Tech

ANN ARBOR--In a finding that runs counter to a common assumption in physics, researchers at the University of Michigan ran a light emitting diode (LED) with electrodes reversed in order to cool another device mere nanometers away.

The approach could lead to new solid-state cooling technology for future microprocessors, which will have so many transistors packed into a small space that current methods can't remove heat quickly enough.

"We have demonstrated a second method for using photons to cool devices," said Pramod Reddy, who co-led the work with Edgar Meyhofer, both professors of mechanical engineering.

The first--known in the field as laser cooling--is based on the foundational work of Arthur Ashkin, who shared the Nobel prize in Physics in 2018.

The researchers instead harnessed the chemical potential of thermal radiation--a concept more commonly used to explain, for example, how a battery works.

"Even today, many assume that the chemical potential of radiation is zero," Meyhofer said. "But theoretical work going back to the 1980s suggests that under some conditions, this is not the case."

The chemical potential in a battery, for instance, drives an electric current when put into a device. Inside the battery, metal ions want to flow to the other side because they can get rid of some energy--chemical potential energy--and we use that energy as electricity. Electromagnetic radiation, including visible light and infrared thermal radiation, typically does not have this type of potential.

"Usually for thermal radiation, the intensity only depends on temperature, but we actually have an additional knob to control this radiation, which makes the cooling we investigate possible," said Linxiao Zhu, a research fellow in mechanical engineering and the lead author on the work.

That knob is electrical. In theory, reversing the positive and negative electrical connections on an infrared LED won't just stop it from emitting light, but will actually suppress the thermal radiation that it should be producing just because it's at room temperature.

"The LED, with this reverse bias trick, behaves as if it were at a lower temperature," Reddy said.

However, measuring this cooling--and proving that anything interesting happened--is hideously complicated.

To get enough infrared light to flow from an object into the LED, the two would have to be extremely close together--less than a single wavelength of infrared light. This is necessary to take advantage of "near field" or "evanescent coupling" effects, which enable more infrared photons, or particles of light, to cross from the object to be cooled into the LED.

Reddy and Meyhofer's team had a leg up because they had already been heating and cooling nanoscale devices, arranging them so that they were only a few tens of nanometers apart--or less than a thousandth of a hair's breadth. At this close proximity, a photon that would not have escaped the object to be cooled can pass into the LED, almost as if the gap between them did not exist. And the team had access to an ultra-low vibration laboratory where measurements of objects separated by nanometers become feasible because vibrations, such as those from footsteps by others in the building, are dramatically reduced.

The group proved the principle by building a minuscule calorimeter, which is a device that measures changes in energy, and putting it next to a tiny LED about the size of a grain of rice. These two were constantly emitting and receiving thermal photons from each other and elsewhere in their environments.

"Any object that is at room temperature is emitting light. A night vision camera is basically capturing the infrared light that is coming from a warm body," Meyhofer said.

But once the LED is reverse biased, it began acting as a very low temperature object, absorbing photons from the calorimeter. At the same time, the gap prevents heat from traveling back into the calorimeter via conduction, resulting in a cooling effect.

The team demonstrated cooling of 6 watts per meter squared. Theoretically, this effect could produce cooling equivalent to 1,000 watts per meter squared, or about the power of sunshine on Earth's surface.

This could turn out to be important for future smartphones and other computers. With more computing power in smaller and smaller devices, removing the heat from the microprocessor is beginning to limit how much power can be squeezed into a given space.

With improvements of the efficiency and cooling rates of this new approach, the team envisions this phenomenon as a way to quickly draw heat away from microprocessors in devices. It could even stand up to the abuses endured by smartphones, as nanoscale spacers could provide the separation between microprocessor and LED.

The research is to be published in the journal Nature on Feb. 14, 2019, titled, "Near-field photonic cooling through control of the chemical potential of photons."

GOLDEN, Colorado (Feb. 13, 2019) -- Shape memory alloys are well known for their remarkable properties -- superelasticity, shape memory and actuation allow them to be crumpled up and then spring back to a "remembered" original shape.

But the advanced material remains drastically underutilized in commercial applications, uses that could include morphing the shape of airplane structures to make flight more efficient or deploying communication dishes and solar arrays in space.

Researchers from Colorado School of Mines are working to better understand how their complex internal microstructures change during shape memory behaviors and the results of their first-of-their-kind experiments were recently published by three major materials science and mechanics journals, Acta Crystallographica, Journal of the Mechanics and Physics of Solids and Scripta Materialia.

"Discovered over 70 years ago, the promise of shape memory alloys (SMAs) has led to over 10,000 patents in the U.S. and 20,000 worldwide. However, that promise has not been matched by its technological impact -- only a limited number of these 20,000 SMA patents have been realized as commercially viable products," said Ashley Bucsek PhD '18, lead author of the three papers and now a President's Postdoctoral Fellow at the University of Minnesota. "The story is similar for many other advanced materials, taking decades to move from development to implementation. One reason for this gap between development and implementation is that researchers are literally just scratching the surface with conventional microscopy techniques, when most of the micromechanisms in SMAs are 3D, out-of-plane and sensitive to internal constraints."

To bridge that gap, Bucsek and her fellow researchers put nickel titanium -- the most widely used and available SMA -- under some of the most powerful 3D microscopes available today, located at the Cornell High Energy Synchrotron Source (CHESS) at Cornell University in upstate New York.

Specifically, she used near-field and far-field high-energy diffraction microscopy (HEDM), which fall under the umbrella of 3D X-Ray Diffraction techniques, allowing her to visualize the material's interior microstructure in three dimensions while it's responding in real time.

"Even though HEDM has been developed at CHESS and other synchrotrons around the world for over a decade now, the procedures for applying HEDM to studying advanced materials with features like low-symmetry phase mixtures and large crystal size disparities were essentially nonexistent," Bucsek said. "As a result, each of these three experiments required the development of novel experimental, data analysis and data visualization techniques to extract the desired information. Many of the results were surprising, shedding light on decades-old areas of contention in SMA micromechanics."

