Tech

PORTLAND, Ore. - A new study suggests that roughly half of the opioid prescriptions written by dentists in the United States exceed the three-day supply recommended by federal dental pain-management guidelines.

The research also showed that during the five-year study period, a more powerful narcotic than necessary was prescribed almost 3 times of out 10.

The findings, published today in the American Journal of Preventive Medicine, are important because dentists are responsible for 10% of all opioids prescribed in the United States, which has been in the throes of an opioid-fueled public health crisis for more than two decades.

"Dental procedures like extractions can leave patients with a lot of pain that needs to be managed, and many dentists are doing a wonderful job of managing their patients' pain appropriately and responsibly," said Jessina McGregor, a researcher in the Oregon State University College of Pharmacy who took part in the study. "But our findings suggest that there's room for improvement among some dentists, improvement that could make a huge difference in our society as we try to combat the opioid crisis."

Traced to over-prescribing that began in the 1990s, the opioid epidemic claims more than 40,000 American lives per year, according to the U.S. Department of Health and Human Services. Ten million people a year misuse prescription opioids, and 2 million suffer from an opioid use disorder.

Occurring naturally in the opium poppy, opioids are a class of drugs that block pain signals between the body and brain and also make some people feel relaxed, happy or high. They can be highly addictive and exist both as prescription painkillers like hydrocodone and oxycodone and street drugs such as heroin.

The research collaboration that included McGregor and was led by Katie Suda of the University of Pittsburgh assessed more than half a million adult dental visits from 2011 to 2015 within the Truven Health MarketScan Research Databases.

The study is the largest analysis to date of dental visits that resulted in an opioid prescription. The median age of the study population was 46, and the male-female ratio was 52:48.

Fifty-three percent of the time, patients were given more than the three-day supply recommended by the Centers for Disease Control and Prevention. And based on a standard measure for opioid potency - morphine equivalent - the prescribed opioids were more powerful than deemed medically necessary 29% of the time.

"One large potential area for improvement is the almost 30% percent of opioids that were prescribed following procedures where the pain intensity was expected to be mild and manageable by non-opioid analgesics like ibuprofen or acetaminophen," said McGregor, who also holds an adjunct appointment with the Oregon Health & Science University-Portland State University School of Public Health.

Men, patients ages 18-34, people living in the South, and patients receiving oxycodone, which is 50% more powerful than morphine, were most likely to be prescribed drugs that were stronger than needed - research has shown that all of those groups have a higher than average risk of addiction and overdose.

"Our statistical models suggest that even something as simple and straightforward as substituting a lower-potency opioid like hydrocodone for oxycodone could make an enormous reduction in overprescribing, as much as a 20% reduction," McGregor said.

HOUSTON -- (Feb. 4, 2020) -- Rice University engineers have created a deep learning computer system that taught itself to accurately predict extreme weather events, like heat waves, up to five days in advance using minimal information about current weather conditions.

Ironically, Rice's self-learning "capsule neural network" uses an analog method of weather forecasting that computers made obsolete in the 1950s. During training, it examines hundreds of pairs of maps. Each map shows surface temperatures and air pressures at five-kilometers height, and each pair shows those conditions several days apart. The training includes scenarios that produced extreme weather -- extended hot and cold spells that can lead to deadly heat waves and winter storms. Once trained, the system was able to examine maps it had not previously seen and make five-day forecasts of extreme weather with 85% accuracy.

With further development, the system could serve as an early warning system for weather forecasters, and as a tool for learning more about the atmospheric conditions that lead to extreme weather, said Rice's Pedram Hassanzadeh, co-author of a study about the system published online this week in the American Geophysical Union's Journal of Advances in Modeling Earth Systems.

The accuracy of day-to-day weather forecasts has improved steadily since the advent of computer-based numerical weather prediction (NWP) in the 1950s. But even with improved numerical models of the atmosphere and more powerful computers, NWP cannot reliably predict extreme events like the deadly heat waves in France in 2003 and in Russia in 2010.

"It may be that we need faster supercomputers to solve the governing equations of the numerical weather prediction models at higher resolutions," said Hassanzadeh, an assistant professor of mechanical engineering and of Earth, environmental and planetary sciences at Rice. "But because we don't fully understand the physics and precursor conditions of extreme-causing weather patterns, it's also possible that the equations aren't fully accurate, and they won't produce better forecasts, no matter how much computing power we put in."

In late 2017, Hassanzadeh and study co-authors and graduate students Ashesh Chattopadhyay and Ebrahim Nabizadeh decided to take a different approach.

"When you get these heat waves or cold spells, if you look at the weather map, you are often going to see some weird behavior in the jet stream, abnormal things like large waves or a big high-pressure system that is not moving at all," Hassanzadeh said. "It seemed like this was a pattern recognition problem. So we decided to try to reformulate extreme weather forecasting as a pattern-recognition problem rather than a numerical problem."

Deep learning is a form of artificial intelligence, in which computers are "trained" to make humanlike decisions without being explicitly programmed for them. The mainstay of deep learning, the convolutional neural network, excels at pattern recognition and is the key technology for self-driving cars, facial recognition, speech transcription and dozens of other advances.

"We decided to train our model by showing it a lot of pressure patterns in the five kilometers above the Earth, and telling it, for each one, 'This one didn't cause extreme weather. This one caused a heat wave in California. This one didn't cause anything. This one caused a cold spell in the Northeast,'" Hassanzadeh said. "Not anything specific like Houston versus Dallas, but more of a sense of the regional area."

