Culture

Hybrid enzyme catalysts synthesized by a de novo approach for expanding biocatalysis

image: Synthesizing hybrid enzyme catalysts in situ to improve and expand enzymatic catalysis is an important way to address challenges of industrial biocatalysis. In this account, the construction principles, the structure-function relationship, the integration of biocatalysis and metal catalysis, and other key factors are introduced regarding the rational design of hybrid enzyme catalysts. This account sheds light on the development of rationally structurally designed hybrid enzyme catalysts for expanding biocatalysis in more chemical manufacturing processes.

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Chinese Journal of Catalysis

The two major challenges in industrial enzymatic catalysis are the limited number of chemical reaction types that are catalyzed by enzymes and the instability of enzymes under harsh conditions in industrial catalysis. Expanding enzyme catalysis to a larger substrate scope and greater variety of chemical reactions and tuning the microenvironment surrounding enzyme molecules to achieve high enzyme performance are urgently needed.

Recently, a research team led by Prof. Jun Ge from Tsinghua University, China reviewed their efforts using the de novo approach to synthesize hybrid enzyme catalysts that can address these two challenges and the structure-function relationship is discussed to reveal the principles of designing hybrid enzyme catalysts. The results were published in Chinese Journal of Catalysis.

In 2012, they first reported a coprecipitation method to prepare enzyme-inorganic-crystal composites. The coprecipitation method is general for preparing hybrid enzyme catalysts with various inorganic crystals, including MOFs. In 2014, they first proposed a coprecipitation strategy for directly synthesizing protein-embedded MOFs. The coprecipitation strategy for synthesizing enzyme-MOF composites is widely used in different types of MOFs, enzymes, proteins, DNA, siRNA, antibodies, and even cells. The mechanisms of enhancement of activity and stability of enzymes in the confined environment of MOFs were discussed. In addition to this, they constructed multienzyme-MOF composites to enhance the cascade reaction in a confined scaffold and developed a coarse-grained, particle-based model to understand the origin of the activity enhancement.

The apparent activity of enzymes in MOFs with a limited pore size is usually compromised when the enzyme substrate has a relatively high molecular weight. By introducing defects within the MOF matrix to generate larger pores, diffusional restrictions can be alleviated. Therefore, they developed methods for introducing defects into MOFs during coprecipitation. Tuning the concentration of precursors of MOFs, defected and even amorphous MOFs can be synthesized. These defects created mesopores in the composites, facilitated access of the substrates to the encapsulated enzymes and improved the apparent enzyme activity. The mechanism of defect generation was thoroughly studied and understood.

Moreover, instead of enzyme encapsulation, small inorganic crystals can grow in situ in a confined environment on the surface of an enzyme to combine enzymatic catalysis and chemocatalysis. They demonstrated how to construct an enzyme-metal hybrid catalyst to efficiently combine enzyme catalysis and metal cluster catalysis. Single lipase-polymer conjugates as confined nanoreactors were utilized for the in situ generation of Pd nanoparticles/clusters to accomplish chemoenzymatic dynamic kinetic resolution (DKR) of amines. The distinct size-dependent activity of Pd nanoparticles was observed. Experiments and simulations suggested that the engineering of the oxidation state of Pd plays an important role in the activity of Pd in the hybrid catalyst. This strategy for constructing enzyme-metal hybrid catalysts with excellent compatibility between enzymatic and metal-catalytic activities leads to many potential applications in chemical industry.

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Dalian Institute of Chemical Physics, Chinese Academy Sciences

Highly fit teenagers coped better with COVID-19 later in life

image: Agnes af Geijerstam, Sahlgrenska Academy, University of Gothenburg.

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Photo: University of Gothenburg

Of the Swedish men in their late teens who performed well in the physical fitness tests for military conscription, a relatively high proportion were able to avoid hospital care when they became infected with COVID-19 during the pandemic up to 50 years later. This has been shown by University of Gothenburg researchers in a register study, with results now published in the BMJ Open.

The study is based on the Swedish Conscription Register, which contains particulars of over 1.5 million young Swedish men who began their military service in the years 1969-2005. Almost all of these men then underwent both a bicycle test and a strength test. Some 2,500 of the men included in the Conscription Register were later, in spring 2020, hospitalized with COVID-19.

For their study, the scientists divided the men into three groups based on their results in the fitness and strength tests. The data were merged with three other Swedish registers: the National Inpatient Register (IPR, also known as the Hospital Discharge Register), Intensive Care Register, and Cause of Death Register. The findings show a clear association between fitness and strength in youth and the risk of needing hospital care for COVID-19 infection 15-50 years after conscription.

"At the population level, we can see that both good fitness and good muscle strength in the late teens are protective factors for severe COVID. For those with good fitness at the time of conscription, the risk of dying in spring 2020 was half as high as for the least fit. For those whose strength was good back then, too, we see a similar protective effect," says Agnes af Geijerstam, PhD student at the University of Gothenburg's Sahlgrenska Academy, who is the lead author of the study.

However, since the oldest men in the study had not reached age 70, deaths from COVID-19 were uncommon in the study.

The Conscription Register also contains data on the young men's height and weight.

"Previous studies have shown that obesity is a risk factor for severe COVID. But we see that good fitness and strength are protective factors for everyone, including men with overweight or obesity," says Professor Lauren Lissner, senior coauthor of the study.

Moreover, the study showed a link between the men's height to the risk of COVID-19 infection.

"The taller the men were, the greater their risk of needing advanced care when they had gotten COVID; but per centimeter this increase in risk is very small. Also, unlike fitness and strength, there is no way to influence our height" af Geijerstam says.