In SMAs, it is often the high-symmetry phase called "austenite" that is stable at a higher temperature, but if enough stress is applied or the temperature is decreased, it will phase transform to a low-symmetry phase called "martensite."

The first paper, "Measuring stress-induced martensite microstructures using far-field high-energy diffraction microscopy," published in September in Acta Crystallographica Section A: Foundations and Advances, looked to predict the specific variety of martensite that would form.

"Using this approach, we found that martensite microstructures within SMAs strongly violated the predictions of the maximum transformation work criterion, showing that the application of the widely accepted maximum transformation work criterion needs to be modified for cases where SMAs may have engineering-grade microstructure features and defects," Bucsek said.

The second experiment tackled load-induced twin rearrangement, or martensite reorientation, a reversible deformation mechanism by which materials can accommodate large loads and deformations without damage through rearrangements of crystallographic twins.

The paper, "Ferroelastic twin reorientation mechanisms in shape memory alloys elucidated with 3D X-ray microscopy," is set to be published in March in Journal of the Mechanics and Physics of Solids.

"A specific sequence of twin rearrangement micromechanisms occurs inside macroscopic deformation bands as they propagate through the microstructure, and we showed that the strain localization inside these bands causes the lattice to curve up to 15 degrees, which has important implications on elastic strain, resolved shear stress, and maximizing the twin rearrangement," Bucsek said "These findings will guide future researchers in employing twin rearrangement in novel multiferroic technologies."

Solid-state actuation is one of the most important applications of SMAs, used in a number of nanoelectromechanical and microelectromechanical systems, biomedical, active damping and aerospace actuation systems.

The target of the final experiment was a phenomenon in which special high-angle grain boundaries emerge inside austenite grains when SMAs are actuated. During actuation, phase transformation from austenite to martensite then back to austenite is induced by heating, cooling and then reheating the SMA while under a constant load.

The paper, "3D in situ characterization of phase transformation induced austenite grain refinement in nickel-titanium," will appear in March in Scripta Materialia.

"Using electron microscopy, it has been observed that the austenite can exhibit large rotations when the sample is reheated, which is detrimental to both work output and fatigue. However, because of the small sample sizes required for electron microscopy, these rotations were observed very inconsistently, appearing but then not appearing under the same loading conditions, or appearing after a few cycles but then not appearing after a few thousand cycles," Bucsek said. "Our results showed that these grain rotations can occur after just one cycle in moderate condition. But because of the low volume and heterogenous dispersion of the rotations, a bulk volume is required to observe them."

Funding for Bucsek's research came from the National Science Foundation (NSF) Graduate Research Fellowship, as well as the 2015 NSF CAREER Award of her PhD advisor and co-author, Aaron Stebner, Rowlinson Associate Professor of Mechanical Engineering at Mines. Additional funding to use the high-performance computers needed to analyze the data came from the NSF XSEDE program.

"Dr. Bucsek's thesis work documented in these articles shows the importance of using 3D techniques to study the 3D structure of materials. She was able to observe and understand mechanisms that have been postulated and debated for over 50 years for the first time," Stebner said. "The biggest hindrance to adopting new materials, like most technologies, is fear of the unknown. Such understanding will undoubtedly lead to wider acceptance and application of these miraculous materials, as it improves our confidence in developing means to certify and qualify them."

The operation of the Cornell High Energy Synchrotron Source, which was used to perform the X-ray microscopy measurements, was also provided by NSF.

"Throughout her thesis work, Dr. Bucsek developed new, creative ways to apply HEDM methods to the study of shape memory alloy systems," said Darren Pagan, staff scientist at CHESS. "Her ability to overcome challenges associated with data processing and interpretation enabled new insights to be gained into the micromechanics of shape memory alloy deformation."

Vivid dreams involving drinking and drug use are common among individuals in recovery. A study from the Massachusetts General Hospital (MGH) Recovery Research Institute, published in the January issue of the Journal of Substance Abuse Treatment after online release in October 2018, finds these relapse dreams are more common in those with more severe clinical histories of alcohol and other drug problems.

"Anecdotally, the occurrence of drinking and drug-using dreams is a known phenomenon among people in recovery, but very little is known from an epidemiological standpoint about the prevalence of such dreams, their relation to relapse risk, and how they decay with time in recovery," says lead author John F. Kelly, PhD, founder and director of the Recovery Research Institute. "Given that these dreams can be deeply unnerving, more information could help treatment providers, those in recovery and their families know what to expect going forward."

Recovery from every kind of substance use disorder - alcohol, heroin, cocaine, cannabis - has been characterized by dreams that follow a common pattern: in the dream the person has a drink or ingests their primary substance. They experience disbelief and are overcome with fear, guilt and remorse until they wake up, relieved to realize it was only a dream.

Among a nationally representative group of more than 2,000 people who had resolved a significant alcohol or drug use problem, around one-third reported having experienced relapse dreams after entering recovery. The frequency of such dreams lessened the longer an individual was in recovery.

"We found that the individuals in recovery who reported at least one such dream had received help from treatment and mutual-help organizations in the past, reflecting a more serious clinical disorder and impact on the central nervous system," says Kelly, who is the Spallin Associate Professor of Psychiatry in the Field of Addiction Medicine at Harvard Medical School.

Reports of relapse dreams are so common in clinical and recovery support service settings that Kelly and co-author M. Claire Greene, PhD, of Johns Hopkins Bloomberg School of Public Health, were surprised that the majority of those studied reported never having experienced one. Those who did tended to have had more severe substance use histories.

"The association between the decreasing frequency of these dreams and the length of time in recovery suggests that, as the body and mind gradually adapt to abstinence and a new lifestyle, psychological angst about relapse diminishes," Kelly says. "REM sleep and deep wave sleep undergo important changes, even long after people enter recovery, and these relapse dreams may be indicative of the healing process and brain-mind stabilization that occurs with time in recovery."

