Tech

NASA's Terra satellite obtained visible imagery of recently formed Tropical Depression 14W as it strengthened into a tropical storm. Terra satellite imagery showed the storm was organizing.

Dolphin developed from Tropical Depression 14W. 14W formed on Sept. 20 about 366 miles east-southeast of Kadena Air Base, Okinawa Island, Japan. By 5 a.m. EDT (0900 UTC) on Sept. 21, the storm organized and strengthened into a tropical storm.

NASA Satellite View: Dolphin's Organization

The Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Terra satellite captured a visible image of Tropical Storm Dolphin on Sept. 21. Satellite imagery revealed a persistent deep convection and development of thunderstorms wrapping into a low-level circulation center. That is an indication of consolidation and better organization.

The satellite image was created using NASA's Worldview product at NASA's Goddard Space Flight Center in Greenbelt, Md.

Tropical Storm Dolphin on Sept. 21

Tropical storm Dolphin was located about 625 nautical miles south-southwest of Yokosuka, Japan, near latitude 25.7 degrees north and longitude 135.0 degrees east. It was moving slowly to the north-northeast at 4 knots and had maximum sustained winds 45 knots (52 mph/83 kph).

Dolphin's Forecast and Track

The Joint Typhoon Warning Center (JTWC) forecasts that Dolphin will move north. Then later it is expect to turn to the northeast and strengthen to 55 knots.

JTWC forecasters expect the system to take on additional subtropical characteristics as it moves into an area of decreasing sea surface temperatures and increasing vertical wind shear. The storm's upper level outflow is also expected to become more strongly associated with the robust westerly wind flow associated with the jet stream. By 11 a.m. EDT (1500 UTC) on Sept. 22, the system will begin extratropical transition and will complete that transition to the south of Japan.

A team of scientists from the National Center for Advancing Translational Sciences (NCATS) and Naval Research Laboratory (NRL) in Washington, D.C., has developed a new tool that mimics how SARS-CoV-2 -- the virus that causes COVID-19 -- infects a cell, information that could potentially speed the search for treatments against the disease.

The tool is a fluorescent nanoparticle probe that uses the spike protein on the surface of SARS-CoV-2 to bind to cells and trigger the process that pulls the virus into the cell. The probe could be used in tests to rapidly gauge the ability of biologics, drugs and compounds to block the actual virus from infecting human cells. The researchers' findings appeared online Aug. 26 in ACS Nano.

"Our goal is to create a screening system to find compounds that block SARS-CoV-2 from binding to cells and infecting them," explained Kirill Gorshkov, Ph.D., a translational scientist at NCATS and a co-corresponding author of the study.

However, using the actual virus in such screening studies would be difficult and require special facilities. Instead, Gorshkov and Eunkeu Oh, Ph.D., a research biophysicist at NRL and co?corresponding author of the study, and their colleagues wanted to use nanoparticles to mimic the viral function of binding to and invading the host human cell.

The NCATS and NRL researchers collaborated to design and test the probe, combining their complementary skill sets to deliver results far sooner than separate research efforts would have. The NRL team, led by Mason Wolak, Ph.D., an expert in optical nanomaterials, put the initial collaboration together.

"We at NRL are experts in nanoparticles, and the NCATS researchers are experts in drug screening using cellular systems," explained Oh. "So, it was the perfect match."

To create the probe, NRL scientists built a fluorescent nanoparticle called a quantum dot, fashioned from cadmium and selenium. At around 10 nanometers in size, these spherical nanoparticles are 3,000 times smaller than the width of a human hair.

The NCATS-NRL research team then studded the quantum dots' surfaces with a section of the SARS-CoV-2 spike protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor on human cells. The union of the spike protein with ACE2 is the first step in the pathway to viral infection.

The glow from the quantum dots allows scientists to track the dots' behavior under a microscope. "Because they're such bright fluorescent objects, the quantum dots give us a powerful system to track viral attachment and effects on the cell in real time," explained Gorshkov.

The investigators tracked how the quantum dot probes interacted with human cells that have ACE2 on their surfaces. They watched the nanoparticle probes attach to ACE2, which combined with the probes and pulled them into the cells. The quantum dot probes did the same in a lung cell line commonly used in coronavirus assays. Safety data showed that the probes were not toxic to the test cells at the concentrations and exposure times used in the study.

The quantum dots followed the SARS-CoV-2 pathway into cells, but the research team found the probes also mimicked the virus in the presence of antibodies. Antibodies are proteins made by the immune system that can neutralize viruses such as SARS-CoV-2. The antibodies proved to be potent inhibitors of the quantum dot probes as well, preventing them from binding to ACE2 and entering human cells.

That antibody response means the quantum dot probes could help researchers rapidly test the ability of potential therapeutic agents to block the virus from entering and infecting cells. Assays using the probes also could determine the concentrations at which potential treatments may safely and effectively block infection.

"Using the quantum dots, we could create tests to use in drug screening and drug repurposing, using libraries of compounds that have activity but that also are approved by the U.S. Food and Drug Administration," Gorshkov said. "Such assays could rapidly identify promising, safe treatments for COVID-19."

ACE2 may not be the only receptor SARS-CoV-2 targets, and the quantum dot probe's flexible design will allow researchers to swap in spikes that bind to other receptors. With the probe, researchers also could test how mutations in the spike change the way the virus behaves -- and how well treatments work -- by adding the mutated spikes to the quantum dots.