At the time, Hassanzadeh, Chattopadhyay and Nabizadeh were barely aware that analog forecasting had once been a mainstay of weather prediction and even had a storied role in the D-Day landings in World War II.

"One way prediction was done before computers is they would look at the pressure system pattern today, and then go to a catalog of previous patterns and compare and try to find an analog, a closely similar pattern," Hassanzadeh said. "If that one led to rain over France after three days, the forecast would be for rain in France."

He said one of the advantages of using deep learning is that the neural network didn't need to be told what to look for.

"It didn't matter that we don't fully understand the precursors because the neural network learned to find those connections itself," Hassanzadeh said. "It learned which patterns were critical for extreme weather, and it used those to find the best analog."

To demonstrate a proof-of-concept, the team used model data taken from realistic computer simulations. The team had reported early results with a convolutional neural network when Chattopadhyay, the lead author of the new study, heard about capsule neural networks, a new form of deep learning that debuted with fanfare in late 2017, in part because it was the brainchild of Geoffrey Hinton, the founding father of convolutional neural network-based deep learning.

Unlike convolutional neural networks, capsule neural networks can recognize relative spatial relationships, which are important in the evolution of weather patterns.
"The relative positions of pressure patterns, the highs and lows you see on weather maps, are the key factor in determining how weather evolves," Hassanzadeh said.

Another significant advantage of capsule neural networks was that they don't require as much training data as convolutional neural networks. There's only about 40 years of high-quality weather data from the satellite era, and Hassanzadeh's team is working to train its capsule neural network on observational data and compare its forecasts with those of state-of-the-art NWP models.

"Our immediate goal is to extend our forecast lead time to beyond 10 days, where NWP models have weaknesses," he said.

Though much more work is needed before Rice's system can be incorporated into operational forecasting, Hassanzadeh hopes it might eventually improve forecasts for heat waves and other extreme weather.

"We are not suggesting that at the end of the day this is going to replace NWP," he said. "But this might be a useful guide for NWP. Computationally, this could be a super cheap way to provide some guidance, an early warning, that allows you to focus NWP resources specifically where extreme weather is likely."

Hassanzadeh said his team is also interested in finding out what patterns the capsule neural network uses to make its predictions.

"We want to leverage ideas from explainable AI (artificial intelligence) to interpret what the neural network is doing," he said. "This might help us identify the precursors to extreme-causing weather patterns and improve our understanding of their physics."

In physics, there are very different types of particles: Elementary particles are the fundamental building blocks of matter. Other particles, such as atoms, are bound states consisting of several smaller constituents. And then there are so-called "quasi-particles" - excitations in a system that consists of many particles, which in many ways behave just like a particle themselves.

Such a quasiparticle has now been discovered in computer simulations at TU Wien (Vienna) and named pi-ton. It consists of two electrons and two holes. The new particle is presented in the journal "Physical Review Letters", the article also describes how the pi-ton can be detected experimentally.

A hole is almost a particle

"The simplest quasi-particle is a hole", explains Prof. Karsten Held from the Institute for Solid State Physics at TU Wien. "Let us imagine, for example, that many atoms are arranged in a regular pattern in a crystal and that there is a moving electron at each atom. Only at one particular atom the electron is missing - this is called a hole". Now an electron can move up from the neighbouring atom. The original hole is closed, a new hole opens.

Instead of describing the motion of constantly moving electrons, it is easier to study the motion of the hole. If the electrons move to the right, the hole moves to the left - and this movement follows certain physical rules, just like the movement of an ordinary particle. However, unlike an electron, which can also be observed outside the crystal, the hole only exists in conjunction with the other particles. In this case we speak of a "quasi-particle".

"However, the dividing line between particles and quasi-particles is not as clear as one might think," says Karsten Held. "Strictly speaking, even ordinary particles can only be understood in the context of their environment. Even in a vacuum, particle-hole excitations occur constantly, albeit for a very short time. Without them, the mass of an electron for example would be completely different. In this sense, even in experiments with ordinary electrons, what we see is really a quasi-particle electron."

More complicated bonds

But there are also more complex quasi-particles: The exciton, for example, which plays an important role in semiconductor physics. It is a bound state consisting of an electron and a hole, which is created by light. The electron is negatively charged, the hole is the absence of a negative charge - and thus positively charged. Both attract each other and can form a bond.

"We actually wanted to investigate such excitons", report Dr. Anna Kauch and Dr. Petra Pudleiner, the first authors of the paper. "We developed computer simulations to calculate quantum physical effects in solids." But soon Anna Kauch, Petra Pudleiner and their colleague Katharina Astleithner realized that they had come across something totally different in their calculations - a completely new type of quasi-particle. It consists of two electrons and two holes that couple to the outside world via photons.

The team gave this previously unknown object the name pi-ton". "The name pi-ton comes from the fact that the two electrons and two holes are held together by charge density fluctuations or spin fluctuations that always reverse their character by 180 degrees from one lattice point of the crystal to the next - i.e. by an angle of pi, measured in radians," explains Anna Kauch. "This constant change from plus to minus can perhaps be imagined like a change from black to white on a chessboard," says Petra Pudleiner. The pi-ton is created spontaneously by absorbing a photon. When it disappears, a photon is emitted again.