Human beings are not the only ones who suffer from stress - even microorganisms can be affected. Now, researchers from Chalmers University of Technology, Sweden, have devised a new method to study how single biological cells react to stressful situations. Understanding these responses could help develop more effective drugs for serious diseases. As well as that, the research could even help to brew better beer.

All living organisms can experience stress during challenging situations. Cells and microorganisms have complicated systems to govern how they adapt to new conditions. They can alter their own structure by incorporating or releasing many different substances into the surroundings. Due to the complexity of these molecular processes, understanding these systems is a difficult task.

Chalmers researchers Daniel Midtvedt, Erik Olsén, Fredrik Höök and Gavin Jeffries have now made an important breakthrough, by looking at how individual yeast cells react to changes in the local environment - in this case an increased osmolarity, or concentration, of salt. They both identified and monitored the change of compounds within the yeast cells, one of which was a sugar, glycerol.
Furthermore, they were able to measure the exact rate and amount of glycerol produced by different cells under various stress conditions. Their results have now been published in the renowned scientific journal Nature Communications.

"Yeast and bacteria have very similar systems when it comes to response to stress, meaning the results are very interesting from a medical point of view. This could help us understand how to make life harder for undesirable bacteria which invade our body - a means to knock out their defence mechanisms," says Daniel Midtvedt, researcher in biological physics at Chalmers, and lead writer of the scientific paper.

He has been researching the subject since 2015, and, together with his colleagues, has developed a variant of holographic microscopy to study the cells in three dimensions. The method is built upon an interference imaging approach, splitting a laser beam into two light paths. One passes through a cell sample, and one does not. The two beams are then recombined at a slight offset angle. This makes it possible to read changes in the cell's properties through the variations in beam phase offsets.

With this method of investigating a cell, researchers can see what different microorganisms produce under stress - without needing to use different types of traditional 'label-based' strategies. Their non-invasive strategy allows for multiple compounds to be detected simultaneously, without damaging the cell.

The researchers now plan to use the new method in a large collaboration project, to look at the uptake of targeted biomedicines.

"Hopefully, we can contribute to improved understanding of how drugs are received and processed by human cells. It is important to be able to develop new type of drugs, with the hope that we can treat those illnesses which today are untreatable," says Chalmers professor Fredrik Höök, who further leads the research centre Formulaex, where AstraZeneca is the leading industry partner.

As well as the benefit to medical researchers, improved knowledge of the impact of stress on yeast cells could be valuable for the food and drink industry - not least, when it comes to brewing better beer.

"Yeast is essential for both food and drink preparation, for example in baking bread and brewing beer. This knowledge of yeast cells' physical characteristics could be invaluable. We could optimise the products exactly as we want them," says Daniel Midtvedt.

A team of scientists led by researchers at the University of Georgia Center for Food Safety in Griffin has developed a machine-learning approach that could lead to quicker identification of the animal source of certain Salmonella outbreaks.

In the research, published in the January 2019 issue of Emerging Infectious Diseases, Xiangyu Deng and his colleagues used more than a thousand genomes to predict the animal sources, especially livestock, of Salmonella Typhimurium.

Deng, an assistant professor of food microbiology at the center, and Shaokang Zhang, a postdoctoral associate with the center, led the project, which also included experts from the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the Minnesota Department of Health and the Translational Genomics Research Institute.

According to the Foodborne Disease Outbreak Surveillance System, close to 3,000 outbreaks of foodborne illness were reported in the U.S. from 2009 to 2015. Of those, 900 -- or 30 percent -- were caused by different serotypes of Salmonella, including Typhimurium, Deng said.

"We had at least three outbreaks of Typhimuirum, or its close variant, in 2018. These outbreaks were linked to chicken, chicken salad and dried coconut," he said. "There are more than 2,600 serotypes of Salmonella, and Typhimurium is just one of them, but since the 1960s, about a quarter of Salmonella isolates linked to outbreaks reported to U.S. national surveillance are Typhimurium."

The researchers trained the "machine," an algorithm called Random Forest, with more than 1,300 S. Typhimurium genomes with known sources. After the training, the "machine" learned how to predict certain animal sources of S. Typhimurium genomes.

For this study, the scientists used Salmonella Typhimurium genomes from three major surveillance and monitoring programs: the CDC's PulseNet network; the FDA's GenomeTrakr database of sources in the United States, Europe, South America, Asia and Africa; and retail meat isolates from the FDA arm of the National Antimicrobial Resistance Monitoring System.

"With so many genomes, machine learning is a natural choice to deal with all these data.

We used this big collection of Typhimurium genomes as the training set to build the classifier," said Deng who was awarded the UGA Creative Research Medal in 2017 for his work in this area. "The classifier predicts the source of the Typhimurium isolate by interrogating thousands of genetic features of its genome."

Overall, the system predicted the animal source of the S. Typhimurium with 83 percent accuracy. The classifier performed best in predicting poultry and swine sources, followed by bovine and wild bird sources. The machine also detects whether its prediction is precise or imprecise. When the prediction was precise, the machine was accurate about 92 percent of the time, Deng said.

"We retrospectively analyzed eight of the major zoonotic outbreaks that occurred in the U.S. from 1998 to 2013," he said. "The classifier attributed seven of them to the correct livestock source."

Deng says the tool has limitations; it cannot predict seafood as a source and it has difficulty predicting Salmonella strains that "jump around among different animals."

"I'd call this approach a proof of concept. It will get better as more genomes from various sources become available," he said.

In tweets about the study, Frank Yiannas, deputy director of the FDA, called the machine learning of whole genome sequences project "a new era of smarter food safety and epidemiology."

To the average person, the success of this project means strains of Salmonella Typhimurium could be traced back to the source faster. Identifying what causes a foodborne illness outbreak is key to stopping it and preventing further illnesses.

