Tech

A Russian physicist and his international colleagues studied a quantum point contact (QCP) between two conductors with external oscillating fields applied to the contact. They found that, for some types of contacts, an increase in the oscillation frequency above a critical value reduced the current to zero - a promising mechanism that can help create nanoelectronics components. This research supported by the Russian Science Foundation (RSF) was published in the Physical Review B journal.

A persistent trend in the modern electronics, miniaturization has spurred demand for new nano-sized devices that boast advanced performance and leverage quantum effects with electrons behaving as particles and waves at the same time. Of particular importance is precise control of charge transport by means of external electric and magnetic fields. This can be achieved in a tiny QPC comparable in size to an atom (several angstroms) and with just a few electron wavelengths fitting in. Such contacts can be obtained experimentally by connecting two massive electrodes with a layer of two-dimensional electron gas, i.e. gas with particles freely moving in two directions only, and then applying voltage to the plates. The higher the voltage, the larger the forbidden area for the electrons and the narrower the contact.

The authors did theoretical research on two conductors connected by a QPC subjected to external oscillating fields. The charge carriers in the conductors were assumed to have different initial concentrations. At low oscillation frequencies, the current at the contact tends to equalize the concentrations. However, the scientists discovered that, for a certain type of contacts, the current drops to zero and the concentrations are never equal at frequencies above the critical value. This provides telling evidence of a non-equilibrium phase transition ? a dynamic phenomenon which accounts for the fundamental difference between the system properties below and above the critical value of an external parameter, in this case, oscillation frequency.

"This striking effect is best illustrated by a simple example. Imagine two vessels filled with water and their bottoms connected by a tube. If the water levels are different, water will keep flowing from one vessel to the other until its levels are the same in both vessels. Now imagine that we shake the tube with a frequency above some critical value. Water will stop flowing and will never balance out to the same level. Of course, this does not happen to water in real life, but it does happen to electrons flowing through a quantum contact "shaken" by external electric and magnetic fields," explains Oleg Lychkovskiy, a PhD in physics and mathematics and a senior research scientist at the Skolkovo Institute of Science and Technology (Skoltech), Moscow Institute of Physics and Technology and (MIPT) and V.A. Steklov Mathematical Institute of RAS.

This research can pave the way for new nanometer-scale electronic devices with a broad range of potential applications. Electronic devices and systems based on quantum effects are a promising avenue of research, considering that the Russian nanoelectronics and photonics market may balloon to 20 billion rubles by 2027.

A team of researchers from Russia and Israel applied a new algorithm to classify the severity of autistic personality traits by studying subjects' brain activity.

The article 'Brief Report: Classification of Autistic Traits According to Brain Activity Recoded by fNIRS Using ε-Complexity Coefficients' is published in the Journal of Autism and Developmental Disorders.

When diagnosing autism and other mental disorders, physicians increasingly use neuroimaging methods in addition to traditional testing and observation. Such diagnostic methods are not only more objective, but also often reveal the presence of a disorder in cases where the doctor has insufficient behavioural data, such as when the patient is young in age.

An important task in the development of diagnostic methods is the selection of an algorithm that can identify certain brain activity patterns. Since brain cells generate many electrical impulses per second, the raw data is often insufficient to make any conclusions. The data must first be processed.

A team of researchers from Russia and Israel studied one of these algorithms. The experiment involved 26 healthy subjects, though 5 were excluded from the final sample due to noisy signals. First, the participants completed the Autism Spectrum Quotient, and based on the test result, they were divided into two groups: those with strong autistic traits and those with weak autistic traits.

Then the participants performed an interpersonal synchronized movement task: each subject was asked to move their right hand in synchronization with that of the researcher for several minutes while their brain activity was recorded. Interpersonal synchronization tasks are often used in the diagnosis of autism spectrum disorders because people with ASD have difficulty coordinating joint actions.

Instead of traditional MRI or EEG, the researchers chose functional near infrared spectroscopy (fNIRS) to record subjects' brain activity.

FNIRS technology is based on measuring oxygen levels in the blood vessels of the brain using infrared light. Unlike fMRI, fNIRS is a more affordable and portable technology that does not make noise, so this neuroimaging technique is well suited for studying the brain activity of people with autism.

To analyse the brain activity data, the researchers used ε-complexity coefficients. This relatively new mathematical approach allowed the researchers to extract meaningful information from complex and noisy patterns. Based on the data processed in this way, the researchers used classical classification methods to divide the subjects into groups depending on the characteristics of brain activity when performing the synchronization task.

Experimenting with these algorithms, scientists were able to achieve prediction accuracy of more than 90%: in 9 out of 10 cases, the assessment of the severity of autistic traits in subjects using neuroimaging coincided with the results of the questionnaire that the participants filled out at the beginning.

The new technology can be used as a diagnostic tool for autism spectrum disorders, as it is more accessible and convenient when working with people with ASD compared to fMRI.

In addition, this study has successfully applied ε-complexity theory for the first time to decode data recorded with fNIRS. This opens up the possibility of using the new algorithm in other studies with fNIRS technology.

'We used ε-complexity methodology, which has been developed over the past few years by dr. Darkhovsky B.S., in our study to develop an algorithm for classifying patients based on fNIRS records of brain activity. The resulting model-free technology for time series analysis can be used in cases where the prerequisites of traditional methods of analysis are violated -- for example, when working with significantly non-stationary ECG and EEG signals. Therefore, this technology can be used to study other mental disorders and features, the patterns of which appear in the data,' says study co-author Yuri Dubnov https://www.hse.ru/en/staff/dubnov, a senior lecturer of computer science at HSE University.

MUSC Hollings Cancer Center researcher Yongxia Wu, Ph.D., identified a new target molecule in the fight against graft-versus-host disease (GVHD). Bone marrow transplant, a treatment for certain blood cancers, is accompanied by potentially life-threatening GVHD in nearly 50% of patients. A January 2021 paper published in Cellular and Molecular Immunology revealed that activating a molecule called STING may be a new approach to reduce GVHD.

