Tech

Mass spectrometry (MS) is a powerful method for biomarker analysis because it enables highly sensitive and accurate measurement of target molecules in clinical samples. The application of MS to clinical diagnosis, such as neonatal metabolic screening, has been progressing with a focus on metabolite markers. MS measurement of proteins is currently mainly used for novel marker discovery studies, but there is a growing interest in its application in clinical marker diagnosis as an alternative to immunoassays.

MS-based quantification of protein biomarkers is mainly performed by a bottom-up approach using peptide fragments obtained by enzymatic protein digestion with trypsin. Standard digestion protocols require a reaction time of more than 20 hours, which is a rate-limiting factor in sample preparation workflows.

Although protein quantification by MS is highly sensitive, plasma and serum proteome are highly complex, and interference by other components poses a significant challenge. For high-precision detection of target markers, approaches for pre-removal of major serum protein components such as albumin or selective enrichment of target markers using antibody columns have been reported, but the off-target effect on quantitative results and the difficulty of processing multiple samples remain obstacles.

In this study, we focused on dissolvable polyacrylamide gels using N,N'-Bis(acryloyl)cystamine (BAC) as a cross-linker to solve these problems. BAC cross-linked polyacrylamide gels readily dissolve by reduction treatment, allowing the recovery of proteins that have escaped into the solution. We found that the recovered proteins were suitable for rapid trypsin digestion under high temperature conditions, and we succeeded in establishing a high-throughput sample preparation method for MS-based biomarker quantification, which we named BAC-DROP (BAC-Gel Dissolution to Digest PAGE-Resolved Objective Proteins).

High-resolution proteome fractionation with BAC-DROP is particularly effective for MS quantification of targeted trace marker proteins derived from clinical samples. By introducing BAC-DROP into the MS-based quantification workflow of the inflammatory biomarker C-reactive protein (CRP), we were able to complete the sample pretreatment in only 5 hours and successfully quantified CRP from a 0.5 μL human serum sample. We also succeeded in a serological diagnosis of hepatitis B virus (HBV) infection by HBsAg quantification combined with BAC-DROP and MS. Recently, interest in MS diagnosis of viral infections has been rapidly increasing, as exemplified by the diagnosis of COVID-19. The high-throughput sample preparation approach by BAC-DROP shown in this study will be applicable not only to HBV but also to other infectious viral disease samples.

Positron Emission Tomography (PET) plays a major role in the early detection of various types of cancer. A research group led by Specially Appointed Professor Katsumi Kaneko of the Research Initiative for Supra-Materials (RISM), Shinshu University have discovered a method to separate oxygen-18 from oxygen-16, an essential isotope for PET diagnosis, at high speed and high efficiency. The results of this research were recently published online in the journal Nature Communications.

The novel method for the rapid and efficient separation of O-18 from O2-16, which is abundant in the atmosphere, was carried out with nanoporous carbon, which is made of pores smaller than 1 nanometer. When a mixture of O2-16 and O2-18 is introduced into the nanoporous carbon, the O2-18 is preferentially adsorbed and is efficiently separated from O2-16. The experimental separation of O2-18 from O2-16 was also conducted using the low-temperature waste heat from a natural gas storage facility.

O-18 plays a major role in the early detection of cancer. Taking advantage of the property of cancer cells which take up much more glucose than normal cells, doctors inject a drug called 18F-FDG (fluorodeoxyglucose), which is an index of glucose metabolism and uses a PET machine to clarify which part of the body has cancer. 18F-FDG is a drug in which fluorine-18 (18F), which emits positive electricity, is attached to glucose. 18F-FDG is produced by a nuclear reaction in which O-18 is introduced before the protons are injected. Therefore, O-18 is an important substance indispensable for PET diagnosis but was difficult to procure because only 0.2% of naturally occurring oxygen is O-18. In order to separate O-18 from the majority of O-16 found in the atmosphere, it was necessary to distill O-18 from O-16, even though they have very similar boiling points. This distillation required precise technology and took more than 6 months to complete.

The novel method using nanoporous carbon to distill O-18 can be used not only for PET diagnosis but for research on dementia, and this novel method can be applied to the separation of carbon and nitrogen isotopes, and other molecules useful for isotopic analysis methods and therapeutic cancer drugs. The group expects more demand for this method and substance in the future.

A team of researchers has devised a method using smartphones in order to measure food consumption--an approach that also offers new ways to predict physical well-being.

"We've harnessed the expanding presence of mobile and smartphones around the globe to measure food consumption over time with precision and with the potential to capture seasonal shifts in diet and food consumption patterns," explains Andrew Reid Bell, an assistant professor in New York University's Department of Environmental Studies and an author of the paper, which appears in the journal Environmental Research Letters.

Food consumption has traditionally been measured by questionnaires that require respondents to recall what they ate over the previous 24 hours, to keep detailed consumption records over a three-to-four-day period, or to indicate their typical consumption patterns over one-week to one-month periods. Because these methods ask for participants to report behaviors over extended periods of time, they raise concerns about the accuracy of such documentation.

Moreover, these forms of data collection don't capture "real-time" food consumption, preventing analyses that directly link nutrition with physical activity and other measures of well-being--a notable shortcoming given the estimated two billion people in the world who are affected by moderate to severe food insecurity.

Finally, while food consumption as well as food production have a significant impact on the environment, "we do not yet have the tools to analyze food consumption in the same ways as we do for environmental variables and food production," write the study's authors, who also include Mary Killilea, a clinical professor in NYU's Department of Environmental Studies, and Mari Roberts, an NYU graduate student. "This is a critical gap, as it hampers our understanding of how environmental shocks carry through to become consumption shocks to households, communities, or regions and how responses to these shocks feed back into further environmental stress."

The team, which also included researchers from the University of Minnesota, Imperial College London, the Palli Karma-Sahayak Foundation, and Duke Kunshan University, turned to smartphones as an alternative means to track food consumption and its relationship to physical activity.