Beyond SARS-CoV-2, researchers could revise the nanoparticle probe to mimic other viruses and reveal their pathways to infection. The quantum dot probes also could be useful when testing potential therapies for other diseases, Gorshkov said. The quantum dots also might deliver drugs directly to cells, narrowing treatment to specific cell types, organs or cancers.

ITHACA, N.Y. - Until now, the history of superconducting materials has been a tale of two types: s-wave and d-wave.

Now, Cornell researchers - led by Brad Ramshaw, the Dick & Dale Reis Johnson Assistant Professor in the College of Arts and Sciences - have discovered a possible third type: g-wave.

Their paper, "Thermodynamic Evidence for a Two-Component Superconducting Order Parameter in Sr2RuO4," published Sept. 21 in Nature Physics. The lead author is doctoral student Sayak Ghosh, M.S. '19.

Electrons in superconductors move together in what are known as Cooper pairs. This "pairing" endows superconductors with their most famous property - no electrical resistance - because, in order to generate resistance, the Cooper pairs have to be broken apart, and this takes energy.

In s-wave superconductors - generally conventional materials, such as lead, tin and mercury - the Cooper pairs are made of one electron pointing up and one pointing down, both moving head-on toward each other, with no net angular momentum. In recent decades, a new class of exotic materials has exhibited what's called d-wave superconductivity, whereby the Cooper pairs have two quanta of angular momentum.

Physicists have theorized the existence of a third type of superconductor between these two so-called "singlet" states: a p-wave superconductor, with one quanta of angular momentum and the electrons pairing with parallel rather than antiparallel spins. This spin-triplet superconductor would be a major breakthrough for quantum computing because it can be used to create Majorana fermions, a unique particle which is its own antiparticle.

For more than 20 years, one of the leading candidates for a p-wave superconductor has been strontium ruthenate (Sr2RuO4­), although recent research has started to poke holes in the idea.

Ramshaw and his team set out to determine once and for all whether strontium ruthenate is a highly desired p-wave superconductor. Using high-resolution resonant ultrasound spectroscopy, they discovered that the material is potentially an entirely new kind of superconductor altogether: g-wave.

"This experiment really shows the possibility of this new type of superconductor that we had never thought about before," Ramshaw said. "It really opens up the space of possibilities for what a superconductor can be and how it can manifest itself. If we're ever going to get a handle on controlling superconductors and using them in technology with the kind of fine-tuned control we have with semiconductors, we really want to know how they work and what varieties and flavors they come in."

As with previous projects, Ramshaw and Ghosh used resonant ultrasound spectroscopy to study the symmetry properties of the superconductivity in a crystal of strontium ruthenate that was grown and precision-cut by collaborators at the Max Planck Institute for Chemical Physics of Solids in Germany.

However, unlike previous attempts, Ramshaw and Ghosh encountered a significant problem when trying to conduct the experiment.

"Cooling down resonant ultrasound to 1 kelvin (minus 457.87 degrees Fahrenheit) is difficult, and we had to build a completely new apparatus to achieve this," Ghosh said.

With their new setup, the Cornell team measured the response of the crystal's elastic constants - essentially the speed of sound in the material - to a variety of sound waves as the material cooled through its superconducting transition at 1.4 kelvin (minus 457 degrees Fahrenheit).

"This is by far the highest-precision resonant ultrasound spectroscopy data ever taken at these low temperatures," Ramshaw said.

Based on the data, they determined that strontium ruthenate is what's called a two-component superconductor, meaning the way electrons bind together is so complex, it can't be described by a single number; it needs a direction as well.

Previous studies had used nuclear magnetic resonance (NMR) spectroscopy to narrow the possibilities of what kind of wave material strontium ruthenate might be, effectively eliminating p-wave as an option.

By determining that the material was two-component, Ramshaw's team not only confirmed those findings, but also showed strontium ruthenate wasn't a conventional s- or d-wave superconductor, either.

"Resonant ultrasound really lets you go in and even if you can't identify all the microscopic details, you can make broad statements about which ones are ruled out," Ramshaw said. "So then the only things that the experiments are consistent with are these very, very weird things that nobody has ever seen before. One of which is g-wave, which means angular momentum 4. No one has ever even thought that there would be a g-wave superconductor."

Now the researchers can use the technique to examine other materials to find out if they are potential p-wave candidates.

However, the work on strontium ruthenate isn't finished.

"This material is extremely well studied in a lot of different contexts, not just for its superconductivity," Ramshaw said. "We understand what kind of metal it is, why it's a metal, how it behaves when you change temperature, how it behaves when you change the magnetic field. So you should be able to construct a theory of why it becomes a superconductor better here than just about anywhere else."

When we think about sponges, we tend to think of something soft and squishy. But researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) are using the glassy skeletons of marine sponges as inspiration for the next generation of stronger and taller buildings, longer bridges, and lighter spacecraft.

In a new paper published in Nature Materials, the researchers showed that the diagonally-reinforced square lattice-like skeletal structure of Euplectella aspergillum, a deep-water marine sponge, has a higher strength-to-weight ratio than the traditional lattice designs that have used for centuries in the construction of buildings and bridges.

"We found that the sponge's diagonal reinforcement strategy achieves the highest buckling resistance for a given amount of material, which means that we can build stronger and more resilient structures by intelligently rearranging existing material within the structure," said Matheus Fernandes, a graduate student at SEAS and first author of the paper.