"Using our method, investigators can better link cases of the same outbreak and better match isolates from food or food processing environments to isolates from sick people," he said. "This will give investigators more confidence to implicate a specific source that is behind the outbreak."

AUGUSTA, Ga. (Feb. 11, 2019) - When a car crash or explosion results in an optic nerve injury, eliminating an enzyme known to promote inflammation appears to aid recovery, scientists report.

They have shown for the first time in a mouse model of tough-to-treat optic nerve trauma, that removing the enzyme arginase 2, which increases with injury, decreases neuron death in the retina as well as the degeneration of nerve fibers that connect neurons to each other and ultimately the brain, they report in the journal Frontiers in Neuroscience.

"Right now when an optic nerve crush injury happens, there is not a lot we can do to help the eye recover," says Dr. Ruth B. Caldwell, cell biologist in the Vascular Biology Center at the Medical College of Georgia at Augusta University.

"We know we can't prevent the initial damage, there is going to be some acute injury, but what deleting this enzyme seems to do is prevent subsequent amplification of the original injury. Collateral damage is less," says Caldwell, the study's corresponding author.

The findings elucidate both the role A2 plays in retinal damage following trauma and highlight A2's potential as a logical treatment target, the scientists write.

The optic nerves connect the eyes to the brain and collect impulses the retina generates from light so that we can see. There is currently no therapy that targets optic nerve trauma largely because understanding of all the damaging players is unclear, they write.

While little also is known about A2's normal function, it appears to be the polar opposite of arginase 1, an enzyme key to helping our liver eliminate ammonia. As the scientists recently found, A1 can suppress destructive inflammation that results when conditions like diabetes and glaucoma reduce blood flow to the retina. When A1 levels decrease, which they are finding happens in a variety of types of eye injuries, A2 levels increase and so do inflammation and damage.

In their model of optic nerve injury, they again found increased A2 expression after the injury and that neurons in the retina as well as retinal ganglion cells, the primary cell type in the optic nerve, began to die. While some death of retinal ganglion cells obviously occurs immediately following this type injury, destruction can continue out seven days or more, the scientists say.

Higher A2 also increased glial cell activation following injury. Glial cells are a different type brain cell that nourish and otherwise support neurons. But when they are activated, they forgo their supportive role, Caldwell says.

The destructive results turned around, when they removed A2 from the equation. Neuron loss diminished as did the degeneration of nerve fibers, called axons that connect retinal ganglion cells to the brain, and glial activation was reduced. There were other signs of support, like an increase in brain derived neurotrophic factor, also known to support the survival of neurons and axons.

"We are showing for the first time that there is a connection between brain derived neurotrophic factor and arginase 2," says Dr. Abdelrahman Y. Fouda, postdoctoral fellow in Caldwell's lab and a study coauthor.

They even saw some axons sprouting past the point of the crush injury, Fouda says.

"We have some evidence that possibly the axons are trying to repair themselves," Caldwell adds of these early indicators of the neurons' ability to reconnect with each other and ultimately the brain. "It looks like they are trying to get there," she says, "but we have a lot more work to do to prove that."

There also was more growth associated protein 43, or GAP43, which is known to help axons regenerate. In fact, the scientists found one way brain derived neurotrophic factor may benefit the optic nerve is by, in turn, helping increase the levels of GAP43. A2 deletion also inhibited injury associated-increases in inflammation-promoting immune cells like interleukin.

"We have already seen A2 go up in other types of injury," says Caldwell, referencing problems that also include retinal damage that occurs in premature babies as well as the ischemic retinopathy found in conditions like diabetes.

"What we know now is that when we delete A2, it makes recovery better from an optic nerve crush," Caldwell says.

To date in all their models, which now include optic nerve trauma, when A2 levels go up, A1 goes down.

They suspect that by giving a more stable but still human grade of A1, as they already are doing in other eye injury models, it will help drive down A2 in optic nerve crush injury as well, and are pursuing this and other lines of investigation.

Lesbian, gay, bisexual, transgender and questioning (LGBTQ) youths are more likely to end up in foster care or unstable housing and suffer negative outcomes, such as substance abuse or mental health issues, while living in the child welfare system, according to new research from The University of Texas at Austin.

In a Feb. 11 paper in the journal Pediatrics, researchers looked at 593,241 youths living in California in grades 6-12. Less than 1 percent of the sample was living in foster care or unstable housing. But researchers found that more than 30 percent of the youths surveyed who were living in foster care identified as LGBTQ. More than 25 percent of those surveyed who were living in unstable housing, defined as living at a friend's house, motel, shelter or other transitional housing, identified as LGBTQ.

"People have been concerned for some time that LGBTQ youth are over-represented in the child welfare system, but there has been little evidence -- until now," said Stephen T. Russell, chair of the Department of Human Development and Family Sciences at The University of Texas at Austin.

Researchers also found that LGBTQ youths living in foster care or unstable housing were more likely to be bullied, suffer from mental health problems, have lower grades, skip school because they felt unsafe and have higher levels of substance abuse.

"There has been a lot of concern that the child welfare system is over-burdened in the first place, and that issues like LGBTQ youth discrimination and their distinct needs are an additional complexity for youth who are already vulnerable, just by definition of being in the child welfare system," Russell said. "We aren't investing enough in the systems and focusing enough on the distinct needs of some of the most vulnerable kids, including LGBTQ kids."

LGBTQ youths are probably ending up in the foster care system or unstable housing for several reasons, including rejection by their families or running away because they felt unsafe, Russell said, but more research is needed to understand why they are ending up in the foster system or unstable housing.

In a companion paper earlier this month, which appeared in the journal Child Abuse and Neglect, Russell and colleagues looked at a nationally representative sample and found that lesbian, gay and bisexual youths were nearly 2.5 times as likely to end up in the foster system as their heterosexual peers. Gender identity was not examined in that study.

Researchers pointed out that only 13 states protect youths in the child welfare system from discrimination on the basis of sexual orientation.