Xue-Zhong Yu, M.D., professor in the Department of Microbiology and Immunology, focuses on understanding the intricate immune mechanisms that regulate GVHD development and anti-tumor activity.

Recently, STING (stimulator of interferon genes) has been highly studied in the context of cancer. Data from other groups has shown that STING activation in T cells helps the immune cells fight cancer. Cancer cells are essentially a "bad" version of the body's own cells and an appropriate target for its immune system. In contrast, in the case of GVHD, T cells fight the body's own "good" cells - in essence, the body attacks itself. Based on the previous data, it seemed logical that high STING activation, though good when it comes to cancer, would be bad in the context of GVHD. Yu's findings in a mouse model of GVHD confirmed this hypothesis. In the mouse model, which was obtained from collaborator Chih-Chi Andrew Hu, Ph.D., a Wistar Institute professor of Pathology and Laboratory Medicine, GVHD was induced by bone marrow transplant, which closely models the disease development in humans.

To understand how GVHD develops after bone marrow transplantation, one must consider two immune systems: the donor's and the recipient's. The key immune cells are the antigen-presenting cells and the T cells. The immune system knows what to attack based on specific "tags," called antigens, that are shown to the T cells by the specialized antigen-presenting cells. Dendritic cells are the most effective antigen-presenting cells, and they play a critical role in GVHD.

Work from other research groups in cancer has demonstrated that STING signaling can regulate antigen- presenting cell function. STING is an important molecule in a DNA-sensing pathway that results in the production of inflammatory cytokines. But it is not known how STING regulates these cells in the context of GVHD.

The researchers used the mouse models to determine whether GVHD improved or worsened when STING was 1) absent in the donor immune cells, 2) absent in the recipient immune cells and 3) overexpressed in the recipient immune cells. GVHD severity was not changed when STING was absent from the donor immune cells. However, GVHD was more severe and mortality rates were higher when STING was missing from the recipient immune cells.

Yu and collaborators then looked at different cell subsets to try and understand which cells were most impacted by the loss of STING. Surprisingly, STING expression in the recipient mouse's antigen-presenting cells (dendritic cells) reduced donor T cell expansion and migratory ability after bone marrow transplant. In other words, it made it less likely that the T cells of the recipient mouse would attack its "good" cells and lead to GVHD. This finding was confirmed using a pharmacological drug that turned on the STING molecule. Activating STING in the host before transplantation reduced GVHD severity.

The finding in a mouse model that activating STING with a pharmacological drug reduced GVHD could be clinically relevant in that it suggests the possibility that a STING-activating drug might protect bone marrow transplant recipients from GVHD. Much more basic and clinical research will be required to assess that possibility, but Yu's findings suggest that such research is warranted.

To understand why the research team observed what they did, they will continue to unravel the biological functions of the STING molecule. Unanswered questions include what makes STING function differently in different immune cell subsets.

"Tools such as the mice from our collaborator allow us to study this more thoroughly. Total-body deletion of a protein does not allow for specific study in cell subsets, and we think that STING must have different roles in different cells," explained Yu.

Scientists at the Fralin Biomedical Research Institute at VTC have identified a new zebrafish model that could help advance glioblastoma multiforme research. Glioblastoma is an aggressive form of primary brain tumor - fewer than one in 20 patients survive five years after diagnosis.

The research team previously discovered that human-derived brain cancer cells in mice use the brain's blood vessels like highways to spread away from the original mass. In the new study, published in ACS Pharmacology and Translational Science, they show clear cross-over between mammals and fish and describe similar observations in zebrafish.

"Our hope is that this new work in zebrafish will help researchers efficiently evaluate new, much-needed therapeutics in a pre-clinical animal model to target these aggressive and devastating tumors," said Harald Sontheimer, formerly a professor at the Fralin Biomedical Research Institute at the time of the study.

When brain cancer cells disperse, they become harder to locate and delete. Even when the original tumor is surgically removed, migratory glioblastoma cells can linger - undetected by diagnostic imaging - eventually forming new satellite tumors if they can endure chemotherapy or radiation therapies.

As the cancer cells migrate, they also leave a destructive wake.

"Our previous research showed that glioma cells exploit the brain's blood vessels. Tumor cells use blood vessels as a pathway to invade within the brain and consequently break down the blood-brain barrier," said Robyn Umans, postdoctoral associate in Sontheimer's laboratory at the Fralin Biomedical Research Institute and the study's lead author.

But what if there were a way to block glioma cells from leveraging blood vessels to control cancer cell migration?

Rodent studies led by other researchers revealed that gliomas need a key signaling pathway - Wnt, named for the wingless flies it was first observed in - in order to exploit blood vessels. When Umans added a Wnt inhibitor molecule to the zebrafish's water, they noticed a change in glioma cell behavior -- the cancer cells had reduced attachments to the brain's vasculature.

Zebrafish skin and scales are crystal clear. Scientists can put the fish under a microscope and, with fluorescent markers, watch cancer cells grow, migrate, and interact with other cells - all in real-time.

Fast-growing zebrafish are also efficient, less expensive to maintain than other preclinical models, and they share 70 percent of the same DNA as humans.

"For me, seeing is believing. With zebrafish models I can see biological mechanisms underlying aggressive cancers come to life in real-time, gaining this unprecedented visibility into the tumor microenvironment," Umans said. "Our hope is that these proof-of-principal experiments validate the zebrafish model as an additional platform for cancer drug discovery."

The researchers also wanted to see if the glioma cells also metastasized using blood vessels outside of the brain, so they injected a handful of cells into the fish's peripheral tissue. This group of cancer cells attempted to travel to the brain, but they didn't latch onto any pre-existing blood vessels. Instead, nearby vessels appeared to stem offshoots that grew toward the cancer cells like a magnet, suggesting angiogenesis, the growth of new blood vessels - a hallmark of many cancers that helps assure steady nutrient supply.

"This was a rare and special opportunity to, as a postdoc, establish a new model organism for a lab," Umans said. "This study was an exciting collaboration because two of the authors were undergraduate researchers who contributed significantly to imaging and analysis, as well as a senior principal investigator. It was really rewarding to mentor these amazing, young scientists and see a study go from the creation of a fish room to a publication."

