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The use of extreme ultraviolet light sources in making advanced integrated chips has been considered, but their development has been hindered owing to a paucity of efficient laser targets. Scientists at Tokyo Institute of Technology (Tokyo Tech) recently developed an extremely low-density tin "bubble," which makes the generation of extreme ultraviolet reliable and low cost. This novel technology paves the way for various applications in electronics and shows potential in biotechnology and cancer therapy.

Development of next-generation devices requires that their core, called the integrated circuit chip, is more compact and efficient than existing ones. Manufacturing these chips requires powerful light sources. The use of light sources in the extreme ultraviolet (EUV) range (an extremely short-wavelength radiation) has become popular in recent times, but their generation is challenging.

One solution is the use of high-intensity lasers: Recent advances in laser technology have led to the development of lasers with increased power and lower prices. High-intensity lasers implement laser plasmas, and their first practical application is the generation of EUV light to manufacture semiconductor integrated circuits. In this process, these lasers irradiate an appropriate "target," and as a result, a high-temperature and high-density state is created. From this state, 13.5 nm light is generated with high brightness, which can be used in the manufacturing of integrated chips. But this is not an easy feat: control of target density that can produce light in the EUV range has been difficult. Tin has been considered as an option, but its development has been greatly delayed owing to the inability to control its dynamics.

To this end, a team of scientists, including Associate Professor Keiji Nagai from Tokyo Tech and Assistant Professor Christopher Musgrave from University College, Dublin, set out to find efficient laser targets. In a study published in Scientific Reports, they describe a novel type of low-density material, which is scalable and low-cost. Prof Nagai says, "EUV light has become crucial in today's world but is expensive owing to the high-volume manufacturing."

To begin with, the scientists created a tin-coated microcapsule or "bubble," a very low-density structure--weighing as little as 4.2 nanogram. For this, they used polymer electrolytes (dissolution of salts in a polymer matrix), which act as surfactants to stabilize the bubbles. The bubbles were then coated with tin nanoparticles. Prof Nagai explains, "We produced polyelectrolyte microcapsules composed of poly(sodium 4-styrene-sulfonate) and poly(allylamine hydrochloride) and then coated them in a tin oxide nanoparticle solution."

To test the use of this bubble, the scientists irradiated it using a neodymium-YAG laser. This, indeed, resulted in the generation of EUV light, which is within the 13.5 nm range. In fact, the scientists even found that the structure was compatible with conventional EUV light sources that are used to manufacture semiconductor chips. But, the biggest advantage was that the laser conversion efficiency with the tin bubble, a measure of the laser power, matched that of bulk tin. Prof Nagai explains, "Overcoming the limitations of liquid tin dynamics can be very advantageous in generating EUV light. Well-defined low-density tin targets can support a wide range of materials including their shape, pore size, density etc."

Prof Nagai and his research team have been developing low-density materials for laser targets for many years but had been suffering limitations with manufacturing costs and mass productivity. Now, combining new low-density tin targets made of bubbles offers an elegant solution for mass producing a compact 13.5 nm light source at a low cost. In addition to its applications in electronics, Prof Nagai is optimistic that their novel technology consisting of "bubble" laser targets could even be used in cancer therapy. He concludes, "This method could be utilized as a potential small scale/compact EUV source, and future quantum beam sources such as electrons, ions, and x-rays by changing the coating to other elements." Through this opportunity, Prof Nagai and his team wish to collaborate with large laser facilities in Japan and overseas.

Skoltech scientists modeled the behavior of nanobubbles appearing in van der Waals heterostructures and the behavior of substances trapped inside the bubbles. In the future, the new model will help obtain equations of state for substances in nano-volumes, opening up new opportunities for the extraction of hydrocarbons from rock with large amounts of micro- and nanopores.

The van der Waals nanostructures hold much promise for the study of tiniest samples with volumes from 1 cubic micron down to several cubic nanometers. These atomically thin layers of two-dimensional materials, such as graphene, hexagonal boron nitride (hBN) and dichalcogenides of transition metals, are held together by weak van der Waals interaction only. Inserting a sample between the layers separates the upper and bottom layers, making the upper layer lift to form a nanobubble. The resulting structure will then become available for transmission electron and atomic force microscopy, providing an insight into the structure of the substance inside the bubble.

The properties exhibited by substances inside the van der Waals nanobubbles are quite unusual. For example, water trapped inside a nanobubble displays a tenfold decrease in its dielectric constant and etches the diamond surface, something it would never do under normal conditions. Argon which typically exists in liquid form when in large quantities can become solid at the same pressure if trapped inside very small nanobubbles with a radius of less than 50 nanometers.

Scientists led by professor Iskander Akhatov of the Skoltech Center for Design, Manufacturing and Materials (CDMM) built a universal numerical model of a nanobubble that helps predict the bubble's shape under certain thermodynamic conditions and describe the molecular structure of the substance trapped inside.

"In a practical sense, the bubbles in the van der Waals structures are most often regarded as flaws that experimenters are eager to get rid of. However, from the standpoint of straintronics, the bubbles create strain, and its effect on the electronic structure can be used to create practical devices, such as transistors, logic elements and ROM," Petr Zhilyaev, a senior research scientist at Skoltech, commented on the study.

