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Bottom Line: Younger patients with resected melanoma had some benefit from adjuvant treatment with the anti-VEGF therapeutic bevacizumab (Avastin) while older patients with resected melanoma did not.

Preclinical data showed that VEGF, a protein that promotes angiogenesis and is the target of bevacizumab, decreased with age, and was superseded by the protein sFRP2 in promoting angiogenesis.

Journal in Which the Study was Published: Clinical Cancer Research, a journal of the American Association for Cancer Research

Author: Ashani Weeraratna, PhD, a Bloomberg Distinguished Professor of Cancer Biology and an E.V. McCollum professor and chair in the Department of Biochemistry and Molecular Biology at the Johns Hopkins School of Public Health and professor in the Department of Oncology at Johns Hopkins School of Medicine in Baltimore

Background: "Over the years, it has become increasingly clear that we cannot rely on a one-size-fits-all approach when selecting treatments for patients with cancer," said Weeraratna. "Our work highlights the fact that younger patients can have very different responses to a given therapy compared with older patients. Understanding that the age of a patient can affect response to treatment is critical to providing the best care for all patients."

How the Study was Conducted & Results: Weeraratna and colleagues analyzed data from the phase III AVAST-M clinical trial, which evaluated bevacizumab as an adjuvant treatment among 1,343 patients with resected melanoma. Previous studies demonstrated that treatment with bevacizumab resulted in a slight improvement in disease-free survival compared with those who did not receive bevacizumab. However, these prior analyses did not consider age as a variable, Weeraratna noted.

In their post-hoc trial analysis, Weeraratna and colleagues aimed to determine if there was an interaction between age and response to adjuvant bevacizumab. They found that among younger patients with resected melanoma (those under the age of 45), those who received bevacizumab had significantly longer disease-free survival with a 29 percent decreased risk in disease progression compared with those who did not receive bevacizumab. There was also a 25 percent decreased risk in overall mortality, but this finding was not statistically significant. However, among older patients with resected melanoma (those over the age of 45), there was no significant impact of bevacizumab therapy on disease-free survival or overall survival.

Bevacizumab inhibits the protein VEGF, a cytokine that promotes angiogenesis (the development of new blood vessels), which is a process that facilitates tumor growth. To understand how age impacts angiogenesis, Weeraratna and colleagues analyzed whole tumor samples from young and aged melanoma patients. They found that blood vessel density was significantly increased in patients over the age of 65 compared with those under the age of 65, indicating that aging increases angiogenesis among patients with melanoma. However, when the researchers analyzed age-stratified melanoma samples from The Cancer Genome Atlas (TCGA) database, they found that the expression of both VEGF and its associated receptors were significantly decreased among aged patients.

"This finding was really surprising to us, as we assumed that an increase in angiogenesis would correspond with an increase in VEGF expression among aged melanoma patients," said Weeraratna.

Because the increase in age-related angiogenesis was not accompanied by increased expression of VEGF, and because older patients with melanoma did not appear to benefit from treatment with adjuvant bevacizumab, the researchers hypothesized that other factors were driving angiogenesis in this patient population. Weeraratna and colleagues performed extensive preclinical analyses and found that the proangiogenic factor sFRP2 (for secreted frizzle-related protein 2) superseded VEGF as the predominant angiogenic factor during aging.

"While sFRP2 levels increase in the aged tumor microenvironment, accounting for the increase in angiogenesis, VEGF levels decrease, which explains why anti-VEGF treatment is no longer effective in older patients with melanoma," said Mitchell Fane, PhD, a postdoctoral fellow in the Weeraratna lab and one of the three lead authors of this study, along with Brett Ecker, MD, and Amanpreet Kaur, PhD.

Author's Comments: "Our results underscore the importance of considering age in designing preclinical studies, in clinical trial enrollment, and when interpreting trial results," Weeraratna added.

Study Limitations: Because the AVAST-M trial was not designed to assess the impact of age on the effectiveness of adjuvant bevacizumab and therefore was not adjusted for patient age in the randomization process, these post-hoc data must be interpreted with caution, Weeraratna said. She also noted that much of their preclinical findings have yet to be corroborated in patient samples, representing another limitation of the study.

Funding & Disclosures: This study was sponsored by the National Institutes of Health, a Melanoma Research Alliance/L'Oréal Paris-USA Women in Science Team Science Award, and the Wistar Science Discovery Fund.

Weeraratna declares no conflicts of interest.

Extreme events occur in many observable contexts. Nature is a prolific source: rogue water waves surging high above the swell, monsoon rains, wildfire, etc. From climate science to optics, physicists have classified the characteristics of extreme events, extending the notion to their respective domains of expertise. For instance, extreme events can take place in telecommunication data streams. In fiber-optic communications where a vast number of spatio-temporal fluctuations can occur in transoceanic systems, a sudden surge is an extreme event that must be suppressed, as it can potentially alter components associated with the physical layer or disrupt the transmission of private messages.

Recently, extreme events have been observed in quantum cascade lasers, as reported by researchers from Télécom Paris (France) in collaboration with UC Los Angeles (USA) and TU Darmstad (Germany). The giant pulses that characterize these extreme events can contribute the sudden, sharp bursts necessary for communication in neuromorphic systems inspired by the brain's powerful computational abilities. Based on a quantum cascade laser (QCL) emitting mid-infrared light, the researchers developed a basic optical neuron system operating 10,000× faster than biological neurons. Their report is published in Advanced Photonics.

Giant pulses, fine tuning

Olivier Spitz, Télécom Paris research fellow and first author on the paper, notes that the giant pulses in QCLs can be triggered successfully by adding a "pulse-up excitation," a short-time small-amplitude increase of bias current. Senior author Frédéric Grillot, Professor at Télécom Paris and the University of New Mexico, explains that this triggering ability is of paramount importance for applications such as optical neuron-like systems, which require optical bursts to be triggered in response to a perturbation.