There have already been many studies showing the protective effect of good physical fitness in numerous medical conditions, including infections. It has been established that the immune system is strengthened and the propensity to inflammation is reduced by physical activity. Fitness in adolescence is also likely to be associated with active and otherwise healthy lifestyles throughout adult life.

"It's interesting to see that the high fitness and strength levels those men had so many years ago can be linked to protection against severe COVID. Today, young people are becoming ever more sedentary, and that means there's a risk of major problems arising in the long term -- including a reduced resistance to future viral pandemics. Children and adolescents must get ample scope to move around," af Geijerstam says.

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University of Gothenburg

Sample preparation in forensic toxicological analysis may have huge impacts

(Boston)--As analytical instrumentation (gas- and liquid-chromatographs coupled with mass spectrometers) increase in sensitivity and speed, forensic scientists may find themselves still hindered by the process of preparing samples (blood, urine, etc.) for analysis and seeking more efficient approaches.

In an article in WIRES Forensic Science, researchers from Boston University School of Medicine's (BUSM) Biomedical Forensic Sciences program, provide an overview of sample preparation techniques and information on routine sample types that may be encountered in forensic toxicology cases.

Forensic toxicology encompasses a large variety of scenarios including drug-facilitated crimes, understanding the role alcohol or other drugs may have played in an individuals' deaths, as well as complex polydrug use in driving under the influence cases. As variable as the cases, so too are the composition of biological matrices in addition to how to identify drugs or other compounds in biological samples. This has provided a vast array of sample preparation approaches that scientist have in their 'toolbox.' "Our work highlights the variability in sample types that toxicological analysis encompasses as well as vast array of sample preparation techniques that are currently available," said corresponding author Sabra R. Botch-Jones, MS, MS, MA, assistant professor of anatomy and neurobiology at BUSM.

According to the researchers, the choice of biological matrix is dependent on the anticipated answer the toxicologist is trying to get. Is suspected drug use recent? If so, a blood or oral fluid sample may be best to assess the drugs present and how much is in the sample. In cases of driving while impaired, it is essential to obtain a sample that is appropriate to assess if the drug effected the driver's ability to operate the vehicle safely. When drugs are used, the human body will break down, or metabolize, the drug and eventually excrete it. Drugs and their metabolites may be excreted or removed from the body over a course of hours and even days. For example, if there has been a delay in obtaining a sample or reporting a crime in which drugs are suspected, a urine sample may be best. If extensive amounts of time have elapsed, a hair sample may be a viable option to determine exposure to a suspected drug or other compound.

As with the instrumentation, sample preparation tools have also advanced over time. Solid phase and, more recently supported liquid extraction, allows the unwanted materials in the biological sample to be retained on a solid surface composed of natural materials such as silica or diatomaceous earth. These extraction tools can provide clean extracts containing the drugs of interest and help to recover a large variety of drugs, which can aid in laboratory efficiency when dealing with poly-drug cases.

"Researchers have a number of biological samples to choose from when trying to identify what substances may be in the human body, however it important that they choose the right one to help answer their research question. As equally important is the choice of how to prepare the sample for analysis. This work provides an overview of the routine biological samples, their components, and ways to process them for downstream analysis," explains Botch-Jones.

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Boston University School of Medicine

Handwriting beats typing and watching videos for learning to read

video: Though writing by hand is increasingly being eclipsed by the ease of computers, a new study finds we shouldn't be so quick to throw away the pencils and paper: handwriting helps people learn certain skills surprisingly faster and significantly better than learning the same material through typing or watching videos.

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Johns Hopkins University

Though writing by hand is increasingly being eclipsed by the ease of computers, a new study finds we shouldn't be so quick to throw away the pencils and paper: handwriting helps people learn certain skills surprisingly faster and significantly better than learning the same material through typing or watching videos.

"The question out there for parents and educators is why should our kids spend any time doing handwriting," says senior author Brenda Rapp, a Johns Hopkins University professor of cognitive science. "Obviously, you're going to be a better hand-writer if you practice it. But since people are handwriting less then maybe who cares? The real question is: Are there other benefits to handwriting that have to do with reading and spelling and understanding? We find there most definitely are."

The work appears in the journal Psychological Science.

Rapp and lead author Robert Wiley, a former Johns Hopkins University Ph.D. student who is now a professor at the University of North Carolina, Greensboro, conducted an experiment in which 42 people were taught the Arabic alphabet, split into three groups of learners: writers, typers and video watchers.

Everyone learned the letters one at a time by watching videos of them being written along with hearing names and sounds. After being introduced to each letter, the three groups would attempt to learn what they just saw and heard in different ways. The video group got an on-screen flash of a letter and had to say if it was the same letter they'd just seen. The typers would have to find the letter on the keyboard. The writers had to copy the letter with pen and paper.

At the end, after as many as six sessions, everyone could recognize the letters and made few mistakes when tested. But the writing group reached this level of proficiency faster than the other groups - a few of them in just two sessions.

Next the researchers wanted to determine to what extent, if at all, the groups could generalize this new knowledge. In other words, they could all recognize the letters, but could anyone really use them like a pro, by writing with them, using them to spell new words and using them to read unfamiliar words?

The writing group was better - decisively - in all of those things.

"The main lesson is that even though they were all good at recognizing letters, the writing training was the best at every other measure. And they required less time to get there," Wiley said.

The writing group ended up with more of the skills needed for expert adult-level reading and spelling. Wiley and Rapp say it's because handwriting reinforces the visual and aural lessons. The advantage has nothing to do with penmanship - it's that the simple act of writing by hand provides a perceptual-motor experience that unifies what is being learned about the letters (their shapes, their sounds, and their motor plans), which in turn creates richer knowledge and fuller, true learning, the team says.