"In many fields, such as aerospace engineering, the strength-to-weight ratio of a structure is critically important," said James Weaver, a Senior Scientist at SEAS and one of the corresponding authors of the paper. "This biologically-inspired geometry could provide a roadmap for designing lighter, stronger structures for a wide range of applications."

If you've ever walked through a covered bridge or put together a metal storage shelf, you've seen diagonal lattice architectures. This type of design uses many small, closely spaced diagonal beams to evenly distribute applied loads. This geometry was patented in the early 1800s by the architect and civil engineer, Ithiel Town, who wanted a method to make sturdy bridges out of lightweight and cheap materials.

"Town developed a simple, cost-effective way to stabilize square lattice structures, which is used to this very day," said Fernandes. "It gets the job done, but it's not optimal, leading to wasted or redundant material and a cap on how tall we can build. One of the main questions driving this research was, can we make these structures more efficient from a material allocation perspective, ultimately using less material to achieve the same strength?"

Luckily, the glass sponges, the group to which Euplectella aspergillum -- otherwise known as Venus' Flower Basket belongs -- had a nearly half billion-year head start on the research and development side of things. To support its tubular body, Euplectella aspergillum employs two sets of parallel diagonal skeletal struts, which intersect over and are fused to an underlying square grid, to form a robust checkerboard-like pattern.

"We've been studying structure-function relationships in sponge skeletal systems for more than 20 years, and these species continue to surprise us," said Weaver.

In simulations and experiments, the researchers replicated this design and compared the sponge's skeletal architecture to existing lattice geometries. The sponge design outperformed them all, withstanding heavier loads without buckling. The researchers showed that the paired parallel crossed-diagonal structure improved overall structural strength by more than 20 percent, without the need to add additional material to achieve this effect.

"Our research demonstrates that lessons learned from the study of sponge skeletal systems can be exploited to build structures that are geometrically optimized to delay buckling, with huge implications for improved material use in modern infrastructural applications," said Katia Bertoldi, the William and Ami Kuan Danoff Professor of Applied Mechanics at SEAS and a corresponding author of the study.

WASHINGTON -- Researchers have demonstrated a new endoscope that uniquely combines photoacoustic and fluorescent imaging in a device about the thickness of a human hair. The device could one day provide new insights into the brain by enabling blood dynamics to be measured at the same time as neuronal activity.

"Combining these imaging modalities could improve our understanding of the brain's structure and behavior in specific conditions such as after treatment with a targeted drug," said research team leader Emmanuel Bossy from the CNRS/ Université Grenobe Alpes Laboratoire Interdisciplinaire de Physique. "The endoscope's small size helps minimize damage to tissue when inserting it into the brains of small animals for imaging."

In The Optical Society (OSA) journal Biomedical Optics Express, Bossy's research team, in collaboration with Paul C. Beard's team from University College London, describe their new multi-modality endoscope and show that it can acquire photoacoustic and fluorescent images of red blood cells and fluorescent beads.

Two images are better than one

Acquiring fluorescence and photoacoustic images with the same device provides automatically co-registered images with complementary information. Fluorescent signals, which are created when a fluorescent marker absorbs light and re-emits it with a different wavelength, are most useful for labeling specific regions of tissue. On the other hand, photoacoustic images, which capture an acoustic wave generated after the absorption of light, do not require labels and thus can be used to image blood dynamics, for example.

The new endoscope uses a technique called optical wavefront shaping to create a focused spot of light at the imaging tip of a very small multi-mode optical fiber. "Light propagating into a multi-mode fiber is scrambled, making it impossible to see through the fiber," said Bossy. "However, this type of fiber is advantageous for endoscopy because it is extremely small compared to the bundles of imaging fibers used for many medical endoscopic devices."

To see through the multi-mode optical fiber, the researchers used the spatial light modulator to send specific light patterns through the fiber and create a focus spot at the imaging end. When the focus spot hits the sample, it creates a signal that can be used to build up an image point by point by raster scanning the spot over the sample. Although other researchers have used multimode fibers for fluorescence endoscopy, the new work represents the first time that photoacoustic imaging has been incorporated into this type of endoscope design.

Adding sound sensitivity

The researchers added photoacoustic imaging by incorporating an additional, very thin optical fiber with a special sensor tip that is sensitive to sound. Because commercially available fiber optic acoustic sensors are not sensitive or small enough for this application, the researchers used a very sensitive fiber optic sensor recently developed by Beard's research team.

"The focused spot of light allows us to build the image pixel by pixel while also increasing the strength of fluorescence and photoacoustic signals because it concentrates the light at the focal spot," explained Bossy. "This concentrated light combined with a sensitive detector made it possible to obtain images using only one laser pulse per pixel, whereas commercial fiber optic acoustic sensors would have required many laser pulses."

The researchers fabricated a prototype microendoscope that measured just 250 by 125 microns squared and used it to image fluorescent beads and blood cells using both imaging modalities. They successfully detected multiple 1-micron fluorescent beads and individual 6-micron red blood cells.

Because fluorescence endoscopy in rodent's brain has been performed by other scientists, the researchers are confident that their dual modality device will work in similar conditions. They are now continuing work to increase the device's acquisition speed, with a goal of acquiring a few images per second.