The team's optical neuron system demonstrates behaviors like those observed in biological neurons, such as thresholding, phasic spiking, and tonic spiking. Fine tuning of modulation and frequency allows control of time intervals between spikes. Grillot explains, "The neuromorphic system requires a strong, super-threshold stimulus for the system to fire a spiking response, whereas phasic and tonic spiking correspond to single or continuous spike firing following the arrival of a stimulus." To replicate the various biological neuronal responses, interruption of regular successions of bursts corresponding to neuronal activity is also required.

Quantum cascade laser

Grillot notes that the findings reported by his team demonstrate the increasingly superior potential of quantum cascade lasers compared to standard diode lasers or VCSELs, for which more complex techniques are currently required to achieve neuromorphic properties.

Experimentally demonstrated for the first time in 1994, quantum cascade lasers were originally developed for use under cryogenic temperatures. Their development has advanced rapidly, allowing use at warmer temperatures, up to room temperature. Due to the large number of wavelengths they can achieve (from 3 to 300 microns), QCLs contribute to many industrial applications such as spectroscopy, optical countermeasures, and free-space communications.

According to Grillot, the physics involved in QCLs is totally different than that in diode lasers. "The advantage of quantum cascade lasers over diode lasers comes from the sub-picosecond electronic transitions among the conduction-band states (subbands) and a carrier lifetime much shorter than the photon lifetime," says Grillot. He remarks that QCLs exhibit completely different light emission behaviors under optical feedback, including but not limited to giant pulse occurrences, laser responses to modulation, and frequency comb dynamics.

Recent FDA chief Dr. Scott Gottlieb argued that he'd "rather try to get everyone in masks" and "try to get them in high-quality masks because we know it's going to slow down the transmission."

Against this backdrop, a new study published in Risk Analysis, "Reinventing cloth masks in the face of pandemics," by Stephen Salter, P.Eng., describes how Effective Fiber Mask Programs (EFMPs) can help communities find a balance between the economy and curbing community spread.

A separate study by Stadnytskyi, et al. estimates that one minute of loud speaking generates at least 1,000 virion-containing droplets that remain airborne for more than eight minutes. If everyone uses effective masks, the benefit is compounded because each person's mask reduces the number of particles they transmit, and also the number of particles they inhale.

The new study in Risk Analysis suggests that the effectiveness of cloth masks can be improved by using a non-woven material such as cotton batting. Increasing the surface area of fibers exposed to moving air improves filtering efficiency because the smaller particles are absorbed onto the fibers. In May and June of 2020, 17 handmade cotton batting masks underwent 35 tests using commercial quantitative fit testing equipment to determine their filtering effectiveness. The results showed average filtering effectiveness of 76 to 90 percent against aerosol particles.

If an Effective Fiber Mask (EFM) costs $6 and can be used 30 times for four hours each, the cost per hour of use would be $0.05. Another study, by Abaluck et al., estimated the value of cloth masks during the COVID-19 pandemic, and concluded, "...the benefits of each additional cloth mask worn by the public are conservatively in the $3,000-$6,000 range due to their impact in slowing the spread of the virus." This cost-benefit ratio suggests governments should consider subsidizing the cost of EFMs for the public.

Governments can take a leadership role by rapidly implementing EFMPs to help reduce transmission of COVID-19, according to Salter. To implement an EFMP, a government would set performance standards for cloth masks, invite manufacturers to submit their mask designs for testing, allow manufacturers to label their approved designs, ask or require the public to wear only approved cloth masks, educate the public to use face masks correctly, and encourage manufacturers to continuously improve their designs.

"I am confident Effective Fiber Masks can play an important role in reducing the risk of transmission of COVID-19," states Salter. "Every country can rapidly implement an Effective Fiber Mask Program, and I hope leaders will act quickly to reduce suffering in this way."

A study from Winship Cancer Institute of Emory University (Winship) has the potential to change how patients whose prostate cancer recurs after prostatectomy are treated. The study will be featured in both the plenary session and press program of the American Society for Radiation Oncology (ASTRO) Annual Meeting on Monday, October 26.

The Emory Molecular Prostate Imaging for Radiotherapy Enhancement, or EMPIRE-1 trial (NCT01666808), is the first randomized trial of men with prostate cancer with recurring cancer to show that treatment based on advanced molecular imaging can improve disease-free survival rates. The molecular imaging agent used in the study, the radiotracer fluciclovine (18F) PET, was invented and developed at Emory and Winship.

The phase II/III trial was led by Winship radiation oncologist and prostate cancer specialist Ashesh B. Jani, MD, MSEE, FASTRO, and Winship nuclear radiology specialist David M. Schuster, MD, FACR. The trial enrolled 165 patients whose cancer recurred after having undergone prostatectomies. One group received radiation therapy based on conventional imaging. The other group received treatment that was finalized based on imaging with the fluciclovine PET radiotracer. Those whose treatment was adjusted according to the results of the advanced molecular imaging showed an improvement in the cancer control end point.

"At three years, the group getting treatment guided by PET fluciclovine had a 12 percent better cancer control rate, and this persisted at four years as well, with a 24% improvement," says Jani. "We think the improvement was seen because the novel PET allowed for better selection of patients for radiation, better treatment decisions, and better radiation target design."

The study, "Initial Report of a Randomized Trial Comparing Conventional- vs Conventional plus Fluciclovine (18F) PET/CT Imaging-Guided Post-Prostatectomy Radiotherapy for Prostate Cancer," is one of only three studies featured in the ASTRO Plenary session, which highlights abstracts deemed to have the highest merit and greatest impact on radiation oncology research and practice.

"We knew that diagnostic performance of this PET radiotracer was better than conventional imaging. We also knew it changes management. But did it change management in the right direction? This study has allowed us to take it one step further and determine if using this imaging influences outcomes for the better. And it does," says Schuster.

The study used a type of PET known as fluciclovine (fluorine-18, or 18F) which was invented by a multidisciplinary team at Emory and is now commercialized by Blue Earth Diagnostics.