"With writing, you're getting a stronger representation in your mind that lets you scaffold toward these other types of tasks that don't in any way involve handwriting," Wiley said.

Although the participants in the study were adults, Wiley and Rapp expect they'd see the same results in children. The findings have implications for classrooms, where pencils and notebooks have taken a backseat in recent years to tablets and laptops, and teaching cursive handwriting is all but extinct.

The findings also suggest that adults trying to learn a language with a different alphabet should supplement what they're learning through apps or tapes with good old-fashioned paperwork.

Wiley, for one, is making sure the kids in his life are stocked up on writing supplies.

"I have three nieces and a nephew right now and my siblings ask me should we get them crayons and pens? I say yes, let them just play with the letters and start writing them and write them all the time. I bought them all finger paint for Christmas and told them let's do letters."

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Johns Hopkins University

Populist anti-foreign aid rhetoric has an impact on the public - but only among fans of populist politicians, study shows

Populist anti-foreign aid rhetoric works - but only fans of populist politicians are convinced by hostile messages about charity abroad, a new study shows. Those who distrust populist politicians are significantly less susceptible to these messages.

The research shows international aid institutions and non-populist politicians should not be unduly worried about the impact of populism on global development cooperation.

Those wanting to convince the public about the importance of foreign aid should focus on communicating their message transparently and clearly, and using local partnerships.

The research, by A. Burcu Bayram from the University of Arkansas and Catarina Thomson from the University of Exeter, is published in the International Studies Quarterly.

Dr. Thomson said: "Populists are not converting pro-aid individuals with their rhetoric; they are preaching to those predisposed to be converted. Populist parties and politicians continue to portray overseas aid spending as the enemy of prosperity "at home", and this has an impact on public attitudes.

"We have found those most likely to be swayed by anti-foreign aid populist rhetoric are those who have favourable views of populist leaders. This means the situation for those wanting to make the case for foreign aid isn't necessarily as bleak as many fear. The Conservative Party backlash to cuts is a good example of this.

"The effect of negative comments about foreign aid is moderated by whether people think populist leaders stand up for the little guy or scapegoat those in other nations. The future of global development might not be as bleak as previously feared in the age of populism."

Dr Bayram said: "We found people who trust populist leaders are more persuaded by populist rhetoric against aid than those who are suspicious of populists. Populist rhetoric against foreign development aid has a larger impact on the willingness to provide such aid when people think populist leaders represent the will of the people than when they think populist leaders scapegoat others."

Academics surveyed 1,600 American and 1,200 British adults during 2017 and 2018. First they measured their political views, asking if they saw populist leaders as the kind of leaders who "stand up for the little guy" or "scapegoat out-groups" for America or Britain's problems. Participants were asked to read a hypothetical scenario showing how leaders had handled multilateral development aid in different ways. One group were told the U.S. President or Prime Minister had said people prefer to help children in their country first; another were told the President or Prime Minister blamed elites for exaggerating the situation of global poverty and manipulating the people and another were told the President or Prime Minister said it was not their country's responsibility to help. A control group was told the President or Prime Minister had called for a congressional or parliamentary committee to evaluate a request from UNICEF's for more funding.

Participants were then asked about their willingness to contribute funds to UNICEF, and if the American or British government should provide additional funds to UNICEF.

In the UK, among the participants exposed to anti-aid populist rhetoric, those who believe that populist leaders scapegoat others were 31 percentage points less likely to want to reduce aid funding compared to those who believe populist leaders stand up for "the little guy". They find similar results in the U.S..

About 12 per cent of British respondents expressed strong support for funding UNICEF while about 22 percent said they were strongly opposed. Around 16 percent of Americans were strongly in favour of funding UNICEF and 23 percent were strongly opposed.

Those in the UK told their leader wanted to help children in their country first, global poverty was exaggerated or it was not their country's responsibility to help, were 6 percentage points more likely to say funding should definitely not be given to UNICEF, compared with those told their leader would get an outside body to consider the charity's request.

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University of Exeter

Icequakes likely rumble along geyser-spitting fractures in Saturn's icy moon Enceladus

image: Ice shelves floating on Earth's Southern Ocean rise and fall with tides, causing rifts, fractures. Icequakes occur most frequently when falling tides pull the rifts apart. Models suggest seismic activity on Enceladus likely correspond to the tides inside the moon. From figure 1 of the new study.

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AGU/ JGR: Planets

WASHINGTON--Tidal stresses may be causing constant icequakes on Saturn's sixth largest moon Enceladus, a world of interest in the search for life beyond Earth, according to a new study. A better understanding of seismic activity could reveal what's under the moon's icy crust and provide clues to the habitability of its ocean.

Enceladus is about 500 kilometers in diameter and almost entirely covered in ice. The moon is nearly 10 times as far away from the Sun as Earth and its bright surface reflects most sunlight, making it very cold, yet researchers have long speculated that the ice encases an underlying liquid ocean.

The moon likely experiences massive tidal forces caused by Saturn and the planet's other, larger moons--similar to the way Earth's Moon causes tides on Earth. These tidal motions inside Enceladus warm its interior, crack the surface and sometimes squeeze tall geysers of water vapor through notable cracks called the tiger stripe fractures.

The new study used observations of Antarctic ice shelves to suggest tides on Enceladus may also cause small quakes in the ice at the moon's fractures, like icequakes observed on Antarctica's floating ice sheets.