The particle that came out of the computer

So far, the pi-ton has been discovered and verified by computer simulations. For the research team, there is no doubt about the existence of the pi-ton: "We have now investigated the phenomenon of the pi-ton using various models - it shows up again and again. Therefore, it should definitely be detectable in a variety of different materials. ", Karsten Held is convinced. "Some experimental data obtained with the material samarium titanate already seem to point to the pi-ton. Additional experiments with photons and neutrons should soon provide clarity."

Even though we are constantly surrounded by countless quasiparticles - the discovery of a new quasiparticle species is something very special. Besides the exciton, there is now also the pi-ton. In any case, this contributes to a better understanding of the coupling between light and solids, a topic that plays an important role not only in basic research but also in many technical applications - from semiconductor technology to photovoltaics.

Habitat loss, hunting, logging and climate change have put many of the world's most charismatic species at risk. A new study, led by the University of Arizona, has found that not only are larger plants and animals at higher risk of extinction, but their loss would fundamentally degrade life on earth.

The study, published today in Nature Communications, is based on computer simulations that compared the state of the natural world during the Pleistocene (a past epoch long before human-caused extinctions began), the present day, and a future world in which all large plants and animals had gone extinct.

Results showed that the continued loss of large animals alone would lead to a 44% reduction in the total amount of wild animal biomass on the planet. It would also lead to a 92% reduction in soil fertility, which underpins the ability of the earth to grow plants and sustain life.

"This research shows there are fundamental scientific principles that explain why large animals and trees matter for the health and integrity of all life on Earth," said lead author Brian Enquist, professor of ecology and evolutionary biology at the University of Arizona. "Protecting big, charismatic species does have an umbrella effect to protect the wider ecosystem."

A key reason for these results lies with the transport of nutrients. When large animals eat in one location and defecate or urinate in another, they transport nutrients, often moving them from nutrient-rich areas to other, less fertile parts of the land and oceans. Similarly, the largest trees are the most productive, and contain and stir more nutrients and carbon.

"Ecosystems with larger trees and animals are also more productive and provide more vital ecological services," Enquist said. "I use this analogy: The largest banks and corporations in the economy are the most productive and have the most impact on the economy, so when those large banks failed during the great recession in 2009, we had to prop them up economically, or they would have had a disproportionate negative impact on economy. It's a similar principle with large plants and animals across ecosystems."

Unfortunately, these large organisms are more susceptible to human pressures and climate change and take longer to recover from shocks, making them more prone to extinction.

"For hundreds of millions of years, Earth has been a planet of giants. In the last few thousand years, these large animals and plants have been whittled away, and this process continues today. Our paper shows why this loss of these giants matters for the very fabric of life on Earth, and why we must do everything possible to protect and restore them," said Yadvinder Malhi, leader of the ecosystems group at the Environmental Change Institute at the University of Oxford.

The findings help to answer an ongoing debate about where to channel limited conservation resources. While charismatic species such as the tiger or redwood tree have historically been most appealing and therefore effective at pulling in donations, some scientists worried that the focus on a certain subset of plants and animals could be coming at the cost of protecting other, less well-loved species.

"Our findings instead point to the importance of policies that emphasize the promotion of large trees and animals, as such policies will have a more disproportionate impact on biodiversity, ecosystem processes and climate mitigation," Enquist said. "We can use this model to focus our conservation concerns. For example, we can identify the forest that still contains some of the largest tress on the planet, or forests that have healthy size structure and prioritise them because they're more productive and resilient."

During a typical Canadian winter, snow accumulation and melt--combined with sudden rainfalls--can lead to bottlenecks in storm drains that can cause flooding.

With that in mind, researchers at UBC's Okanagan campus have been examining urban stormwater drainage systems, and they too have concerns about the resilience of many urban drainage systems.

A recently published paper from the School of Engineering says existing design methods for urban drainage systems aren't going far enough to withstand possible catastrophic storms or even unpredictable failures during a moderate storm.

"As engineers, we run simulations of possible catastrophic events, and current systems often do not fare well," says doctoral student Saeed Mohammadiun. "We are seeing sources of overloading such as structural failures, severe rainfalls or abrupt snowmelt stressing these systems."

Add any extreme situation including quick snowmelt or a heavy and sudden rainfall, and Mohammadiun says many systems aren't built to handle these worst-case scenarios. Mohammadiun has conducted several case studies of drainage systems in major urban areas around the world. He has determined many current urban standards designed for a 10-to-50 or even 100-year storm scenario are not meeting the increasing demands of climate change as well as intrinsic failure risk of networks' elements.

"Conventional, reliability-based design methods only provide acceptable performance under expected conditions of loading," he says. "Depending on the system, if something breaks down or there is a blockage, it can result in a failure and possible flooding."

According to Mohammadiun, the resiliency of a system is not just dependent on the load it can handle, but also on its design and build. Many do not take into account the effects of climate change or unexpected weather conditions.

To establish an efficient resilient system, Mohammadiun says it is important to consider various sources of uncertainty such as rainfall characteristics, heavy snowfalls followed by a quick melt and different possible malfunction scenarios along with budget constraints, he says.