Fluciclovine was originally developed by Mark M. Goodman, PhD, Winship researcher and professor of radiology and imaging sciences at Emory University School of Medicine, and colleague Timothy Shoup, PhD, currently at Massachusetts General Hospital. In 1999, Goodman, Shoup, and Winship neurosurgeon Jeffrey J. Olson, MD, published a study on the use of fluciclovine for brain tumor imaging.

Over a decade ago, researchers decided to explore if fluciclovine could also work for prostate cancer because of its low native urinary excretion. Jani and Schuster commenced a clinical trial in 2012 to determine if fluciclovine could be used to guide radiotherapy decisions and treatment volumes post-prostatectomy.

The technology was licensed to Blue Earth Diagnostics in 2014, and in 2016 the U.S. Food and Drug Administration approved the use of fluciclovine to diagnose men with recurrent prostate cancer with elevated blood levels of prostate-specific antigen after previous treatment. It is the first FDA-approved fluorinated PET radiotracer (trade name Axumin) for prostate cancer staging.

Funded by a $2.2 million grant from the National Institutes of Health, Jani and Schuster began the EMPIRE-1 trial in 2012 to further establish the role of advanced molecular imaging with fluciclovine in post-prostatectomy decision-making and treatment volumes. Jani and Schuster say the work behind this study represents the best of team science.

"The invention and development of this imaging technology speaks to the strength of collaborative science and breadth of expertise at Winship," said Winship Executive Director Walter J. Curran, Jr., MD. "This study would not have been possible without Winship's comprehensive cancer center infrastructure."

Jani and Schuster are leading another NIH-funded ($3.7 million) trial, EMPIRE-2, to investigate a newer type of advanced molecular imaging, PSMA or prostate specific membrane antigen PET. The new radiotracer targets a receptor on the surface of prostate cancer cells. Investigators hope to discover whether this newer type of PET scan could be even more effective than fluciclovine in improving cancer control for prostate cancer patients with recurring cancer.

LAWRENCE -- A team led by an astronomer from the University of Kansas has crunched data from NASA's TESS and Spitzer space telescopes to portray for the first time the atmosphere of a highly unusual kind of exoplanet dubbed a "hot Neptune."

The findings concerning the recently found planet LTT 9779b were published today in Astrophysical Journal Letters. The paper details the very first spectral atmospheric characterization of any planet discovered by TESS, the first global temperature map of any TESS planet with an atmosphere and a hot Neptune whose emission spectrum is fundamentally different from the many larger "hot Jupiters" previously studied.

"For the first time, we measured the light coming from this planet that shouldn't exist," said Ian Crossfield, assistant professor of physics & astronomy at KU and lead author of the paper. "This planet is so intensely irradiated by its star that its temperature is over 3,000 degrees Fahrenheit and its atmosphere could have evaporated entirely. Yet, our Spitzer observations show us its atmosphere via the infrared light the planet emits."

While LTT 9779b is extraordinary, one thing is certain: People probably wouldn't like it there very much.

"This planet doesn't have a solid surface, and it's much hotter even than Mercury in our solar system -- not only would lead melt in the atmosphere of this planet, but so would platinum, chromium and stainless steel," Crossfield said. "A year on this planet is less than 24 hours -- that's how quickly it's whipping around its star. It's a pretty extreme system."

Hot Neptune LTT 9779b was discovered just last year, becoming one of the first Neptune-sized planets discovered by NASA's all-sky TESS planet-hunting mission. Crossfield and his co-authors used a technique called "phase curve" analysis to parse the exoplanet's atmospheric makeup.

"We measure how much infrared light was being emitted by the planet as it rotates 360 degrees on its axis," he said. "Infrared light tells you the temperature of something and where the hotter and cooler parts of this planet are -- on Earth, it's not hottest at noon; it's hottest a couple of hours into the afternoon. But on this planet, it's actually hottest just about at noon. We see most of the infrared light coming from the part of the planet when its star is straight overhead and a lot less from other parts of the planet."

Readings of the the planet's temperature is seen as a way to characterize its atmosphere.

"The planet is much cooler than we expected, which suggests that it is reflecting away much of the incident starlight that hits it, presumably due to dayside clouds," said co-author Nicolas Cowan of the Institute for Research on Exoplanets (iREx) and McGill University in Montreal, who helped in the analysis and interpretation of the thermal phase curve measurements. "The planet also doesn't transport much heat to its nightside, but we think we understand that: The starlight that is absorbed is likely absorbed high in the atmosphere, from whence the energy is quickly radiated back to space."

According to Crossfield, the results are just a first step into a new phase of exoplanetary exploration as the study of exoplanet atmospheres steadily moves toward smaller and smaller planets.

"I wouldn't say we understand everything about this planet now, but we've measured enough to know this is going to be a really fruitful object for future study," he said. "It's already being targeted for observations with the James Webb Space Telescope, which is NASA's next big multibillion-dollar flagship space telescope that's going up in a couple of years. What our measurements so far show us are what we call the spectral absorption features -- and its spectrum indicates carbon monoxide and or carbon dioxide in the atmosphere. We're starting to get a handle on what molecules make up its atmosphere. Because we see this, and because of how this global temperature map looks, it also tells us something about how the winds are circulating energy and material around through the atmosphere of this mini gas planet."

Crossfield explained the extreme rarity of Neptune-like worlds found close to their host stars, a region typically so devoid of planets astronomers call it the "hot Neptune desert."

"We think this is because hot Neptunes aren't massive enough to avoid substantial atmospheric evaporation and mass loss," he said. "So, most close-in hot exoplanets are either the massive hot Jupiters or rocky planets that have long ago lost most of their atmospheres."

A companion paper to this research led by Diana Dragomir, University of New Mexico physics and astronomy assistant professor, investigates the expoplanet's atmospheric composition via secondary eclipse observations with the Spitzer Infrared Array Camera (IRAC) of the hot Neptune.

Although LTT 9779b isn't suitable for colonization by human beings or any other known life form, Crossfield said evaluating its atmosphere would hone techniques that someday could be used to find more welcoming planets for life.

"If anyone is going to believe what astronomers say about finding signs of life or oxygen on other worlds, we're going to have to show we can actually do it right on the easy stuff first," he said. "In that sense these bigger, hotter planets like LTT 9779b act like training wheels and show that we actually know what we're doing and can get everything right."