"In our recent study, we created a model which describes a specific shape that flat nanobubbles assume in the subnanometer dimension range only. We discovered that the vertical size of these nanostructures can only take discrete values divisible by the size of the molecules trapped. In addition, the model enables changing the size of nanobubbles by controlling the temperature of the system and the physicochemical parameters of the materials," explained a senior research scientist at Skoltech, Timur Aslyamov.

Upwelling is a process in which deep, cold water rises toward the surface. Typically, water that rises to the surface as a result of upwelling is colder and rich in nutrients. This is the reason why coastal upwelling ecosystems are some of the most productive ecosystems in the world and support many of the world's most important fisheries.

For example, the Eastern Boundary Upwelling Systems (EBUS), such as the California Current System (CalCS), the Canary Current System (CanCS), the Humboldt Current System (HCS), and the Benguela Current System (BenCS), are among the most productive marine ecosystems, supplying up to 20% of the global fish catches, although they only cover approximately 1% of the total ocean. Surface alongshore winds, force the offshore water transport and the divergence of the surface flow, thereby lifting nutrient-rich deep waters into the euphotic layer. The nutrient-rich upwelled water, in addition to the sunlight, sustains the blooms of phytoplankton that are the foundation of the aquatic food web.

Understanding the drivers and monitoring changes across EBUS is becoming increasingly important: many studies have in fact documented trends and changes at decadal scale in the EBUS ecosystem structure. Coastal warming increases the water stratification and it might limit the effectiveness of upwelling to bring nutrient-rich deep waters up to the surface. Increasing or decreasing of the upwelling-favourable winds might also mitigate or amplify the effect of coastal warming. Coastal waves may also influence the water column stratification modulating coastal biogeochemical conditions and triggering vertical displacements of the thermocline, which controls subsurface anomalies (e.g., salinity), and thus the impact on EBUS productivity.

Moreover, we have to mention the influence of the main large-scale ocean-atmosphere processes: the El Nin?o Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO), the North Pacific Gyre Oscillation (NPGO), the North Atlantic Oscillation (NAO), the Atlantic Multidecadal Oscillation (AMO) seem to play a role in controlling the upwelling variability.

A study published on Nature Scientific Reports was aimed at understanding the coherent and non-coherent low frequency variability across the EBUS, and to explore how it is linked to large-scale climate modes, with the aim of modelling and studying the interannual to decadal variability of the major Eastern Boundary Upwelling Systems. The study, led by scientist Giulia Bonino, researcher at the CMCC ODA - Ocean modeling and Data Assimilation Division, and co-authored by CMCC scientists Simona Masina and Dorotea Iovino, and by Emanuele Di Lorenzo from Georgia Institute of Technology, focuses on quantifying forcing dynamics (e.g. alongshore winds, wind stress curl, thermocline depth) that controls low-frequency modulations in each EBUS while aiming at identifying how the forcing is linked to large-scale climate dynamics, to finally understand the extent to which large-scale climate dynamics imprint a coherent signal across EBUS.

Researchers modelled ocean dynamics in upwelling areas using a global eddy-permitting configuration of the NEMO model from 1958 to 2015. To quantify the upwelling, they introduced an ensemble of passive tracers in the simulation, which are continuously released in the subsurface layer (150-250 m) in each EBUS over a region from the coast to 50 km offshore.

"The results highlight the uniqueness of each EBUS in terms of drivers and climate variability", explains Giulia Bonino. "The local (e.g., wind forcing, stratification and thermocline depth) and the remote (e.g. passage of coastal trapped waves) forcing, with different contribution in each EBUS, appear to control the interannual upwelling variability. Thus, in order to predict and to propose hypotheses on the long-term variations in upwelling, identifying a proper index of upwelling in relation to the major drivers of each domain is essential. In particular, both the coastal wind variations and the stratification have to be considered as potentially competitive or complementary drivers of upwelling variability under climate change."

The second important issue addressed in the study is the influence of the large-scale climate variability on long-term upwelling and the degree to which there is coherent low-frequency variability across EBUS. "The variability associated with climate modes could be of importance to predict future perturbations at interannual to decadal time scales", explains Giulia Bonino. "Our results show that signs of global warming, characterized by strong upwelling winds in a changing climate, are evident only over the Benguela system. From a broader climate prospective, EBUS do not share variability, except from the well-known influence of ENSO on the Pacific systems. Therefore, Atlantic and Pacific upwelling systems appear to be independent. Extending the current analysis to a longer period, with coupled models and with the same passive tracers approach, will help to clarify these issues, enabling the results to be compared, and to confirm any unexpected teleconnections between upwelling systems."

A Finnish study coordinated by the Research Centre of Applied and Preventive Cardiovascular Medicine at the University of Turku, Finland, shows that exposure to parental smoking in childhood and adolescence is associated with poorer learning ability and memory in midlife.

With the aging population, cognitive deficits such as difficulties in learning and memory are becoming more common. Active smoking is known to be detrimental to cognitive function and to contribute to the occurrence of cognitive deficits. Similar short-term associations have been observed for secondhand smoking. Results from a longitudinal Finnish study show that the harmful effects of childhood secondhand smoking exposure may carry over to midlife learning ability and memory function.

