Tech

Light flips genetic switch in bacteria inside transparent worms

image: Light-responsive bacteria fed to worms are visible in images of the worms' gastrointestinal tracts. Engineers programmed the bacteria to produce a red fluorescent protein called mCherry so they would be easy to see under a microscope. When exposed to green light, the bacteria also produce a green fluorescent protein called sfGFP, which causes them to glow green. When exposed to red light, they do not produce the green protein. Worms in the left column were treated with red light. Worms in the right column were treated with green light.

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Image courtesy of Jeff Tabor/Rice University

HOUSTON - (Dec. 22, 2020) - Baylor College of Medicine researcher Meng Wang had already shown that bacteria that make a metabolite called colanic acid (CA) could extend the lifespan of worms in her lab by as much as 50%, but her collaboration with Rice University synthetic biologist Jeffrey Tabor is providing tools to answer the bigger question of how the metabolite imparts longer life.

In a study published in eLife, Wang, Tabor and colleagues showed they could use different colors of light to turn gut bacteria genes on and off while the bacteria were in the intestines of worms. The work was made possible by an optogenetic control system Tabor has been developing for more than a decade.

"Meng's group discovered that the CA compound could extend lifespan but they couldn't say for sure whether this was a dietary ingredient that was being digested in the stomach or a metabolite that was being produced by bacteria in the intestines," said Tabor, an associate professor of bioengineering and of biosciences at Rice. "We were able to restrict production of CA to the gut and show that it had a beneficial effect on cells in the intestines."

For the experiments, Tabor's lab engineered strains of E. coli to make CA when exposed to green, but not red, light. To make sure the bacteria worked properly, the team added genes to make different colors of fluorescent proteins that would show up brightly under a microscope. One color was always present, to make it easy to see where the bacteria were inside the worms, and a second color was made only when the bacteria were producing CA.

In collaboration with the Wang lab, Tabor's lab kept the bacteria under a red light and fed them to worms, a species called Caenorhabditis elegans (C. elegans) that's commonly used in life sciences. Researchers tracked the bacteria's progress through the digestive tract and switched on the green light when they made it to the intestines.

"When exposed to green light, worms carrying this E. coli strain also lived longer. The stronger the light, the longer the lifespan," said Wang, the Robert C. Fyfe Endowed Chair on Aging, a professor of molecular and human genetics at the Huffington Center on Aging at Baylor and a Howard Hughes Medical Institute investigator.

In the cells of C. elegans and other higher order life, from humans to yeast, specialized organelles called mitochondria supply most of the energy. Thousands of mitochondria work around the clock in each cell and maintain a dynamic balance between fission and fusion, but they become less efficient over time. As people and other organisms age, the dysfunction of mitochondria leads to functional decline in their cells.

In prior experiments with C. elegans, Wang and colleagues showed that CA can regulate the balance between mitochondrial fission and fusion in both intestinal and muscle cells to promote longevity. The worms typically live about three weeks, but Wang's lab has shown that CA can extend their lives to 4.5 weeks -- 50% longer than usual.

Tabor said this raises a host of questions. For instance, if CA is produced in the gut, do intestinal cells benefit first? Is the beneficial effect of CA related to its level? And most important, do the mitochondrial benefits spread throughout the body from the intestines?

In the eLife study, the researchers found that CA production in the gut directly improved mitochondrial function in intestinal cells in a short time. They did not find evidence of such direct, short-term mitochondrial benefits in the worms' muscle cells. Thus, the longevity-promoting effect of CA starts from the gut and then spreads into other tissues over time.

"With our technology, we can use light to turn on CA production and watch the effect travel through the worm," Tabor said.

He said the precision of the optogenetic technology could allow researchers to ask fundamental questions about gut metabolism.

"If you can control the timing and location of metabolite production with precision, you can think about experimental designs that show cause and effect," he said.

Showing that gut bacteria directly impact health or disease would be a major achievement.

"We know gut bacteria affect many processes in our bodies," Tabor said. "They've been linked to obesity, diabetes, anxiety, cancers, autoimmune diseases, heart disease and kidney disease. There's been an explosion of studies measuring what bacteria you have when you have this illness or that illness, and it's showing all kinds of correlations."

But there is a big difference between showing correlation and causality, Tabor said.

"The goal, the thing you really want, is gut bacteria you can eat that will improve health or treat disease," he said.

But it's difficult for researchers to prove that molecules produced by gut bacteria cause disease or health. That's partly because the gut is difficult to access experimentally, and it's especially difficult to design experiments that show what is happening in specific locations inside the gut.