Crossfield said his peek into the atmosphere of such a strange and distant planet also was valuable on its own merits.

"As someone who studies these, there's just a lot of interesting planetary science we can do in measuring the properties of these planets -- just like people study the atmospheres of Jupiter, Saturn and Venus -- even though we don't think those will host life," he said. "They're still interesting, and we can learn about how these planets formed and the broader context of planetary systems."

Crossfield said much work is left to do in order to better understand LTT 9779b and similar hot Neptunes not yet discovered. (A companion paper concerning LTT 9779b's atmospheric composition via analysis of its secondary eclipse "spectrum" is being published concurrently, which Crossfield co-wrote.)

"We want to continue observing it with other telescopes so that we can answer more questions," he said. "How is this planet able to retain its atmosphere? How did it form in the first place? Was it initially larger but has lost part of its original atmosphere? If so, then why is its atmosphere not just a scaled-down version of the atmospheres of ultra-hot larger exoplanets? And what else might be lurking in its atmosphere?"

Some of the KU researcher's co-authors on the paper also plan to continue study of the improbable exoplanet.

"We detected carbon monoxide in its atmosphere and that the permanent dayside is very hot, while very little heat is transported to the night side," said Björn Benneke of iREx and the Université de Montréal. "Both findings make LTT 9779b say that there is a very strong signal to be observed making the planet a very intriguing target for future detailed characterization with JWST. We're now also planning much more detailed phase curve observations with NIRISS on JWST."

N-heterocycles are organic substances used in the chemical industry and medicine. To produce them, expensive catalysts made from noble metals are used. A chemist from RUDN University developed a nanocatalyst for N-heterocycles that consists of zinc oxide and niobium and can be obtained using orange peel without any additional chemical agents. The catalyst makes the reaction almost 100% effective, thus increasing the efficiency and reducing the cost of N-heterocycles production. The results of the study were published in the Catalysis Today journal.

N-heterocycles are used in the production of plastics and medicinal drugs (quinine, morphine, pyramidon) and as dyes. Their synthesis requires the use of catalysts based on expensive noble metals such as gold, palladium, or iridium. All previous attempts to use other elements had been unsuccessful due to low efficiency or instability of the end products. However, a chemist from RUDN University developed a nanocatalyst based on cheaper metals--niobium and zinc. The new catalyst provides for almost 100% efficiency of N-heterocycle synthesis, and its precursor (or platform molecule) is levulinic acid.

"Levulinic acid is one of the top-10 most promising platform molecules that can be easily obtained from biomass. The transformation of levulinic acid into N-heterocycles has recently become a popular topic because N-heterocycles proved to be useful in the pharmaceutical, agrochemical, and polymer industries", said Rafael Luque, PhD, the head of the Molecular Design and Synthesis of Innovative Compounds for Medicine Science Center at RUDN University.

His team used a mechanochemical method to create the nanocatalyst: it means, its components were simply mixed in a special grinder without solvents or other additives. Orange peel served as a template for the catalyst preparation. Ground peel, dry zinc acetate, and 18 1-cm steel balls were put in the grinder and mixed at 350 revolutions per minute for 20 minutes. After that, the mixture was heated at 200? for two hours. As a result, zinc oxide nanoparticles were formed. Orange peel was used to give zinc acetate a surface to concentrate on, and also to help form intermediary compounds. The remains of the peel were partially removed from the mix in the course of heating. After that, zinc oxide nanoparticles were combined in the grinder with niobium-containing particles so that the concentration of the metal in the end product would reach 2.5% to 10%.

To test the new nanocatalyst, the chemists used it to transform levulinic acid into an N-heterocycle. The team selected the most efficient ratio of the catalyst: 10% of niobium to 90% of zinc oxide. In this case, almost all levulinic acid (94.5%) was turned into the end product without byproducts, and N-heterocycles accounted for 97.4% of the yield.

"This work shows that if we play with the catalyst structure, valuable compounds can be developed from biowaste. Using organic waste and eco-friendly methods, we can offer an alternative to the modern-day chemical industry that is extremely dependent on fossil fuels," added Rafael Luque.

LA JOLLA, CA--Scientists from Scripps Research and Los Alamos National Laboratory have devised a method for mapping in unprecedented detail the thickets of slippery sugar molecules that help shield HIV from the immune system.

Mapping these shields will give researchers a more complete understanding of why antibodies react to some spots on the virus but not others, and may shape the design of new vaccines that target the most vulnerable and accessible sites on HIV and other viruses.

The sugar molecules, or "glycans," are loose and stringy, and function as shields because they are difficult for antibodies to grip and block access to the protein surface. The shields form on the outermost spike proteins of HIV and many other viruses, including SARS-CoV-2, the coronavirus that causes COVID-19, because these viruses have evolved sites on their spike proteins where glycan molecules--normally abundant in cells--will automatically attach.

"We now have a way to capture the full structures of these constantly fluctuating glycan shields, which to a great extent determine where antibodies can and can't bind to a virus such as HIV," says the study's lead author Zachary Berndsen, PhD, a postdoctoral research associate in the structural biology lab of Scripps Research Professor Andrew Ward, PhD.

The same wavy flexibility that makes these sugary molecules resistant to antibodies has made them impossible for researchers to capture with traditional atomic-scale imaging. In the new study, which appears in the Proceedings of the National Academy of Sciences, the scientists developed techniques that, for the first time, allow these elusive molecules to be mapped in great detail on the surface of the HIV spike protein, known as "Env."

The Scripps Research team collaborated with the lab of Gnana Gnanakaran, PhD, staff scientist at Los Alamos National Laboratory, which is equipped with high-performance computing resources that enabled fresh approaches for modeling the glycans.

The researchers combined an atomic-scale imaging method called cryo-electron microscopy (cryo-EM) with sophisticated computer modeling and a molecule-identifying technique called site-specific mass spectrometry. Cryo-EM relies on averaging tens or hundreds of thousands of individual snapshots to create a clear image, thus highly flexible molecules like glycans will appear only as a blur, if they show up at all.