- Previous studies have focused on adulthood exposure or on the short-term effects of childhood exposure, whereas this study brings novel information on the long-term associations between secondhand smoking exposure in childhood and cognitive function in midlife, says Senior Researcher Suvi Rovio from the Research Centre of Applied and Preventive Cardiovascular Medicine at the University of Turku.

The results of this study highlight that the focus of prevention of secondhand smoking exposure should be on children and adolescents in order to promote brain health in adulthood. In addition to protecting children and adolescents from starting active smoking, attention should be paid to their secondhand smoking exposure at home and elsewhere.

The cognitive performance of over 2,000 participants was measured at the age of 34-49 years. The results showed that participants who had been exposed to parental smoking in childhood had worse learning ability and poorer memory in midlife than those participants whose parents did not smoke in their presence. This association was present regardless of the participants' own smoking either in adolescence or adulthood. The difference in cognitive performance between those participants who had been exposed to parental smoking and those with non-smoking parents was equivalent to the difference caused by up to five years of aging.

The study is part of the ongoing national Cardiovascular Risk in Young Finns Study coordinated by the Research Centre of Applied and Preventive Cardiovascular Medicine at the University of Turku. The researchers of the follow-up study have studied 3,596 participants repeatedly over 31 years for their cardiovascular risk factors from childhood to adulthood.

Researchers at School of Biological Sciences and Swire Institute of Marine Science, The University of Hong Kong have developed a new method for determining what corals eat, and demonstrated that reliance on certain nutritional sources underpins their bleaching susceptibility in warming oceans.

The research, published in the prestigious journal Science Advances, solves a conundrum scientists have struggled with for decades; determining the diet of a coral involves measuring how much prey it captures with stinging tentacles as well as how much food is provided by the photosynthetic algae inside their cells. To overcome this challenge, the team, led by Dr Inga Conti-Jerpe, compared the stable isotope "fingerprint" of hundreds of corals collected in Hong Kong to that of their associated algae. The results showed that some corals have isotopic fingerprints that match that of their algae, indicating the two partners share nutrients. Other corals have fingerprints distinct from their algae due to a diet based on the capture and consumption of prey particles in the water. The researchers found that more predatory corals had significantly larger polyps (an individual coral unit - much like an anemone) than corals more dependent on photosynthesis, a previously contentious relationship first proposed in 1974.

"We knew that polyp size is a factor that affects the surface area to volume ratio of a coral, a trait that other scientists have observed might be linked to delayed bleaching in the field. We decided to run a warming experiment with our Hong Kong corals to see if their diet accurately predicted how long they could withstand elevated temperatures without bleaching - and it did." explains Dr Conti-Jerpe.

These results have implications for how coral reefs will change as climate change progresses. Corals dependent on photosynthesis bleach faster while predatory corals can withstand warming temperatures longer. "The results of our study help predict which coral species are more likely to survive as oceans warm. Unfortunately, what we found is that the most susceptible species are those that are commonly used in coral reef restoration efforts. To ensure the long-term success of reef rehabilitation, restoration initiatives should shift their focus to bleaching-resistant species." said Dr David Baker, Associate Professor of School of Biological Sciences and Swire Institute of Marine Science who supervised the study.

While predatory nutrition can confer protection from bleaching, the scientists note that given sustained elevated temperatures, all the species in the study eventually bleached. "Capturing a lot of food doesn't save corals from bleaching," explains Dr Conti-Jerpe, "it just buys them a little more time - time that they desperately need." The findings of this study will help scientists, conservationists and policy makers anticipate which corals will disappear first and how this will change reef ecosystems overall, including the services they provide.

Stable isotope data are an established tool for investigating diet - they are derived from measuring the different forms of common elements, such as carbon and nitrogen that have the same function biologically but differ ever so slightly in mass. For instance, nitrogen - an essential building block for DNA and protein - comes in a common 'light' isotope (14N) and a rare 'heavy' isotope (15N). When it comes to diet, animals accumulate 15N if they are sitting higher on the food chain - a carnivore will have more 15N than an herbivore. The corals in this study that had stable isotope values different from that of their algae had more 15N and thus must be more predatory.

Intestinal stem cell metabolism is facilitated by mitochondria - the in-cell power plants. Chronic inflammation processes inhibit the cells' metabolism and lead to functional loss of these stem cells.

In collaboration with the Helmholz Zentrum München and the Université de Paris, a TUM research team has discovered this connection by analyzing intestinal epithelial cells of Crohn's disease patients and comparing them to mouse model findings.

The interrelated role of stem cells and Paneth cells

Stem cells are indispensable for the maintenance and regeneration of tissues. Intestinal stem cells inside the intestines are intermingled with so-called Paneth cells, which are responsible for the local immune defense and for creating an environment in which the stem cells can prosper, thus termed guardians of the stem cell niche.

Patients suffering from Crohn's disease have fewer Paneth cells and furthermore, these are limited in their functionality. The research group examined the causes for alterations in Paneth cells and attempted to determine the importance of stem cell metabolism in this context.