"Access to mobile devices is changing how we gather information in many ways, all the way down to the possibility of reaching respondents on their own time, on their own devices, and in their own spaces," explains Bell.

Participants included nearly 200 adults in Bangladesh who reported which among a set of general food types (e.g., nuts and seeds, oils, vegetables, leafy vegetables, fruits, meat and eggs, fish, etc.) their household had consumed in the immediately preceding 24 hours as well as which specific food items within the more general food types they had consumed (e.g., rice, wheat, barley, maize, etc.) and how much they ate. Finally, participants reported the age, gender, literacy, education level, occupation, height, and weight of each member of their household and as well as the following measures of their own physical well-being: whether they could stand up on their own after sitting down, whether they could walk for 5 kilometers (3.1 miles), and whether they could carry 20 liters (5.3 gallons) of water for 20 meters (65.6 feet). All of the information was entered by the participants on their phones using a data-collection app, with response rates as high as 90 percent.

"Food stress is dynamic, and people's needs--particularly for expectant mothers and young children--can change quickly," explains Bell. "Reaching respondents in real time allows us to map those changes in a way conventional approaches don't capture."

"Mainstreaming data collection by respondents themselves, through their own devices, would be transformative for understanding food security and for empirical social science in general," he adds. "It would mean their voices being counted through participation on their own time and terms, and not only by giving up a half-day or longer of work. For researchers, it would mean having connections to rural communities and a picture of their well-being all the time, not just when resources flow to a place in response to crisis, potentially unearthing an understanding of resilience in the face of stressors that has never before been possible."

The authors recognize concerns about smartphone availability in both rural and impoverished communities. However, they point to recent studies that show how digital technologies, such as mobile phones and satellites, have offered new ways for rural populations in developing countries to access savings, credit, and insurance.

"We now see mobile phone penetration almost everywhere in the world, with smartphone and mobile broadband subscriptions following the same trend," says Bell.

Air pollution levels may have exceeded air quality standards during the development of some Marcellus Shale natural gas wells in Pennsylvania, potentially impacting more than 36,000 people in one year alone during the drilling boom, according to Penn State scientists.

"The construction and drilling of these wells are a relatively short-term thing, and assessment of the impact on air quality is something that often falls through the cracks," said Jeremy Gernand, associate professor of industrial health and safety at Penn State. "But there are thousands and thousands of wells drilled depending on the year, and we wanted to see what the impact would be if we added it all up."

More than 20,000 unconventional Marcellus Shale gas wells have been drilled since Pennsylvania's boom began around 2005. Large diesel-powered equipment and gas turbines used during the drilling and hydraulic fracturing stages of shale gas development emit air pollution, and these emissions can affect air quality within the vicinity of shale well sites and farther downwind, the scientists said.

The scientists found emissions at some of the sites could have impacted air quality for people who live beyond the 500-foot setbacks required by state regulations.

"We found in one year alone, 36,000 people, or about 1% of the population of Pennsylvania's Marcellus Shale region, could have been exposed to pollution levels exceeding air quality standards," Gernand said. "However, we found doubling the required setback distance reduced that number by about half."

The scientists developed a dispersion model to estimate concentrations of fine particulate matter (PM 2.5) resulting from well development. One form of air pollution created by the burning of fossil fuels, PM 2.5 are tiny particles that can be inhaled and cause lung damage, according to the scientists.

"Very few studies have investigated local residents' exposure to PM 2.5 emissions from shale gas development, specifically in the Marcellus region of Pennsylvania," Gernand said.

The model considered meteorological conditions during well development, indicating how factors like wind carried emissions from individual well sites, the scientists said. The team then used census data to estimate how many people were in the areas affected by higher levels of air pollution.

Their findings, published in Energy Policy, showed a small number of wells near populated areas contributed to most of the exposures to elevated levels of air pollution.

"I think the main message is that a one-size-fits-all policy to constrain the impacts of industry probably isn't the most effective approach," Gernand said. "In this case, there are real benefits to making some alterations to setback regulations. We only need to push certain sites back farther from inhabited areas to see a big reduction in the number of people whose air quality is affected by this."

Setback policy is shown to be an effective method to reduce exposure exceedances, but the scientists said their results indicate the policies should consider the number of wells per well pad and local conditions to further limit air quality impacts.

The scientists said drilling activity has moved closer to populated areas as Marcellus development progressed in Pennsylvania. And while the construction, drilling and fracking stages are relatively short, sites now often have multiple wells so development can extend for months.

"Staying back 500 feet was probably fine when we drilled one well per pad and moved on, but under the current conditions that's not really sufficient anymore," Gernand said. "We really need to take into consideration things like how much construction and drilling activity will take place and for how long and population density in the area and use those things in some kind of decision framework."

Having trouble coping with COVID?

Go take a hike. Literally.

Researchers have long been aware of the positive impact of a connection with nature on psychological health and, according to a new study published in the journal Personality and Individual Differences, the pandemic hasn't decreased the power of nature to improve mental well-being.

"Thinking about the natural world in an interconnected and harmonious way corresponds to improved psychological health, no matter where you are," says Brian W. Haas, the lead author of the new study and an associate professor in the Behavioral and Brain Sciences Program at the University of Georgia.

Haas and his collaborators - Fumiko Hoeft, a professor of psychological sciences at UConn and director of UConn's Brain Imaging Research Center; and Kazufumi Omura, faculty of Education, Art and Science at Yamagata University in Japan - used a survey in America and Japan to measure worldviews on nature as well as how much the pandemic impacted people's lives, and their current psychological health.

The survey sought to gauge whether the participants had a worldview in harmony with nature - being in tune or connected with the natural world, or a worldview of mastery over nature - the belief that people have the ability to control the natural world. They also reported on their stress levels and were asked if the COVID-19 pandemic has affected them personally or impacted their employment or finances.