But by integrating cryo-EM with the other technologies, the researchers were able to recover this lost glycan signal and use it to map sites of vulnerability on the surface of Env.

"This is the first time that cryo-EM has been used along with computational modeling to describe the viral shield structure in atomic detail," says Srirupa Chakraborty, PhD, co-lead author and post-doctoral researcher in the Gnanakaran lab at Los Alamos National Laboratory.

The new combined approach revealed the glycans' structure and dynamic nature in extreme detail and helped the team better understand how these complex dynamics affect the features observed in the cryo-EM maps. From this wealth of information, the team observed that individual glycans do not just wiggle around randomly on the spike protein's surface, as once was thought, but instead clump together in tufts and thickets.

"There are chunks of glycans that seem to move and interact together," Berndsen says. "In between these glycan microdomains is where antibodies apparently have the opportunity to bind."

Experimental HIV vaccines rely on modified, lab-made Env proteins to elicit antibody responses. In principle, these vaccines' effectiveness depends in part on the positioning and extent of the shielding glycans on these lab-made viral proteins. Therefore, Berndsen and colleagues applied their method to map the glycans on a modified HIV Env protein, BG505 SOSIP.664, which is used in an HIV vaccine currently being evaluated in clinical trials.

"We found spots on the surface of this protein that normally would be covered with glycans but weren't--and that may explain why antibody responses to that site have been noted in vaccination trials," Berndsen says.

That finding, and others in the study, showed that Env's glycan shield can vary depending on what type of cell is being used to produce it. In HIV's infections of humans, the virus uses human immune cells as factories to replicate its proteins. But viral proteins used to make vaccines normally are produced in other types of mammalian cells.

In another surprise discovery, the team observed that when they used enzymes to slowly remove glycans from HIV Env, the entire protein began to fall apart. Berndsen and colleagues suspect that Env's glycan shield, which has been considered merely a defense against antibodies, may also have a role in managing Env's shape and stability, keeping it poised for infection.

The team expect that their new glycan-mapping methods will be particularly useful in the design and development of vaccines--and not only for HIV. Many of the techniques can be applied directly to other glycan-shielded viruses such as influenza viruses and coronaviruses, and can be extended to certain cancers in which glycans play a key role, the researchers say.

New Rochelle, NY, October 23, 2020--The National Commission on Correctional Health Care (NCCHC) (https://www.ncchc.org/) has awarded the contract to publish Journal of Correctional Health Care (https://home.liebertpub.com/publications/journal-of-correctional-health-care/664/overview) to Mary Ann Liebert, Inc., publishers, (https://www.liebertpub.com/) effective January 2021. The Journal adds a strong component to the company's portfolio of mission-driven journals including Health Equity, Transgender Health, LGBT Health, and AIDS Patient Care and STDs.

"Mary Ann Liebert, Inc. is dedicated to supporting the health care of underserved populations through our publications. Journal of Correctional Health Care provides critically important education for health care providers to the incarcerated population, which is more important than ever during the COVID crisis. We could not be more excited about our new partnership with NCCHC," says Bob Vrooman, Publisher, New Business Development at Mary Ann Liebert, Inc.

Journal of Correctional Health Care is the only national, peer-reviewed scientific journal focusing on this complex and evolving field. An invaluable resource for clinicians, allied health practitioners, and administrators, it provides the latest research and developments in clinical care for chronic and infectious disease, mental health care, substance abuse treatment, health services management, quality improvement, medical records, medical-legal issues, discharge planning, staffing, cost analysis, and other topics as they relate to correctional health care. Coverage includes empirical research, case studies, best practices, literature reviews, and letters, plus NCCHC position statements.

"Correctional health care is a vitally important component of public health, residing at the intersection of health care, mental health, and criminal justice. And yet it doesn't always get the attention it deserves," says Deborah Ross, NCCHC's CEO. "We appreciate Mary Ann Liebert, Inc.'s understanding of the role of correctional health care, the company's passion for cutting-edge topics and research, and its reputation for excellent service. We are confident that JCHC will be in good hands and look forward to seeing it thrive."

Journal of Correctional Health Care will continue to be published quarterly in print and online with open access options under the leadership of Editor-in-Chief John R. Miles, MPA. Authors are invited to begin submitting their manuscripts now for publication in 2021.

For further information, please visit the Journal of Correctional Health Care (https://home.liebertpub.com/publications/journal-of-correctional-health-care/664/overview) website.

A new study has found that anxiety and stress directly linked to COVID-19 could be causing a number of body image issues amongst women and men.

The research, led by Professor Viren Swami of Anglia Ruskin University (ARU) and published in the journal Personality and Individual Differences, involved 506 UK adults with an average age of 34.

Amongst women, the study found that feelings of anxiety and stress caused by COVID-19 were associated with a greater desire for thinness. It also found that anxiety was significantly associated with body dissatisfaction.

Amongst the male participants, the study found that COVID-19-related anxiety and stress was associated with greater desire for muscularity, with anxiety also associated with body fat dissatisfaction.

Negative body image is one of the main causes of eating disorders, such as anorexia and bulimia, and this new study adds to recent research indicating that fears around COVID-19, and the consequences of the restrictions introduced to help tackle it, could be contributing to a number of serious mental health issues.

Lead author Viren Swami, Professor of Social Psychology at Anglia Ruskin University (ARU), said: "In addition to the impact of the virus itself, our results suggest the pandemic could also be leading to a rise in body image issues. In some cases, these issues can have very serious repercussions, including triggering eating disorders.

"Certainly during the initial spring lockdown period, our screen time increased, meaning that we were more likely to be exposed to thin or athletic ideals through the media, while decreased physical activity may have heightened negative thoughts about weight or shape. At the same time, it is possible that the additional anxiety and stress caused by COVID-19 may have diminished the coping mechanisms we typically use to help manage negative thoughts

"Our study also found that when stressed or anxious, our pre-occupations tend to follow gender-typical lines. During lockdown, women may have felt under greater pressure to conform to traditionally feminine roles and norms, and messaging about self-improvement may have led to women feeling dissatisfied with their bodies and having a greater desire for thinness.