Cisplatin is one of the most effective chemotherapy agents, used in just under half of pediatric cancer cases. Permanent hearing loss is a common side effect of this medication, but until now, studies have been too small and too varied to accurately characterize this risk. Today in The Lancet Child & Adolescent Health, investigators at Children's Hospital Los Angeles published results of the largest study of cisplatin-induced hearing loss to date. The study establishes the first benchmarks for the prevalence of hearing loss, and reveals that the risk of hearing loss is affected not only by how much drug is given, but by how that drug is delivered--dosing schedules, complementary treatments, and more. These findings will allow oncologists to deliver more information to patients, and to plan treatment schedules to minimize this side effect.

The large number of variables involved means that permanent hearing loss can occur in anywhere from 20-90% of cisplatin-treated patients. This variable range is due to the fact that circumstances differ for many patients (their age, cancer type and other factors). But the new study reveals that another important aspect of chemotherapy can impact a child's risk for hearing loss.

"We found that how we infuse the drug can significantly alter the risk of side effects," says Etan Orgel, MD, MS, who designed and led the study. "Cisplatin has been used to treat cancers in children and adults for more than fifty years, but for the first time, we have insights into how something as simple as adjusting our dosing approach may prevent hearing loss and still maintain effective treatments."

Dr. Orgel and a team of investigators, including CHLA's Diana Moke, MD, MS, collected information from over 1,400 patients treated in hospitals across the United States and Canada. A data pool of this size is no small feat. "Pediatric cancers are rare, so they're hard to study," says Dr. Moke, who treats children with many of the included cancers. "We have gathered data from the largest group ever of cisplatin-treated children and adolescents with a wide variety of cancers," she says. "This information will help us have important conversations with families about the risks they face during therapy."

Overall, the study showed that 44% of pediatric patients treated with cisplatin suffered from moderate to severe hearing loss. But the data showed that not all treatment schedules came with the same risk. Children who received higher doses of the chemotherapy were more likely to experience hearing loss, even when the total amount of cisplatin over the course of the therapy was the same. The group also uncovered another, previously unknown, risk factor for hearing loss: concurrent use of vincristine, a second chemotherapy agent often added to treatment regimens.

The team addressed another barrier to understanding cisplatin-induced hearing loss: variation in interpreting audiology scores. Many international medical centers categorize hearing loss differently, making direct comparisons impossible. To overcome this issue, the team reviewed all of the study data using the same international consensus system for cisplatin-induced hearing loss (developed by the International Society of Pediatric Oncology), enabling investigators to compare hearing loss using more than 2,000 tests from patients treated at 19 different institutions.

Uncovering how real-world variables affect risk of side effects allows oncologists to better serve each child. "Studies like these are a crucial first step in developing a truly individualized approach to each patient," says Bruce Carleton, PharmD, who led the Canadian arm of the study. "Data provided by this study will help oncologists identify patients that might be at higher risk of hearing loss so that protective strategies can be considered."

"We've developed these powerful tools to effectively fight cancer," says Dr. Orgel. "Now we can focus in on how to use these tools in a way that maintains their power but minimizes their footprint."

If you're poor and terminally ill in southern Mexico, there's far less chance you'll get the painkillers you need for palliative care than your cousins in more prosperous regions, particularly those pharmacy-rich areas along Mexico-U.S. border, say UCLA researchers and colleagues who studied opioid dispensing levels across the country.

What's more, the researchers' paper in the journal The Lancet Public Health suggests it's likely that some of the opioids intended for Mexican citizens are ending up in American pockets.

Despite a Mexican government initiative launched in 2015 to improve access to prescription opioids among palliative care patients, the country has seen only a marginal increase in dispensing levels, and inequities in dispensing have left many of the nation's poorest residents without comfort in their final days, said lead author Dr. David Goodman-Meza, an assistant professor of medicine in the infectious diseases division at the David Geffen School of Medicine at UCLA.

"People in the poorest areas of Mexico are dying in pain," Goodman-Meza said. "A lot of work needs to be done to increase access to opioids for those who have a medical need for them in Mexico."

The researchers analyzed data on prescription drug dispensing from August 2015 to October 2019 for all 32 Mexican states and six large metropolitan areas. They compared opioid prescribing levels against the expected need for the drugs based on the burden of disease in each state.

While they found that opioid dispensing had increased overall by an average of 13% per quarter over that period, they also discovered that dispensing levels were nearly 10 times higher in states whose populations had the highest socioeconomic status than in those with the lowest. In addition, higher socioeconomic status was also associated with increased opioid dispensing within individual neighborhoods in the six metropolitan areas.

The states with the highest opioid prescribing rates were Baja California (234.5 prescriptions per 10,000 residents), Mexico City (65.8 per 10,000), Nuevo Leon (58.7 per 10,000), Sonora (56.5 per 10,000) and Jalisco (51.9 per 10,000). Those with the lowest rates were Tlaxacala (0 per 10,000), Guerrero (0.6 per 10,000), Durango (2.7 per 10,000), Mexico state (4.3 per 10,000), and Tabasco (4.4 per 10,000).

Baja California, Nuevo Leon and Sonora all border the U.S., while Mexico City is its own state and sits between Mexico state and Tlaxacala in central Mexico.

Fentanyl was the most frequently dispensed of the medications, at 35.7% of the total, followed by methadone (26.5%), morphine (23.8%), tapentadol (7.3%), oxycodone (6.9%) and hydromorphone (0.2%).

The researchers note that large referral hospitals, where advanced-stage diseases are treated, tend to be concentrated in Mexico's larger, more prosperous cities and states. In addition, the high cost of the medications may put them out of reach for poorer populations, disincentivizing pharmacies in poorer areas from carrying them.

The researchers also say that many pharmacies' close proximity to entry ports along the northern border may make it easier for people in the U.S. to cross over and obtain these drugs, putting a strain on U.S. efforts to curb its opioid epidemic. Though the researchers did not focus on this and do not have cross-border purchase data, they note in the paper that these potential pathways into the U.S. bear monitoring.