The researchers found that, while participants in general report greater stress levels during the pandemic, individuals with a harmony-with-nature worldview were coping better regardless of whether they lived in Japan or in the United States.

"Clearly there's great need for study as relates to the pandemic, not just now during COVID, but also of previous pandemics and for possible future pandemics," says Hoeft. "I feel like this is a really great lesson, and a moment for us to really appreciate that things like our relationship with nature do matter and make an impact on more tangible things, like our mental health, which we often forget."

The researchers found that the difference between the two cultures, however, became apparent when looking at individuals with a mastery-over-nature worldview.

"We found that the Americans who believed that humans are, and should be, the masters of the natural world did not tend to cope well during the pandemic," Haas says. "While this was not the case in Japan."

Rather, in Japan, having a mastery-over-nature worldview was not correlated with poor coping. The researchers suggest the difference might be rooted in the concept of naïve dialecticism - the acceptance or tolerance of contradiction.

"In other cultures outside of the United States, people tend to be more comfortable with contradiction; in other cultures, it is generally more accepted to possess conflicting ideas within your mind at the same time," Haas says. "But in the United States, it's not. We can apply this concept to nature and the current global pandemic. For instance, if I hold a view that I am the master of the natural world, and then a global pandemic happens, this is a clear natural disaster. If I believe that I am the master of the natural world, then surely I would never allow a natural disaster to happen. These concepts are inconsistent with one another, and a consequence of inconsistency is often negative mood."

While the study offers only a snapshot view of just two cultures, Haas believes other cultures would likely demonstrate a similar positive association with a harmony-with-nature worldviews, predicting that "it's likely a universal phenomenon."

Both Haas and Hoeft say that, in an increasingly virtual and technology driven world, taking a moment to appreciate nature has clear benefits regardless of where you live.

"In Japanese, there's this word called 'forest-bathing,'" Hoeft says. "It's basically when you go out into nature, and enjoy being surrounded by trees. It's usually for forests, but you go walking and it's supposed to refresh you. People often talk about how they went out 'forest bathing.' I love thinking about these kinds of old phrases - do they have some real impact or real scientific background in the end? And I think this is one of them where this really does have a connection. There is some scientific truth behind this."

"Think about taking a step away from Zoom for a moment and taking a walk and listening to the birds chirp," Haas says. "I mean, just the benefit of that, and understanding that we have a role in this natural world, and we're part of it. I think that's really intuitive and it's obvious, but I think it's also really, really important. We're showing very convincingly with empirical data that, during a very difficult time like we are in now, that it's important to do these things to maintain your psychological health."

In the late 1980s and 1990s, researchers at ETH Zurich discovered the first indications that the amount of sunlight reaching the Earth's surface had been steadily declining since the 1950s. The phenomenon was known as "global dimming". However, a reversal in this trend became discernible in the late 1980s. The atmosphere brightened again at many locations and surface solar radiation increased.

"In previous studies, we showed that the amount of sunlight that reaches the Earth's surface is not constant over many decades but instead varies substantially - a phenomenon known as global dimming and brightening," says ETH Professor Martin Wild of the Institute for Atmospheric and Climate Science.

Natural variations or air pollution?

Yet little is known about the reasons for these fluctuations, which have been observed for decades. One particularly controversial point is whether the fluctuations are caused by air pollution, with aerosols blocking the sunlight, or whether they are a result of natural variations in the climate system.

A number of scientists suspected that cloud cover may have changed over the years, absorbing the sun's rays more effectively during the dimming phase than during the brightening phase.

This is why Wild and colleagues from other research institutes analysed measurements collected between 1947 and 2017 in the Potsdam radiation time series, which is renowned among climate researchers. The series offers one of the longest, most homogeneous, continuous measurements of solar radiation on the Earth's surface.

Dimming also occurred in cloud-free conditions

In this new study, they were able to show that rather than these fluctuations being due to natural changes in the cloud cover, they are instead generated by varying aerosols from human activity. The paper was published in the journal Geophysical Research Letters.

"In our analysis, we filtered out the effects of cloud cover to see whether these long-term fluctuations in solar radiation also occurred in cloud-free conditions," Wild explains. As it turned out, the decadal fluctuations in the sunlight received at the Earth's surface were apparent even when skies were clear.

The researchers identified aerosols entering the atmosphere due to air pollution as the major contributor to global dimming and brightening. "Although we'd already assumed as much, we'd been unable to prove it directly until now," he says.

Brightening after economic collapse

The fact that the transition from dimming to brightening coincided with the economic collapse of the former communist countries in the late 1980s supports the argument that these variations have a human cause. Moreover, around this time, many western industrialised nations introduced strict air pollution regulations, which improved air quality significantly and facilitated the transfer of the sunbeams through the atmosphere. Lastly, the atmosphere was recovering from the volcanic eruption of Mount Pinatubo, which had ejected vast amounts of aerosols into the air in 1991.

Wild and his colleagues had already ruled out fluctuations in solar activity in an earlier study. "The sun itself had only an infinitesimal, negligible effect, which in no way accounts for the magnitude of the intensity changes that had been observed over the years at the surface," Wild says.

Dimming reduced evaporation and precipitation

Surface solar radiation is a key parameter for climate issues. Not only does it govern the temperature, it also has a fundamental impact on the water cycle by regulating evaporation, which, in turn, governs cloud formation and affects precipitation. During the global dimming, less water evaporated from the Earth's surface, causing precipitation to decline worldwide.

Solar radiation also affects the cryosphere, i.e. glaciers, snow and ice. "Glacial retreat accelerated when the atmosphere began brightening again," Wild says, adding: "It's also becoming increasingly important for the solar industry to gain a better understanding of these fluctuations when it comes to planning new facilities."