Metamaterials--nanoengineered structures designed for precise control and manipulation of electromagnetic waves--have enabled such innovations as invisibility cloaks and super-resolution microscopes. Using transformation optics, these novel devices operate by manipulating light propagation in "optical spacetime," which may be different from the actual physical spacetime. According to Igor Smolyaninov of the University of Maryland, "One of the more unusual applications of metamaterials was a theoretical proposal to construct a physical system that would exhibit two-time physics behavior on small scales." That proposal was recently realized experimentally by demonstration of two-time (2T) behavior in ferro-fluid-based hyperbolic metamaterials by Smolyaninov and a team of researchers from Towson University, led by Vera Smolyaninova. The observed 2T behavior has potential for use in ultrafast all-optical hypercomputing.

2T physics

The familiar three spatial dimensions and one temporal dimension of conventional spacetime find an alternative paradigm in 2T physics, which has two spatial and two temporal dimensions. Pioneered through theoretical investigation and modeling by physicists Paul Dirac and Andrei Sakharov in the 1960s, 2T space-time was more recently explored by Smolyaninov with Evgenii Narimanov of Purdue University. Their theoretical model predicted that light waves might exhibit 2T behavior in hyperbolic metamaterials.

Nonlinear hyperbolic metamaterials for precision light control

Hyperbolic metamaterials are extremely anisotropic, behaving like a metal in one direction and like a dielectric in the orthogonal direction. Originally introduced to improve optical imaging, hyperbolic metamaterials demonstrate a number of novel phenomena, such as very low reflectivity, extreme thermal conductivity, high temperature superconductivity, and interesting gravity theory analogues.

Smolyaninov explains that the gravity analogues are a coincidental mathematical parallel: the mathematical equations that describe propagation of light in hyperbolic metamaterials also describe particle propagation in the physical, or Minkowski, spacetime in which one of the spatial coordinates behaves as a "time-like variable." Smolyaninov explains further that nonlinear optical effects "bend" this flat Minkowski spacetime, resulting in "effective gravitational force between extraordinary photons." According to Smolyaninov, experimental observation of the effective gravity in such a system should enable observation of the emergence of the gravitational arrow of time along a spatial direction. Together with conventional physical time, the two time-like variables guide evolution of the light field in a hyperbolic metamaterial.

Experimental progress in this exciting field has been relatively slow until recently, due to difficulties associated with the 3D nanofabrication techniques necessary to produce large-volume 3D nonlinear hyperbolic metamaterials. The research team developed an alternative way to fabricate large-volume 3D nonlinear hyperbolic metamaterials using self-assembly of magnetic metallic nanoparticles in a ferrofluid subjected to external magnetic field. Smolyaninov explains, "Due to nonlinear optical Kerr effect in the strong optical field of a CO2 laser, light propagating inside the ferrofluid indeed exhibits pronounced gravity-like effects, leading to emergence of the gravitational arrow of time."

As predicted by the earlier theoretical work, the experimentally observed dynamics of self-focused light filaments may indeed be described mathematically using the 2T physics model.

Ultrafast all-optical hypercomputing

According to Smolyaninov, ultrafast all-optical hypercomputing involves mapping a computation performed during a given period of time onto a much faster computation performed using a given spatial volume of a hyperbolic metamaterial--a possibility enabled by the observed 2T behavior. Smolyaninov notes that hypercomputing schemes may be useful in time-sensitive applications, such as real-time computing, flight control, or target recognition.

A UCLA-led report published today in the Journal of the American Medical Association Internal Medicine exposes what the authors call a weakness in the high-profile "Best Hospitals Honor Roll" published annually by U.S. News and World Report.

The data used to compile the rankings are collected from multiple sources, including outcomes reported to the Joint Commission, an accreditation agency. Every three years, hospitals are required to complete a comprehensive review by the Joint Commission to earn or maintain accreditation.

None of the top 20 hospitals in the 2020-21 U.S. News rankings reported to the Joint Commission on how they deliver smoking cessation care and treatment for tobacco dependence -- which the paper calls a significant disconnect.

The authors suggest that reporting on tobacco treatment should be a required measure, not an elective one, for accreditation and recognition.

"An honor roll for best hospitals is missing the mark if these hospitals aren't helping smokers quit," said Linda Sarna, dean of the UCLA School of Nursing and the report's lead author. "The good news is that there are cost-effective treatments that work if health care providers include them as an expected part of care."

According to the paper, almost 500,000 Americans die annually from tobacco use, and 16 million have serious tobacco-induced chronic diseases, which results in $170 billion in health care costs. Of the 34 million Americans addicted to nicotine, the authors write, too few receive cessation assistance from health care professionals.

"Including smoking treatment as part of hospital care just makes sense," said Dr. Michael Fiore, director of the University of Wisconsin Center for Tobacco Research and Intervention, and a co-author of the report. "How can a hospital be designated as 'best' if it neglects to help people overcome the biggest risk to their health?"

Given the lethality of tobacco dependence, the authors write that addressing it should be a priority, especially since tobacco use affects all of the health conditions on which hospital rankings are based.

"Our analysis of data from the Joint Commission demonstrates a major missed opportunity for our leading hospitals to focus vigorously on helping their patients who smoke to quit," said Dr. Steven Schroeder, professor of medicine at UC San Francisco and the paper's other co-author. "They could not only improve the health of their patients but also set an example for the rest of the country."

New research presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD), held online this year, shows that having a greater exercise capacity is associated with a significantly decreased all-cause mortality risk of between 25-33% in people with type 2 diabetes (T2D). The study was conducted by Dr Yun-Ju Lai and colleagues at Puli branch, Taichung Veterans General Hospital, Nantou, Taiwan.