"As the U.S. has tried to curb the epidemic related to prescription opioids by instituting structural mechanisms such as closing 'pill mills' and instituting prescription drug monitoring programs, individuals may be getting around them by going to Mexico to get opioids," Goodman-Meza said. "Continued surveillance at border crossings is necessary to avoid unmonitored entry of opioids into the U.S."

The study findings are limited by several other factors, among them a lack of patient- or provider-level data, the fact that the researchers did not analyze differences between the many medical systems providing care and the possibility that some institutions did not submit data to the Mexican government.

A novel computer algorithm, or set of rules, that accurately predicts the orbits of planets in the solar system could be adapted to better predict and control the behavior of the plasma that fuels fusion facilities designed to harvest on Earth the fusion energy that powers the sun and stars.

The algorithm, devised by a scientist at the U.S. Department of Energy's (DOE) Princeton Plasma Physics Laboratory (PPPL), applies machine learning, the form of artificial intelligence (AI) that learns from experience, to develop the predictions. "Usually in physics, you make observations, create a theory based on those observations, and then use that theory to predict new observations," said PPPL physicist Hong Qin, author of a paper detailing the concept in Scientific Reports. "What I'm doing is replacing this process with a type of black box that can produce accurate predictions without using a traditional theory or law."

Qin (pronounced Chin) created a computer program into which he fed data from past observations of the orbits of Mercury, Venus, Earth, Mars, Jupiter, and the dwarf planet Ceres. This program, along with an additional program known as a "serving algorithm," then made accurate predictions of the orbits of other planets in the solar system without using Newton's laws of motion and gravitation. "Essentially, I bypassed all the fundamental ingredients of physics. I go directly from data to data," Qin said. "There is no law of physics in the middle."

The program does not happen upon accurate predictions by accident. "Hong taught the program the underlying principle used by nature to determine the dynamics of any physical system," said Joshua Burby, a physicist at the DOE's Los Alamos National Laboratory who earned his Ph.D. at Princeton under Qin's mentorship. "The payoff is that the network learns the laws of planetary motion after witnessing very few training examples. In other words, his code really 'learns' the laws of physics."

Machine learning is what makes computer programs like Google Translate possible. Google Translate sifts through a vast amount of information to determine how frequently one word in one language has been translated into a word in the other language. In this way, the program can make an accurate translation without actually learning either language.

The process also appears in philosophical thought experiments like John Searle's Chinese Room. In that scenario, a person who did not know Chinese could nevertheless "translate" a Chinese sentence into English or any other language by using a set of instructions, or rules, that would substitute for understanding. The thought experiment raises questions about what, at root, it means to understand anything at all, and whether understanding implies that something else is happening in the mind besides following rules.

Qin was inspired in part by Oxford philosopher Nick Bostrom's philosophical thought experiment that the universe is a computer simulation. If that were true, then fundamental physical laws should reveal that the universe consists of individual chunks of space-time, like pixels in a video game. "If we live in a simulation, our world has to be discrete," Qin said. The black box technique Qin devised does not require that physicists believe the simulation conjecture literally, though it builds on this idea to create a program that makes accurate physical predictions.

The resulting pixelated view of the world, akin to what is portrayed in the movie The Matrix, is known as a discrete field theory, which views the universe as composed of individual bits and differs from the theories that people normally create. While scientists typically devise overarching concepts of how the physical world behaves, computers just assemble a collection of data points.

Qin and Eric Palmerduca, a graduate student in the Princeton University Program in Plasma Physics, are now developing ways to use discrete field theories to predict the behavior of particles of plasma in fusion experiments conducted by scientists around the world. The most widely used fusion facilities are doughnut-shaped tokamaks that confine the plasma in powerful magnetic fields.

Fusion, the power that drives the sun and stars, combines light elements in the form of plasma -- the hot, charged state of matter composed of free electrons and atomic nuclei that represents 99% of the visible universe -- to generate massive amounts of energy. Scientists are seeking to replicate fusion on Earth for a virtually inexhaustible supply of power to generate electricity.

"In a magnetic fusion device, the dynamics of plasmas are complex and multi-scale, and the effective governing laws or computational models for a particular physical process that we are interested in are not always clear," Qin said. "In these scenarios, we can apply the machine learning technique that I developed to create a discrete field theory and then apply this discrete field theory to understand and predict new experimental observations."

This process opens up questions about the nature of science itself. Don't scientists want to develop physics theories that explain the world, instead of simply amassing data? Aren't theories fundamental to physics and necessary to explain and understand phenomena?

"I would argue that the ultimate goal of any scientist is prediction," Qin said. "You might not necessarily need a law. For example, if I can perfectly predict a planetary orbit, I don't need to know Newton's laws of gravitation and motion. You could argue that by doing so you would understand less than if you knew Newton's laws. In a sense, that is correct. But from a practical point of view, making accurate predictions is not doing anything less."

Machine learning could also open up possibilities for more research. "It significantly broadens the scope of problems that you can tackle because all you need to get going is data," Palmerduca said.

The technique could also lead to the development of a traditional physical theory. "While in some sense this method precludes the need of such a theory, it can also be viewed as a path toward one," Palmerduca said. "When you're trying to deduce a theory, you'd like to have as much data at your disposal as possible. If you're given some data, you can use machine learning to fill in gaps in that data or otherwise expand the data set."

UPTON, NY--Scientists at the U.S. Department of Energy's Brookhaven National Laboratory, Stony Brook University (SBU), and other collaborating institutions have uncovered dynamic, atomic-level details of how an important platinum-based catalyst works in the water gas shift reaction. This reaction transforms carbon monoxide (CO) and water (H2O) into carbon dioxide (CO2) and hydrogen gas (H2)--an important step in producing and purifying hydrogen for multiple applications, including use as a clean fuel in fuel-cell vehicles, and in the production of hydrocarbons.

But because platinum is rare and expensive, scientists have been seeking ways to create catalysts that use less of this precious metal. Understanding exactly what the platinum does is an essential step.