"Building or improving the resilience of urban stormwater drainage systems is crucial to ensuring these systems are protected against failure as much as possible, or they can quickly recover from a potential failure," he adds. "This resilient capacity will provide urban drainage systems with the desired adaptability to a wide range of unexpected failures during their service life."

The research points to several measures municipalities can proactively address the issue. Municipalities could build bypass lines and apply an appropriate combination of relief tunnels, storage units, and other distributed hydraulic structures in order to augment drainage system capacities in a resilient manner.

With the recent heavy snowfalls across Canada, Mohammadiun says the silver lining when it comes to drainage is that it takes snow time to melt whereas heavy rainfall puts an immediate stress on these systems. But from the engineering point of view, it is necessary to consider both acute and chronic conditions.

Not surprising, the research shows that urban drainage and stormwater systems that are built or modified to be more resilient, will handle extreme weather events more effectively and efficiently than conventional designs.

A group of researchers from ITMO University has come up with the concept of a new drug against cancer: a nanorobot made of DNA fragments, which can potentially be used not only to destroy cancer cells but also to locate them in the body. The research is published in Chemistry - A European Journal.

The development of effective cancer treatment drugs without severe side effects is now one of the most important tasks faced by chemists, pharmacists, and biologists. Scientists have high hopes for gene therapy, which combats mutations that occur in cells.

"DNA is the foundation of the cell, it contains its genetic material, which is needed to encode proteins that are vital for the existence of the cell," shares Ekaterina Goncharova, a co-author of the research. "When a cell becomes cancerous, it leads to the change in the genome, after which it begins to synthesize "bad" proteins, not the ones that our body needs. As a result, the cells begin to multiply uncontrollably and the tumor grows bigger and bigger."

However, if the production of disease-related proteins is blocked, the cancer cells will no longer be able to multiply and will start to die out. DNA enzymes called deoxyribozymes can, under certain conditions, cleave bonds in an RNA strand. The researchers decided to use this property and created the so-called nanorobots based on artificially synthesized deoxyribozymes.

"Our DNA-based nanorobot consists of two parts: a detection one and a therapeutic one," explains Ekaterina Goncharova. "The therapeutic part destroys a pathogenic RNA strand: the more we destroy it, the less harmful protein is produced. The second part of our robot allows us to detect pathogenic cells: if there is an "incorrect" RNA molecule in the cell, our substance binds with an chemically modified oligonucleotide, which is artificially introduced into the cell, cleave it, and a fluorescence occurs."

Another significant advantage of the newly proposed concept is its price. The creation of such a nanorobot for laboratory research costs just about USD 15 to 25.

At the moment, the experiments have been carried out in chemically created environments using the KRAS gene, which serves in most oncological diseases as a "molecular switch" for the induction of cell division. The nanorobot was able to detect a pathogenic RNA strand and destroy it. These experiments will be followed by experiments on living cells and, potentially, on animals. One of the most important problems that the researchers have to solve is how to deliver the nanorobot to the affected cells. The work on such a drug delivery system is currently carried out at various laboratories, including ITMO University.

International survey results on public's behaviours around cancer released

Alarming contrast in responses between socio-economic groups

ESMO highlights improved prevention knowledge and wider accessibility to care
as key priorities

Lugano, Switzerland, 4 February - Today on World Cancer Day, ESMO, the leading organisation for medical oncology, joins the Union for International Cancer Control (UICC) in its call to reduce the global cancer burden and commits to reinforcing its core educational mission to reach a larger base of medical professionals to play a critical role in cancer prevention.

An annual initiative led by UICC, World Cancer Day aims to mobilise urgent action from individuals, governments, and the global cancer community. This year, to mark the 20th anniversary of this appointment, UICC launched a global survey (1) of more than 15,000 adults across 20 countries to form an up-to-date picture of the public's experiences, views and behaviours around cancer.

The results of the survey highlight the urgent need to close the clear and unacceptable gaps in cancer risk awareness between higher and lower socio-economic groups and the subsequent impact on their health-promoting behaviours.

"Research speaks very clearly for prevention," said ESMO President Solange Peters. "With the number of cancer cases expected to rise to 29.5 million by 2040 (2), we must act now. ESMO is committed to educating doctors on all aspects of cancer control, which should begin well before a cancer diagnosis."

"In the face of this emergency, which is rendered even more salient by the results of the report, we must work to enlarge the basis of doctors who are properly educated and trained in key prevention measures," Peters added. "General practitioners and organ specialists are in the front line to guide and support patients on their quest for healthy lifestyles and reliable ways to detect cancer early."

On a global level, 69% of survey respondents state they have taken some steps to reduce their risk of cancer in the past 12 months, with the most common preventive measure being an increase in consumption of healthy food.

"Our role as oncologists is pivotal, too," she stressed: "We are exposed to a growing number of questions from our patients who want to know exactly what to do and what to avoid. Even if we deal with individuals who have already been diagnosed, our contribution to prevention is fundamental as we are the cancer specialists, those who are expected to know everything about these diseases."

The starkest contrast in responses, alarmingly, is drawn along socio-economic lines. Irrespective of where people live in the world, those surveyed with a relatively lower education or income level appear less aware of the main risk factors associated with cancer and appear less likely to proactively take the steps needed to reduce their cancer risk than those from a high-income household or with a university education.