"[Moons like] these are places that are exciting because they might have life," said Kira Olsen, a geophysicist at NASA's Goddard Space Flight Center. She said that since life is thought to have first developed in our oceans, liquid oceans under the ice of other worlds could be a good place to search for life. The icy crust of Enceladus might also protect the water below from radiation, making it more habitable.

The new study was published in the Journal of Geophysical Research: Planets, AGU's journal for research on the formation and evolution of the planets, moons and objects of our solar system and beyond.

"We have ideas of how thick the ice could be, but we don't have direct observation. Studying ice quakes is a way to get at that information," Olsen said.

Internal tides

To learn more about how Enceladus' tiger fractures might be moving, Olsen and her colleagues turned to floating ice shelves in Antarctica as the closest analogue on Earth for the types of activity they were seeing on Enceladus. They could then use their knowledge about how certain surface features on our planet produce seismic activity to estimate what kind of seismic activity is happening on the distant moon.

The researchers analyzed data collected by seismometers along the Ross Ice Shelf in the southern continent between 2014 and 2016 and compared these to satellite images of the area. They paid particular attention to two seismometers placed next to large rifts on the ice slab.

They related the seismic activity to the stress occurring along these rifts. The majority of icequakes on the Ross Ice Shelf occurred when the rifts were pulling apart, which happens when tides are falling.

We have no measurements of seismic activity on Enceladus, but Olsen and her colleagues created models that compared the types of fractures they saw on the moon's surface with those on the Ross Ice Shelf.

These models showed that the largest amount of seismic activity on Enceladus likely corresponded to the tides. Peak seismic activity there occurs when Enceladus is 100 degrees past the nearest approach to Saturn during its orbit. The ocean underneath the ice at this point acts something like water inside a sloshing balloon. The ice fractures are created at the points of highest stress, where the balloon would break apart.

The icequakes aren't massive along these cracks, even at the peak periods of stress. Olsen describes them more like "almost continuous little pops and fractures.

Mark Panning, a research scientist at NASA's Jet Propulsion Laboratory who was not involved in the new study, said that while the Cassini spacecraft revealed the moon is geologically active, it's difficult to tell how that translates to seismic activity. "The study represents a really key way of investigating what seismicity on Enceladus and other tidally activated icy worlds may look like by looking at the best analogs we can find on Earth," he said.

Olsen said scientists should aim to place seismometers within 10 kilometers of these fractures in any future missions to Enceladus to learn more about what's going on below.

"It's not a quiet out of the way place, but it's a pretty good place to study," she said.

More information about the seismic activity could then teach us more about the thickness of the ice crust on Enceladus. For now, no missions to Enceladus have been planned, but the European Space Agency is planning the JUICE mission to one of Jupiter's icy moons, Europa.

Olsen said that similar work could then be conducted on Titan, Saturn's largest moon, a world also covered with ice that may conceal liquid oceans and is another top pick for potential extraterrestrial life. NASA's Dragonfly mission is scheduled to visit Titan in 2036.

"This kind of work is one of the best ways to try to get an idea of what behaviors we may see on a planetary body that would be an incredible place to do more science," Panning said.

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American Geophysical Union

Advocacy for a digital oral health that leaves no one behind

demic have already had a dramatic impact on the prevailing oral health care model and will continue to do so. The paper "Advocacy for a Digital Oral Health That Leaves No One Behind," published in the JDR Clinical & Translational Research (JDR CTR), promotes the use of digital tools to offer opportunities to improve healthy behavior, lower risk factors common to oral diseases and other noncommunicable diseases and contribute to reducing oral health inequalities.

To mitigate the impact of the COVID-19 pandemic lockdowns, systems were quickly put in place in most countries to respond to dental emergencies, giving priority to distance screening, advice to patients by remote means and treatment of urgent cases while ensuring continuous care. Digital health was widely adopted as a central component of this new approach, leading to new practices and tools that, in turn, demonstrated their potential, limitations and possible excesses.

Authors Nicolas Giraudeau, University of Montpellier, France, and Benoit Varenne, World Health Organization (WHO), Oral Health Programme, Geneva, Switzerland, believe that digital tools can accelerate the implementation of universal health coverage and help achieve the World Health Organization 2030 Sustainable Development Agenda, leaving no one behind. TheWHO mOralHealth program is structured in four modules (literacy, training, early detection, and surveillance). "Digital oral health should be one of the pillars of oral healthcare post-COVID-19. Universal access to digital oral health should be promoted globally. The WHO's mOralHealth programme aims to do that."

"The use of digital health has led to a new way of understanding both general and oral health," said JDR CTR Editor-in-Chief Jocelyne S. Feine, McGill University, Montréal, Quebec, Canada. "This paper calls for political leaders to be made aware of the universal availability of digital technology and make use of it as a safe and equitable means of delivering oral health care to the public."

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International Association for Dental, Oral, and Craniofacial Research

Protein supplements work for women and not men, during fasted carb-restricted training

Consuming a protein supplement, specifically protein hydrolysate, during carbohydrate-restricted training was helpful for improving training intensity in women, but not in men.

That's according to new research which will be part of a presentation this week at The Physiological Society's Annual Conference Physiology 2021.

Most nutrition guidelines for athletes are based on research in men only. This study, by Tanja Oosthuyse and her colleagues, emphasizes that this shouldn't be the case, because nutritional research findings in men don't always apply to women.

While the protein supplement helped training intensity in women, it did not improve training intensity and instead resulted in modest negative effect in men. It made exercise feel harder for them because their bodies were working harder to break down the supplement, as compared to when they were drinking just plain water.

