their cell membranes.

The new study by researchers at the University of Leeds, published today in Communications Biology, provides detailed insight into the regulation of TRPC5 ion channels, which allow positively charged ions such as calcium, sodium and potassium to flow in and out of cells.

TRPC5 channels are considered potential therapeutic targets for the treatment of a range of conditions, including anxiety, kidney disease and cardiovascular disease.

Led by Dr Robin Bon, Associate Professor of Chemical Biology in the School of Medicine, and Dr Stephen Muench, Associate Professor of Membrane Biology in the School of Biomedical Sciences, the study reveals how a drug-like small molecule, called Pico145, binds to the TRPC5 channel, thereby preventing the channel from opening.

Dr David Wright, first author of the study, said: "Using cryo-electron microscopy performed in the Astbury BioStructure Laboratory, we determined high-resolution structures of the TRPC5 channel in the presence and absence of Pico145. These structures show, for the first time, how Pico145 can displace a lipid bound to each of the four TRPC5 proteins. Further studies revealed the importance of individual amino acid residues in the Pico145 binding site of TRPC5."

Many diseases are linked to defects in ion channel function, so controlling the opening and closing of specific ion channels is a highly successful therapeutic strategy.

But drug discovery efforts are often hindered by gaps in understanding of how drug-like small molecules can be designed to control ion channel activity.

Dr Muench said: "It amazes me that you think you understand how a small molecule may influence the activity of a protein - and then you find something unexpected.

"The displacement of a lipid opens up some interesting new directions of research into how this important family of proteins functions at a fundamental level and how we may develop new therapies in the future."

Dr Bon said: "The opening and closing of TRPC channels is regulated by many factors, including dietary components such as lipids, minerals and antioxidants, as well as environmental toxins. Overactivity of TRPC channels is linked to a range of diseases. Therefore, small molecules that can stop TRPC channels from opening are increasingly considered as potential therapeutic agents.

"Indeed, several pharmaceutical companies now have drug discovery programmes that focus on finding new inhibitors of TRPC channels including TRPC5.

"Pico145, which was developed by a US-based pharmaceutical company, belongs to the most potent and selective class of molecules (called xanthines) to target TRPC5 and related TRPC channels.

"In Leeds, we have done a lot of work to understand how xanthines regulate TRPC channel activity. Our structures represent a break-through that may provide new, rational approaches to the development of drug candidates that target TRPC channels.

"In addition to its relevance to drug discovery, our study also provides new insights into how physiological and dietary factors such as lipids and zinc ions may regulate TRPC channels. Therefore, our work has opened up several new lines of research."

Scientists at the University of Birmingham have developed a new sensor to measure weak magnetic signals in the brain, which has the potential to increase understanding of connectivity in the brain, and detect signs of traumatic brain injury, dementia and schizophrenia.

Magnetic signals in the brain are measured by magnetoencephalography (MEG). They are easier to localise than the electrical signals measured by EEG, so they are likely to have greater utility for earlier and more accurate diagnostic techniques.

Physicist Dr Anna Kowalczyk led a team of scientists from the Quantum Gases group at the School of Physics and Astronomy and the Neuronal Oscillation group at the School of Psychology who designed a new Optically Pumped Magnetometer (OPM) sensor. These sensors, which are used in MEG laboratories, use polarized light to detect changes in the orientation of the spin of atoms when they are exposed to a magnetic field.

Their work is published in NeuroImage, and University of Birmingham Enterprise has filed a patent application covering the design of the new sensor and its use in medical diagnostic equipment.

The new sensor is more robust in detecting the brain signals and distinguishing them from background magnetic noise compared to commercially available sensors.

The team was also able to reduce the sensor size by removing the laser from the sensor head, and made further adjustments to decrease the number of electronic components, in a move that will reduce interference between sensors.

Benchmarking tests took place in the state-of-the-art facilities at University of Birmingham's Centre for Human Brain Health, and showed good performance in environmental conditions where other sensors do not work. Specifically, the researchers showed that the new sensor is able to detect brain signals against background magnetic noise, raising the possibility of MEG testing outside a specialised unit or in a hospital ward.

Dr Anna Kowalczyk commented: "Existing MEG sensors need to be at a constant, cool temperature and this requires a bulky helium-cooling system, which means they have to be arranged in a rigid helmet that will not fit every head size and shape. They also require a zero-magnetic field environment to pick up the brain signals. The testing demonstrated that our stand-alone sensor does not require these conditions. Its performance surpasses existing sensors, and it can discriminate between background magnetic fields and brain activity."