"This is problematic," said the ESMO President. "Not just because it reflects widespread inequalities in the face of cancer risk, but also because prevention must be the cornerstone of any country's strategy to make cancer care sustainable in the future. In some areas, unfortunately, prevention measures cannot be implemented as we would like them to be, because of weak economic conditions, cultural barriers, and other factors. This requires us to target our approaches and learn to set clear priorities."

As part of World Cancer Day's 'I Am and I Will' campaign, which calls on each person to make a commitment - big or small - ESMO supports UICC's recommendations:

Use World Cancer Day as an opportunity to improve your understanding of cancer risk factors and share your knowledge with others

Make a personal commitment to reduce your cancer risks like quitting smoking, eating healthily, exercising regularly, and using sunscreen

Take advantage of what your health system can provide, including getting a check-up, getting screened, and getting vaccinated

Los Angeles - An interdisciplinary team of researchers at the UCLA Jonsson Comprehensive Cancer Center has developed a medicated patch that can deliver immune checkpoint inhibitors and cold plasma directly to tumors to help boost the immune response and kill cancer cells.

The thumb-sized patch has more than 200 hollow microneedles that can penetrate the skin and enter the tumor tissue. The cold plasma is delivered through the hollow structure, destroying cancer cells, which facilitates the release of tumor-specific antigens and boosts an immune response. The immune checkpoint inhibitors -- antibodies that block checkpoint proteins, which interferes with immune system function and prevents the immune system from destroying cancer cells -- are also released from the sheath of microneedles to boost the T cell-mediated anti-cancer effects.

In the study, which is published in the Proceedings of the National Academy of Sciences, the UCLA researchers found that delivering the two therapies to mice with melanoma using the patch enabled the immune system to better attack the cancer, significantly inhibiting the growth of the tumor and prolonging the survival of the mice.

The team also found that the therapy not only inhibit the growth of the targeted tumor, but it also could inhibit the growth of tumors that had spread to other parts of the body.

"Immunotherapy is one of the most groundbreaking advances in cancer treatment," said study senior author Zhen Gu, professor of bioengineering at the UCLA Samueli School of Engineering and member of the Jonsson Cancer Center. "Our lab has been working on engineering new ways to apply or deliver drugs to the diseased site that could help improve the effectiveness of cancer immunotherapy, and we found the patch to be a quite promising delivery system."

The study is also the first to demonstrate that cold plasma can be effective in synergizing cancer immunotherapy. Plasma, which is usually hot, is an ionized gas that comprises more than 99% of the universe. Here, cold plasma is generated by a small device operating at atmospheric pressure and room temperature. Therefore, cold plasma can be applied directly to the body -- internally or externally.

"This study represents an important milestone for the field of plasma medicine," said co-senior author Richard Wirz, professor of mechanical and aerospace engineering at UCLA Samueli. "It demonstrates that the microneedle patch can realize the plasma delivery while also working with the drug to improve the effectiveness of cancer therapy."

"Plasma can generate reactive oxygen species and reactive nitrogen species, which are a group of chemical species that can destroy cancer cells," said Guojun Chen, who is the co-first author of the study and a postdoctoral fellow in Gu's laboratory.

"Those cancers can then release tumor-associated antigens, which can enhance immune response to kill cancers," said Zhitong Chen, who is the other co-first author and a postdoctoral fellow in Wirz's lab.

The team tested the cold plasma patch on mice with melanoma tumors. The mice that received the treatment showed an increased level of dendritic cells, which are a specific type of white blood cells that alert the immune system of a foreign invader and initiate a T cell-mediated immune response.

The group of mice also showed delayed tumor growth compared to the untreated group and 57% were still alive at 60 days, while mice in other control groups had all died.

"This treatment strategy can potentially go beyond cancer immunotherapy," said Gu, who is also a member of the California NanoSystems Institute at UCLA. "Integrated with other treatments, this minimally invasive method can be extended to treat different cancer types and a variety of diseases."

The patch will have to go through further testing and approvals before it could be used in humans. But the team members believe the approach holds great promise.

CAMBRIDGE, MA -- A team of MIT chemists has discovered the structure of a key influenza protein, a finding that could help researchers design drugs that block the protein and prevent the virus from spreading.

The protein, known as BM2, is a proton channel that controls acidity within the virus, helping it to release its genetic material inside infected cells.

"If you can block this proton channel, you have a way to inhibit influenza infection," says Mei Hong, an MIT professor of chemistry and senior author of the study. "Having the atomic-resolution structure for this protein is exactly what medicinal chemists and pharmaceutical scientists need to start designing small molecules that can block it."

MIT graduate student Venkata Mandala is the lead author of the paper, which appears today in Nature Structural and Molecular Biology. Other authors include graduate students Alexander Loftis and Alexander Shcherbakov and associate professor of chemistry Bradley Pentelute.

Atomic-scale resolution

There are three classes of influenza virus -- A, B, and C -- and each of them produces a different version of the M2 protein. M2 is an ion channel that carries protons through the virus's outer membrane, known as the lipid envelope. These protons usually flow into the virus, making the interior more acidic. This acidity helps the virus to merge its lipid envelope with the membrane of a cellular compartment called an endosome, allowing it to release its DNA into the infected cell.

Until now, most structural studies of the M2 protein have focused on the version of M2 found in influenza A, which is usually the most common form, especially earlier in the flu season. In this study, the researchers focused on the version of M2 found in influenza B viruses, which usually dominate in March and April. However, in contrast to previous patterns of seasonal flu infections, this winter, influenza B has been unusually dominant, accounting for 67 percent of all flu cases reported to the U.S. Centers for Disease Control since last September.