The new study, published in Nature Communications, identifies the atoms involved in the catalyst's active site, resolving earlier conflicting reports about how the catalyst operates. The experiments provide definitive evidence that only certain platinum atoms play an important role in the chemical conversion.

"Part of the challenge is that the catalyst itself has a complex structure," explained lead author Yuanyuan Li, a research scientist at SBU's Materials Science and Chemical Engineering Department who has a guest appointment in Brookhaven Lab's Chemistry Division and works under the guidance of Brookhaven/SBU joint appointee Anatoly Frenkel.

"The catalyst is made of platinum nanoparticles (clumps of platinum atoms) sitting on a cerium oxide (ceria) surface. Some of those platinum atoms are on the surface of the nanoparticle, some are in the core; some are at the interface with ceria, and some of those are at the perimeter--the outside edges--of that interface," Li said. "Those positions and how you put the particles on the surface may influence which atoms will interact with the support or with gas molecules, because some are exposed and some are not."

Earlier experiments had produced conflicting results about whether the reactions occur on the nanoparticles or at single isolated platinum atoms, and whether the active sites are positively or negatively charged or neutral. Details of how the ceria support interacts with the platinum to activate it for catalytic activity were also unclear.

"We wanted to address these questions," said Li. "To identify the active site and determine what is really happening at this site, it is better if we can investigate this type of catalyst at the atomic level," she noted.

The team, which included scientists from Brookhaven's Center for Functional Nanomaterials (CFN) and other institutions throughout the U.S. and in Sweden, used a range of techniques to do just that. They studied the catalyst under reaction conditions and, unexpectedly, captured a peculiar effect that occurred when the catalysts reached their active state in reaction conditions.

"The platinum atoms at the perimeter of the particles were 'dancing' in and out of focus in an electron microscopy experiment carried out by our collaborators, while the rest of the atoms were much more stable," Frenkel said. Such dynamic behavior was not observed when some of the reactants (CO or water) were removed from the stream of reacting molecules.

"We found that only the platinum atoms at the perimeter of the interface between the nanoparticles and ceria support provide the catalytic activity," Li said. "The dynamic properties at these perimeter sites allow the CO to get oxygen from the water so it can become CO2, and the water (H2O) loses oxygen to become hydrogen."

Now that the scientists know which platinum atoms play an active role in the catalyst, they may be able to design catalysts that contain only those active platinum atoms.

"We might assume that all the surface platinum atoms are working, but they are not," Li said. "We don't need them all, just the active ones. This could help us make the catalyst less expensive by removing the atoms that are not involved in the reaction. We believe that this mechanism can be generalized to other catalytic systems and reactions," she added.

Experimental details

Electron microscopy "snapshots" at the CFN and at the National Institute of Standards and Technology revealed the dynamic nature of the perimeter platinum atoms. "In some images, the perimeter site is there, you can see it, but in some images it is not there. This is evidence that these atoms are very dynamic, with high mobility," Li said.

Infrared (IR) spectroscopy studies in Brookhaven's Chemistry Division revealed that the appearance of the perimeter sites coincided with "oxygen vacancies"--a kind of defect in the cerium oxide surface. These studies also showed that CO tended to migrate across the platinum nanoparticle surface toward the perimeter atoms, and that hydroxy (OH) groups lingered on the ceria support near the perimeter platinum atoms.

"So it seems like the perimeter platinum atoms bring the two reactants, CO and OH (from the water molecules) together," Li said.

X-ray photoelectron spectroscopy studies in Chemistry revealed that perimeter platinum atoms also became activated--changed from a nonmetallic to a metallic state that could capture oxygen atoms from the OH groups and deliver that oxygen to CO. "This really shows that these activated perimeter platinum sites enable the reaction to take place," Li said.

A final set of experiments--x-ray absorption spectroscopy studies conducted at the Advanced Photon Source (APS) at DOE's Argonne National Laboratory--showed the dynamic structural changes of the catalyst.

"We see the structure is changing under reaction conditions," Li said.

Those studies also revealed an unusually long bond between the platinum atoms and the oxygen on the ceria support, suggesting that something invisible to the x-rays was occupying space between the two.

"We think there is some atomic hydrogen between the nanoparticle and the support. X-rays can't see light atoms like hydrogen. Under reaction conditions, those atomic hydrogens will recombine to form H2," she added.

The structural features and details of how the dynamic changes are connected to reactivity will help the scientists understand the working mechanism of this particular catalyst and potentially design ones with better activity at lower cost. The same techniques can also be applied to studies of other catalysts.

In far too many cases over the years, scientists have discovered promising new cancer treatments, only to report later that the tumor cells found ways to become resistant. These disappointing results have made overcoming drug resistance a major goal in cancer research.

Now, experts at Cincinnati Children's report success at averting drug resistance in a subtype of brain tumors called glioblastomas. Importantly, the research indicates that the approach may also work in other cancers, such as melanoma, that exhibit a similar pathway of drug resistance.

The method involves inhibiting a protein called SCD and reducing the expression of the transcription factor FOSB (which regulates SCD), so that the tumor cells cannot acquire resistance to the SCD inhibitor. Results were published online Feb. 10, 2021, in the journal Science Advances.

"This is one of the most significant findings from our lab in recent years," says principal investigator Biplab Dasgupta, PhD, Division of Oncology.

Much more research is needed before this approach can be tested in people with glioblastomas, but animal model experiments reveal that mice bearing brain tumors survive longer when treated with a combination therapy that includes SCD and FOSB inhibition.

Additionally, using the standard of care chemotherapeutic agent temozolomide (TMZ), mice with advanced tumors initially showed "significant" tumor reduction, but all of the mice relapsed and 80% had died by 50 days post treatment. In contrast, when treated with TMZ in combination with the SCD inhibitor, 80% of the mice survived past 50 days.

How the combination therapy works

The new approach was based on their discovery that some brain tumors have surprisingly low amounts of an enzyme called Stearoyl Co-A Desaturase (SCD). Typically, cancer cells use elevated levels of this enzyme to fuel their uncontrolled growth, which has inspired a number of drugs that target SCD to treat tumors.