Laura Baams of the University of Groningen and Bianca Wilson of the University of California also contributed to the research. The research was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development, the Communities for Just Schools Fund and the Priscilla Pond Flawn Endowment at The University of Texas at Austin.

PITTSBURGH, Feb. 11, 2019 - Every 40 seconds, someone in the United States suffers a stroke and available therapies, such as clot busting drugs or clot removal devices, are focused on limiting the extent of brain damage. Now, research from the University of Pittsburgh School of Medicine and the VA Pittsburgh Healthcare System shows that a brain protein called UCHL1 may be critical to how nerve cells repair themselves after stroke damage. The research, conducted in animal models, could aid in the development of therapies that enhance stroke recovery by improving the underlying biological repair process.

"Even though traditional stroke therapies are very effective when available, the treatment must be started in the first hours after a stroke and most patients are not able to get these treatments. So there is a clear need for new approaches that can improve recovery days after a patient experiences a stroke," said co-senior author Steven Graham, M.D., Ph.D., professor of neurology at Pitt's School of Medicine, and associate chief of staff for research at VA Pittsburgh. "We think we have identified a protein that is at the root of how the brain recovers from stroke, making it an attractive target for developing drugs that help improve recovery."

UCHL1 is an enzyme that is highly active in the brain and plays a role in clearing away abnormal proteins. Mutations in the gene coding for UCHL1 have been thought to cause motor function deficits in humans. Previous research from Graham's lab had provided some hints as to UCHL1's function, showing that cyclopentenone prostaglandins (CyPgs) - fatty acid molecules - released in nerve cells after a stroke bind to UCHL1 and impair its function.

Graham teamed up with Feng Zhang, Ph.D., an assistant professor of neurology at Pitt's School of Medicine and a co-senior author on the current study published in the Proceedings of the National Academy of Sciences, to tease out the exact role of UCHL1 in stroke and to determine if it could be a viable drug target.

The researchers created a mouse model in which they inserted an altered version of the UCHL1 gene that was resistant to the effects of the CyPgs. They then surgically modelled the effect of a stroke in both genetically engineered and normal mice to compare how the nerve cells recovered.

Preventing CyPgs from inhibiting UCHL1 decreased the amount of injury to the axons after stroke when compared to normal mice. Axons - the long cables projecting outward from the center of the nerve cell - are needed to carry electrical signals and connect to other neurons and make up the bulk of the 'white matter' in the brain.

Further experiments showed that keeping UCHL1 active after a stroke helped preserve the function of neurons and brain tissue by activating cellular repair mechanisms that quickly cleaned up damaged proteins, preventing further nerve cell loss. The mice with the resistant form of UCHL1 also had improved recovery of waking, balance and other motor functions.

"While most stroke therapies focus on preventing neuronal death, preserving axonal integrity and decreasing white matter injury could be equally important for improved recovery," said Graham, who also is a neurologist at the UPMC Stroke Institute. "UCHL1 is a central player in that process."

Graham and his colleagues are now engaged in efforts to identify new drugs that could prevent CyPgs from binding to UCHL1 or to replace damaged UCHL1 proteins with a derivative that can be given intravenously.

Researchers from Aarhus University, Denmark, have discovered that insects leave tiny DNA traces on the flowers they visit. This newly developed eDNA method holds a vast potential for documenting unknown insect-plant interactions, keeping track of endangered pollinators, such as wild bees and butterflies, as well as in the management of unwanted pest species.

Environmental DNA (eDNA) can provide an overview of the DNA sequences in complex samples such as water and soil, and thereby a snapshot of the species inhabiting the particular ecosystem. In previous analyses of water samples from lakes and oceans, researchers have fx found DNA traces from insects, amphibians, fish and whales.

Flowers as DNA collectors

Flower-rich grassland habitats like meadows are typically visited by hundreds of species of insects such as bees, butterflies, flies and beetles, which collect food from the flowers. However, it can obviously be quite difficult to keep track of which insect species visit which flower.

But now, Associate professor Philip Francis Thomsen and Postdoc Eva Egelyng Sigsgaard from the Department of Bioscience, Aarhus University, have undertaken eDNA analyses of 50 flowers from seven different plant species.

"I have worked with DNA from water and soil samples for several years and have often thought that DNA is probably much more common in the environment than would initially imagine. With this study we wanted to test if eDNA from flowers can reveal which insects the flowers have interacted with", says Philip Francis Thomsen, who heads a research group focusing on eDNA.

The researchers were quite surprised by the analyses, which revealed that the flowers have been visited by at least 135 different species of butterflies, moths, bees, flies, beetles, aphids, plant bugs, spiders, etc. The list goes on.

The flowers therefore function as passive DNA collectors that store data about each flower-visiting insect - a discovery that is published today in the prestigious international scientific journal Ecology and Evolution.

Efficient monitoring of our insect fauna

The method opens up completely new possibilities of studying the interactions between specific plants and insects. The knowledge gained can be used within many research areas, including applied research in pest control.

The new method also holds major perspectives in the management of endangered species like wild pollinators, which is an urgent task since many groups of flower-visiting insects are threatened. Thus, the populations of several wild bees and butterflies have decreased significantly in recent decades and many species have now become locally extinct.

"The eDNA method might provide a comprehensive overview of the insects involved in the pollination of various plants. Earlier the focus has almost entirely been on bees, butterflies and hoverflies, but we have found DNA from a wide range of other insects such as moths and beetles that may in fact also be important pollinators" says Philip Francis Thomsen.

Perovskites -- a broad category of compounds that share a certain crystal structure -- have attracted a great deal of attention as potential new solar-cell materials because of their low cost, flexibility, and relatively easy manufacturing process. But much remains unknown about the details of their structure and the effects of substituting different metals or other elements within the material.

Conventional solar cells made of silicon must be processed at temperatures above 1,400 degrees Celsius, using expensive equipment that limits their potential for production scaleup. In contrast, perovskites can be processed in a liquid solution at temperatures as low as 100 degrees, using inexpensive equipment. What's more, perovskites can be deposited on a variety of substrates, including flexible plastics, enabling a variety of new uses that would be impossible with thicker, stiffer silicon wafers.