The researchers expect these more robust sensors will extend the use of MEG for diagnosis and treatment, and they are working with other institutes at the University to determine which therapeutic areas will benefit most from this new approach.

Neuroscientist Professor Ole Jensen, who is co-director of the Centre for Human Brain Health commented: "We know that early diagnosis improves outcomes and this technology could provide the sensitivity to detect the earliest changes in brain activity in conditions like schizophrenia, dementia and ADHD. It also has immediate clinical relevance, and we are already working with clinicians at the Queen Elizabeth hospital to investigate its use in pinpointing the site of traumatic brain injuries."

The team at the CHBH has also recently been awarded Partnership Resource Funding from the UK Quantum Technology Hub Sensors and Timing to further develop new OPM sensors.

The researchers are now seeking commercial and research partnerships that will lead to better diagnostics for neurological injury, neurological disorders such as dementia, and psychiatric disorders such as schizophrenia.

As the global coronavirus pandemic continues, scientists are not only trying to find vaccines and drugs to combat it, but also to continuously learn more about the virus itself. "By now we can expect the coronavirus to become seasonal," explains Ralf Bartenschlager, professor in the Department of Infectious Diseases, Molecular Virology, at Heidelberg University. "Thus, there is an urgent need to develop and implement both prophylactic and therapeutic strategies against this virus." In a new study, Bartenschlager, assisted by the Schwab team at EMBL Heidelberg and using EMBL's Electron Microscopy Core Facility, performed a detailed imaging analysis to determine how the virus reprograms infected cells.

Cells that become infected by SARS-CoV-2 die rather quickly, within only 24 to 48 hours. This indicates that the virus harms the human cell in such a way that it is rewired and essentially forced to produce viral progeny. The main aim of the project was therefore to identify the morphological changes within a cell that are inherent to this reprogramming. "To develop drugs which suppress the viral replication and thereby the consequence of the infection, as well as the virus-induced cell death, is key to have a better understanding of the biological mechanisms driving the virus' replication cycle," explains Bartenschlager. The team used the imaging facilities at EMBL and state-of-the art imaging techniques to determine the 3D architecture of SARS-CoV-2-infected cells, as well as alterations of cellular architecture caused by the virus.

The team was able to create 3D reconstructions of whole cells and their subcellular compartments. "We are providing critical insights into virus-induced structural changes in the studied human cells," explains Ralf Bartenschlager. The images revealed an obvious and massive change in the endomembrane systems of the infected cells - a system that enables the cell to define different compartments and sites. The virus induces membrane changes in such a way that it can produce its own replication organelles. These are mini replication compartments where the viral genome is amplified enormously. To do this, the virus requires membrane surfaces. These are created by exploiting a cellular membrane system and creating an organelle, which has a very distinct appearance. The scientists describe it as a massive accumulation of bubbles: two membrane layers forming a big balloon. Within these balloons - which form a very shielded compartment - the viral genomes are multiplied and released to become incorporated into new virus particles.

This striking change can be seen in the cells only a few hours after infection. "We saw how and where the virus replicates within the cell, and how it hijacks its host machinery to be released after multiplication," Schwab says. Until now, little was known about the origin and development of the effects that SARS-CoV-2 causes in the human body. This includes a lack of knowledge about the mechanism by which the infection leads to the death of infected cells. Having this information now will foster the development of therapies reducing virus replication and, thus, disease severity.

The team has made sure that the collected information and, in particular, the unprecedented repository of 3D structural information about virus-induced substructures can be used by everyone. "I believe we are setting a precedent on the fact that we are sharing all data that we produced with the scientific community. It represents an impressive resource to the community," says Yannick Schwab. "This way we can support the global effort to study how SARS-CoV-2 interacts with its host." The team hopes that their collected information will help in the development of antiviral drugs.

The team managed to produce the study in an incredibly short time, despite the challenging circumstances. "Half the world - and of course Heidelberg as well - were in full lockdown and we had to improvise almost on a daily basis to adapt to the situation. Whether at EMBL or from home, all were deeply involved and generously gave their time and deep knowledge," says Schwab. "The speed at which we worked, and the amount of data that was produced, is remarkable."