However, through analysis of publicly available glioblastoma genetic datasets, Dasgupta and research fellow Nicole Oatman, PhD, discovered that the SCD gene is both deleted as well as its expression suppressed through epigenetic mechanisms in a large subset of glioblastoma patients.

"This finding was surprising given the requirement of SCD in most cancers," says Dasgupta.

While the Dasgupta Lab is still working to understand how glioblastomas survive without SCD, potentially by using alternative pathways that bypass SCD, they determined that glioblastoma cell lines that retain SCD are exquisitely sensitive to SCD inhibitors.

They also found that like most cancer cells, SCD inhibitor-sensitive glioblastomas ultimately acquire resistance to SCD inhibitors. They discovered that FOSB protein plays a central role in regulating SCD levels. When a drug knocks down SCD, FOSB kicks in to rapidly build SCD levels back up. This reinforcing effect overwhelms the anti-SCD medication effects and allows tumors to come roaring back.

Turning off the FOSB protein essentially silences the call for reinforcements, which allows the SCD-inhibiting drugs to be dramatically more effective. The team then expanded their work by finding similar outcomes when testing the combination therapy to treat melanoma, a severe form of skin cancer.

By understanding how this process works, Dasgupta says it will help many scientists re-assess clinical trial results for SCD-inhibiting drugs, which may reveal that some past discoveries that appeared to be failures might still have value in cancer treatment.

Seismic monitoring devices linked to the internet are vulnerable to cyberattacks that could disrupt data collection and processing, say researchers who have probed the devices for weak points.

Common security issues such as non-encrypted data, insecure protocols, and poor user authentication mechanisms are among the biggest culprits that leave seismological networks open to security breaches, Michael Samios of the National Observatory of Athens and colleagues write in a new study published in Seismological Research Letters.

Modern seismic stations are now implemented as an Internet-of-Things (IoT) station, with physical devices that connect and exchange data with other devices and systems over the Internet. In their test attacks on different brands of seismographs, accelerographs and GNSS receivers, Samios and his colleagues identified threats to the equipment that information technology security professionals commonly find in IoT devices.

"It seems that most seismologists and network operators are unaware of the vulnerabilities of their IoT devices, and the potential risk that their monitoring networks are exposed to," said Samios. "Educating and supporting seismologists on information security is imperative, as in most cases unauthorized users will try to gain access through a legitimate user's computer to abuse monitoring networks and IoT devices."

By exploiting these vulnerabilities, a malicious user could alter geophysical data, slow down data transmission and processing, or produce false alarms in earthquake early warning systems, the researchers noted, causing the public to lose trust in seismic monitoring and potentially affecting emergency and economic responses to a seismic event.

Samios and colleagues launched a security assessment of seismic and GNSS devices attached to their own monitoring networks after a security incident at one of their seismic stations. There are several potential weak points in the security of these devices, they noted, including physical security in sometimes remote locations, difficulties and costs of updating security of hardware and software, usage of non-encrypted protocols, and default or easy login credentials.

Using their cybersecurity skills, the researchers tested these weak points using a typical "ethical hacking" process to surveil, scan and gain access to geophysical devices with their default settings. The most notable security issues, they discovered, were a lack of data encryption, weak user authentication protocols and the absence of a secure initial-default configuration

Samios and colleagues were able to demonstrate a launch of a successful denial-of-service or DOS attack against the devices, causing them to be unavailable for the period of the attack, as well as retrieve usernames and passwords for some of the devices.

"Security weaknesses between different devices do not depend on the type of the device, but whether this device uses insecure protocols, outdated software and a potentially insecure default configuration," Samios said. "It is interesting, though, that while these vulnerabilities normally appear on low-cost IoT devices priced at $50 or less, it was also confirmed that they are observed even in seismological and GNSS devices that cost many times more."

As part of their tests, the research team was also able to intercept seismological data transferred through the SeedLink protocol, a data transmission service used by many seismologists. SeedLink may lack some of the necessary encryption and authentication protocols to keep data safe, Samios said. He noted that in a follow-up lab experiment not included in the SRL paper the researchers were able to manipulate waveforms transferred by SeedLink.

"This could potentially generate or conceal alarms on earthquake early warning and seismic monitoring systems, leading to disturbing situations," he said.

While device manufacturers and data transmission services should take steps to improve security functions such as data encryption, Samios said, seismic network operators can work with information security experts to help them develop safer user practices and enhance hardware and software systems.

A team of researchers, led by a Texas A&M University professor, has found that some energy drinks have adverse effects on the muscle cells of the heart.

The study, led by Dr. Ivan Rusyn, a professor in the Veterinary Integrative Biosciences (VIBS) Department at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVMBS), was published in Food and Chemical Toxicology. In it, researchers observed cardiomyocytes - human heart cells grown in a laboratory - exposed to some energy drinks showed an increased beat rate and other factors affecting cardiac function.

When placed in the context of the human body, consumption of these beverages has been linked to improper beating of the heart, cardiomyopathy (disease of the heart muscle which makes it difficult for the heart to pump blood), increased blood pressure, and other heart conditions.

With the global sales of energy drinks estimated at $53 billion in 2018 and rapidly growing, it is important to understand the potential unintended health consequences associated with these beverages, according to Rusyn.

"Because the consumption of these beverages is not regulated and they are widely accessible over the counter to all age groups, the potential for adverse health effects of these products is a subject of concern and needed research," Rusyn said. "Indeed, the consumption of energy drinks has been associated with a wide range of adverse health effects in humans, many of them are concerning the effects on the heart."

Researchers evaluated 17 widely available over-the-counter brands. They then treated cardiomyocytes with each drink.

Researchers also studied the composition of the energy drinks using novel methods. By comparing the effects and differing ingredient concentrations in each drink, they were able to infer which ingredients may be contributing more to adverse effects on the treated cardiomyocytes. Using mathematical models, researchers determined that the possible presence of theophylline, adenine and azelate, substances which can have negative effects on the heart.