The conclusion from this research is that women should ingest protein supplements during fasted carbohydrate-restricted exercise, while men should be aware that it will increase their perception of effort.

Future studies need to determine whether ingesting protein hydrolysate supplements during carbohydrate-restricted training over a longer time frame of weeks or months will be beneficial.

In this study, the researchers did not consider menstrual phase. Follow up studies are needed to determine whether the improved training intensity when ingesting a protein hydrolysate compared with placebo-water is specific to menstrual phase.

Commenting on the study, first author Tanja Oosthuyse said,

"The application of the findings from our study are purely for the specialised training tactic of overnight fasted carbohydrate-restricted exercise that aims to enhance training.

Racing nutrition, however, is very different and at the moment guidelines are standard for both men and women. We need to specify potential differences so that both men and women can train and race at the highest possible calibre."

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The Physiological Society

Better-placed rodent traps more effectively prevent food contamination

ITHACA, N.Y. - Placing rodent traps and bait stations based on rat and mouse behavior could protect the food supply more effectively than the current standard of placing them set distances apart, according to new research from Cornell University.

Rodents cause billions of dollars in losses to the food supply each year, and carry pathogens that can sicken and kill humans, including salmonella, E. coli and Leptospira.

In the 1940s and 50s, scientists recommended that farmers, food manufacturers and distributors evenly space rodent traps or bait boxes in their facilities. But in fact, a new study finds placement based on rat and mouse behavior is more effective.

"From there, it just became a mantra without anybody scientifically evaluating it to see whether this was working," said first author Matt Frye, community extension educator with the New York State Integrated Pest Management Program (NYSIPM) based at Cornell.

"For a long time, inspectors would actually bring tape measures with them and measure the distance between devices," he said. "If it was different from the guidelines, the facilities would get penalized. The yardstick approach makes it very easy for facilities and auditors to implement programs, but it doesn't really lead to effective pest management."

In the new study, Frye and Jody Gangloff-Kaufmann, senior extension associate at NYSIPM, found traps placed near areas with attractive features, like warmth and shelter, captured more rodents, while more than half of traps never caught anything.

In addition to smarter trap placements, the researchers also recommend fewer traps - a counterintuitive suggestion that pest control companies and food safety auditors may balk at -because both technicians and rodents can develop "device fatigue." Rodents may avoid devices that have been in the same place for too long because they're no longer interesting to explore.

Researchers found the south and, especially, west sides of buildings, motors and refrigeration compressors all provide warmth and are attractive to pests, and should be a focus of pest management efforts.

Researchers hope this work will help food suppliers to adopt the stricter standards of the Food Safety Modernization Act, which emphasizes preventing food contamination instead of just responding to it.

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Cornell University

Team find brain mechanism that automatically links objects in our minds

image: Objects often paired together, according to the study, displayed in a heat map-style image.

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Johns Hopkins University

When people see a toothbrush, a car, a tree -- any individual object -- their brain automatically associates it with other things it naturally occurs with, allowing humans to build context for their surroundings and set expectations for the world.

By using machine-learning and brain imaging, researchers measured the extent of the "co-occurrence" phenomenon and identified the brain region involved. The findings appear in Nature Communications.

"When we see a refrigerator, we think we're just looking at a refrigerator, but in our mind, we're also calling up all the other things in a kitchen that we associate with a refrigerator," said corresponding author Mick Bonner, a Johns Hopkins University cognitive scientist. "This is the first time anyone has quantified this and identified the brain region where it happens."

In a two-part study, Bonner and co-author, Russell Epstein, a psychology professor at the University of Pennsylvania, used a database with thousands of scenic photos with every object labeled. There were pictures of household scenes, city life, nature -- and the pictures had labels for every mug, car, tree, etc. To quantify object co-occurrences, or how often certain objects appeared with others, they created a statistical model and algorithm that demonstrated the likelihood of seeing a pen if you saw a keyboard, or seeing a boat if you saw a dishwasher.

With these contextual associations quantified, the researchers next attempted to map the brain region that handles the links.

While subjects were having their brain activity monitored with functional magnetic resonance imaging, or fMRI, the team showed them pictures of individual objects and looked for evidence of a region whose responses tracked this co-occurrence information. The spot they identified was a region in the visual cortex commonly associated with the processing of spatial scenes.

"When you look at a plane, this region signals sky and clouds and all the other things," Bonner said. "This region of the brain long thought to process the spatial environment is also coding information about what things go together in the world."

Researchers have long-known that people are slower to recognize objects out of context. The team believes this is the first large-scale experiment to quantify the associations between objects in the visual environment as well as the first insight into how this visual context is represented in the brain.

"We show in a fine-grained way that the brain actually seems to represent this rich statistical information," Bonner said.

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Johns Hopkins University

Inhaled COVID-19 vaccine prevents disease and transmission in animals

In a new study assessing the potential of a single-dose, intranasal COVID-19 vaccine, a team from the University of Iowa and the University of Georgia found that the vaccine fully protects mice against lethal COVID-19 infection. The vaccine also blocks animal-to-animal transmission of the virus. The findings were published July 2 in the journal Science Advances.

"The currently available vaccines against COVID-19 are very successful, but the majority of the world's population is still unvaccinated and there is a critical need for more vaccines that are easy to use and effective at stopping disease and transmission," says Paul McCray, MD, professor of pediatrics-pulmonary medicine, and microbiology and immunology at the UI Carver College of Medicine, and co-leader of the study. "If this new COVID-19 vaccine proves effective in people, it may help block SARS-CoV-2 transmission and help control the COVID-19 pandemic."