The A and B versions of M2 vary significantly in their amino acid sequences, so Hong and her colleagues set out to study what structural differences these proteins might have, and how those differences influence their functions. One key difference is that the BM2 channel can allow protons to flow in either direction, whereas the AM2 channel only allows protons to flow into the viral envelope.

To investigate the structure of BM2, the researchers embedded it into a lipid bilayer, similar to a cell membrane, and then used nuclear magnetic resonance (NMR) spectroscopy to analyze the structure with atomic-scale resolution. Very few ion channels have been studied at such high resolution because of the difficulty of studying proteins embedded within membranes. However, Hong has previously developed several NMR techniques that allow her to obtain accurate structural information from membrane-embedded proteins, including their orientation and the distances between atoms of the protein.

The M2 channel is made of four helices that run parallel to each other through the membrane, and Hong found that the alignment of these helices changes slightly depending on the pH of the environment outside the viral envelope. When the pH is high, the helices are tilted by about 14 degrees, and the channel is closed. When the pH goes down, the helices increase their tilt to about 20 degrees, opening up like a pair of scissors. This scissoring motion creates more space between the helices and allows more water to get into the channel.

Previous studies have found that as water flows into the M2 channel, the amino acid histidine grabs protons from the water in the top half of the channel and passes them to water molecules in the lower half of the channel, which then deliver the excess protons into the virion.

Unlike the AM2 channel, the BM2 channel has an extra histidine at the virion-facing end of the channel, which the MIT team believes to explain why protons can flow in either direction through the channel. More study is needed to determine what kind of advantage this may provide for influenza B viruses, the researchers say.

Blocking the channel

Now that chemists know the structure of both the open and closed states of the BM2 channel at atomic resolution, they can try to come up with ways to block it. There is precedent for this type of drug development: Amantadine and rimantadine, both used to treat influenza A, work by wedging themselves into the AM2 channel pore and cutting off the flow of protons. However, these drugs do not affect the BM2 channel.

Hong's research group is now investigating another one of BM2's functions, which is generating curvature in lipid membranes in order to allow progeny viruses to be released from cells. Preliminary studies suggest that a portion of the protein that sticks out from the membrane forms a structure called a beta sheet that plays a role in inducing the membrane to curve inward.

Rutgers researchers say gender bias and stereotypes corresponding to certain occupations are prevalent on digital and social media platforms.

The study, published in the Journal of the Association for Information Science and Technology, finds that online images of men and women in four professions - librarian, nurse, computer programmer, and civil engineer - tend to represent and reinforce existing gender stereotypes.

In the study, Rutgers researchers analyzed search results for images of people in each of the four occupations on four digital media platforms: Twitter, NYTimes.com, Wikipedia, and Shutterstock. They also compared the search results to the gender representation of each occupation as per the U.S. Bureau of Labor Statistics.

The results showed gender stereotypes and biases to be prevalent. Women were overrepresented as librarians and nurses and underrepresented as computer programmers and civil engineers, especially when the collection and curation of content is largely automated by an algorithm, such as on Twitter.

However, on platforms where individuals can generate and curate content more directly, such as the NYTimes.com and Shutterstock, stereotypes were more likely to be challenged. Search results of NYTimes.com, for example, produced images of civil engineers who are women, and nurses who are men, more often than would be expected given their representation in the Labor Statistics.

"More direct content curation will help counter gender stereotypes," said Vivek Singh, an assistant professor of library and information science in Rutgers' School of Communication and Information.

While women generally tend to be underrepresented in male-dominated professions on digital media platforms, Singh noted some progress toward equity in the gendered presentation of images from 2018 to 2019. For instance, more women were shown in images for male-dominated professions on Twitter in 2019 than in 2018.

"Gender bias limits the ability of people to select careers that may suit them and impedes fair practices, pay equity and equality," said co-author Mary Chayko, a sociologist and interdisciplinary teaching professor at the School of Communication and Information. "Understanding the prevalence and patterns of bias and stereotypes in online images is essential, and can help us challenge, and hopefully someday break, these stereotypes."

The researchers said that the study could help prevent biases from being designed into digital media platforms, algorithms, and artificial intelligence software. And while human beings indeed construct algorithms, the study's results may help content creators and platform designers identify whether algorithm-heavy or human-heavy curation may be better suited to a task.

The study was co-authored by Raj Inamdar, a research associate at Rutgers' Behavioral Informatics Lab and Diana Floegel, a doctoral student at Rutgers' School of Communication and Information.

Most modern electronic devices rely on tiny, finely-tuned electrical currents to process and store information. These currents dictate how fast our computers run, how regularly our pacemakers tick and how securely our money is stored in the bank.

In a study published in Nature Physics, researchers at the University of British Columbia have demonstrated an entirely new way to precisely control such electrical currents by leveraging the interaction between an electron's spin (which is the quantum magnetic field it inherently carries) and its orbital rotation around the nucleus.

"We have found a new way to switch the electrical conduction in materials from on to off," said lead author Berend Zwartsenberg, a Ph.D. student at UBC's Stewart Blusson Quantum Matter Institute (SBQMI). "Not only does this exciting result extend our understanding of how electrical conduction works, it will help us further explore known properties such as conductivity, magnetism and superconductivity, and discover new ones that could be important for quantum computing, data storage and energy applications."