"The gut is a hard place to access, especially in large mammals," Tabor said. "Our intestines are 28 feet long, and they're very heterogeneous. The pH changes throughout and the bacteria change quite dramatically along the way. So do the tissues and what they're doing, like the molecules they secrete.

"To answer questions about how gut bacteria influence our health, you need to be able to turn on genes in specific places and at particular times, like when an animal is young or when an animal wakes up in the morning," he said. "You need that level of control to study pathways on their own turf, where they happen and how they happen."

Because it uses light to trigger genes, optogenetics offers that level of control, Tabor said.

"To this point, light is really the only signal that has enough precision to turn on bacterial genes in the small versus the large intestine, for example, or during the day but not at night," he said.

Tabor said he and Wang have discussed many ways they might use optogenetics to study aging.

"She's found two dozen bacterial genes that can extend lifespan in C. elegans, and we don't know how most of them work," Tabor said. "The colanic acid genes are really intriguing, but there are many more that we'd like to turn on with light in the worm to figure out how they work. We can use the exact technique that we published in this paper to explore those new genes as well. And other people who are studying the microbiome can use it too. It's a powerful tool for investigating how bacteria are benefiting our health."

Credit: 
Rice University

Perspective: Why opioids cannot fix chronic pain

A broken heart is often harder to heal than a broken leg. Now researchers say that a broken heart can contribute to lasting chronic pain.

In a reflections column published Dec. 21 in the Annals of Family Medicine, pain experts Mark Sullivan and Jane Ballantyne at the University of Washington School of Medicine, say emotional pain and chronic physical pain are bidirectional. Painkillers, they said, ultimately make things worse.

Their argument is based on new epidemiological and neuroscientific evidence, which suggests emotional pain activates many of the same limbic brain centers as physical pain. This is especially true, they said, for the most common chronic pain syndromes - back pain, headaches, and fibromyalgia.

Opioids may make patients feel better early on, but over the long term these drugs cause all kinds of havoc on their well-being, the researchers said.

"Their social and emotional functioning is messed up under a wet blanket of opioids," Sullivan said.

The researchers said new evidence suggests that the body's reward system may be more important than tissue damage in the transition from acute to chronic pain.

By reward system, they are referring, in part, to the endogenous opioid system, a complicated system connected to several areas of the brain, The system includes the natural release of endorphins from pleasurable activities.

When this reward system is damaged by manufactured opioids, it perpetuates isolation and chronic illness and is a strong risk factor for depression, they said.

"Rather than helping the pain for which the opioid was originally sought, persistent opioid use may be chasing the pain in a circular manner, diminishing natural rewards from normal sources of pleasure, and increasing social isolation," they wrote.

Both Sullivan and Ballantyne prescribe opioids for their patients and say they have a role in short-term use.

"Long-term opioid therapy that lasts months and perhaps years should be a rare occurrence because it does not treat chronic pain well, it impairs human social and emotional function, and can lead to opioid dependence or addiction," they wrote.

What Sullivan recommends is if patients are on high-dose long-term opioids and they are not having clear improvement in pain and function, they need to taper down or switch to buprenorphine. If available, a multidisciplinary pain program using a case manager to monitor their care and well-being, similar to those for diabetes and depression care, may be of benefit.

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University of Washington School of Medicine/UW Medicine

Enzyme discovery can help rein in blood vessels that fuel cancer

LA JOLLA, CA--Most living things need oxygen to grow and thrive. Even cancerous tumors. That's why tumors will readily sprout new blood vessels if their oxygen is starved, creating new lifelines for survival.

A study published today from Scripps Research pinpoints the precise molecular machinery that makes this happen, providing scientific insights that can potentially be translated into medicines that help kill tumors and stop cancer from spreading in the body.

The findings also may enable new interventions that promote healthy blood-vessel development for people with heart disease and other conditions, says the study's leader Xiang-Lei Yang, PhD, a professor In the Department of Molecular Medicine at Scripps Research.

The research appears in the journal PLOS Biology.

"We've uncovered a key regulation step that drives blood-vessel development for tissues deprived of adequate oxygen--finally creating a more complete picture of the complex process that enables cancer tumors to adapt and survive," says Yang. "By blocking this process on a molecular level, we found it's possible to inhibit tumor growth."

The study culminates a years-long project initiated by first author Yi Shi, PhD, who began the work as a staff scientist in Yang's lab but recently finished his contributions from Nankai University in Tianjin, China, where he is now a faculty member.

Over the past decade, Yang and her team have published several key discoveries relating to how cells create blood vessels, delving into previously unknown roles of genes that regulate this function. Prior studies dealt with genes known as c-Myc and HIF-1, which promote blood vessel development and have strong links to cancer.