Germany's National Meteorological Service, the Deutscher Wetterdienst, operates an observatory in Potsdam that has been measuring solar radiation since 1937. This means the station boasts one of the world's longest radiation time series. "I'm extremely grateful to have access to decades' worth of data; after all, it is only thanks to measurement series such as this that we're able to record and show changes in our environment and climate," Wild says, adding that this makes it imperative to support monitoring networks around the world for prolonged periods of time. Admittedly, this task isn't particularly spectacular, making it difficult to secure funding. "But if we want to understand climate change and clarify the impact of human activities, we need time series that go back far enough," he says. To this end, ETH maintains the Global Energy Balance Archive (GEBA), an unparalleled database of surface energy fluxes worldwide.

Annapolis, MD; February 17, 2021--When the invasive spotted lanternfly arrived in the United States in 2014, it was immediately recognized for the threat it posed to native plants and crops. A community of researchers and experts in science, agriculture, and government sprang into action to respond, improving our chances for containing the pest and curbing its potential for damage.

While the effort continues, a new collection curated by the Entomological Society of America's family of journals showcases the growing body of research that is helping us understand the spotted lanternfly's biology and how to contain it. The collection features 25 articles published in ESA journals since 2015, with 16 of them new additions since June 2020.

The spotted lanternfly (Lycorma delicatula) is a treehopper native to Asia but was discovered in Pennsylvania in 2014, and it has since spread to five other northeastern states. Its primary host is tree of heaven (Ailanthus altissima), but it is known to feed on more than 100 types of plants--mostly trees, shrubs, and stout vines. Valuable crops the spotted lanternfly can damage include grapes, apples, and peaches, as well as hardwood trees. One study of the lanternfly's potential range in the U.S., based on environmental and climatic conditions, suggests most of New England and the mid-Atlantic states as well as parts of the central U.S. and Pacific Northwest are vulnerable to establishment of the spotted lanternfly if it finds its way there.

Melody Keena, Ph.D., research entomologist at the U.S. Forest Service, is co-editor-in-chief of the ESA journal Environmental Entomology and compiled the collection on spotted lanternfly. Like many, Keena was struck by the insect's potential when she first learned about it. "I was surprised because it is so much bigger than the treehoppers that are native. I was also surprised by the large numbers congregating on single trees," she says.

Early on, the U.S. Department of Agriculture's Animal Plant Health Inspection Service and the state of Pennsylvania led the charge, says Keena, while more states and groups have joined in as the spotted lanternfly has spread.

"Both federal and university groups--with Pennsylvania State University taking the early lead--have developed a lot of knowledge and tools rapidly for dealing with this pest, as this collection demonstrates," Keena says.

Engaging the public has been critical as well.

"The public has taken an interest in it because of the major nuisance the adults are in the fall, with all the honey dew the lanternflies produce and black sooty mold that grows on it," Keena says. "They are willing to help in any way they can, like removing its egg masses or smashing adults they find or allowing researchers to use their property."

The research collection showcases progress made so far, as continued awareness and research will be necessary to slow the spotted lanternfly's spread.

"Multiple tools for trapping and killing spotted lanternfly have been developed but still need improvement, especially for adults. Biological control organisms have been found and are being evaluated. Prospects for managing it are good," says Keena. "We don't yet know how far it will successfully be able to spread, but there are indications that it may have some climatic limitations. Current work to understand how humans are aiding its spread, and how to cut off those avenues, is underway."

By 2030 only EV's will be in production, meaning manufacturers are racing to create a high-energy battery that's affordable and charges efficiently, but conventional battery cathodes cannot reach the targets of 500Wh/Kg

Lithium-excess cathodes offer the ability to reach 500Wh/Kg but unlocking their full capacity means understanding how they can store charge at high voltages.

A new X-ray study lead by WMG, University of Warwick has resolved how the metals and oxygen facilitate the charge storage at high voltages.

High energy storage batteries for EVs need high capacity battery cathodes. New lithium-excess magnesium-rich cathodes are expected to replace existing nickel-rich cathodes but understanding how the magnesium and oxygen accommodate charge storage at high voltages is critical for their successful adaption. Research led by WMG, University of Warwick in collaboration with U.S. researchers employed a range of X-ray studies to determine that the oxygen ions are facilitating the charge storage rather than the magnesium ions.

Electric vehicles will one day dominate UK roads and are critical for eliminating CO2 emissions, but a major issue car manufacturers face is how to make an affordable long-lasting energy-dense battery that can be charged quickly and efficiently. There is therefore a race to make EV batteries with an energy storage target of 500 Wh/Kg, but these targets are not possible without changing to new cathode materials.

Although progress has continued over the last 10 years to push the performance of state-of-the-art nickel-rich cathodes for EV, the material is unable to provide the energy density needed. To increase the capacity more lithium needs to be used, which means going beyond the ability of nickel to store electron charge.

Lithium-excess magnesium-rich cathodes offer sufficient energy density but to reach ultimately reach energy storage targets of 500Wh/Kg we need to understand how the electron charge is stored in the material. Simply put, is the electron charge stored on the magnesium or oxygen sites.

In the paper, 'Whither Mn Oxidation in Mn-Rich Alkali-Excess Cathodes?', published in the Journal ACS Energy Letters today the 17th of February, researchers from WMG, University of Warwick have overcome a significant milestone in understanding of charge storage in lithium-excess magnesium-rich cathodes.

Li-excess compounds that involve conventional and non-conventional redox, conventional refers to metal ions changing their electron density. Reversibly changing the electron density on the oxygen (or oxygen redox) without it forming O2 gas is unconventional redox. Various computational models exist in the literature describing different mechanisms involving both, but careful x-ray studies performed while the battery is cycling (operando) are ultimately required to validate these models.

Researchers between the UK and US, led by WMG at the University of Warwick, performed operando x-ray studies to precisely quantify magnesium and oxygen species at high voltages. They demonstrated how x-ray beams could irreversibly drive highly oxidized magnesium (Mn7+) to trapped O2 gas irreversibly in other materials.