In addition to mouse studies, the researchers analyzed intestinal biopsies from Crohn's disease patients, characterizing the stem cell niche meticulously. After six months, the patients' intestines were examined again endoscopically focusing on finding signs of inflammation.

Predicting Crohn's disease recurrence by observing the appearance of stem cells

The study showed that microscopic alterations in stem cell niche were particularly prevalent in those patients who showed symptoms of a relapse of inflammation after six months.

"These changes in the stem cell niche are a very early indicator for the start of inflammatory processes. Therefore, the appearance of the stem cell niche can be used to evaluate the probability of a disease recurrence after the resection of originally affected parts of the small intestine. This presents a reasonable starting point for therapeutic intervention," explained Dirk Haller, Professor for Nutrition and Immunology at TUM.

Restoring stem cell function

In both human patients and mouse models, alterations in Paneth and stem cells coincided with decreased mitochondria functionality.

Knowing that a lowered mitochondrial respiration leads to alterations in the stem cell niche, the researchers used dichloracetate (DCA), a substance applied in cancer therapy leading to an increase in mitochondrial respiration.

The shift in cellular metabolism induced by DCA was able to restore the intestinal stem cell functionality of mice suffering from inflammation, as demonstrated in intestinal organoids, organ-like structures cultured ex vivo.

Therapeutic approach for prolonging the inflammation-free phases of Crohn's disease

"These findings point to a new therapeutic approach for prolonging the inflammation-free remission phases of Crohn's disease," said Eva Rath, scientist at the TUM School of Life Sciences Weihenstephan and co-author of the study.

The aim of further research is to investigate the effect of DCA in animal models and patients in more detail. A so-called metabolic intervention - making targeted changes in the cells' metabolism - could prevent functional loss of stem cells and Paneth cells, which both maintain the intestinal barrier. This could lead to preventing subsequent inflammation.

The latest tropical cyclone to develop in the Southern Indian Ocean is no threat to land areas. NASA-NOAA's Suomi NPP satellite provided forecasters with a visible image of Tropical Storm Jeruto on April 15, 2020.

Visible imagery from NASA satellites help forecasters understand if a storm is organizing or weakening. The visible image created by the Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard Suomi NPP showed Jeruto was being affected by wind shear after it developed. Vertical wind shear, that is, winds outside of a tropical cyclone at different heights in the atmosphere (the troposphere) push against a tropical cyclone and tear it apart.

The shape of a tropical cyclone provides forecasters with an idea of its organization and strength, and NASA-NOAA's Suomi NPP satellite showed the storm appeared elongated, as outside winds were pushing clouds away from the center of circulation.

On April 15 at 5 a.m. EDT (0900 UTC), Jeruto's center was located near latitude 15.8 degrees south and longitude 84.3 degrees east. Jeruto was moving west-southwest near 10 knots (12 mph/19 kph). Maximum sustained winds were near 40 knots (46 mph/76 kph).

The Joint Typhoon Warning Center noted vertical wind shear (wind speeds) will increase and will likely dissipate the storm within a couple of days.

Millions of people have been tested for the novel coronavirus, most using a kit that relies on the polymerase chain reaction (PCR). This sensitive method amplifies SARS-CoV-2 RNA from patient swabs so that tiny amounts of the virus can be detected. However, as the pandemic surges, this laboratory workhorse is showing signs of strain. Now, researchers reporting a proof-of-concept study in ACS Nano have developed a potentially more accurate diagnostic based on plasmonic photothermal sensing.

Health experts agree that expanded testing is crucial for controlling the spread of COVID-19. However, testing in many countries, including the U.S., has lagged behind because of limited supplies of some reagents and a backlog of samples awaiting available PCR machines and laboratory personnel. In addition, a number of false-negative and -positive test results have been reported. Other methods, such as computed tomography (known as "CT") scanning and culturing, do not provide quick or real time results. Jing Wang and colleagues wanted to develop a faster, potentially more accurate COVID-19 test for detecting the SARS-CoV-2 virus that could be a practical alternative to PCR.

The researchers based their test on a technique called localized surface plasmon resonance, which can detect interactions between molecules on the surface of a constructed metallic nanostructure as a local change in refractive index. The team made DNA probes that recognized specific SARS-CoV-2 RNA sequences and attached them to gold nanoparticles. When they added pieces of the virus's genome, the RNA attached to the complementary probes like a zipper being closed. The team used a laser to heat up the nanoparticles, making it more difficult for imperfectly matched sequences to remain attached, reducing false-positives. For example, a nucleic acid "zipper" missing a couple of teeth -- indicating a partial mismatch -- would unzip under these conditions. In this way, the researchers could discriminate between SARS-CoV-2 and its close relative, SARS-CoV-1. The assay detected amounts of viral RNA below those present in respiratory swabs in a matter of minutes. Although the test still needs to be tested on intact viral RNA from patient samples, it could help relieve the current pressure on PCR-based tests, the researchers say.

FINDINGS

A study by researchers at the UCLA Jonsson Comprehensive Cancer Center has identified a possible new drug that could help prevent cognitive decline in people who undergo radiation therapy for brain tumors. The researchers found when the drug was given to mice 24 hours after the animals were exposed to a dose of radiation, it completely prevented cognitive decline from occurring, and that it did not reduce the efficacy of the radiation treatment.