Flipping the switch on metal-insulator transitions

Broadly, all materials can be categorized as metals or insulators, depending on the ability of electrons to move through the material and conduct electricity.

However, not all insulators are created equally. In simple materials, the difference between metallic and insulating behavior stems from the number of electrons present: an odd number for metals, and an even number for insulators. In more complex materials, like so-called Mott insulators, the electrons interact with each other in different ways, with a delicate balance determining their electrical conduction.

In a Mott insulator, electrostatic repulsion prevents the electrons from getting too close to one another, which creates a traffic jam and limits the free flow of electrons. Until now, there were two known ways to free up the traffic jam: by reducing the strength of the repulsive interaction between electrons, or by changing the number of electrons.

The SBQMI team explored a third possibility: was there a way to alter the very quantum nature of the material to enable a metal-insulator transition to occur?

Using a technique called angle-resolved photoemission spectroscopy, the team examined the Mott insulator Sr2IrO4, monitoring the number of electrons, their electrostatic repulsion, and finally the interaction between the electron spin and its orbital rotation.

"We found that coupling the spin to the orbital angular momentum slows the electrons down to such an extent that they become sensitive to one another's presence, solidifying the traffic jam." said Zwartsenberg. "Reducing spin-orbit coupling in turn eases the traffic jam and we were able to demonstrate a transition from an insulator to a metal for the first time using this strategy."

"This is a really exciting result at the fundamental physics level, and expands the potential of modern electronics," said co-author Andrea Damascelli, principal investigator and scientific director of SBQMI. "If we can develop a microscopic understanding of these phases of quantum matter and their emergent electronic phenomena, we can exploit them by engineering quantum materials atom-by-atom for new electronic, magnetic and sensing applications."

Scientists are constantly searching for the source of things like the origin of the universe, matter or life. Scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory, in a collaboration with the Massachusetts Institute of Technology (MIT) and several other universities, have demonstrated a way to experimentally detect the most hidden aspect of all chemical reactions — the extremely short-lived transition state that occurs at their initiation. This pivotal discovery could become instrumental in gaining the ability to predict and externally control the outcomes of chemical processes.

“The transition state is key in all of chemistry because it controls the products of molecular reactions,” said Kirill Prozument, lead author and chemist in Argonne’s Chemical Sciences and Engineering division. Armed with more complete knowledge of certain chemical reactions starting from the transition state, researchers might be able to improve industrial processes involving production of enormous quantities of a chemical — saving tremendous amounts of energy and money, as well as reducing waste. The same principle might also find application in the synthesis of new, life-saving drugs.

The life of this transition phase is brief, as short as quadrillionths of a second. The problem has been that it has not been possible to experimentally observe the structure of this fleeting state or even to extract sufficient details about it indirectly from the chemical products created by it, until now.

“The transition state is key in all of chemistry because it controls the products of molecular reactions.” — Kirill Prozument, lead author and chemist in Argonne’s Chemical Sciences and Engineering division

“Physicists cannot directly observe the Big Bang, which happened almost 14 billion years ago, or the transition state that led to the formation of our universe,” explained Prozument. “But they can measure various messengers remaining from the Big Bang, such as the current distribution of matter, and thereby uncover many things about the origin and evolution of our universe. A similar principle holds for chemists studying reactions.”

Central to this achievement is the team’s experimental technique, chirped-pulse millimeter-wave spectroscopy, which allows characterization of multiple competing transition states on the basis of the vibrationally excited molecules that result in the immediate aftermath of a reaction. This technique is unrivalled in its precision at determining molecular structure and resolving transitions that originate from different vibrational energy levels of the product molecules.

Many hands contributed to the refinement of this experimental technique to expand its scope from the microwave to millimeter region, including Prozument and Robert Field, the Robert T. Haslam and Bradley Dewey Professor of Chemistry at MIT and the senior author on the study.

With this powerful technique, the team analyzed the reaction between vinyl cyanide and ultraviolet light produced by a special laser, which forms various products containing hydrogen, carbon and nitrogen. They were able to measure the vibrational energies associated with the newly formed product molecules and the fractions of molecules in various vibrational levels. The former indicates the amplitudes of which atoms within a molecule move relative to each other. The latter provides information about the geometry of groups of atoms at the transition state as they are giving birth to a product molecule — in this case, the extent of bending excitation in the bond angle between the hydrogen, carbon and nitrogen atoms. Based upon their measurements, the team identified two transition states that govern different pathways by which the molecule hydrogen cyanide (HCN) springs to life from the reaction.

“Our work demonstrates that the experimental technique works in principle,” Prozument says. “The next step will be to apply it to more complex reactions and different molecules.” The team’s work could thus one day have a major impact on the field of chemistry.

Worldwide declines in insect populations have sparked considerable concern among researchers and members of the general public alike. To date, however, significant research gaps exist, and many insect threats remain under-investigated and poorly understood. For instance, despite their charismatic bioluminescent displays and cultural and economic importance, the 2000-plus species of firefly beetles have yet to be the subject of a comprehensive threat analysis.