However, by performing careful operando x-ray studies that circumvented beam damage and observe only trace amounts of Mn7+ forming upon charging in Li-excess cathodes during battery cycling.

Professor Louis Piper, from WMG, University of Warwick explains:

"We have ultimately resolved that oxygen rather than metal redox is driving the higher capacity, which means we can now design better strategies to improve cycling and performance for this class of materials."

Cygnus X-1, a binary star system first discovered in 1964, comprises one of the closest black holes to Earth. New observations of this black hole, the first ever detected, have led astronomers to question what they know about the Universe's most mysterious objects.

An international team, including researchers from the National Astronomical Observatories of the Chinese Academy of Sciences (NAOC), recently found that the stellar-mass black hole in the Cygnus X-1 binary system has a mass 21 times the mass of the Sun and rotates at a speed close to the speed of light.

The study was published in Science on Feb. 18.

The researchers used the Very Long Baseline Array - a continent-sized radio telescope made up of 10 dishes spread across the United States - together with a clever technique to measure distances in space.

"If we can view the same object from different locations, we can calculate its distance away from us by measuring how far the object appears to move relative to the background," said Prof. James Miller-Jones, a researcher at Australia's Curtin University and the International Centre for Radio Astronomy Research (ICRAR), who is first author of the study.

"If you hold your finger out in front of your eyes and view it with one eye at a time, you'll notice your finger appears to jump from one spot to another. It's exactly the same principle," said Prof. Miller-Jones.

Over six days, the researchers observed a full orbit of the black hole around its companion blue supergiant variable star. They then compared the new data with observations of the same system taken with the same telescope array in 2011. Their new observations and measurements showed that the system is further away than previously thought.

With this new distance information, the researchers re-estimated the mass of the Cygnus X-1 black hole and found it to be more than 20 times the mass of our Sun - a 50 percent increase over previous estimates.

Prof. GOU Lijun of NAOC is a co-author of the study and led the study's spin measurement.

"Using the updated measurements for the black hole's mass and its distance away from Earth, we were able to confirm that Cygnus X-1 is spinning incredibly quickly - very close to the speed of light and faster than any other black hole found to date," said Prof. GOU.

Co-author Prof. Ilya Mandel, a scientist from Australia's Monash University and the ARC Centre of Excellence in Gravitational Wave Discovery (OzGrav), said the black hole is so massive and rotating so fast that it is actually challenging astronomers' thoughts on how black holes formed.

"Stars lose mass to their surrounding environment through stellar winds that blow away from their surface. But to make a black hole this heavy and rotating so quickly, we need to dial down the amount of mass that bright stars lose during their lifetimes," he said.

The black hole in the Cygnus X-1 system began life as a star approximately 60 times the mass of the Sun and collapsed tens of thousands of years ago. Incredibly, it's orbiting its companion star every five-and-a-half days at just one-fifth the distance between the Earth and the Sun.

Accompanying the publication in Science, two further papers focusing on different aspects of this work have also been published today in The Astrophysical Journal.

CHAMPAIGN, Ill. -- Workers with science, technology, engineering and math backgrounds are typically in high demand - but the demand isn't so overwhelming that a "skills gap" exists in the labor market for information technology help desk workers, one of the largest computer occupations in the U.S., says new research from a University of Illinois Urbana-Champaign expert who studies labor economics and work issues.

The incidence of prolonged hiring difficulties for STEM workers is modest, with only 11%-15% of IT help desks in the U.S. showing vacancy patterns that might be consistent with persistent hiring frictions, said Andrew Weaver, a professor of labor and employment relations at Illinois.

"There's a prevailing narrative in which the world changed with the computer revolution and workers never got the memo," he said. "Technology does have an impact on the labor market, but the data doesn't really support the 'skills gap' formulation. Hiring frictions do exist, but organizational characteristics, management strategy and the structure of the labor market turn out to be more predictive of hiring problems than skill requirements. In other research on manufacturing and on hiring lab technicians, I also found similar results."

Published in the journal ILR Review, the paper presents evidence from an original, nationally representative survey of information technology help desks that shows skills-based hiring frictions, but not a skills gap.

"When people generically bemoan skills gaps, they're often parroting unverified talking points," Weaver said. "They're only focusing on the supply side, the availability of workers in the labor market, while ignoring the role of firms and their influence on the demand side, which also matters a lot. If you want to make labor markets work better for everyone, you've got to think about both sides of the equation. You can't just have STEM-skill blinders on. You can't just tell people 'Learn to code' and assume that all our hiring problems are solved. That's not a good way to think about workers or labor markets."

Organizations that had implemented formal management systems such as Lean or Six Sigma also show a higher incidence of long-term vacancies. Such management practices could function as a signal to potential applicants for work intensification and a challenging job environment, thereby making the job less appealing to candidates, according to the paper.

"It runs against conventional wisdom, but the factors that are most associated with hiring difficulties involve insufficient human resources outreach efforts, management strategy and the structure of the labor market," he said. "Organizational factors play an important role. Employers that have recently decreased job training or that have a history of underinvestment in past recruitment efforts are more likely to report persistent unfilled vacancies."

As an occupation, IT help desk technician makes for a ripe target to study, Weaver said.

"It's the second-largest detailed computer-related occupation in the Bureau of Labor Statistics' classification system," he said. "So studying this particular job can reveal patterns that have national implications."

The results not only indicate that the incidence of persistent hiring difficulties is modest, but that the skill demands that predict hiring challenges often involve nontechnical skills that run counter to conventional wisdom. These include advanced writing and "soft skills" such as the ability to initiate new tasks without guidance from management.

"In the process of designing the survey, I interviewed IT help desk managers and talked to them about hiring difficulties," Weaver said. "A number of them mentioned that writing skills were really important because an IT help desk typically has all these angry people complaining about computer problems. So you have to be able to convey technical information in a sensitive, easily understandable way through written communication."