Exercise improves insulin sensitivity, reduces the risk of cardiovascular disease, and inhibits inflammatory cytokines: types of signalling proteins which trigger an inflammatory response. These cytokines are produced by cells of the immune system and are a vital part of how the body responds to the presence of potential disease-causing agents, but excessive chronic production can contribute to inflammatory diseases (which include diabetes). Despite this, the effect of exercise on all-cause mortality in people with T2D has not been fully explored.

The research was based on data drawn from the National Health Interview Survey (NHIS) and the National Health Insurance research database in Taiwan. The NHIS has taken place every four years from 2001 onwards, and details of individuals participating were obtained at baseline through face to face interviews.

The study used information about the characteristics of each participant, including their socioeconomic status, health behaviours, and exercise habits obtained from surveys performed in 2001, 2005, 2009, and 2013. Comorbidities among individuals taking part in the surveys were confirmed by referencing National Health Insurance research database records from 2000-2016, and their health status was followed-up until 31 December 2016. Finally, the team performed statistical analyses to evaluate the relationship between exercise capacity and all-cause mortality, the latter having been determined by referencing the National Registration of Death System in Taiwan.

The details of 4,859 adult Survey participants with T2D were used in the study; 2,389 (49%) were male, and the mean age was 59.5 years. The authors found that those with a higher exercise capacity had a significantly lower risk of all-cause mortality compared with those who reported no exercise habits. Individuals who performed a moderate amount of exercise (defined as 0-800 kcal/week energy expenditure) had a 25% lower all-cause mortality rate, while participants who were classed as having a high exercise level (more than 800 kcal/week energy expenditure) had a 32% lower all-cause mortality risk.

The team conclude: "Among people with type 2 diabetes, those with increased exercise capacity had a significantly decreased risk of all-cause mortality. Further studies should investigate the type and dose of exercise that is most helpful to promote health and prolong life expectancy."

Lugano, Switzerland, 20 September 2020 - Post-operative radiotherapy (PORT) used in patients with non-small-cell lung cancer (NSCLC) following complete resection and after (neo) adjuvant chemotherapy shows no statistically significant difference in 3-year disease-free survival (DFS), according to data presented at ESMO 2020. These results give the oncology community a long-awaited answer. (1)

PORT in completely resected NSCLC patients has been a subject of debate for many years in patients with mediastinal nodal involvement (pN2), since a meta-analysis in 1998 threw doubt on the benefits associated with it. (2)

However, more recent times have seen better selection, (neo)-adjuvant chemotherapy in stage III resected patients, as well as improved radiotherapy and more recent non prospective studies suggested modern PORT could improve outcome. (3,4,5,6,7)

As such, there was a clear need for a large, randomised trial to assess the role of modern mediastinal PORT in adequately staged and surgically treated patients. This study provides more robust data to help clinicians to decide the best course of action for these patients.

The large randomised controlled trial presented at ESMO 2020, explored the role of modern mediastinal PORT in patients with completely resected NSCLC with histo/cytologically proven nodal involvement.

A total of 501 patients were entered into the intention-to-treat analysis, of which 252 received PORT over five weeks, and 249 entered the control arm (no PORT). Safety analysis was carried out in 487 patients.

Disease-free survival was of 47.1% in the PORT arm and 43.8% in the control arm, thus not statistically significant, with a hazard ratio of = 0.85 (95% CI = [0.67;1.07]; p value = 0.16) for patient receiving PORT compared to control.

Overall survival at three years was 66.5% (95% CI = [59;73]) of patients in the PORT arm compared to 68.5% (95% CI = [61;75]) in the control arm.

Study author Dr Cecile Le Pechoux, radiation oncologist from Institut Gustave Roussy, Paris, France, said: "PORT cannot be recommended for all patients with stage II and III NSCLC with mediastinal nodal involvement. Possibly, however, for some patients it might be useful because it does decrease the rate of mediastinal relapse by 50%. This must be put into balance with the risk of over-added cardio-pulmonary toxicity. We need to do further analysis to determine if certain patients, in particular, could benefit from it" she added.

Prof Rafal Dziadziuszko, radiation oncologist from the Medical University of Gdansk, Poland, commented on the findings. "Radiotherapy to the mediastinum after surgery, after adjuvant chemotherapy shouldn't be recommended as standard of care. This will change the practice of many institutions that adopted standard use of radiotherapy in these patients. We can safely say there is no net benefit from such treatment but there is also potential harm, which we see from this study, so any potential benefits in some patients are offset by the predominantly higher risk of cardiopulmonary toxicities."

Solar storm analysis carried out by an army of citizen scientists has helped researchers devise a new and more accurate way of forecasting when Earth will be hit by harmful space weather.
Scientists at the University of Reading added analysis carried out by members of the public to computer models designed to predict when coronal mass ejections (CMEs) - huge solar eruptions that are harmful to satellites and astronauts - will arrive at Earth.

The team found forecasts were 20% more accurate, and uncertainty was reduced by 15%, when incorporating information about the size and shape of the CMEs in the volunteer analysis. The data was captured by thousands of members of the public during the latest activity in the Solar Stormwatch citizen science project, which was devised by Reading researchers and has been running since 2010.