In the new study, Yang's team looked at negative regulators of blood vessel growth--or proteins that turn the function off--to find out what causes them to become inactivated when tissues are deprived of oxygen, which is what happens within a solid tumor.

Their central focus was an enzyme known as SerRS (seryl-tRNA synthetase), most commonly known to exist in the gel-like substance within cells. There, the enzyme kicks off the first step of making new proteins. However, the enzyme is also found within the nucleus, performing an entirely different but vital job: Limiting unhealthy blood vessel growth by tamping down the function of c-Myc and HIF-1.

In the study, the researchers found that SerRS can be "silenced" by proteins known as ATM/ATR, which manage DNA damage responses. These proteins activate when tissues are deprived of oxygen. When this happens, new blood vessel growth can go unchecked and tumors can flourish.

Through separate experiments involving mice and human breast cancer cells, the team confirmed that by blocking the effect of ATM/ATR on SerRS, they were able to successfully reduce tumor growth.

Notably, Yang says, SerRS is part of an evolutionarily ancient family of enzymes called tRNA synthetases, which begin the process of making proteins that go on to form blood, skin, bones and other essential elements of human life. The findings of this study show that SerRS has evolved extra functions beyond making proteins.

"It's possible that SerRS regulates more than blood vessel development," Yang says. "This is a compelling finding that opens the door to further investigation into how broad its influence may reach in the human body."

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Scripps Research Institute

Hand-held device measures aerosols for coronavirus risk assessment

image: A plot showing how much the aerosol from a sneeze spreads in each direction.

Image: 
Daniel Bonn, University of Amsterdam

WASHINGTON, December 22, 2020 -- Because of the role they play in coronavirus transmission, understanding aerosol concentrations and persistence in public spaces can help determine infection risks. However, measuring these concentrations is difficult, requiring specialized personnel and equipment.

That is, until now.

Researchers from the Cardiology Centers of the Netherlands and the University of Amsterdam demonstrate that a commercial hand-held particle counter can be used for this purpose and help determine the impacts of risk-reducing measures, like ventilation improvements. They describe the quick and easy, portable process in the journal Physics of Fluids, from AIP Publishing.

The key challenge with using hand-held particle counters is dealing with the background dust prevalent in public spaces. The question then becomes, can you distinguish these dust particles from aerosols that arise from breathing, speaking, sneezing, and coughing?

Because dust and aerosols inhaled into human lungs differ in size, the researchers developed a way to subtract the dust signal in the particle counter by measuring the dust for some time, and watching how the signal changes after aerosols are added to the mix.

"There's a lot of fine dust, so we can't really measure aerosols in that range, but there's a reasonable sized range where you can detect the aerosols," said Daniel Bonn, one of the authors.

They compared the aerosol concentration determined by this method to laboratory-based techniques and found the results match up perfectly. Though this work reports on one specific hand-held particle counter -- the Fluke 985, which is used to monitor the dust and air quality in clean rooms -- Bonn noted the results aren't unique to this device and can be extended to other particle counters as well.

Though the method does not directly measure the presence of viral particles, the detected aerosol concentration can be combined with virus data from other studies to obtain a practical risk assessment for a specific type of public space. The findings suggest well-ventilated areas can have aerosol concentrations more than 100 times lower than poorly ventilated areas, such as public elevators or restrooms.

"There are people worried about going to the gym, coming to the office, taking the train. All that can at least be evaluated," Bonn said. "The motto remains ventilation, ventilation, ventilation."

He said while ventilation plays a large role in indoor spaces, aerosols are not the only route to infection, and social distancing and hand-washing remain vital.

Credit: 
American Institute of Physics

Americans underestimate public support for key gun policies

COLUMBUS, Ohio - Gun safety policies, including universal background checks and mandatory waiting periods, receive wide support among American gun owners, yet most Americans fail to recognize this fact, a new study suggests.

That disconnect may make it hard to adopt these policies, according to the researchers.

The study found that when people learned about the true levels of support for these policies, they were more likely to say both in public and private that they would support the policies. That was true for gun owners as well as those who don't own guns.

"Many Americans misperceive the opinion climate about gun safety, and that may inhibit their willingness to express their support in public," said Graham Dixon, lead author of the study and assistant professor of communication at The Ohio State University.

"When corrected, both gun owners and non-gun owners express stronger public support for these policies."

The study was published today in JAMA Network Open.

The researchers examined support for three gun-safety policies: universal background checks, mandatory waiting periods, and safe storage laws.