From a policy standpoint, the data implies that an overly narrow focus on STEM skills may not be the most appropriate strategy for improving labor-market outcomes, Weaver said.

"It's only by taking all these measures into account that we can arrive at an accurate picture of the nature of hiring frictions and labor-market challenges," he said.

One remedy for employers would be better funding and investment in human resources in the hiring process.

"Companies that underinvest in outreach or don't have sufficient personnel to cast their nets wide enough to do a good job at recruiting - that's very predictive of hiring difficulties," Weaver said.

The paper also points to evidence that reducing internal employee training tends to exacerbate hiring frictions.

"How an organization operates, its characteristics and its approach to human resources - all of that matters in the labor market," he said.

One result from the study involves market structure: Employers that have market power over employees tend to experience fewer long-term unfilled vacancies. Ultimately, more research is needed to flesh out the ways in which labor-market competition and power imbalances interact with hiring frictions, Weaver said.

"The bottom line is that all of these factors cast doubt on simple stories about technology-driven hiring problems and point to the importance of examining a broader range of organizational factors and market forces when addressing workforce challenges in STEM jobs," he said.

Neutralizing antibodies develop within two weeks of a SARS-CoV-2 infection, but their durability and intensity can vary by individual, prompting concerns about the prospects of long-lasting immunity and efficacy of COVID-19 vaccines.

In a PLOS ONE paper, published online February 11, 2021, researchers at University of California San Diego School of Medicine report that individual immune response to SARS-CoV-2, the virus that causes COVID-19, may be limited by the major histocompatibility complex or MHC, a set of variable genes that code for cell surface proteins essential for the adaptive immune system.

Specifically, senior authors Maurizio Zanetti, MD, professor of medicine, Hannah Carter, PhD, associate professor of medicine and colleagues examined how the MHC interacts with two kinds of lymphocytes or immune cells called T and B.

"The immune system responds to invading pathogens by producing antibodies aimed at intercepting and neutralizing the pathogen," said Zanetti. "The production of antibodies against proteins requires productive cooperation between the T lymphocyte and the B lymphocyte, which must both recognize adjacent antigen sequences initiated by the MHC on B cells. Peptide sequences in close proximity engage the two cells preferentially and non-randomly. The MHC serves as the link between the T and B lymphocytes in this process."

Based on this reasoning, the researchers computationally analyzed all possible fragments of the spike protein RBM, which is a trigger for both the human immune response and for vaccine activity, in connection with the more than 5,000 different MHC molecules represented in the global human population.

To their surprise, the authors found that the average propensity of the MHC to display RBD-derived peptides is low. Since MHC binding is an indirect measure of the probability that the T cell will be activated and stimulate the B lymphocyte into producing antibodies against the RBM, the authors said it follows that the production of RBM-specific antibodies could be hampered by the poor fitting of these portions of the virus to the MHC.

"This then could lead to poorer neutralizing antibody responses," said first author Andrea Castro, a member of Carter's lab. "And in the case of SARS-CoV-2, the poor presentation of key RBD fragments by many MHC alleles could stand as an obstacle to the production of neutralizing antibodies targeting the RBM."

The scientists suggest that the immunological history of individuals may play a role in T cell response and subsequent activation of B lymphocytes that can produce robustly targeted neutralizing antibodies.

The potential implications of the study are twofold, said Carter.

"One is that the ability to generate antibodies with potent neutralization activity may vary considerably from individual to individual within the general population, reflecting the large genetic diversity of the MHC. The other is that lack of effective cooperation between T and B lymphocytes may affect the longevity of neutralizing antibody responses in infected people."

The authors note that multiple studies have reported that neutralizing antibodies in infected persons (hospitalized patients, health care workers and convalescent individuals) drop within three months.

"To these considerations, one may add the impact of the newly discovered mutations in the RBM, such as those in the UK, South African and Brazilian variants of the virus," said Zanetti. The topology of the mutations in these new variants is indicative of further potential breakdown of the immunological relay between T and B lymphocytes, with additional negative impact on the ability of individuals in the global population to generate high quality and long-lived neutralizing antibody responses against SARS-CoV-2."

American values, attitudes and activities have changed dramatically during COVID-19, according to a new study of online behavior.

Researchers from UCLA and Harvard University analyzed how two types of internet activity changed in the U.S. for 10 weeks before and 10 weeks after March 13, 2020 -- the date then-President Donald Trump declared COVID-19 a national emergency. One was Google searches; the other was the phrasing of more than a half-billion words and phrases posted on Twitter, blogs and internet forums.

The study is the lead research article in a special issue of the journal Human Behavior and Emerging Technologies dedicated to the pandemic.

Patricia Greenfield, a UCLA distinguished professor of psychology and senior author of the research, said the study determined that the pandemic inspired a resurgence of community-oriented values, with people thinking more about supporting one another. Use of the word "help" on Twitter increased by 37% in the period after March 13, while use of the word "share" increased by 24%.

Thinking about others

The research also found that use of the word "sacrifice" more than doubled on Twitter from before the pandemic to the period after March 13.

"'Sacrifice' was a complete nonstarter in U.S. culture before COVID," Greenfield said.

The change, the authors wrote, signified that Americans were placing more value on the welfare of others -- even if it meant putting their own lives at risk. One example was people's willingness to participate in the large Black Lives Matter demonstrations, even in the midst of a pandemic, said Noah Evers, a Harvard undergraduate psychology major and the study's lead author.

At the same time, there was strong evidence of the nation's collective mindset returning to a more rural form of society. The use of words referring to basic needs for food, clothing and shelter increased significantly across Google searches, Twitter, internet forums and blogs. For instance, Google searches increased by 344% for "grow vegetables" and by 207% for "sewing machine," while Twitter mentions of "Home Depot" increased by 266%.