The findings support the inclusion of wide-field CME imaging cameras on board space weather monitoring missions currently being planned by agencies like NASA and ESA.

Dr Luke Barnard, space weather researcher at the University of Reading's Department of Meteorology, who led the study, said: "CMEs are sausage-shaped blobs made up of billions of tonnes of magnetised plasma that erupt from the Sun's atmosphere at a million miles an hour. They are capable of damaging satellites, overloading power grids and exposing astronauts to harmful radiation.

"Predicting when they are on a collision course with Earth is therefore extremely important, but is made difficult by the fact the speed and direction of CMEs vary wildly and are affected by solar wind, and they constantly change shape as they travel through space.

"Solar storm forecasts are currently based on observations of CMEs as soon as they leave the Sun's surface, meaning they come with a large degree of uncertainty. The volunteer data offered a second stage of observations at a point when the CME was more established, which gave a better idea of its shape and trajectory.

"The value of additional CME observations demonstrates how useful it would be to include cameras on board spacecraft in future space weather monitoring missions. More accurate predictions could help prevent catastrophic damage to our infrastructure and could even save lives."

In the study, published in AGU Advances, the scientists used a brand new solar wind model, developed by Reading co-author Professor Mathew Owens, for the first time to create CME forecasts.

The simplified model is able to run up to 200 simulations - compared to around 20 currently used by more complex models - to provide improved estimates of the solar wind speed and its impact on the movement of CMEs, the most harmful of which can reach Earth in 15-18 hours.

Adding the public CME observations to the model's predictions helped provide a clearer picture of the likely path the CME would take through space, reducing the uncertainty in the forecast. The new method could also be applied to other solar wind models.

The Solar Stormwatch project was led by Reading co-author Professor Chris Scott. It asked volunteers to trace the outline of thousands of past CMEs captured by Heliospheric Imagers - specialist, wide-angle cameras - on board two NASA STEREO spacecraft, which orbit the Sun and monitor the space between it and Earth.

The scientists retrospectively applied their new forecasting method to the same CMEs the volunteers had analysed to test how much more accurate their forecasts were with the additional observations.

Using the new method for future solar storm forecasts would require swift real-time analysis of the images captured by the spacecraft camera, which would provide warning of a CME being on course for Earth several hours or even days in advance of its arrival.

An immunotherapy drug called 'avelumab' has been shown to significantly improve survival in patients with the most common type of bladder cancer, according to results from a phase III clinical trial led by Queen Mary University of London and Barts Cancer Centre, UK.

This is the first time an immune therapy has resulted in a survival advantage in this setting in bladder cancer, and will potentially benefit thousands of patients each year.

The results were published in the New England Journal of Medicine and found that avelumab led to a 31 per cent reduction in risk of death of bladder cancer and extended median survival in advanced bladder cancer by more than seven months.

Approximately 550,000 new cases of bladder cancer are diagnosed each year (10,200 of which are in the UK), making it the tenth most common cancer worldwide. This trial focused on the group of these patients whose cancer had spread beyond the bladder (advanced or stage 4 disease), which is difficult to treat and results in more than 200,000 deaths each year worldwide.

Chemotherapy is the current initial standard of care in the treatment of these advanced cancers. After chemotherapy is finished, patients are checked regularly because the cancer tends to return quickly. When it returns it is difficult to treat and outcomes are poor.

The phase III global trial, named JAVELIN Bladder 100 and funded by Pfizer and Merck KGaA Darmstadt, Germany, evaluated the efficacy of the immunotherapy drug 'avelumab' in patients with locally advanced or metastatic urothelial carcinoma, whose disease had not progressed after chemotherapy.

A total of 700 patients from over 200 sites around the world were then assigned to two treatment groups after the completion of chemotherapy - one group receiving regular checking (standard care) on its own, and the other receiving avelumab in addition to standard care.

Treatment with avelumab resulted in a 31 per cent reduction in risk of death and median overall survival of 21.4 months compared with 14.3 months in patients who did not receive the drug. Side effects were in line with expectations with immune therapy and 11 per cent of patients stopped avelumab due to treatment problems.

Study lead Thomas Powles, Professor of Genitourinary Oncology at Queen Mary University of London, and Director of Barts Cancer Centre, Barts Health NHS Trust, said: "This is the first time that an immune therapy clinical trial has shown a survival benefit for first-line therapy in metastatic bladder cancer.

"We saw a meaningful reduction in the risk of death and a significant overall survival benefit with avelumab, which underscores the potential for this immunotherapy to be practice-changing for patients. This highlights the potential benefits of a maintenance approach with avelumab in patients to prolong their lives following chemotherapy."

In the UK, an early access medicine scheme (EAMS) for avelumab is an option for bladder cancer patients who have benefited from chemotherapy, consistent with the Javelin Bladder trial criteria. Avelumab will now be available in the UK to advanced/metastatic urothelial carcinoma patients through the EAMS scheme.

In the US, the Food and Drug Administration (FDA) has approved avelumab for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy based on the JAVELIN Bladder 100 results.

Avelumab is a type of immunotherapy, known as a checkpoint inhibitor, which blocks a protein called PD-L1 on the surface of tumour cells. When PD-L1 is active it helps cancers hide from the immune system. By blocking PD-L1 the immune system finds it easier to identify and kill the cancer.

Australian researchers and their colleagues from Russia and China have shown that it is possible to study the magnetic properties of ultrathin materials directly, via a new microscopy technique that opens the door to the discovery of more two-dimensional (2D) magnetic materials, with all sorts of potential applications.