This experiment represents one of a very few instances in which a drug reduced cognitive decline in animals after radiation treatment.

The drug, NSPP, was identified in 2019 by scientists at the UCLA Center for Medical Countermeasures against Radiation.

BACKGROUND

Aside from surgery, radiation therapy is one of the most effective treatments for people with brain cancer or other cancers that have spread to the brain. Because more people with brain cancer are now surviving longer, more people are experiencing long-term side effects from the treatment.

Those side effects, like memory loss and difficulty with learning new things, can occur months or years after exposure to radiation. That can be particularly problematic for children and young adults who survive cancer, because their brains are still developing; their cognitive function can decline by as much as one to two IQ points per year over the course of their adulthood. Current treatments don't offer a way to avoid that result, other than when doctors can take steps to keep radiation away from critical structures in the brain during treatment.

METHOD

NSPP had already been shown to prevent acute radiation syndrome in mice. Using normal mouse brains and glioblastoma tumor cells derived from patients, the researchers tested whether the drug could also affect neural stem cells and progenitor cells -- types of cells that can repair tissue damage in the brain -- without affecting tumor cells. To assess cognitive function in mice, the team used three behavioral tests: a novel object test, an object-in-place test and a contextual learning test. The study found NSPP was not toxic to normal cells and did not interfere with the growth-delaying effects of radiation in tumor cells.

IMPACT

The study provides evidence that NSPP has the potential to help prevent cognitive decline in people who undergo radiation for the treatment of a brain tumor, without taking away from the efficacy of the radiation treatment.

New data throws more support behind the theory that neutrinos are the reason the universe is dominated by matter.

The current laws of physics do not explain why matter persists over antimatter - why the universe is made of 'stuff'. Scientists believe equal amounts of matter and antimatter were created at the beginning of the universe, but this would mean they should have wiped each other out, annihilating the universe as it began.

Instead, physicists suggest there must be differences in the way matter and antimatter behave that explain why matter persisted and now dominates the universe. Each particle of matter has an antimatter equivalent, and neutrinos are no different, with an antimatter equivalent called antineutrinos.

They should be exact opposites in their properties and behaviour, which is what makes them annihilate each other on contact.

Now, an international team of researchers that make up the T2K Collaboration, including Imperial College London scientists, have found the strongest evidence yet that neutrinos and antineutrinos behave differently, and therefore may not wipe each other out. The results are published today in Nature.

Dr Patrick Dunne, from the Department of Physics at Imperial, said: "This result brings us closer than ever before to answering the fundamental question of why the matter in our universe exists. If confirmed - at the moment we're over 95 per cent sure - it will have profound implications for physics and should point the way to a better understanding of how our universe evolved."

Previously, scientists have found some differences in behaviour between matter and antimatter versions of subatomic particles called quarks, but the differences observed so far do not seem to be large enough to account for the dominance of matter in the universe.

However, T2K's new result indicates that the differences in the behaviour of neutrinos and antineutrinos appear to be quite large. Neutrinos are fundamental particles but do not interact with normal matter very strongly, such that around 50 trillion neutrinos from the Sun pass through your body every second.

Neutrinos and antineutrinos can come in three 'flavours', known as muon, electron and tau. As they travel, they can 'oscillate' - changing into a different flavour. The fact that muon neutrinos oscillate into electron neutrinos was first discovered by the T2K experiment in 2013.

To get the new result, the team fired beams of muon neutrinos and antineutrinos from the J-PARC facility at Tokai, Japan, and detected how many electron neutrinos and antineutrinos arrived at the Super-Kamiokande detector 295km away.

They looked for differences in how the neutrinos or antineutrinos changed flavour, finding neutrinos appear to be much more likely to change than antineutrinos.

The available data also strongly discount the possibility that neutrinos and antineutrinos are as just likely as each other to change flavour. Dr Dunne said: "What our result shows is that we're more than 95 per cent sure that matter neutrinos and antineutrinos behave differently. This is big news in itself; however we do already know of other particles that have matter-antimatter differences that are too small to explain our matter-dominated universe.

"Therefore, measuring the size of the difference is what matters for determining whether neutrinos can answer this fundamental question. Our result today finds that unlike for other particles, the result in neutrinos is compatible with many of the theories explaining the origin of the universe's matter dominance."

While the result is the strongest evidence yet that neutrinos and antineutrinos behave differently, the T2K Collaboration is working to reduce any uncertainties and gather more data by upgrading the detectors and beamlines, including the new Hyper-Kamiokande detector to replace the Super-Kamiokande. A new experiment, called DUNE, is also under construction in the US. Imperial is involved in both.

Imperial researchers have been involved in the T2K Collaboration since 2004, starting with conceptual designs on whiteboards and research and development on novel particle detector components that were key to building this experiment, which was finally completed and turned on in 2010.

For the latest result, the team contributed to the statistical analysis of the results and ensuring the signal they observe is real, as well as including the effects of how neutrinos interact with matter, which is one of the largest uncertainties that go into the analysis.