Drawing conclusions about shifting psychology from search engine and social media activity might seem to be a stretch, but Greenfield said there are good reasons to put stock in the findings. For one thing, Greenfield said, "language provides a window into people's concerns, values and behavior." In addition, the same types of shifts were evident in both types of internet activity the authors studied.

Internet activity also revealed a dramatic increase in people's concerns about mortality. After March 13, when the death toll began increasing dramatically, search activity for the word "survive" increased by 47%, for "cemeteries" by 41%, for "bury" by 23% and for "death" by 21%.

And during the 10 weeks after Trump's emergency declaration, there were 115% more mentions on Twitter of the phrase "fear of death" than in the 10 weeks before.

"Death went from something taboo to something real and inevitable," Evers said, adding that he frequently discussed plans for death with his family for the first time during that period.

Survival mindset

Of all the words the authors analyzed, the one whose usage increased the most during the pandemic was "sourdough," as baking bread became a trendy pastime while people were instructed to stay at home.

Google searches for "sourdough" increased by 384% after the pandemic began, and Twitter mentions shot up by 460%. "Baking bread" surged as well: Google searches for the phrase increased by 265%, and Twitter mentions rose 354%.

"Given that bread is considered the most basic food, the fact that increases in 'sourdough' and 'baking bread' were so large across Google searches and social media suggests that the survival motive is an important factor in shifting values and activities during the pandemic," Greenfield said.

Greenfield said the psychological and behavioral changes remind her of social interactions she observed in an isolated Mayan village in Chiapas, Mexico, that she has studied since 1969. When she began her work there, life expectancy was very low, approximately 35% of children died before age 4 and basic resources like food were scarce.

"Death was very much a part of life," she said. "People would go to the cemetery every week to put food and drink on family graves and would look after one another," she said. "With greater focus on mortality and helping others, we're moving in that direction.

"It's remarkable how quickly these changes have occurred in the United States during the pandemic. As mortality rose during the pandemic and people lost their jobs, the lifestyles of 21st century America began, in many fundamental ways, to increasingly resemble those of that Maya village."

How lasting will the changes be? Greenfield expects the behavioral trends will likely reverse as the threat from COVID-19 recedes and Americans feel more prosperous and safer. However, based on the aftermath of the Great Recession of 2007 to 2009, she predicts the changes will be more enduring for American teenagers and people in their 20s, whose values are more likely to be shaped by the pandemic.

Said Evers: "Perhaps this means that today's youth will, in the future, create a country more attuned to sharing and helping others, or just that baking sourdough bread will always have a special place in our hearts."

Throughout nature, there are instances of animals aiding one another and living together in mutually beneficial relationships that have helped shape the world's landscapes and biodiversity.

These domesticator-domesticate relationships form when one species provides multigenerational support to another species in exchange for a resource or service that benefits both species. An example of this type of relationship is how early humans domesticated gray wolves. The wolves were attracted to the human encampments, which provided them with protection and resources, and the wolves, in turn, helped the humans increase their hunting proficiency.

One area of the world where these mutually beneficial relationships could be examined further, however, is underwater.

A new study involving researchers from the University of Delaware looked at how a mutually beneficial relationship formed in the waters of Belize. Researchers discovered that longfin damselfish aggressively defend algal farms on which they feed, which provides a protective refuge for planktonic mysid shrimps, which in turn excrete nutrients onto the farms, enriching the algae on which the damselfish feed.

The paper was recently published in Nature Communications. Rohan Brooker, a former post-doctoral researcher at UD, served as the lead author and Danielle Dixson, associate professor in University of Delaware's School of Marine Science and Policy in the College of Earth, Ocean and Environment, served as one of the co-authors on the study.

The research was conducted in the field on the shallow reef habitat surrounding the Smithsonian's Carrie Bow Cay Research Station in Belize from January through April of 2018, however the idea and initial data was conducted when Brooker was a post-doctoral researcher in Dixson's lab and continued through his post-doctoral position at the University of Saskatchewan, Canada.

Aggressive fish

Dixson said that longfin damselfish are known to aggressively defend the algal farms that they consider to be their turf, and while they aren't a very big fish, they are tenaciously territorial.

"They will come after you if you go into their territory," said Dixson. "They'll try and bite you, and they'll try to scare everything away. They're really aggressive even though they're not very big. So they create this bubble that they protect, and one of the things that they don't bother chasing off are these mysids."

Mysids are tiny, clear planktonic crustaceans that live together by the hundreds in cloud-like structures. Using the damselfish as a kind of fence or a security system for their area, the mysids that lived within the damselfish farms were attacked less often than mysids that lived outside of the farms.

In return for this protection, the mysids provide a benefit to the damselfish by excreting nutrients onto the algae that the damselfish eat.

The damselfish that hosted the mysids in their communities exhibited a better body condition than those fish who did not host mysids in their communities.

To determine the effect of mysids on longfin damselfish body condition, the researchers looked at the hepatosomatic index (HSI), which can reflect the health or stored energy of a fish's liver and can indicate the relationship between the diet and physical condition of the damselfish. They compared the HSI of the fish who lived with the mysids to those who lived without the mysids and found that those fish living with the mysids had a higher HSI than those who had no mysids on their alga farms.

This could be for several reasons. For instance, within the mysid-associated farms, the algal composition was significantly different than those farms without mysids. Mysid-associated farms contained a significantly higher proportion of brown algae, which increases the structural complexity of damselfish farms and can serve as a catalyst for the growth of palatable turf-algae, the preferred food source for the damselfish.

Dixson said that it was interesting to see this relationship form in a natural environment and could lead to more studies looking at domesticator-domesticate relationships in the wild.

"We know that domesticator-domesticate relationships happen in nature," said Dixson. "But this is the first example we have found of this type of relationship underwater. Maybe this paper could spark other people to examine different commensal pathways or mutualistic behaviors that we see as potentially being something similar to this."