Published in the journal Advanced Materials, the findings are significant because current techniques used to characterise normal (three-dimensional) magnets don't work on 2D materials such as graphene due to their extremely small size - a few atom thick.

"So far there has been no way to tell exactly how strongly magnetic a 2D material was," said Dr Jean-Philippe Tetienne from the University of Melbourne School of Physics and Centre for Quantum Computation and Communication Technology.

"That is, if you were to place the 2D material on your fridge's door like a regular fridge magnet, how strongly it gets stuck onto it. This is the most important property of a magnet."

To address the problem, the team, led by Professor Lloyd Hollenberg, employed a widefield nitrogen-vacancy microscope, a tool they recently developed that has the necessary sensitivity and spatial resolution to measure the strength of 2D material.

"In essence, the technique works by bringing tiny magnetic sensors (so-called nitrogen-vacancy centres, which are atomic defects in a piece of diamond) extremely close to the 2D material in order to sense its magnetic field," Professor Hollenberg explained.

To test the technique, the scientists chose to study vanadium triiodide (VI3) as large 3D chunks of VI3 were already known to be strongly magnetic.

Using their special microscope, they have now shown that 2D sheets of VI3 are also magnetic but about twice as weak as in the 3D form. In other words, it would be twice as easy to get them off the fridge's door.

"This was a bit of a surprise, and we are currently trying to understand why the magnetisation is weaker in 2D, which will be important for applications," Dr Tetienne said.

Professor Artem Oganov of Skolkovo Institute of Science and Technology (Skoltech) in Moscow said the findings have the potential to trigger new technology.

"Just a few years ago, scientists doubted that two-dimensional-magnets are possible at all. With the discovery of two-dimensional ferromagnetic VI3, a new exciting class of materials emerged. New classes of material always mean that new technologies will appear, both for studying such materials and harnessing their properties."

The international team now plan to use their microscope to study other 2D magnetic materials as well as more complex structures, including those that are expected to play a key role in future energy-efficient electronics.

An international research team of Tokyo Medical and Dental University (TMDU) and Harvard Medical School (HMS) has discovered that controlling the nuclear localization of the PD-L1 immune checkpoint protein can enhance the efficacy of immunotherapy for cancer treatment

Tokyo, Japan - For most people, there is no scarier diagnosis than that of cancer. While treatments including chemotherapy and radiotherapy have been used since the 1940s and late 1800s, respectively, immunotherapy has more recently emerged as a viable and successful approach to cancer treatment. Indeed, evasion of the host immune system is an essential feature of tumorigenesis. Figuring out how cells do this, and disrupting it, to allow the patient's own immune system to eliminate the cancer cells, is the basis of immunotherapy.

In a study published in August 2020 in Nature Cell Biology, a team including researchers from Tokyo Medical and Dental University (TMDU) and Harvard Medical School (HMS) have identified the regulatory mechanisms through which the PD-L1 immune check-point protein dictates the efficacy of anti-PD-L1 immunotherapy.

"We already knew that immunotherapies targeting immune-checkpoint inhibitors were somewhat successful in treating some cancer types," says co-author Naoe Taira Nihira. "However, only a subset of patients achieved long-lasting results."

PD-L1 expression is tightly controlled, and patients with increased PD-L1 expression in tumors are likely to respond well to PD-L1 blockade; however, the reasons why increased PD-L1 expression leads to increased PD-L1 blockade sensitivity have remained unclear. The research team examined a specific kind of PD-L1 modification, called acetylation, and found that removal of this modification allows PD-L1 to enter the nucleus and interact with DNA to regulate the immune response.

Using a variety of advanced molecular, biochemical, and bioinformatics approaches, the researchers examined PD-L1 acetylation, localization, function, and interactions. They found that plasma membrane localized PD-L1 translocates to the nucleus by interacting with transport pathway components. Specifically, by introducing a series of mutations into PD-L1 and expressing different acetyltransferases, they determined that PD-L1 is acetylated by p300 at a specific residue within the cytoplasm called Lys263. Using similar approaches, and protein depletion by short-interfering RNAs, they also discovered that histone deacetylase (HDAC) specifically interacts with and deacetylates PD-L1.

Protein modifications, including acetylation, can affect protein stability, dimerization, or localization. However, when the team reduced the amount of HDAC2 protein in the cells, consequently increasing the acetylation level, there were no observable changes in protein stability or dimerization. Co-author Akira Nakanishi explains: "These results mean that the acetylation and deacetylation of PD-L1 at this residue play a critical role in its nuclear translocation."

In the nucleus, PD-L1 regulates the expression of pro-inflammatory and immune-response-related genes, indicating that PD-L1 could function to regulate the local tumor immune environment to control its sensitivity to immune checkpoint-blockade therapy .

Given the health and economic burdens of cancer worldwide, new treatment approaches with increased efficacy are continually being sought. The results presented by this team indicate that targeting PD-L1 translocation can be used to enhance the efficacy of PD-1/PD-L1 blockade-based immunotherapy approaches.

The perovskite NaOsO3 has a complicated, but interesting temperature dependent metal-insulator transition (MIT). A team led by Drs. Raimundas Sereika and Yang Ding from the Center for High Pressure Science and Technology Advanced Research (HPSTAR) showed that the insulating ground state in NaOsO3 can be preserved up to at least 35 GPa with a sluggish MIT reduction from 410 K to a near room temperature and possible transformation to a polar phase. The work published in the npj Quantum Materials.