Professor Yoshi Uchida said: "When we started, we knew that seeing signs of differences between neutrinos and antineutrinos in this way was something that could take decades, if they could ever be seen at all, so it is almost like a dream to have our result be celebrated on the cover of Nature this week."

Two internationally renowned stem cell experts have found an abundance of abnormal stem cells in the lungs of patients who suffer from Chronic Obstructive Pulmonary Disease (COPD), a leading cause of death worldwide. Frank McKeon, professor of biology and biochemistry and director of the Stem Cell Center, and Wa Xian, research associate professor at the center, used single cell cloning of lung stem cells to make their discovery. Now they are targeting the cells for new therapeutics.

"We actually found that three variant cells in all COPD patients drive all the key features of the disease. One produces tremendous amounts of mucins which block the small airways, while the other two drive fibrosis and inflammation which together degrade the function of the lung," Xian reports in the May 14 issue of the journal Cell. "These patients have normal stem cells, though not many of them, but they are dominated by the three variant cells that together make up the disease," she said.

COPD is a progressive inflammatory disease of the lungs marked by chronic bronchitis, small airway occlusion, inflammation, fibrosis and destruction of alveoli, tiny air sacs in the lungs which exchange oxygen and carbon dioxide molecules in the blood. The Global Burden of Disease Study reports 251 million cases of COPD globally in 2016.

"It's a frustrating disease to care for. We can try and improve the symptoms, but we don't have anything that can cure the disease or prevent death," said UConn Health pulmonologist and critical care doctor Mark Metersky, who gathered the stem cells from lung fluid while performing bronchoscopies.

Despite its accounting for more deaths than any single disease on the planet, relatively little has been written or understood about the root cause of COPD.

Over the past decade, Xian and McKeon developed technology for cloning stem cells of the lungs and airways and have been at it since, noting that different parts of the airways give different stem cells, related but distinguishable.

"It's quite remarkable," said McKeon. "In the deep lung, the distal airway stem cells gave rise to both the distal tubes and the alveoli and our research indicates those are the stem cells that make it possible for lungs to regenerate on their own." Xian and McKeon discovered lung regeneration in 2011 in their studies of subjects recovering from infections by an H1N1 influenza virus that was nearly identical to that which sparked the 1918 pandemic.

Xian and McKeon found that, in contrast to normal lungs, COPD lungs were inundated by three unusual variant lung stem cells that are committed to form metaplastic lesions known to inhabit COPD lungs, but seen by many as a secondary effect without a causal link to the pathology of COPD. After the team's postdoctoral fellow, Wei Rao, transplanted each of the COPD clones into immunodeficient subjects, the team found they not only gave rise to the distinct metaplastic lesions of COPD, but they separately triggered the triad of pathologies of COPD including mucus hypersecretion, fibrosis and chronic inflammation.

"The long-overlooked metaplastic lesions in COPD were, in fact, driving the disease rather than merely secondary consequences of the condition," said McKeon.

Now that the team knows the identity of the cells that cause inflammation, fibrosis and small airway obstruction, they are hard at work screening them against libraries of drug-like molecules to discover new therapeutics.

"As we now know the specific cells responsible for COPD pathology, we can target them, much as we would cancer, with specific drugs that selectively kill them off and leave the normal cells to regenerate normal lung tissue," said Xian.

APRIL 15, 2020, NEW YORK-- A Ludwig Cancer Research study has discovered a novel means by which bacterial colonies in the small intestine support the generation of regulatory T cells--immune cells that suppress autoimmune reactions and inflammation. The study, led by Ludwig MSK Director Alexander Rudensky and published in Nature, demonstrates that a microbial metabolite--the organic acid isoDCA--boosts the local generation of the immunosuppressive immune cells in the colon. Such locally generated, or "peripheral", regulatory T cells (Tregs) help dampen chronic intestinal inflammation, a major driver of colorectal cancers.

Though the study does not directly address cancer prevention, its findings have intriguing implications for the field--which is why the study was funded in part by the colon cancer prevention and early detection initiative launched in 2015 by Ludwig and the Conrad N. Hilton Foundation.

"People have been thinking about using commensal microbes to treat inflammatory disorders of the colon," says Rudensky. "One approach is to develop a new class of drugs made from defined consortia of microbes that would limit inflammation and promote colonic health, reducing the risk of colon cancer in people. Bacterial consortia that produce isoDCA and other metabolites that promote anti-inflammatory activity in colon-resident immune cells could be one of the components of such interventions."

Gut microbes, which are critical to digestion and metabolism, also support many other important processes ranging from immune regulation to brain development. An authority on Tregs, Rudensky has long explored the cross-talk between commensal bacteria and Tregs, which primarily mature in the thymus but can also be induced from precursor T cells in other tissues, especially the intestines. These peripheral Tregs, he has shown, shield beneficial gut microbes from immune attack and suppress chronic intestinal inflammation.

"There are two-way communications between the host and its commensal microbial community, where the host must be informed of the composition of that community and respond to that information," says Rudensky. "This implies that a likely means of communication between the microbial community and the host immune system would be through the metabolic products of commensal bacteria, since metabolic support is among the main services commensal microbes provide to their hosts."