"Similarly, our findings reflect the way in which stress and anxiety impact men's relationships with their bodies, particularly in terms of masculine body ideals. Given that masculinity typically emphasises the value of toughness, self-reliance, and the pursuit of status, COVID-19-related stress and anxiety may be leading men to place greater value on the importance of being muscular."

The brain detects 3D shape fragments (bumps, hollows, shafts, spheres) in the beginning stages of object vision - a newly discovered strategy of natural intelligence that Johns Hopkins University researchers also found in artificial intelligence networks trained to recognize visual objects.

A new paper in Current Biology details how neurons in area V4, the first stage specific to the brain's object vision pathway, represent 3D shape fragments, not just the 2D shapes used to study V4 for the last 40 years. The Johns Hopkins researchers then identified nearly identical responses of artificial neurons, in an early stage (layer 3) of AlexNet, an advanced computer vision network. In both natural and artificial vision, early detection of 3D shape presumably aids interpretation of solid, 3D objects in the real world.

"I was surprised to see strong, clear signals for 3D shape as early as V4," said Ed Connor, a neuroscience professor and director of the Zanvyl Krieger Mind/Brain Institute. "But I never would have guessed in a million years that you would see the same thing happening in AlexNet, which is only trained to translate 2D photographs into object labels."

One of the long-standing challenges for artificial intelligence has been to replicate human vision. Deep (multilayer) networks like AlexNet have achieved major gains in object recognition, based on high capacity Graphical Processing Units (GPU) developed for gaming and massive training sets fed by the explosion of images and videos on the Internet.

Connor and his team applied the same tests of image responses to natural and artificial neurons and discovered remarkably similar response patterns in V4 and AlexNet layer 3. What explains what Connor describes as a "spooky correspondence" between the brain - a product of evolution and lifetime learning - and AlexNet - designed by computer scientists and trained to label object photographs?

AlexNet and similar deep networks were actually designed in part based on the multi-stage visual networks in the brain, Connor said. He said the close similarities they observed may point to future opportunities to leverage correlations between natural and artificial intelligence.

"Artificial networks are the most promising current models for understanding the brain. Conversely, the brain is the best source of strategies for bringing artificial intelligence closer to natural intelligence," Connor said.

A new UNSW study comprehensively reviews the magnetic structure of the multiferroic material bismuth ferrite (BiFeO3 - BFO).

The review advances FLEET's search for low-energy electronics, bringing together current knowledge on the magnetic order in BFO films, and giving researchers a solid platform to further develop this material in low-energy magnetoelectric memories.

BFO is unique in that it displays both magnetic and electronic ordering (ie, is 'multiferroic') at room temperature, allowing for low-energy switching in data storage devices.

MULTIFERROICS: COMBINED MAGNETIC AND ELECTRONIC ORDERING FOR LOW-ENERGY DATA STORAGE

Multiferroics are materials that have more than one 'order parameter'.

For example, a magnetic material displays magnetic order: you can imagine that the material is made up of lots of neatly arranged (ordered), tiny magnets.

BFO cycloid diagram

Spin (magnetic order) in the multi-ferroic material bismuth-ferrite 'cycles' through the crystal, offering potential application in emerging electronics fields such as magnonics

Some materials display electronic order - a property referred to as ferroelectricity - which can be considered the electrical equivalent of magnetism.

In a ferroelectric material, some atoms are positively charged, others are negatively charged, and the way these atoms are arranged in the material gives a specific order to the charge in the material.

In nature, a small fraction of known materials possess both magnetic and ferroelectric order (as is the case for BFO) and are thus referred to as multiferroic materials.

The coupling between magnetic and ferroelectric order in a multiferroic material unlocks interesting physics and opens the way for applications such as energy-efficient electronics, for example in non-volatile memory devices.

Studies at FLEET focus on the potential use of such materials as a switching mechanism.

Ferroelectric materials can be considered the electrical equivalent of a permanent magnet, possessing a spontaneous polarisation. This polarisation is switchable by an electric field.

The storage of data on traditional hard disks relies on switching each bit's magnetic state: from zero, to one, to zero. But it takes a relatively large amount of energy to generate the magnetic field required to accomplish this.

In a 'multiferroic memory,' the coupling between the magnetic and ferroelectric order could allow 'flipping' of the state of a bit by electric field, rather than a magnetic field.

Electric fields are a lot less energetically costly to generate than magnetic fields, so multiferroic memory would be a significant win for ultra-low-energy electronics, a key aim in FLEET.

BFO: A UNIQUE MULTIFERROIC MATERIAL

Bismuth ferrite (BFO) is unique among multiferroics: its magnetic and ferroelectric persist up to room temperature. Most multiferroics only exhibit both order parameters at far below room temperature, making them impractical for low-energy electronics.

(There's no point in designing low-energy electronics if it costs you more energy to cool the system than you save in operation.)

THE STUDY

Co-author Dr Dan Sando preparing materials for study at UNSW

The new UNSW study reviews the magnetic structure of bismuth ferrite; in particular, when it is grown as a thin single crystal layer on a substrate.

The paper examines BFO's complicated magnetic order, and the many different experimental tools used to probe and help understand it.

Multiferroics is a challenging topic. For example, for researchers trying to enter the field, it's very difficult to get a full picture on the magnetism of BFO from any one reference.

"So, we decided to write it," says Dr Daniel Sando. "We were in the perfect position to do so, as we had all the information in our heads, Stuart wrote a literature review chapter, and we had the combined necessary physics background to explain the important concepts in a tutorial-style manner."

The result is a comprehensive, complete, and detailed review article that will attract significant attention from researchers and will serve as a useful reference for many.

Co-lead author Dr Stuart Burns explains what new researchers to the field of multiferroics will gain from the article:

"We structured the review as a build-your-own-experiment starter pack: readers will be taken through the chronology of BFO, a selection of techniques to utilize (alongside the advantages and pitfalls of each) and various interesting ways to modify the physics at play. With these pieces in place, experimentalists will know what to expect, and can focus on engineering new low-energy devices and memory architectures."