Now, researchers have been able to decipher a key aspect of the behavior of perovskites made with different formulations: With certain additives there is a kind of "sweet spot" where greater amounts will enhance performance and beyond which further amounts begin to degrade it. The findings are detailed this week in the journal Science, in a paper by former MIT postdoc Juan-Pablo Correa-Baena, MIT professors Tonio Buonassisi and Moungi Bawendi, and 18 others at MIT, the University of California at San Diego, and other institutions.

Perovskites are a family of compounds that share a three-part crystal structure. Each part can be made from any of a number of different elements or compounds -- leading to a very broad range of possible formulations. Buonassisi compares designing a new perovskite to ordering from a menu, picking one (or more) from each of column A, column B, and (by convention) column X. "You can mix and match," he says, but until now all the variations could only be studied by trial and error, since researchers had no basic understanding of what was going on in the material.

In previous research by a team from the Swiss École Polytechnique Fédérale de Lausanne, in which Correa-Baena participated, had found that adding certain alkali metals to the perovskite mix could improve the material's efficiency at converting solar energy to electricity, from about 19 percent to about 22 percent. But at the time there was no explanation for this improvement, and no understanding of exactly what these metals were doing inside the compound. "Very little was known about how the microstructure affects the performance," Buonassisi says.

Now, detailed mapping using high-resolution synchrotron nano-X-ray fluorescence measurements, which can probe the material with a beam just one-thousandth the width of a hair, has revealed the details of the process, with potential clues for how to improve the material's performance even further.

It turns out that adding these alkali metals, such as cesium or rubidium, to the perovskite compound helps some of the other constituents to mix together more smoothly. As the team describes it, these additives help to "homogenize" the mixture, making it conduct electricity more easily and thus improving its efficiency as a solar cell. But, they found, that only works up to a certain point. Beyond a certain concentration, these added metals clump together, forming regions that interfere with the material's conductivity and partly counteract the initial advantage. In between, for any given formulation of these complex compounds, is the sweet spot that provides the best performance, they found.

"It's a big finding," says Correa-Baena, who in January became an assistant professor of materials science and engineering at Georgia Tech. What the researchers found, after about three years of work at MIT and with collaborators at UCSD, was "what happens when you add those alkali metals, and why the performance improves." They were able to directly observe the changes in the composition of the material, and reveal, among other things, these countervailing effects of homogenizing and clumping.

"The idea is that, based on these findings, we now know we should be looking into similar systems, in terms of adding alkali metals or other metals," or varying other parts of the recipe, Correa-Baena says. While perovskites can have major benefits over conventional silicon solar cells, especially in terms of the low cost of setting up factories to produce them, they still require further work to boost their overall efficiency and improve their longevity, which lags significantly behind that of silicon cells.

Although the researchers have clarified the structural changes that take place in the perovskite material when adding different metals, and the resulting changes in performance, "we still don't understand the chemistry behind this," Correa-Baena says. That's the subject of ongoing research by the team. The theoretical maximum efficiency of these perovskite solar cells is about 31 percent, according to Correa-Baena, and the best performance to date is around 23 percent, so there remains a significant margin for potential improvement.

Although it may take years for perovskites to realize their full potential, at least two companies are already in the process of setting up production lines, and they expect to begin selling their first modules within the next year or so. Some of these are small, transparent and colorful solar cells designed to be integrated into a building's façade. "It's already happening," Correa-Baena says, "but there's still work to do in making these more durable."

Once issues of large-scale manufacturability, efficiency, and durability are addressed, Buonassisi says, perovskites could become a major player in the renewable energy industry. "If they succeed in making sustainable, high-efficiency modules while preserving the low cost of the manufacturing, that could be game-changing," he says. "It could allow expansion of solar power much faster than we've seen."

New Orleans, LA - A multi-center phase II clinical trial investigating pembrolizumab as a first-line and programmed cell death-1 therapy in patients with advanced Merkel cell carcinoma reports lasting tumor control, generally manageable side effects and improved overall survival. The results are published online in the Journal of Clinical Oncology, available at http://ascopubs.org/doi/full/10.1200/JCO.18.01896.

LSU Health New Orleans' Adam Riker, MD, FACS, Professor and Chief of Surgical Oncology, led the study at its School of Medicine and Stanley S. Scott Cancer Center.

"This study shows the amazing ability of our immune system to fight off and destroy an aggressive form of skin cancer called Merkel cell carcinoma," says Dr. Riker. "The study drug, pembrolizumab, which is a new form of immunotherapy, blocks a specific receptor in our bodies, resulting in a super charging of our immune system to both recognize and destroy cancer cells. The overall impressive results show that this form of immunotherapy is quite effective, giving us an important treatment option for patients with Merkel Cell Carcinoma that has spread within the body."

Fifty patients, aged 46 - 91 years, were enrolled in the open-label, nonrandomized study. Patients were given pembrolizumab intravenously every three weeks for up to two years. Fifty-six percent of participants responded to the drug - 24% had a complete response, and 32%, a partial response. The average length of progression-free survival was 26.8 months, with a 24-month rate of 48.3%. The overall survival rate at 24 months was 68.7%.

Nearly all of the participants (96%) experienced some type of treatment-related side effect, and seven patients discontinued the trial because of them. The authors note that one death occurred in a 73-year-old patient with widely metastatic Merkel cell carcinoma and pre-existing atrial fibrillation who withdrew from the trial and died 10 days after a single infusion of pembrolizumab.

According to the National Cancer Institute, Merkel cell carcinoma is a disease in which malignant (cancer) cells form in the skin. Sun exposure and a weak immune system can affect the risk of Merkel cell carcinoma. Though rare, the incidence of Merkel cell carcinoma increased by 95% between 2000 and 2013. The five-year overall survival rate ranges between 14 and 27% for advanced disease.