About 5% of the bile pumped into the intestines to help digest fat is retained in the organ, and some of it is metabolized by commensal bacteria. Rudensky and his colleagues were curious about whether the byproducts of that metabolism influence the local immune environment. To find out, they screened a spectrum of bile acids produced by bacterial metabolism for such effects in co-cultures of the precursor T cells from which Tregs arise and dendritic cells, which help direct the generation of Tregs.

The screen revealed that two products of bacterial bile metabolism--ω-MCA and isoDCA--significantly boosted the conversion of precursor T cells into peripheral Tregs. Focusing on isoDCA, which is more abundant in the human intestine, Rudensky and his colleagues found that the bile acid exerted its effects not on the precursor T cells, but on dendritic cells.

IsoDCA, they found, opposes the signals issued by a bile acid sensor in dendritic cells, the farnesoid X receptor (FXR). This hushes the dendritic cells' expression of genes that induce protective immune responses, pushing them into an anti-inflammatory state in which they drive the generation of peripheral Tregs.

Rudensky and his colleagues next conducted elegant synthetic biology experiments in mouse models to confirm the biological veracity of their findings. The results reflected those obtained in cell culture. Mice colonized with bacteria engineered to make isoDCA had many more peripheral Tregs in their intestines than those colonized with the same bacteria lacking the capability. The same results were obtained using two other similarly engineered species of gut bacteria.

CHAMPAIGN, Ill. -- Biological structures sometimes have unique features that engineers would like to copy. For example, many types of insect wings shed water, kill microbes, reflect light in unusual ways and are self-cleaning. While researchers have dissected the physical characteristics that likely contribute to such traits, a new study reveals that the chemical compounds that coat cicada wings also contribute to their ability to repel water and kill microbes.

The scientists report their findings in the journal Advanced Materials Interfaces.

The researchers looked at the physical traits and chemical characteristics of the wings of two cicada species, Neotibicen pruinosus and Magicicada casinnii. N. pruinosus is an annual cicada; M. casinnii emerges from the soil once every 17 years. Previous studies have shown that both species have a highly ordered pattern of tiny pillars, called nanopillars, on their wings. The nanopillars contribute to the wings' hydrophobicity - they shed water better than a raincoat - and likely play a role in killing microbes that try to attach to the wings.

"We knew a lot about the surface structure of cicada wings before this study, but we knew very little about the chemistry of those structures," said Marianne Alleyne, an entomology professor at the University of Illinois at Urbana-Champaign who led the study with analytical chemist Jessica Román-Kustas, of the Sandia National Laboratories in Albuquerque, New Mexico; Donald Cropek, of the U.S. Army Corps of Engineers' Construction Engineering Research Laboratory; and Nenad Miljkovic, a professor of mechanical science and engineering at Illinois.

To study nanopillar chemistry, Román-Kustas developed a method to gradually extract the compounds on the surface without damaging the overall structure of the wings. She placed each wing in solvent in an enclosed chamber and slowly microwaved each one.

"We extracted all these different compounds over different time periods, and then we analyzed what came off," Román-Kustas said. "And we also looked at the corresponding changes in the nanopillar structure."

The effort revealed that cicada wings are coated in a stew of hydrocarbons, fatty acids and oxygen-containing molecules like sterols, alcohols and esters. The oxygen-containing molecules were most abundant deeper in the nanopillars, while hydrocarbons and fatty acids made up more of the outermost nanopillar layers.

"Finding these particular molecules on the surface is not a surprise," Alleyne said. "Hydrocarbons and fatty acids on insect cuticle is fairly common."

The ratio of surface chemicals differed between the two cicada species, as did their nanopillar structures.

The study revealed that altering the surface chemicals also changed the nanopillar structure. In the N. pruinosis cicadas, the nanopillars began to shift in relation to one another as the chemicals were extracted, and later shifted back to a more parallel configuration. This also changed the wings' wettability and anti-microbial characteristics.

The wings of the M. cassinni cicadas had shorter nanopillars and a higher proportion of hydrophobic compounds on their surface. Their nanopillar configuration orientation did not change as a result of extracting their surface chemicals.

While preliminary, the new findings offer insight into the interplay of structure and chemistry in determining function, Alleyne said. By dissecting these characteristics, the researchers hope to one day design artificial structures with some of the same surface traits. Finding materials that shed water and kill microbes, for example, would be useful in many applications, from agriculture to medicine, she said.

Immunotherapy, which unleashes the power of the body's own immune system to find and destroy cancer cells, has shown promise in treating several types of cancer.

But the disease is notorious for cloaking itself from the immune system, and tumors that are not inflamed and do not elicit a response from the immune system -- so-called cold tumors -- do not respond to immunotherapies.

Researchers at the Pritzker School of Molecular Engineering (PME) at the University of Chicago have taken a step toward solving this problem with a unique immunotherapy delivery system. The system finds tumors by seeking out and binding to the tumors' collagen, then uses a protein called interleukin 12 (IL-12) to inflame the tumor and activate the immune system, thereby activating immunotherapy.

Results from tests in a mouse model are promising: several types of melanoma and breast cancer tumors either regressed or disappeared altogether in response to the treatment.

The results were published April 13 in the journal Nature Biomedical Engineering.