NaOsO3 perovskite undergoes a metal-insulator transition concomitant with the onset of an antiferromagnetic long-range ordering at a Neel temperature of about 410 K which is accompanied by a magnetic ordering without any lattice distortion.

The team carried out a combined experimental and computational study to understand the effect of external pressure on perovskite NaOsO3. They found hidden hysteretic resistance properties with a transient metallic state near 200 K. Also three electronic character anomalies (at 1.7, 9.0, and 25.5 GPa), and a structural transition to the singular polar phase (at ~ 18 GPa) were discovered.

In terms of the MIT, the pressure-dependent electrical transport measurements indicate that the metallic state extends to the lower temperatures very slowly. The TMIT scales almost linearly upon pressure. At around 32 GPa, the MIT becomes much broader, but can still be identified. Importantly, up to this pressure, NaOsO3 preserves the insulating ground state.

In addition, the warming and cooling curves slightly deviate, forming a narrow thermal hysteresis loop below MIT. The hysteresis is progressively attenuated upon pressure but eventually disappears at about 18 GPa. "The observed hysteresis raises a question if MIT is really the second-order type that was initially assigned," Sereika said.

Further, when the pressure is increased, the Raman results show that NaOsO3 experiences a structural change. The Raman spectra in particular demonstrate the enhancement of the number of phonons and the pressure-induced-splitting of phonon mode above 18 GPa.

"Our pressure-dependent Raman measurements support the fact that the crystal symmetry does not change up to 16 GPa at room temperature and indicates that further pressure increase causes structural transformation to a different symmetry," Ding explained.

"At about 26 GPa, the continuous large-scale reduction in intensity is observed as the pressure increases. Finally, the Raman modes almost vanish at 35 GPa, indicating that sample is approaching a metallic state, that is the MIT," Ding added.

By combining theoretical modeling and experimental data all observed phenomena were explained in detail. A rich electronic and structural phase diagram of NaOsO3 shows the different types of transitions occurring in the system when pressure and temperature are applied: insulator-to-bad metal, bad-metal-to-metal, the anomalous metal island in the bad-metal region, and the subtle non-polar to polar structural transition.

At low temperature the system remains insulating up to a certain critical pressure (~20 GPa in DFT) and then transforms into a bad metal due to the closing of the indirect gap. In this pressure range the valence and conduction bands are still separated by a direct gap. This gap closes at very large pressure, indicating that the evolution of the electronic properties upon pressure share similarities with the temperature-induced band gap closing process.

"The magnetically itinerant Lifshitz-type mechanism with spin-orbit and spin-phonon interactions is responsible for these pressure-induced changes," Ding remarked. "Our findings provide another new playground for the emergence of new states in 5d materials by using high-pressure methods."

Ancient historiographers described steppe nomads as violent people dedicated to warfare and plundering. Little archaeological and anthropological data are however available regarding violence in these communities during the early centuries CE. In a new study in the American Journal of Physical Anthropology, an international team led by researchers from the University of Bern and the Russian Academy of Sciences presents new discoveries about the types of violence lived by nomads from Siberia between the 2nd-4th centuries CE. The study "Troubles in Tuva: patterns of perimortem trauma in a nomadic community from Southern Siberia (2nd-4th c. CE)" was performed by Dr. Marco Milella from the Department of Physical Anthropology, Institute of Forensic Medicine (IRM), University of Bern and colleagues.

A late antique cemetery in the heart of Siberia

The Republic of Tuva in Southern Siberia features a rich archaeological record documenting its human occupation since the Paleolithic. Of particular importance are Scythians from the Bronze-Iron Age and Late Antique funerary structures. The site of Tunnug1 is one of the earliest "royal" tombs of Scythian material culture in Siberia known to date, and it has been excavated from 2017 by an archaeological mission co-led by Dr. Gino Caspari from the University of Bern as well as Timur Sadykov and Jegor Blochin from the Russian Academy of Sciences. Recent excavations at Tunnug1 have exposed a peripheral cemetery dating to the 2nd-4th centuries CE including the skeletal remains of 87 individuals. Of these, several presented exceptional traces of violence, not exclusively related to warfare, but possibly also due to rituals.

A research team performed a detailed analysis of the traumas found on the skeletal remains. The researchers were interested in reconstructing the possible scenarios leading to the observed anthropological evidence. In conjunction with this study, the Institute of Forensic Medicine is completing the work on stable isotope ratios and ancient DNA of the bones. This will allow in the next future to reconstruct the diet, mobility, genetic affiliation of these people.

Violence, warfare, and rituals

The study demonstrates that 25% of the individuals died as a consequence of interpersonal violence, mostly related to hand-to-hand combat, often represented by traces of decapitation. Even though violence affected mostly men, also women and children were found among the victims. Some of the individuals from Tunnug1 show traces of throat-slitting and scalping. According to Marco Milella, first author of the study "this suggests that violence was not only related to raids and battles, but probably also due to specific, still mysterious, rituals involving the killing of humans and the collection of war trophies".

Political instability and violence in the past

Marco Milella states: "Our data show that the individuals buried at Tunnug1 experienced high levels of violence. During the early centuries CE the whole area of Southern Siberia went through a period of political instability. Our study demonstrates how political changes affected, in the past like nowadays, the life and death of people."