In January 2019, the research firm Ipsos administered a survey for the researchers with a nationally representative sample of 508 adults. Gun owners represented 30% of the sample, mirroring Gallup's recent finding in a nationally representative poll.

More than 90% of both gun owners and non-gun owners said they supported universal background checks. About 85% of non-gun owners and 72% percent of gun owners supported mandatory waiting periods, and 83% of non-gun owners and 63% of gun owners supported safe storage laws.

"The key finding was that despite high levels of support for these policies, most people significantly underestimated support among gun owners," Dixon said.

Depending on the issue and whether gun owners or non-gun owners were asked, people surveyed underestimated gun owner support for these policies by between 12 and 31 percentage points.

"What's striking is that most gun owners don't realize how much their fellow gun owners support these policies," Dixon said.

What happens when gun owners do find out? The researchers explored that in a second study involving 400 gun owners from across the country. The data were collected by YouGov in April 2020.

In this study, participants were randomly assigned to a message that either informed them of the wide gun owner support for universal background checks and mandatory waiting periods, or excluded that information.

Gun owners who were told about the high level of support for these policies among their fellow owners expressed stronger private support for these policies than those who were not told. The better-informed gun owners also reported that they would publicly disclose stronger support of mandatory waiting periods to others.

"This is important, because it shows that if gun owners recognized how strongly their fellow gun owners support key gun safety policies, they might be more willing to speak out in favor themselves," Dixon said.

A similar study was done with 354 college students, most of whom were not gun owners. As with the gun owners, they were also more likely to privately and publicly support universal background checks and mandatory waiting periods when they were informed of the strong support among gun owners for these policies.

In the studies with the gun owners and college students, the researchers also tested if learning the true level of support for gun safety policies would affect behaviors, such as the willingness to sign petitions on the issue. No changes in behavior were found.

"Simply correcting people's opinion climate on gun policy may not be enough to encourage specific actions, like petition signing or donations to advocacy groups," he said.

But Dixon said he was encouraged that simply providing people with accurate information did affect their private and public support.

"Our findings shed additional light on how people's perceived opinion climates can shape their private and public attitudes toward gun safety policies," he said.

"More practically, our study suggests that correcting misperceived opinion climates might be a useful strategy for policymakers and advocates in encouraging both private and public support for gun safety policies."

Credit: 
Ohio State University

The first endovascular technology that can explore capillaries

video: Harnessing Blood Flow to Navigate Endovascular Microrobots

Image: 
Lucio Pancaldi/EPFL 2020

The cardiovascular system is astonishing. It uses the blood that circulates in our veins and arteries to transport oxygen and nutrients to every tissue in the body. At EPFL, Lucio Pancaldi, a PhD student, and Selman Sakar, an assistant professor, have decided to harness hydrokinetic energy (mechanical energy resulting from the motion of liquids) to get to places in the human body without resorting to invasive methods. "Large proportions of the brain remain inaccessible because the existing tools are unwieldy, and exploring the tiny, intricate cerebral vascular system without causing tissue damage is extremely difficult" says Sakar.

Miniaturizing endovascular devices

Doctors can access patients' arteries by pushing and rotating guidewires, and later sliding hollow tubes called catheters. However, when arteries begin to narrow, especially in the brain, this advancement technique reveals its limits. Scientists at EPFL's MicroBioRobotic Systems (MICROBS) Laboratory, working with colleagues from Prof. Diego Ghezzi's group, engineered tethered microscopic devices that could be introduced into capillaries with unprecedented speed and ease. "Our technology is not intended to replace conventional catheters, but to augment them", says Pancaldi.
Fishing for answers

The devices consist of a magnetic tip and an ultraflexible body made of biocompatible polymers. "Imagine a fishhook gradually released into a river. It will get carried along by the current. We simply hold onto one end of the device and let the blood drag it to the most peripheral tissues. We gently rotate the magnetic tip of the device at bifurcations for choosing a specific path", says Pancaldi. Since no mechanical force is applied directly at the vessel wall, the risk of causing any damage is very low. Moreover, harnessing blood flow could reduce the operation time from several hours to a couple of minutes.

Charting a course through the vascular system

Both the release of the device and magnetic steering are under computer control. Furthermore, there is no need for force feedback as the tip of the device does not push against the vessel walls. "We can envision that a surgical robot will use the detailed map of the vasculature provided by the MRI and CT scans of the patient to autonomously guide devices to target locations. The addition of machine intelligence would transform endovascular operations. Alternatively, a computer program may use the visual information provided by the fluoroscope to localize the device and calculate a trajectory in real-time to facilitate manual operations", says Sakar.