Unlike traditional vaccines that require an injection, this vaccine is administered through a nasal spray similar to those commonly used to vaccinate against influenza. The vaccine used in the study only requires a single dose and it may be stored at normal refrigerator temperatures for up to at least three months. Because it is given intranasally, the vaccine may also be easier to administer, especially for those who have a fear of needles.

"We have been developing this vaccine platform for more than 20 years, and we began working on new vaccine formulations to combat COVID-19 during the early days of the pandemic," says Biao He, PhD, a professor in the University of Georgia's Department of Infectious Diseases in the College of Veterinary Medicine and co-leader of the study. "Our preclinical data show that this vaccine not only protects against infection, but also significantly reduces the chances of transmission."

The experimental vaccine uses a harmless parainfluenza virus 5 (PIV5) to deliver the SARS-CoV-2 spike protein into cells where it prompts an immune response that protects against COVID-19 infection. PIV5 is related to common cold viruses and easily infects different mammals, including humans, without causing significant disease. The research team has previously shown that this vaccine platform can completely protect experimental animals from another dangerous coronavirus disease called Middle Eastern Respiratory Syndrome (MERS).

The inhaled PIV5 vaccine developed by the team targets mucosal cells that line the nasal passages and airways. These cells are the main entry point for most SARS-CoV-2 infections and the site of early virus replication. Virus produced in these cells can invade deeper into the lungs and other organs in the body, which can lead to more severe disease. In addition, virus made in these cells can be easily shed through exhalation allowing transmission from one infected person to others.

The study showed that the vaccine produced a localized immune response, involving antibodies and cellular immunity, that completely protected mice from fatal doses of SARS-CoV-2. The vaccine also prevented infection and disease in ferrets and, importantly, appeared to block transmission of COVID-19 from infected ferrets to their unprotected and uninfected cage-mates.

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University of Iowa Health Care

Better pregnancy outcomes linked to reduction of armed conflict in Colombia

A new study has linked a July 2015 ceasefire of conflict violence in Colombia with better pregnancy outcomes for women who conceived after the ceasefire began. Giancarlo Buitrago of Universidad Nacional de Colombia in Bogotá, Colombia, and Rodrigo Moreno-Serra of the University of York, U.K., present these findings in the open-access journal PLOS Medicine.

Previous research has suggested the possibility that women living in areas with armed violence experience adverse pregnancy outcomes. However, methodological problems or inappropriate data have hampered prior investigations into these associations.

To better understand these associations, Buitrago and Moreno-Serra examined pregnancy outcome data for women who conceived before and after a ceasefire of conflict violence was declared in Colombia on July 20, 2015. The ceasefire called for a halt in violence by the guerrilla group FARC (Fuerzas Armadas Revolucionarias de Colombia), which was later followed by a final peace agreement between the government and FARC.

The analysis included data for more than 3 million women living across Colombia who were pregnant between 2013 and 2017. It found that the women were indeed exposed to fewer conflict events, on average, after the ceasefire began, and this reduction was associated with lower risks of stillbirths and perinatal mortality--death of the child before or shortly after birth.

In areas with greater numbers of FARC-related conflict violence events, stillbirths decreased by up to 9.53 deaths per 1,000 pregnancies, and perinatal mortality decreased by up to 10.69 deaths per 1,000 pregnancies. No statistically significant associations were found between miscarriages and reduced exposure to conflict violence.

These findings are in line with other evidence for the benefits of reduced exposure to conflict violence in early pregnancy, and suggest that the peace process in Colombia is contributing to better population health. The authors note that their findings also highlight the need for countries with long-running armed conflict to make special efforts to protect pregnant women.

The authors add: "The results in our paper uncover some less researched consequences of armed conflicts for health. We find that, beyond the tragic loss of life amid armed conflicts, which in Colombia is estimated to have reached over 200,000 deaths, exposure to conflict violence is also linked to worse pregnancy outcomes. Pregnancies of women exposed to more intense conflict violence in Colombia were more likely to result in a stillbirth or perinatal death, particularly if mothers were exposed to violence during the early stages of pregnancy. This has often been an undocumented, "invisible" health penalty associated with protracted conflicts. While we still need further research to fully understand the most important biological pathways linking violence exposure to pregnancy outcomes, our study has important implications for policy. First, it suggests that the de-escalation in violence brought about by the ongoing Colombian peace process has been contributing to better health, and therefore that the peace process in the country should be protected and strengthened. Second, it indicates the high relevance of devising focused health policies that can protect pregnant women in contexts of protracted violence, as these women represent a particularly vulnerable group in those settings."

Credit: 
PLOS

Artificial intelligence provides faster diagnosis for debilitating blistering disease

image: This picture of a microscopic slide shows the U-shaped pattern (in green) visible in the skin biopsy of an epidermolysis bullosa acquisita patient.

Image: 
UMCG/University of Groningen

Scientists at the University of Groningen have trained an Artificial Intelligence system to recognize a specific pattern in skin biopsies of patients with the blistering disease epidermolysis bullosa acquisita. The pattern is characteristic of a specific variant of the disease which can cause scarring of the skin and mucous membranes and may lead to blindness. The new system is easy to use and is better than most doctors in making the diagnosis. A description of this AI system is published in the American Journal of Pathology.

In patients with epidermolysis bullosa, layers of the skin get detached, causing large blisters. There are different forms of blistering diseases affecting different layers of the skin. One of these, epidermolysis bullosa acquisita (EBA), is an autoimmune disease through which a patient's own antibodies attack the skin. It usually starts around middle age and the blisters can form scars. Scarring on the skin may lead to limiting the movement of joints but scars can also form in mucous membranes. When this happens in the eye, for example, it may lead to blindness. Early diagnosis is required to prevent the damage caused by scarring.