The first drug approved to treat metastatic Merkel cell carcinoma, avelumab, did not gain FDA approval until 2017. The authors add, in 2016, guidelines listed chemotherapy as the sole treatment option for advanced Merkel cell carcinoma. In 2017, pembrolizumab was recommended after chemotherapy; and in 2018, avelumab, nivolumab, and pembrolizumab were all recommended as preferred first-line therapies, ahead of chemotherapy.

The fact that the incidence is highest in people who are immunosuppressed provides some support for the idea that Merkel cell carcinoma is an immunogenic cancer, one that is related to immune function, and a good candidate for immunotherapy. The National Cancer Institute defines immunotherapy as "a type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. Some types of immunotherapy only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG), and some monoclonal antibodies." Pembrolizumab is a monoclonal antibody.

Scientists at the University of Liverpool have discovered a new process to make polymers out of sulfur which could provide a way of making plastic that is less harmful to the environment.

Sulfur is an abundant chemical element and can be found as a mineral deposit across the world. It is also a waste product from the refining of crude oil and gas in the petrochemicals industry, which generates huge stockpiles of sulfur outside refineries.

Whilst being identified as an interesting possible alternative to carbon in the manufacture of polymers, sulfur cannot form a stable polymer on its own but, as revealed in a process called 'inverse vulcanization' it must be reacted with organic crosslinker molecules to make it stable. This process can require high temperatures, long reaction times, and produce harmful by-products.

However, researchers from the University of Liverpool's Stephenson Institute of Renewable Energy, working in the field of materials chemistry have made a potentially game changing discovery.

In a study published in Nature Communications, they report the discovery of a new catalytic process for inverse vulcanization that reduces the required reaction times and temperatures, whilst preventing the production of harmful by-products. It also increases the reaction yields, improves the physical properties of the polymers, and allows a wider range of crosslinkers to be used.

Synthetic polymers are ubiquitous to human life and are among the most extensively manufactured materials on earth. However, with nearly 350 million tonnes of plastic produced annually, coupled with increasing environmental concerns and decreasing petrochemical recourses, there is an urgent need to develop new polymers that are more sustainable.

Dr Tom Hasell, Royal Society University Research Fellow at the University, whose group conducted the research, said: "Making polymers (plastics) out of sulfur is a potential game changer. To be able to produce useful plastic materials from sulfur, a by-product of petroleum, could reduce society's reliance on polymers made from petroleum itself. In addition, these sulfur polymers may be easier to recycle, which opens up exciting possibilities for reducing current use of plastics.

"There is also the scope for unique new polymers with unprecedented properties. The properties of sulfur are very different to carbon, and this has already opened up a world of possible applications for sulfur polymers including thermal imaging lenses, batteries, water purification and human health.

"We made the key discovery when we decided to look to the acceleration of traditional rubber vulcanisation for inspiration. This research now marks a significant step forward in the development of inverse vulcanized polymers. It makes inverse vulcanization more widely applicable, efficient, eco-friendly and productive than the previous routes, not only broadening the fundamental chemistry itself, but also opening the door for the industrialization and broad application of these fascinating new materials in many areas of chemical and material science."

The harmful effects of exposure to tobacco smoke have been known for many years. Cigarette and cigar smokers are at significantly higher risk of contracting all sorts of respiratory maladies, and research linking secondhand smoke to cancer goes back nearly three decades.

But what about the chemicals that stain the walls, ceilings, carpet and upholstery in rooms in which tobacco has been smoked? What about the lingering nicotine on the fingers of smokers? Is there something dangerous in the residue that lingers long after the smoke clears?

Researchers at Cincinnati Children's Hospital Medical Center and the University of Cincinnati have found more evidence of the potentially harmful effects of exposure to the residue and particles left behind by tobacco smoke. In "Nicotine on Children's Hands: Limited Protection of Smoking Bans and Initial Clinical Findings," published Jan. 16 in Tobacco Use Insights, Cincinnati Children's attending physician Melinda Mahabee-Gittens and UC assistant professor Ashley Merianos found that not smoking around children doesn't stop the children of smokers from being exposed to nicotine. They also found that that higher levels of exposure to tobacco smoke residue -- which likely includes carcinogenic tobacco-specific nitrosamines -- may be linked to respiratory problems.

"It just goes to show that indoor smoking bans don't necessarily protect children from tobacco smoke exposure and related pollutants, such as thirdhand smoke," says Merianos.

"It also shows that exposure to tobacco smoke toxicants is more widespread than previously thought because exposure in children is not limited to inhaling secondhand smoke," adds Mahabee-Gittens.

Research staff collected wipes of the dominant hands of 104 children visiting the Cincinnati Children's Pediatric Emergency Department between April 2016 and August 2017 with complaints potentially linked to tobacco smoke exposure and who had at least one caregiver who smoked. The handwipes were then analyzed for nicotine.

The research explored several variables, including the self-reported smoking behaviors of the children's caregivers, as well as the number of smokers living with the child, the number of cigarettes per day smoked by caregivers, the number of cigarettes smoked around the child in any location (such as in the home and the car) and the number of cigarettes smoked around the child inside the home. The research also looked at the medical records of the children for possible smoke exposure-related complaints such as wheezing and cough, as well as past medical histories and discharge diagnoses.

The study found significant levels of nicotine on the hands of children of smokers whose caregivers did not smoke in their presence, averaging 82 nanograms (ng) of nicotine. A similar amount was found on the hands of children whose caregivers smoked between one and five cigarettes per day in their presence. Children whose parents smoked 15 or more cigarettes around them had nicotine levels on their hands in excess of 200 ng.

More than half of the children in the study were under 2 years old. Children in that age group averaged about 69 ng nicotine, while children between the ages of 2 and 4 -- who accounted for 25 percent of the children studied -- averaged nearly three times as much (185.6 ng). Children ages 5 and over were found to have only slightly more nicotine on their hands than the children under 2.