Engineers have developed a technique that allows them to precisely place microscopic devices formed from folded DNA molecules in not only a specific location but also in a specific orientation.

As a proof-of-concept, they arranged more than 3,000 glowing moon-shaped nanoscale molecular devices into a flower-shaped instrument for indicating the polarization of light. Each of 12 petals pointed in a different direction around the center of the flower, and within in each petal about 250 moons were aligned to the direction of the petal. Because each moon only glows when struck by polarized light matching its orientation, the end result is a flower whose petals light up in sequence as the polarization of light shined upon it is rotated. The flower, which spans a distance smaller than the width of a human hair, demonstrates that thousands of molecules can be reliably oriented on the surface of a chip.

This method for precisely placing and orienting DNA-based molecular devices may make it possible to use these molecular devices to power new kinds of chips that integrate molecular biosensors with optics and electronics for applications such as DNA sequencing or measuring the concentrations of thousands of proteins at once.

The research, published on February 19 by the journal Science, builds on more than 15 years of work by Caltech's Paul Rothemund (BS '94), research professor of bioengineering, computing and mathematical sciences, and computation and neural systems, and his colleagues. In 2006, Rothemund showed that DNA could be directed to fold itself into precise shapes through a technique dubbed DNA origami. In 2009, Rothemund and colleagues at IBM Research Almaden described a technique through which DNA origami could be positioned at precise locations on surfaces. To do so, they used a printing process based on electron beams and created "sticky" patches having the same size and shape as the origami did. In particular, they showed that origami triangles bound precisely at the location of triangular sticky patches.

Next, Rothemund and Ashwin Gopinath, formerly a Caltech senior postdoctoral scholar and now an assistant professor at MIT, refined and extended this technique to demonstrate that molecular devices constructed from DNA origami could be reliably integrated into larger optical devices. "The technological barrier has been how to reproducibly organize vast numbers of molecular devices into the right patterns on the kinds of materials used for chips," says Rothemund.

In 2016, Rothemund and Gopinath showed that triangular origami carrying fluorescent molecules could be used to reproduce a 65,000-pixel version of Vincent van Gogh's The Starry Night. In that work, triangular DNA origami were used to position fluorescent molecules within bacterium-sized optical resonators; precise placement of the fluorescent molecules was critical since a move of just 100 nanometers to the left or right would dim or brighten the pixel by more than five times.

But the technique had an Achilles' heel: "Because the triangles were equilateral and were free to rotate and flip upside-down, they could stick flat onto the triangular sticky patch on the surface in any of six different ways. This meant we couldn't use any devices that required a particular orientation to function. We were stuck with devices that would work equally well when pointed up, down, or in any direction," says Gopinath. Molecular devices intended for DNA sequencing or measuring proteins absolutely have to land right side up, so the team's older techniques would ruin 50 percent of the devices. For devices also requiring a unique rotational orientation, such as transistors, only 16 percent would function.

The first problem to solve, then, was to get the DNA origami to reliably land with the correct side facing up. "It's a bit like guaranteeing toast always magically lands butter side up when thrown on the floor," says Rothemund. To the researchers surprise, coating origami with a carpet of flexible DNA strands on one side enabled more than 95 percent of them to land face up. But the problem of controlling rotation remained. Right triangles with three different edge lengths were the researchers' first attempt at a shape that might land in the preferred rotation.

However, after wrestling to get just 40 percent of right triangles to point in the correct orientation, Gopinath recruited computer scientists Chris Thachuk of the University of Washington, co-author of the Science paper, and a former Caltech postdoc; and David Kirkpatrick of the University of British Columbia, also a co-author of the Science paper. Their job was to find a shape which would only get stuck in the intended orientation, no matter what orientation it might land in. The computer scientists' solution was a disk with an off-center hole, which the researchers termed a "small moon." Mathematical proofs suggested that, unlike a right triangle, small moons could smoothly rotate to find the best alignment with their sticky patch without getting stuck. Lab experiments verified that over 98 percent of the small moons found the correct orientation on their sticky patches.

The team then added special fluorescent molecules that jam themselves tightly into the DNA helices of the small moons, perpendicular to the axis of the helices. This ensured that the fluorescent molecules within a moon were all oriented in the same direction and would glow most brightly when stimulated with light of a particular polarization. "It's as if every molecule carries a little antenna, which can accept energy from light most efficiently only when the polarization of light matches the orientation of the antenna," says Gopinath. This simple effect is what enabled the construction of the polarization-sensitive flower.

With robust methods for controlling the up-down and rotational orientation of DNA origami, a wide range of molecular devices may now be cheaply integrated into computer chips in high yield for a variety of potential applications. For example, Rothemund and Gopinath have founded a company, Palamedrix, to commercialize the technology for building semiconductor chips that enable simultaneous study of all the proteins relevant to human health. Caltech has filed patent applications for the work.

Inhibitors based on approved drugs and designed to disrupt the SARS-CoV-2 viral protein Mpro display strong antiviral activity both in vitro and in a transgenic mouse model, a new study reports. While vaccines are an important tool in the fight against COVID-19, it remains a high priority to develop antiviral drugs, especially with the rise of variants that may partially evade vaccines. The viral protein Mpro is a protease that is required for cleaving precursor polyproteins into functional viral proteins. This essential function makes it a key drug target. Jingxin Qiao et al. designed 32 inhibitors based on either Boceprivir or Teleprovir, both of which are protease inhibitors approved to treat hepatitis C virus. Six compounds protected cells from viral infection with high potency and two of these were selected for in vivo studies based on pharmacokinetic experiments. In a SARS-CoV-2 infection transgenic mouse model, treatment with both compounds greatly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats. The work in this paper "represents an important step toward the development of orally available anti-SARS-CoV-2 drugs," the authors say.