The other lead author, Oliver Paull, says "We hope that other researchers in our field will use this work to train their students, learn the nuances of the material, and have a one-stop reference article which contains all pertinent references - the latter in itself an extremely valuable contribution."

Prof Nagy Valanoor added "The most fulfilling aspect of this paper was its style as a textbook chapter. We left no stone unturned!"

The discussion paper includes incorporation of BFO into functional devices that use the cross coupling between ferroelectricity and magnetism, and very new fields such as antiferromagnetic spintronics, where the quantum mechanical property of the spin of the electron can be used to process information.

The Experimentalist's Guide to the Cycloid, or Noncollinear Antiferromagnetism in Epitaxial BiFeO3 was published in Advanced Materials in September 2020 (DOI 10.1002/adma.202003711).

Despite their high accuracy, the majority of the existing instrumental laboratory methods are very laborious and insufficient in terms of quick analysis of the objects under study. A team of scientists of Samara Polytech design cost effective portable analyzers. The recent research results are published in the journal of the American Chemical Society (doi.org/10.1021/acssensors.0c01018).

"Our laboratory works with optical multisensor systems based on various physical principles of spectroscopy, allowing the observations in several spectral ranges", Anastasiia Surkova, Candidate of Chemistry, researcher of the "Multivariate Analysis and Global Modelling" laboratory explains. "The portable analyzers that we designed require no sampling and they work like this: the device illuminates the object under study at selected wavelengths, and the result of the interaction of light and the sample is read by the detector through a light-guide cable. The detected signal is sent to a computer, where the information is processed using a special mathematical model and the received data is decrypted. By the way, our task is both to make the mathematical optimization of the multisensor system for the selected application and to develop the corresponding predictive models".
To control each connected device, including data collection and calculation of the analysis result using the built-in model, special software is required. In order to fulfill this task, several years ago the laboratory staff developed a unique "cloud" application TPT-cloud. Now a company in Spain is engaged in its further professional development.

Optical multisensor systems can be used for quantitative and qualitative analysis of the objects under study in various fields such as medical diagnostics, quality control in the food and pharmaceutical industries, effective environmental monitoring, etc.

A chemist from RUDN University used a copper catalyst in the click reaction of triazole synthesis. Triazoles are bioactive substances that are used to treat fungal diseases and synthesize pharmaceutical drugs and also play a role in polymer chemistry. The catalyst not only accelerated the reaction several times but also helped perform it at room temperature and without any bases or solvents. The reaction turned out to be almost 100% effective and had no by-products. The scientist also studied the mechanism of the reaction and identified its differences from a regular click reaction. An article about the work was published in the Journal of Catalysis.

Click reactions are reactions in which simple molecules (or modules) 'click' together and assemble into a large complex molecule, just like details of a construction kit. They are mainly used in the pharmaceutical industry and polymer chemistry. Using the click reaction of azide-alkyne cycloaddition (or CuACC), manufacturers obtain triazoles, bioactive substances with antibacterial, neuroleptic, and antispastic properties (such as fluconazole and itraconazole). As a rule, these reactions require copper-based catalysts to speed up the process. However, they operated at special conditions (e.g. at higher temperatures or in the presence of additional chemicals) which increases the production cost. A chemist from RUDN University suggested using a copper complex that accelerates the click reaction and lets it go on at room temperatures and without an additional base. Moreover, his team developed the first complete description of the reaction mechanism that had not been fully understood before, especially for different catalyst systems.

"CuAAC can involve different copper catalysts, but in many cases, they require severe conditions (such as high temperatures, additional reagents, and so on). Although the mechanism of this reaction has been thoroughly studied, the details of the catalysis are still being discussed," said Vladimir Larionov, a Candidate of Chemical Sciences, and a researcher at the Department of Inorganic Chemistry, RUDN University.

The team studied a chemical compound that had three copper ions bound with ligands (complex organic ions). The complex was used as a catalyst in the CuACC reaction at room temperature. Dichloromethane, toluene, and other substances were tested as solvents. However, even in their absence the copper complex let the team obtain the required reaction product in 4 hours, while without it the reaction did not happen at all. In the end, 99% of the initial substrate turned into triazole, and there were no by-products.

The team was also the first ever to study the mechanism of this reaction using mass spectrometry and quantum-chemical calculations. The molecules were broken down to charged fragments, and after that their structure was identified based on the mass to charge ratio of each fragment. The catalyst turned out to work in two ways at once: the ligand helped the alkyne lose a proton and enter an active state, while copper ions played a role in the formation of an intermediate. In the course of these processes, bonds were formed between metal ions in the catalyst and the particles of the substrates. Previously, the bond formation between the catalyst and the alkyne (i.e. copper acetilyde) had been considered the slowest step of the reaction. However, the team disproved this belief and confirmed that the formation of the first bond between two reagents sets up the rate of whole reaction depending on catalytic system.

"Our results show that the rate-determining step that determines the rate of the CuACC reaction depends on the catalyst system and reagents. Previously, this fact was underestimated enough," added Vladimir Larionov.

Within the womb, a human fetus benefits from the protection of the placenta, limiting their contact with pathogens. However, once born, babies face a myriad of germs completely new to their bodies. Their immune system must rapidly develop to ensure early protection from infection. But what is exactly the dynamic of the immune system development in the first days of life?

To answer this question researchers from the Precision Vaccines Program at Boston Children's Hospital received funding from the Human Immunology Project Consortium (HIPC)/National Institute of Allergy and Infectious Diseases (NIAID) to study the timing of activation of different components of the immune system during the first week of life. For the first time, they observe an acute immune response starting right after the birth, followed by the progressive increase in key factors of innate immunity.

"Our study has revealed the developmental changes of the immune system during the defining first 7 days of life, in two independent cohorts. Furthermore, we provide insights into the development of the immune system which appears to be initiated by immunological triggers associated with birth" says Dr Hanno Steen lead author of the study published in the open-access journal Frontiers in Immunology.