Pattern

'At the moment, it can take months to years before the diagnosis of EBA is confirmed', explains Joost Meijer, a dermatologist at the University Medical Center Groningen and joint first author of the paper. Diagnosing EBA happens through skin biopsies, where fluorescent markers attach to the autoantibodies in the basal layer of the epidermis. This produces a serrated U-shaped pattern, typical for EBA. 'However, you need to find and recognize this pattern in a relatively large microscopic slide', Meijer continues. The pattern may only be present in small parts of the slide. To give an idea of how small it is, if the microscopic image is digitized as a picture of 20,000 x 12,000 pixels, the pattern could only take up a 30 x 30 pixel space.

Meijer wrote his Master's thesis on diagnostic techniques to recognize this pattern. He then went on to study the problem in his PhD research, in which he teamed up with fellow PhD student Astone Shi at the University of Groningen's Bernoulli Institute for Mathematics, Computer Science and Artificial Intelligence. Shi, the other joint first author of the paper, works with Convoluted Neural Networks (CNNs), a type of system that works with deep learning and is particularly suited for pattern recognition.

Patients

'One challenge was that there is no standard training program for this particular pattern', says Shi. He had to find the best type of CNN and the best way to train it. 'There are millions of parameters in these neural networks, and we had to find the ones that work best.' Another problem is finding data with which to train the CNN. Patients with EBA are rare; at the moment, there are only around 5 to 10 patients diagnosed per year in the Netherlands. Meijer and Shi were able to use biopsies from 46 patients; 42 to train the networks and the remaining four to validate the system.

After training nine different CNNs and repeating the procedure 10 times, the AI system was able to recognize EBA with both specificity and sensitivity equal to 89.3 per cent. This is better than the numbers published by a group of pathologists and dermatologists, and just below the accuracy of a small number of highly trained specialists. Shi: 'This means that our system outperforms most doctors.' The reason for this is probably that the human eye only takes a relatively small portion of a microscopic slide into account. Meijer: 'Observers get a first impression from this, and then search the slide for confirmation. The AI system analyses the entire slide, which results in a more accurate diagnosis.'

European study

The main advantage of this digital system is that it would be easy to use. Meijer: 'We envisage a system where you upload an image and then get a diagnosis from the AI algorithm.' However, it could also be used to train doctors in recognizing the specific U-serrated pattern of EBA. Although the system worked well in this research project, the results need to be confirmed for a new, larger dataset. For this purpose, a prospective European study has been started. Meijer: 'It will take a year to collect the data of new skin biopsies, which will be able to validate the system. Hopefully, we will then have a quicker and easier way to diagnose EBA and prevent the sometimes debilitating scarring.'

Credit: 
University of Groningen

Women and lower-education users more likely to tweet personal information

UNIVERSITY PARK, Pa. -- When it comes to what users share on Twitter, women and users who never attended college voluntarily disclose more personal information than users from other socioeconomic and demographic backgrounds -- potentially making these populations more susceptible to online privacy threats, according to a recent study led by the Penn State College of Information Sciences and Technology.

Additionally, the researchers unexpectedly found that neither socioeconomic status nor demographics is a significant predictor of the use of account security features such as two-factor login authentication, and that users from all backgrounds actually shared less personal information than they recalled.

"We didn't find a strong correlation between people's stated attitudes and their observed behaviors, which is pretty contradictory to what privacy literature has explained about people's digital inequality and privacy divide," said Jooyoung Lee, doctoral student of information sciences and technology and lead author on the research paper.

In the exploratory study, the researchers set out to understand whether socio-demographic factors impact the usage of login verification, a user's likeliness to share personal information online, and whether topics of self-disclosure vary across socio-demographic groups.

"There is a robust literature on self-disclosure, but purely data-driven approaches typically don't allow us access to users' gender, education, occupation, race and other sensitive information," said Sarah Rajtmajer, assistant professor of information sciences and technology. "At the same time, there is growing concern about the inequitable distribution of privacy risk amongst different socio-demographic groups with respect to online information sharing. The experimental approach taken in this work allowed us a first attempt to bridge the gap."

According to Shomir Wilson, assistant professor of information sciences and technology, the researchers were motivated to expand on past work that indicated that people in lower socio-economic brackets had more difficulty understanding online privacy controls.

"The original thing we were expecting to see based on the survey methods and prior work actually didn't bear out in that we got negative results on the socio-economic status," said Wilson. "But we got some other results that surprised us and are leading us into next steps."

The Penn State study is novel in that it explores the contents of personal information in self-disclosure along socio-demographic lines. In prior work, only gender and age variables have been primarily explored.

The researchers surveyed 110 active Twitter users and monitored their posting behaviors in more than 6,900 tweets over the course of a month. Then, using statistical analysis methods, they examined the tweets for mentions of topics in 12 categories of self-disclosure -- such as marital status, or location -- and labeled which of the categories, if any, the tweet fit.

Those categories were then measured against six socio-demographic factors -- income, gender, age, education level, race/ethnicity and occupation -- to analyze users' login verification settings, quantity of self-disclosure, and self-disclosure by topic. Finally, a post-study survey was sent to participants to collect their recollection of self-disclosure, which the researchers measured against their actual posts.

"A key distinction between our work and prior work was that prior work surveyed people for their attitudes and beliefs," said Wilson. "We took this a step further: we not only gave people surveys, but we followed them on Twitter to see how they were behaving and if their behaviors actually correlated with what they thought they were doing. And we found that people were sharing less than they thought they were sharing."