Differential geometry is the study of space geometry. Multiple natural phenomena, from the universe expansion to thermal expansion and contraction, can come down to spatial evolution. The two core conjectures in this field, Hamilton-Tian conjecture and the Partial C0-conjecture, had remained as puzzles for more than 20 years.

"Most of the pebbles on the beach are round. They might have had edges and corners at first, but as time goes by and the tide ebbs and flows, their shape will get closer and closer to perfection and standard. But no matter how perfect the evolution is, there might still be some abnormalities, which are called 'singularities' in geometry."

"The Hamilton-Tian Conjecture is that most of the space is perfect, while the size of the 'singularity' can be restricted to a low-dimensional space", introduced by Prof. CHEN Xiuxiong, the founder of the Institute of Geometry and Physics, University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS).

Prof CHEN, alongside with Prof. WANG Bing from USTC, first proved the aforementioned two conjectures.

Their paper was split into two parts, the first of which was published in 2017, and the second part of 123 pages was published this year on Journal of Differential Geometry, one of the leading publications in the field of geometry which also published Hamilton's fundamental work about Ricci flow, after a long course of 5 years of developing the theory and 6 years of peer-reviewing since its first submission.

This work emphasized on the weak compactness theory for non-collapsed Ricci flows. It introduced many innovative thoughts and methods, which contributed far-reaching implications in the field of geometric analysis, especially for the studies of Ricci flows.

In fact, many other works have been developed based on this article. For example, a new solution for stability of Yau's conjecture based on the structure theory of Ricci flows was given by Prof. CHEN, Prof. WANG and Dr. SUN Song of USTC with their derivation published in the top journal, Geometry and Topology. Before that, they were rewarded Oswald Veblen Prize in Geometry for their provision of the first solution of stability of Yau's conjecture.

The theory and methods presented in this article were also applied into a series of works of Prof. WANG and his cooperators in recent years.

The core ideas of this article were generalized to the research of mean curvature flow by Prof. WANG and Prof. LI Haozhao, who solved the extension problem, and the result was published in Inventions Mathematicae.

The cooperated paper by Prof. WANG, Dr. HUANG Shaosai, and Dr. LI Yu, On the Regular-Convexity of Ricci Shrinker Limit Spaces, published on Crelle's Journal, has proved that the limit of non-collapsed shrinking Ricci solitons must be the cone shape defined by Prof. CHEN and Prof. WANG.

Besides, the work, Heat Kernel on Ricci Shrinkers published on Calculus of Variations and Partial Differential Equations by Prof. WANG and Dr. LI, developed several estimates through the study of the heat kernel on Ricci shrinkers, and provided "necessary tools to analyze short time singularities of the Ricci flows of general dimension".

This breakthrough was honored by the reviewer of the journal and the winner of Fields Metal, Prof. Simon Donaldson, who commented, "this work is a major breakthrough in geometric analysis, and it no doubt will lead many other related research projects."

The organic-inorganic hybrid perovskites (OIHPs) have a multiple application on solar cells, lighting-emitting diodes (LEDs), field effect transistors (FETs) and photodetectors. Among the parameters valuing the power conversion efficiency (PCE) of devices based on perovskite materials, the mobility of carriers undoubtedly captures a high weight.

Although researchers have made massive progress by introducing new components into the structure to control the mobility of the carriers, the understanding on the atom level about how the component affects the performance is still unknown.

To solve the problem, the research team led by Prof. LUO Yi and Prof. YE Shuji from the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS) synthesized a series of 2D OHIPs films with large organic spacer cations.

By a sequence of measurements, including sum frequency generation vibrational spectroscopy (SFG-VS), optical-pump terahertz-probe spectroscopy (OPTPS), current voltage (I-V) measurements, temperature-dependent PL spectroscopy and X-ray diffraction (XRD) measurements, the researchers found the correlation among the conformation of the organic cations, the charge-carrier mobility and broadband emission.

Mobility and broadband emission showed strong dependence on the molecular conformational order of organic cations. The gauche defect and local chain distortion of organic cations are the structural origin of the in-plane mobility reduction and broad emission in 2D OIHP films. The interlayer distance and the conformational order of the organic cations co-regulate the out-of-plane mobility.

The result was published in Nature Communications on Oct. 30.

This work provides a physical understanding of the important role of organic cation conformation in optimizing the optoelectronic properties of 2D OIHPs, revealing the structure-property relationship in the perovskite research at the molecular level.