"Little is known about the ingredients that may contribute to the adverse effects of energy drinks on the heart," Rusyn said. "Specifically, the evidence for cardiovascular effects from studies in humans remains inconclusive, as the controlled clinical trials were largely limited in the number of participants. They were tested only a limited number of energy drink types, and are difficult to compare directly, because they employed different methods to evaluate the function of the cardiovascular system."

Further research is warranted on the ingredients identified in this study to ensure the safety of their consumption, especially by consumers with pre-existing health conditions.

"This study shows that some of the tested energy drinks may have effects on human cardiomyocytes, and these data corroborate other studies in humans," Rusyn said. "Therefore, we hope that the consumers will carefully weigh the performance-enhancing benefits of these beverages versus the emerging data that suggests that they may have real adverse effects.

"We also hope that the Food and Drug Administration takes a closer look at whether these beverages may need to be carefully reviewed with respect to possible labeling of their adverse health effects, and whether certain age groups and susceptible sub-populations should be advised against consumption of these beverages."

Israelis across the political spectrum prefer the status quo to the two-state solution, and Palestinians are only willing to accept a two-state solution that Israelis will be unable to accept, according to a new RAND Corporation report that assesses whether there are any alternative solutions to the conflict that average Israelis and Palestinians would support.

Derived from a series of innovative, structured focus group discussions, the report suggests that the Biden Administration's recent reaffirmation of U.S. policy to support a "mutually agreed two-state solution, one in which Israel lives in peace and security alongside a viable Palestinian state," will face a steep uphill climb.

The analysis focused on five plausible alternatives: two-state solution, one-state solution, confederation approach, Israeli annexation of the West Bank's Area C, and perpetuation of today's status quo. Almost all parties were extremely pessimistic about the feasibility of any. About 60% of Israelis said the status quo could feasibly continue, as it has for decades, and many others believed that it was manageable and preferable to the risk of other alternatives. Peace was considered a "romantic notion" that was simply not attainable at this time.

"One of our key goals was to determine if there were areas of overlap in opinions and feeling among Israelis and Palestinians that might offer avenues for negotiation, leading the parties closer to peace," said Daniel Egel, lead author of the report and an economist at nonprofit, nonpartisan RAND. "Sadly, the data show the opposite. The data highlight the deep distrust and profound animosity of each side for the other."

Resolving the crisis will likely require more holistic "peace deals" than have been previously offered, the researchers found. While previous deals have focused on economic dividends, the international community has shied away from the security guarantees that could help find common ground between these two peoples.

Researchers conducted four-hour-long discussions with 273 individual West Bank Palestinians, Gazan Palestinians, Israeli Jews and Israeli Arabs in 2018 and 2019. The focus groups, based on RAND's Delphi method, aimed to complement extensive polling efforts by others on this topic.

One key finding is that getting Israeli Jews to support any alternative to the status quo will require a shift in both domestic and international politics. "It is hard to imagine a departure from current trends unless strong, courageous leadership among Israelis, Palestinians and the international community articulates a desire for a better future for all," said C. Ross Anthony, co-leader of the report and director of RAND's Israeli-Palestinian Initiative.

Researchers found that among Israeli Jews there are two major impediments to anything but the status quo: a lack of trust in Palestinian objectives and a general belief that none of the other alternatives are feasible. The lack of trust results in fear, xenophobia and a willingness to forgo basic principles of democracy when it comes to the rights of Palestinians.

Another key finding is that Palestinians will likely require international security guarantees for any peaceful resolution. Palestinians perceived all five alternatives as biased against them and primarily serving the interests of the more powerful Israelis.

Palestinians indicated they would be willing to accept a modified two-state solution, with an independent state with geographic contiguity, political autonomy, a standing army and control over the borders. While such a solution would be very difficult for Israel to accept, a two-state solution where the international community made credible commitments to guarantee Palestinian security could be more viable, researchers concluded.

The third key policy finding is that educating Israelis and the Palestinians about the alternatives could help. Pre-testing showed that few focus-group participants started with a clear understanding of any of the alternatives, but receiving a brief overview allowed them to make a more informed decision and some changed their minds.

"An information campaign, educating individuals about all the alternatives, could be an important component of efforts to promote a peaceful resolution to the conflict," said co-author Shira Efron, a senior research fellow at the Institute for National Security Studies (INSS) and special advisor on Israel for RAND.

"We hope that in the coming years Israelis and Palestinians and the international community will have the courage to make the commitments - and sacrifices - to resolve what has been one of the most enduring political challenges in the post-World War II period," said co-author Charles Ries, adjunct senior fellow at RAND.

The number of people who own electric vehicles (EVs) is increasing, but they face a conundrum: Unlike those who own gasoline-burning cars, EV owners can't just pop down to the corner gas station for a fill-up. Particularly in rural areas, charging stations can be few and far between.

Joshua Pearce, Richard Witte Endowed Professor of Materials Science and Engineering and professor of electrical and computer engineering at Michigan Technological University, hopes to change that.

In a model outlined in a paper in the journal Renewable Energy, Pearce and his co-author, graduate student Swaraj Sanjay Deshmukh, note the untapped potential of retail parking lot solar photovoltaic awnings.

The study investigates the energy-related benefits of developing EV charging stations powered with solar photovoltaic (PV) canopies built into the parking infrastructure of large-scale retailers like Walmart.

The case study shows such canopies could generate a potential of 3.1 megawatts per Walmart supercenter in the U.S., providing solar electricity for approximately 100 EV charging stations. Across the country, Walmart could deploy 11.1 gigawatts of solar canopies over parking lots to provide more than 346,000 EV charging stations with solar electricity for their customers. Such a fleet of solar awnings would cover the needs of 90% of the American public living within 15 miles of a Walmart -- just about as prevalent as the corner gas station.

This model could be adopted by any box store because they have a competitive advantage of stand-alone EV charging stations. Solar electricity for EV charging could be made at a profit, solving community charging challenges. The results indicate store owners could increase store selection and profit by providing free PV-EV charging for their customers with four key benefits:

Increasing customer comfort by providing shading and precipitation shelter.

A path for green consumerism.

Incentive for preferential shopping for owners of plug-in hybrid electric vehicles and EVs.