Added Lee, "People don't always remember what they share on social media, which could be a really big problem. Reminding people of their sharing behaviors could be a good solution to help them keep track of what kind of data they're sharing publicly."

Rajtmajer added that this is particularly true about the combined information of what they've shared over time, which led the researchers to ask survey participants whether they remembered sharing specific pieces of personal information.

"We know that, most often, the critical worries derive from inferences about an individual made possible by the aggregation of all the various, and often seemingly harmless, details they share," she said. "These inferences can be used to profile, monetize, manipulate and surveil. Already-vulnerable groups in many cases are most at risk."

According to Wilson, there are also scenarios where users don't realize that they are sharing posts containing personal information with an audience that includes their co-workers or the general public. Conversely, there are cases where people might not share enough, not realizing that there are certain pieces of information that their friends and followers might want to know.

"Aligning those two things helps people better understand their public persona and gives people a greater sense of security when they use online social networks," Wilson said. "And that in itself is valuable."

The study unveils that users often can't accurately construct a mental model of their sharing behaviors over a month-long period, which could potentially lead to design updates for social networks to implement features that help users keep track of their sharing behaviors.

"This provides context to how people use these tools, both for the users and for the people creating them," said Wilson.

Eesha Srivatsavaya, an undergraduate data sciences student at the College of IST, was also involved with the project. The team's paper appears in the July 2021 Proceedings on Privacy Enhancing Technologies. The work was supported in part by an Accelerator Award from the Center for Social Data Analytics at Penn State.

Credit: 
Penn State

The outsized impacts of rudeness in the workplace

Rude behavior is a common form of insensitive and disrespectful conduct that harms employees' performance in the workplace. In a new study, researchers examined the impact of rude behavior on how individuals make critical decisions. The study found that in certain situations, these behaviors can have deadly consequences.

The study, published in the Journal of Applied Psychology, was conducted by researchers at Carnegie Mellon University (CMU), the University of Florida (UF), the University of Maryland, Envision Physician Services, and Thomas Jefferson University Hospital.

The researchers looked at the effect of rudeness on workers' tendency to engage in a judgment bias called anchoring, which is the tendency to rely too heavily or fixate on one piece of information when making a decision.

"While small insults and other forms of rude behavior might seem relatively harmless compared to more serious forms of aggression, our findings suggest that they can have serious consequences," says Binyamin Cooper, a Postdoctoral Fellow at CMU's Tepper School of Business and a member of the Collaboration and Conflict Research Lab, who led the study. "Our work demonstrates how dangerous these seemingly minor behaviors can be, whether they are experienced directly or even if people just observer incidental rudeness.

"Let's say that a doctor walks into a patient's room for the first time, and a family member says 'I think he's having a heart attack,'" says Cooper. "Our findings suggest that if on the way to see the patient, the doctor witnessed a rude event between two other people, he or she would be significantly more likely to settle on a diagnosis of a heart attack, even if that is incorrect."

Cooper and his colleagues tested the effects of rudeness on anchoring in four studies across different settings--from medical simulations to negotiations and general judgment tasks. In one study, anesthesiology residents participated in a simulation on life-sized anatomical human models. The simulation was set up to suggest that a patient could have an allergic reaction to one of his medications, which served as the anchor. Before the simulation started, half the residents witnessed a senior doctor enter the room and yell at their instructor for missing a meeting, while the other half witnessed a neutral interaction.

When the patient's condition began to deteriorate later in the simulation, the residents who were exposed to the rude interaction were more likely to diagnose allergic shock, when in reality the patient was bleeding internally, and the diagnosis affected how they administered care. The study also showed that the reason rudeness was so harmful was that it is related to increased high arousal of negative emotions (such as irritability and distress), which predicted the tendency to engage in anchoring.

The practical implications of the study's findings are many, the authors note. For example, physicians exposed to rudeness may incorrectly treat patients for ailments they do not have, while being unaware of their incorrect diagnosis or the reasons underlying it. "Making the wrong decision at a critical moment means that people end up spending too much time going down the wrong path," explains Cooper. "If there's not enough time to realize the error and make up for it, this could be deadly."

In demonstrating that encounters with rudeness cause anchoring, the authors call on managers and organizations to take steps to reduce rudeness among employees, particularly in high-stakes situations where consequences of judgment errors associated with anchoring can be catastrophic. The authors also identified steps organizations can take to mitigate the effects of rudeness.

For example, organizations can train employees to use two skills--perspective taking and information elaboration--to better equip them to deal with the pernicious effects of exposure to rudeness. Because exposure to rude behavior makes people more likely to narrow their perspectives on their own personal experience, having employees imagine themselves viewing the same problem from another's point of view distances them from the strong feelings that they would overwise experience, according to the authors.

Another option is to practice information elaboration by having employees practice identifying the task at hand, and then taking a few moments to stop and think what information they need to help them make a decision.

"These active steps may seem small, but our work shows that organizations can use them to mitigate the harmful consequences associated with rudeness, which can make a big difference," suggests Cooper. "And they can be used in fields other than medicine, including negotiations, legal sentencing, financial forecasting, social exchange relationships, and pricing decisions."

The authors acknowledge several limitations to their study. First, they focused on anchoring as one of the most common decisions-making biases, but it remains to be seen if the effect of rudeness affects other decision-making biases. Second, except for perspective taking and information elaboration, their study did not examine empathy, experience, or other dispositional and contextual factors that may influence the relationship between rudeness and negative emotions.

Credit: 
Carnegie Mellon University