"Future work should explore the associations of hand nicotine and age to determine how children's changing interactions with their environment and behaviors contribute to increased nicotine in 2- to 4-year-olds, whether handwashing decreases the risk and whether increased levels are associated with increased [secondhand smoke-related] clinical illnesses," according to the research article.

Children whose caregivers smoked five or less cigarettes per day had an average of about 55 ng nicotine on their hands, while children whose caregivers smoked 15 or more per day were found to have an average of 124 ng nicotine on their hands.

Children with higher levels of nicotine found on their hands were significantly more likely to have respiratory symptoms such as wheezing and coughing, Merianos says.

"That's just a preliminary finding," she cautions. "We need to do more work. There's a paucity of literature available on the impact that thirdhand smoke has on health effects in children."

Merianos advocates for caregivers to quit smoking to decrease the exposure of children to nicotine and smoking-related chemicals. For those who do not quit, she recommends handwashing, showering and changing clothes after smoking to minimize thirdhand smoke exposure.

Mahabee-Gittens adds that parental smokers should know that these measures alone are not enough to protect their children since deep-seated reservoirs of toxicants continue to build when smoking continues.

The researchers will continue to study the issue to see if the results are replicated with a larger sample of children.

Not only does Canada continue to have a problem with fish mislabelling, but that problem persists throughout the supply chain, according to a first-ever study by University of Guelph researchers.

In a new study, U of G researchers found 32 per cent of fish were mislabelled and the number of incorrectly identified samples became compounded as the samples moved through the food system.

"We've been doing seafood fraud studies for a decade," said Prof. Robert Hanner, lead author and associate director for the Canadian Barcode of Life Network. "We know there are problems. But this is the first study to move beyond that and look at where the problems are happening throughout the food supply chain."

The findings reveal that mislabelling happens before fish are imported into Canada, as well as throughout the supply chain, Hanner added.

"It seems it's not isolated to foreign markets, but it's also happening at home. The Canadian Food Inspection Agency (CFIA) has partnered with us to actively find solutions to this persistent problem," said Hanner.

Published recently in the journal Food Research International, the study was conducted in collaboration with the Canadian Food Inspection Agency (CFIA).

Hanner is the associate Director for the Canadian Barcode of Life Network, headquartered at the Biodiversity Institute of Ontario, University of Guelph.

"As a science-based regulator, the CFIA works with an array of partners to address mislabelling and promote compliance within industry," said the CFIA's Deputy Chief Food Safety Office, Dr. Aline Dimitri. "It is only through our collective efforts that we will be able to tackle this global issue."

U of G researchers examined 203 samples from 12 key targeted species collected from various importers, processing plants and retailers in Ontario. Of the samples, 141 (69.5 per cent) were from retailers, 51 (25 per cent) from importers and 11 (5.5 per cent) from processing plants.

Researchers identified the samples using DNA barcoding. Developed at U of G, DNA barcoding allows scientists to determine species of organisms using a short, standardized region of genetic material.

The findings revealed 32 per cent of the samples overall were mislabelled. The mislabelling rate was 17.6 per cent at the import stage, 27.3 per cent at processing plants and 38.1 per cent at retailers.

"The higher mislabelling rate in samples collected from retailers, compared to that for samples collected from importers, indicates the role of distribution and repackaging in seafood mislabelling," said Hanner.

He points to a few reasons for the problem.

"It's either economically motivated, meaning cheaper fish are being purposely mislabelled as more expensive fish. Or it's inconsistent labelling regulations between countries and the use of broader common names being used to label fish instead of scientific species names that are leading to mislabelling."

In both Canada and the U.S., fish are labelled using a common name rather than a specific scientific name. For example, a variety of species may be sold as tuna, although different species can significantly vary in price.

"It creates ambiguity and opens the door for fraud or honest mistakes," he said. "It also makes it more difficult to track species at risk or indicate if a fish is a species that has higher mercury content. At the end of the day, Canadian consumers don't really know what type of fish they are eating."

European countries that recently included species names along with common names have seen less fraud, he added.

That might help curb the problem with fish imports, Hanner said, but this new study shows a need for verification testing at multiple points along the supply chain.

"The next step would be to follow one package from import to wholesale to retail and see what happens."

BINGHAMTON, NY -- While most hearing experts would say an eardrum is required for long distance hearing, a new study from Binghamton University and Cornell University has found that Aedes aegypti mosquitos can use their antennae to detect sounds that are at least 10 meters away.

Mosquitoes have been known to use a variety of senses to detect the presence of potential mates and food sources. They can see, smell and most importantly hear what is around them.

However, it was previously believed that their hearing capabilities would be limited. While a vast number of animals hear by detecting tiny sound-induced air motion using fine hairs on their bodies, it has been generally believed that these types of creates can hear only sounds that originate at distances up to a few inches away.

Ron Miles, distinguished professor of mechanical engineering at Binghamton University, worked with professors Ron Hoy and Laura Harrington from Cornell University, who had found that mosquitoes' nerves were sensitive to sounds at long distances.

"We put the mosquitoes into my lab, which is an anechoic chamber," said Miles. "It's designed to absorb sound so that when you're conducting a study, there's no background noise or sound reflections interfering with your results."

With the mosquitoes in the anechoic chamber, the team was able to test their response to various sounds.

"We were able to observe the behavior of male mosquitoes to recorded sounds of either male or female mosquitoes," said Miles. "When the sounds from male mosquitoes were played, the males mostly just sat there. But, when we played the sounds of females, the males took off flying. We were also able to measure the neural response of their antennae and found they can hear sounds from surprisingly far away in the same frequencies that are important for human speech."

The study was not focused on whether that hearing capability was a driving factor in where mosquitoes find their human hosts, but it has been known that hearing is important for mosquitoes to find mates.

For Miles, this study is another step towards building more powerful, directional microphones. He has looked at the hearing of mosquitos previously for inspiration and has even found ways to incorporate spider silk to perfect microphones.