Increase shopping time and money spent at the store to enable more charging.

"The electric car powerhouse Tesla is now the most valuable automobile company in the world, and the more experienced auto manufacturing giant GM has announced gas and diesel vehicles will be extinct by 2035. It is clear EV growth will continue to accelerate," Pearce said. "Retailers have an opportunity to leverage the stranded asset of their parking lots for profit from preferential store selection by the growing army of EV owners. Fast-moving retailers that make the investment in solar canopies and EV charging stations will attract early EV adopters and reap the most profit."

A team of researchers from Immanuel Kant Baltic Federal University obtained magnetic nanoparticles using sweet flag (Acorus calamus). Both the roots and the leaves of this plant have antioxidant, antimicrobial, and insecticide properties. The extract of sweet flag was used as a non-toxic reagent for the manufacture of coated particles. The authors of the work also showed the efficiency of the new nanoparticles against several types of pathogenic fungi that damage cultivated plants. A technology developed by the team provides for the manufacture of nanoparticles from a cheap plant-based raw material and reduces the harmful effect of reagents on the environment.

Because of their unique properties, nanoparticles are used in many areas, from medicine to oil production. Their characteristics depend to a great extent on their size and shape, and the ratio between their surface area and volume plays a key role. The bigger it is, the stronger is a nanoparticle's local effect. Magnetic nanoparticles that can be controlled with an external magnetic field or emit heat under the influence of electromagnetic radiation have potential in biology and medicine. For example, particles with increased magnetic moment are used both in medical diagnostics and for the treatment of various conditions. Some studies also indicate that magnetic nanoparticles can have antifungal properties. For these applications, scientists suggest using barium ferrite nanoparticles in biocompatible coating.

"There are several methods of manufacturing coated nanoparticles with given characteristics, but all of them include toxic reagents. We have developed an environmentally friendly technology for the production of barium ferrite with the use of sweet flag extract. The surface of these particles has additional biological properties and the particles themselves possess all necessary magnetic and geometrical characteristics," said Prof. Larissa Panina, a Ph.D. in Physics and Mathematics from BFU.

The team mixed an extract made from dried sweet flag roots with barium and iron salts and water. Then, the mixture was heated to evaporate the liquid and obtain powder. After that, the powder was sintered at temperatures up to 900°C, and nanoparticles were formed. To study their morphology, the team used scanning electron microscopy. This method is based on scanning the surface of a studied object with an electron beam and applies to fragments that are just several nanometers in size. The average size of the hexagon-shaped nanoparticles was from 20 to 50 nm. The team also studied the crystalline structure and elemental composition of the particles using X-ray structural analysis and energy dispersive spectroscopy and found out that the new particles had no admixtures.

The barium ferrite nanoparticles synthesized by the team were active against four species of fungi that cause various diseases of fruit and flowering plants. Even in small concentrations, the nanoparticles were able to slow down the growth of pathogens. In the course of the Fenton reaction, the ions of iron in barium ferrite reacted with peroxides and reactive oxygen forms (OH radicals) appeared. Being extremely active, they reacted with substances in harmful cell walls, damaged them, and thus slowed down the growth of pathogens. According to the authors of the study, this is a universal mechanism that might make the nanoparticles active against other species of fungi, too.

The GIP receptor in the central nervous system plays a crucial role in the regulation of body weight and food intake. This is shown by a recent study by Helmholtz Zentrum München, ETH Zurich and the German Center for Diabetes Research (DZD). The study, which has now been published in 'Cell Metabolism', identifies new targets for the development of a drug treatment for obesity and type 2 diabetes.

Dual-agonists targeting the receptors for Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are promising novel drug candidates for the treatment of obesity and diabetes. The new study shows how GIP decreases body weight. GIP is a hormone produced by the digestive tract. After food intake, GIP stimulates the release of insulin and thus lowers blood glucose levels. The hormone also has an effect on appetite regulation. However, the mechanisms and organs through which GIP affects body weight are unknown. Until now, it was unclear whether the GIP receptor should be activated or inhibited for body weight reduction and what role the brain plays in the effect of GIP. "The aim of our studies was to find out whether the GIP receptor in the brain plays a special role in the action of GIP," said first author Qian Zhang of the Institute for Diabetes and Obesity at Helmholtz Zentrum München.

GIP lowers body weight through brain-mediated inhibition of food intake

The researchers were able to show that the administration of GIP reduces body weight and food intake in wild-type mice, but not in mice that lack the GIP receptor in the central nervous system.

Does the hormone act on specific areas in the brain? To answer this question, the researchers investigated the brain activity of mice with diet-induced obesity after they had been treated with GIP. "This revealed increased neuronal activity in areas of the hypothalamus associated with appetite control," said Professor Christian Wolfrum of ETH Zurich. The authors conclude that the central regulation of food intake via GIP also includes the activation of important neurons in the hypothalamus.

New targets for the development of a drug treatment for obesity and type 2 diabetes

The new findings are also important for the development of drug treatment for obesity and type-2 diabetes. Researchers at Helmholtz Zentrum München, together with Indiana University, have developed a new therapeutic approach for type-2 diabetes. They combined hormones in a single molecule that act equally at the receptors of the insulin-stimulating hormones GLP-1 and GIP. The dual agonist lowers body weight and improves blood glucose levels1. GLP-1/GIP dual-agonists are already in phase 3 clinical trials. Clinical studies showed that GLP-1/GIP reduces body weight to a greater extent than treatment with GLP-1 alone.

However, these marked differences in weight loss were not observed in mice lacking the GIP receptor in the CNS, says Dr. Timo Müller, last author of the new study and acting Director of the Institute for Diabetes and Obesity. Here, the GLP-1/GIP dual-agonist and the administration of GLP-1 equally reduce body weight. "Our research shows for the first time that the GLP-1/GIP dual-agonist requires the GIP receptor in the brain to reduce body weight and food intake," said DZD-Researcher Dr. Müller. "These findings may aid in the development of novel drug targets that improve the signaling and effect of the GIP receptor. This could help to further increase the metabolic benefits of treatment with GIP and GLP-1/GIP."