The researchers studied the inventory of proteins present in newborn blood plasma, in two independent cohorts in The Gambia (West Africa) and in Papua New Guinea (PNG), at birth and after the first, third, and seventh day of life. This approach enabled them to follow, with high sensitivity, the dynamic of immune components in the blood across the first week of human life.

Firstly, the team observes, right after birth, an increase of plasma proteins involved in an acute inflammatory response, suggesting an activation of the immune system development. This is followed by an increase of components related to an innate immunity pathway called the complement system, starting as early as 24h after birth. The complement pathway has a major role in innate immunity, through the recruitment of several complexes of proteins (C1 to C9) it can induce direct destruction of pathogens. Furthermore, as the majority of the complement proteins are increasing concentrations of complement inhibitors is decreasing, until a new increase on day seven. Finally, the analysis also reveals that antibodies transmitted by the mother are declining rapidly over the first week of life while antibodies related to the complement pathway activation (IgM and IgG1) increase. Altogether, these results suggest that the complement pathway could have a central role in neonatal immunity and could be an important defense mechanism against pathogens in infancy.

A better understanding of the immune system and its development during the first week of life is particularly important given the prevalence of infections in early life. Neonatal infections cause 700,000 annual deaths, representing 40% of mortality in children under five years of age. "Having a better understanding of the immune system at the beginning of life will be pivotal for the development of precision vaccines for the newborns, which is one of the major goals of the Precision Vaccines Program at Boston Children's Hospital" says Steen.

Six years ago, the Nobel Prize in chemistry was awarded to three scientists for finding ways to visualize the pathways of individual molecules inside living cells.

Now, researchers at the University of Rochester and the Fresnel Institute in France have found a way to visualize those molecules in even greater detail, showing their position and orientation in 3D, and even how they wobble and oscillate. This could shed invaluable insights into the biological processes involved, for example, when a cell and the proteins that regulate its functions react to a COVID-19 virus.

"When a protein changes shape, it exposes other atoms that enhance the biological process, so the change of shape of a protein has a huge effect on other processes inside the cell," says Sophie Brasselet, Director of the Fresnel Institute, who collaborated with professors Miguel Alonso and Thomas Brown of The Institute of Optics at Rochester. A way to monitor this change of shape is to look at the orientation of fluorescent molecules attached to the protein of interest.

The "Coordinate and Height super-resolution Imaging with Dithering and Orientation (CHIDO)" technology they describe in Nature Communications was designed and built by co-lead authors Valentina Curcio, a PhD student in Brasselet's group, and Luis A. Aleman-Castaneda, a PhD student in Alonso's group. CHIDO includes a glass plate subjected to uniform stress all around its periphery. Placed in the Fourier plane at the back of a fluorescence microscope, the plate transforms the image of a single molecule into a distorted focal spot, the shape of which directly encodes the 3D information.

In scientific terms, the spatially-varying birefringence phase plate has a birefringence distribution with trigonal symmetry. In effect, it can produce beams that have every possible polarization state.

"This is one of the beauties of optics," Brown says. "If you have a device that can create just about any polarization state, then you also have a device that can analyze just about any possible polarization state."

The plate originated in Brown's lab as part of his long interest in developing beams with unusual polarizations. Alonso, an expert on the theory of polarization, worked with Brown on ways to refine this "very simple but very elegant device" and expand its applications. During a visit to Marseille, Alonso described the plate to Brasselet, an expert in novel instrumentation for fluorescence and nonlinear imaging. Brasselet immediately suggested its possible use in the microscopy techniques she was working on to image individual molecules.

"It's been a very complementary team," Brasselet says.

20 years in the making

In 1873, Ernst Abbe stipulated that microscopes would never obtain better resolution than half the wavelength of light. That barrier stood until Nobel laureates Eric Betzig and William Moerner--with their single-molecule microscopy--and Stefan Hell--with his stimulated emission depletion microscopy--found ways to bypass it.

"Due to their achievements the optical microscope can now peer into the nanoworld," the Nobel committee reported in 2014.

"What was missing in that Nobel Prize and the work in subsequent years was the ability to not only accurately know the location of a molecule, but to be able to characterize its direction and especially its motion in three dimensions," Brown says.

In fact, the solution Brown, Alonso and Brasselet now describe had its origins 20 years ago.

Starting in 1999, Brown and one his PhD students, Kathleen Youngworth, began investigating unusual optical beams that displayed unusual patterns of optical polarization, the orientation of the optical wave. Some of these beams exhibited a spoke-like radial pattern with intriguing properties.

Youngworth demonstrated on a tabletop that, when tightly focused, the beams exhibited polarization components that pointed in almost any direction in three dimensions.

Alexis (Spilman) Vogt, another PhD candidate, then worked with Brown on creating the same effects by applying stress to the edges of a glass cylinder. Brown's brother-in-law, Robert Sampson, a skilled tool and die specialist, was called upon to fabricate some samples and fit them in metal rings for use with a confocal microscope.

This involved heating both the glass and metal rings. "Metal expands at a faster rate when you heat it than glass does," Brown explains, "and so you could heat the glass and metal up very hot, insert the glass in the middle of the metal, and as it cools down the metal would shrink and create a tremendous force on the periphery of the glass."

Sampson inadvertently applied more stress than called for with one of the plates. As soon as his brother-in-law handed it to him, Brown knew the plate had unusual qualities. The Rochester group introduced the term 'stress engineered optic' to describe these elements and, as they learned more about both the physical behavior and the mathematics, they realized that these windows could be the path the solving entirely new problems in microscopy.

And that was the origin of what is now CHIDO. Which, coincidently, happens to be Mexican slang for 'cool'.

"At the time Alexis and I knew the stress-engineered glass was interesting, and would likely have useful applications; we just didn't know at the time what they might be," Brown says. Now, thanks to his collaboration with Alonso and Brasselet, he is hoping CHIDO will "catch the imagination" of other researchers in the field who can help further refine and apply the technology.