Writing in BioScience, Sara M. Lewis of Tufts University and her colleagues aim to fill the gap with a broad overview of the threats facing these diverse and charismatic species--as well as potential solutions that may lead to their preservation into the future. Working as part of the International Union for Conservation of Nature Firefly Specialist Group, the authors surveyed 350 members of the Fireflyers International Network. From the results, Lewis and colleagues catalog numerous threats, foremost among them habitat loss, followed closely by artificial light and pesticide use.

Among survey respondents, habitat loss was expected to pose the largest problem for firefly beetles, especially among species that are habitat specialists. Particularly troublesome is that, in such cases, local extirpations may not be quickly remedied by newly arriving colonizers. Following results from Photinus pyralis, a species that is abundant in the eastern United States, the authors extrapolate: "If this result is applicable to other firefly species, this degree of genetic isolation implies that extirpated populations are unlikely to be rescued by migration."

Pesticides pose additional problems, say the respondents. Despite being banned in the European Union, neonicotinoids remain in use in other areas, and nearly all US corn and soybean seeds are coated with these insecticides. This may cause significant issues for fireflies, describe Lewis and colleagues: "Clothianidin-treated seed showed a 70.4% reduction in adult firefly abundance compared to control plots, most likely because of higher mortality of larvae in soil." The authors go on to describe other threats, including light pollution, which disrupts mating displays and has been associated with reduced reproductive success in some species.

The future is not entirely bleak, however, and the authors shed light on the considerable opportunities to improve the prospects of bioluminescent insects. They focus on four primary goals: (1) preserve suitable habitat, (2) control light pollution, (3) reduce insecticide use, and (4) develop guidelines for sustainable tourism. They argue that the benefits of such actions will accrue to other species and ecosystems, as well. For instance, in describing a Malaysian restoration plan, they report, "identifying and preserving buffer zones adjacent to the riverbank will help ensure sustainable firefly populations and also support high wildlife diversity, including other invertebrates, plants, reptiles, mammals, and birds." Likewise, the reduction of artificial light is expected to "benefit a wide range of culturally and economically important nocturnal animals."

Building on over two decades of research, Mars and the University of California Davis have developed a new methodology to measure cocoa flavanols and procyanidins that is more accurate and more reliable than previous analytical approaches. The method, published in Food & Function, has been developed in partnership with Waters, the world's leading specialty measurement company and chromatography pioneer, and the National Institute of Standards and Technology, U.S. Dept. of Commerce (NIST).

This transferable methodology will support further research into the health effects of flavanols and procyanidins and will provide industry and regulators with much needed tools to allow reliable raw material and product testing to support and ensure the reliability of claims. This methodology could ultimately enable the consistent labeling of products, providing consumers with accurate information on cocoa flavanol content to enable informed purchasing decisions.

Flavanols and procyanidins are bioactive compounds naturally present in various foods including apples, blueberries, grapes, pears and cocoa. These compounds are being widely investigated for their health benefits. The forms of flavanols and procyanidins found in foods are unique to their type, with cocoa containing a distinct mixture of these compounds. Today, there is a strong and growing body of scientific evidence that demonstrates regular intake of the flavanols and procyanidins in cocoa can improve vascular function, as well as positively impact the health of the cardiovascular system. Research has also shown that regular intake of cocoa flavanols can improve cognitive function in healthy adults.

Until now, the chemical complexity of flavanols and procyanidins, and the absence of analytical standards have prevented the development of methods that can measure flavanol and procyanidin content in a consistent way. This newly validated method harnesses cutting-edge High-Performance Liquid Chromatography (HPLC) technology and a new calibration approach, dramatically reducing testing turn-around times and chemical waste.

Catherine Kwik-Uribe, Director, R&D-Scientific and Regulatory Affairs at Mars Edge said: "Since our first publication on cocoa flavanols two decades ago, we have continuously worked to advance methods of analysis. This new methodology leverages the latest advancements in analytical technologies to bring about a more accurate and robust method for the analysis of cocoa flavanols and procyanidins, which can be used across the industry."

Catherine Rimmer, Natural Products Program Coordinator at NIST added: "We are excited by the opportunity to establish a public-private partnership for the development of a cocoa flavanol reference material. We hope that this project serves as a model for future collaborations that demonstrate government and industry can work together to help ensure that foods and dietary supplements are safe and of high quality."

Aphids, small sap-sucking insects, are virus carriers responsible for significant economic losses in many crops worldwide. Many aphids form symbiotic and mutualistic relationships with viruses, an aspect of plant disease that has not been well explored.

Scientists based in Beijing, China, studied how one symbiotic virus, Acyrthosiphon pisum virus (APV), actually helps its host aphid adapt to new plants. APV is primarily located in the aphid's salivary glands and gut. When the aphid feeds on the plant, APV is transferred through the spit.

Importantly, the survival rate of aphids on new plants increases if the aphid carries APV because the virus suppresses the plant's insect defense hormones.

"We were surprised to know symbiotic viruses can function outside hosts, which is quite different from symbiotic bacteria in the gut," said plant pathologist Feng Cui. "This research provides us with the possibility of interrupting aphid-host plant alterations or influencing the dispersal of aphids through the manipulation of these symbiotic viruses."

To learn more about this unique research into symbiotic viruses, read "A Symbiotic Virus Facilitates Aphid Adaptation to Host Plants by Suppressing Jasmonic Acid Responses" in the January issue of Molecular Plant-Microbe Interactions (MPMI).