"This combination really opens a new approach in cancer immunotherapy," said Jeffrey Hubbell, the Eugene Bell Professor in Tissue Engineering who co-authored the research with Melody Swartz, the William B. Ogden Professor, and postdoctoral scientist Jun Ishihara.

Going from cold to hot

Cancer patients often undergo an array of toxic chemotherapy and radiation treatments. Recently, checkpoint inhibitors (CPIs) have offered a new way to treat the disease. These immunotherapy drugs block proteins called checkpoints, which allows the body's own T cells to find and kill cancer cells.

But tumors must be "hot" -- inflamed and therefore able to be found by the immune system -- for CPIs to work, making them ineffective in cancers that create cold tumors, including breast, ovarian, prostate, and pancreatic cancers.

Scientists and engineers have known that IL-12, a cytokine that regulates T cell responses, can turn cold tumors into "hot" tumors. But the protein is so powerful that when administered to humans, it can cause system-wide toxicity and death. Scientists have long looked for ways to administer IL-12 directly to tumors without causing side effects in the rest of the body.

Directing IL-12 and immunotherapy at collagen

Last year, Hubbell and his collaborators developed a drug delivery system that attaches therapies to a blood protein that circulates and binds to collagen in areas of vascular injury. Because tumors are filled with leaky blood vessels, the protein sees those vessels as vascular injury and binds to them, delivering the therapy directly to the tumor's collagen.

Now, the researchers attached IL-12 to the protein and used it with CPI therapies. Once injected intravenously, the protein found the tumor's collagen, bound to it, and released the therapies, turning the cold tumors hot.

In mouse models, most of those with a certain type of aggressive breast cancer -- called triple-negative, immune-excluded EMT6 -- saw the cancer disappear after treatment. The researchers also tested the therapy on several types of melanoma, and found that many of the tumors regressed, resulting in prolonged survival.

"These positive results are in tumors where checkpoint inhibitors normally don't do anything at all," Hubbell said. "We expected this therapy to work well, but just how well it worked was surprising and encouraging."

Creating a less toxic treatment

Because IL-12 was delivered directly to tumors, it reduced the toxicity levels, making the therapy two-thirds less toxic than before.

Next the researchers plan to continue to study the therapy's toxicology, and continue to work on masking IL-12 from the rest of the body. They ultimately hope to move the therapy to clinical trials.

"Once we have a way to make a cold tumor hot, the possibilities for cancer treatment are endless," Hubbell said.

ANN ARBOR--Active older veterans fall more often than their more sedentary peers who never served in the armed forces, but they're less likely to injure themselves when they do, says a University of Michigan researcher.

A new study by Geoffrey Hoffman, U-M assistant professor of nursing, compared risks of noninjury falls and fall-related injuries in veterans and nonveteran populations, including whether risks differed according to physical activity and age. Historically, veterans are more physically active than nonveterans.

Using data from 11,841 veterans and 36,710 nonveterans in the 2006-2015 waves of the Health and Retirement Study at the U-M Institute for Social Research, the study found that veterans had 11% more noninjury falls but 28% fewer injurious falls than nonveterans.

"The inference is that being active puts you at more risk for a fall, but if you are more active/in shape, the fall is more likely to be a minor one and not a serious one resulting in injury," Hoffman said. "A worthwhile trade-off, arguably."

While the risk of noninjury falls increased more with age for veterans than for nonveterans, physical activity was more protective against a noninjury fall for veterans. Hoffman said that because veterans are nearly 100% male, there's not enough data to definitively state if the findings apply to all physically active men, or just veterans.

This research is important because as people age, it's critical to find a good, healthy balance between physical activity and fall risk, Hoffman said.

"Personally, I'd rather not be the older adult who feels it's best to always sit on my couch because I'm too afraid of having a fall, so that when I do fall, it's really serious," he said.

Lack of physical activity carries both emotional and physiological health risks for older adults, including metabolic problems like diabetes, obesity and high blood pressure, and social isolation and depression.

Hoffman said older adults reap the benefits of physical activity from when they were younger, but veterans may benefit even more. It could be that vets have accumulated "health capital" from active lifestyles, including military training and activities while younger. There was also evidence that, even among active older adults, veterans are still more active than nonveterans.

"In an ideal world, we'd hope that you could get the benefits of being active, such as well-being, fitness and happiness, while avoiding all risk and having no falls," Hoffman said. "It seems more probable that being active is, in the longer-term, often protective against serious injury from falls. Maybe when you're active, a fall isn't as risky because you're in better shape, even while physical activity marginally increases nonserious fall risk.

"That's important, I think. A good trade-off can be made: more activity and independence at the cost of some more minor falls. It's up to each older individual with the input of family caregivers to weigh those trade-offs."

The bad news, Hoffman said, is that after a certain age, there's a point of diminishing returns, and the physical activity benefit disappears for even the most active veterans. It's unclear why or at what age physical activity stops having a protective effect.

The study looked primarily at men, but it's "entirely plausible" that the relationship between falls and injury and physical activity also exists in women, Hoffman said.

The study defined moderate activity as gardening, walking at a moderate pace, stretching exercises or home repairs, and vigorous activity as jogging, swimming, tennis or heavy housework.