Researchers at EPFL's School of Engineering tested the device inside artificial microvasculature systems. The next phase will involve tests on animals with state-of-the-art medical imaging systems. Scientists are also hoping to develop other devices with a range of on-board actuators and sensors.

Credit: 
Ecole Polytechnique Fédérale de Lausanne

Masks not enough to stop COVID-19's spread without distancing

image: The device used by researchers to study how masks block simulated respiratory droplets carrying the COVID-19 virus.

Image: 
Javed Akhtar

WASHINGTON, December 22, 2020 -- Simply wearing a mask may not be enough to prevent the spread of COVID-19 without social distancing.

In Physics of Fluids, by AIP Publishing, researchers tested how five different types of mask materials impacted the spread of droplets that carry the coronavirus when we cough or sneeze.

Every material tested dramatically reduced the number of droplets that were spread. But at distances of less than 6 feet, enough droplets to potentially cause illness still made it through several of the materials.

"A mask definitely helps, but if the people are very close to each other, there is still a chance of spreading or contracting the virus," said Krishna Kota, an associate professor at New Mexico State University and one of the article's authors. "It's not just masks that will help. It's both the masks and distancing."

At the university, researchers built a machine that uses an air generator to mimic human coughs and sneezes. The generator was used to blow tiny liquid particles, like the airborne droplets of sneezes and coughs, through laser sheets in an airtight square tube with a camera.

They blocked the flow of the droplets in the tube with five different types of mask materials -- a regular cloth mask, a two-layer cloth mask, a wet two-layer cloth mask, a surgical mask, and a medical-grade N-95 mask.

Each of the masks captured the vast majority of droplets, ranging from the regular cloth mask, which allowed about 3.6% of the droplets to go through, to the N-95 mask, which statistically stopped 100% of the droplets. But at distances of less than 6 feet, even those small percentages of droplets can be enough to get someone sick, especially if a person with COVID-19 sneezes or coughs multiple times.

A single sneeze can carry up to 200 million tiny virus particles, depending on how sick the carrier is. Even if a mask blocks a huge percentage of those particles, enough could escape to get someone sick if that person is close to the carrier.

"Without a face mask, it is almost certain that many foreign droplets will transfer to the susceptible person," Kota said. "Wearing a mask will offer substantial, but not complete, protection to a susceptible person by decreasing the number of foreign airborne sneeze and cough droplets that would otherwise enter the person without the mask. Consideration must be given to minimize or avoid close face-to-face or frontal human interactions, if possible."

The study also did not account for leakage from masks, whether worn properly or improperly, which can add to the number of droplets that make their way into the air.

Credit: 
American Institute of Physics

Even after long-term exposure, bionic touch does not remap the brain

image: Study participants using the neuroprosthetic device shown in the diagram on the left all reported little change in the location of the sensation provided by their device, feeling it in their middle finger, palm, or at the base of the thumb rather than at the tip of their thumb, despite long-term, daily use.

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From Ortiz-Catalan et. al., Cell Reports 2020

Advances in neuroscience and engineering have generated great hope for Luke Skywalker-like prosthetics: robotic devices that are almost indistinguishable from a human limb. Key to solving this challenge is designing devices that not only can be operated with a user's own neural activity, but can also accurately and precisely receive and relay sensory information to the user.

A new study by neuroscientists at the University of Chicago and Chalmers University of Technology, published on December 22 in the journal Cell Reports, highlights just how difficult this may prove to be. In a cohort of three subjects whose amputated limbs had been replaced with neuromusculoskeletal prosthetic limbs, the investigators found that even after a full year of using the devices, the participant's subjective sensation never shifted to match the location of the touch sensors on their prosthetic devices.

The stability of the touch sensations highlights the limits in the ability of the nervous system to adapt to different sensory input.

Three participants with above-elbow amputations were equipped with high-tech neuroprosthetic devices that were affixed directly to their humerus bone. The users could control the prosthetic device thanks to signals received from electrodes implanted in the residual arm muscles, and received sensory feedback via another set of implanted electrodes. A sensor located on the prosthetic thumb triggered stimulation of the nerve, which in turn elicited a touch sensation.

However, because the organization of the nerve is essentially arbitrary, surgeons can't be sure whether their placement of the electrodes will generate a sensation in the correct location on the thumb. In the study, the prosthetic users did not report feeling the sensation on the thumb, but rather in other hand locations, such as their middle finger or the palm.

Participants then wore the prosthesis for upwards of 12 hours a day, every day, using it to manipulate objects during their daily routine for over a year.

"One problem with current neural electrodes is that you can't tell during the implantation surgery which part of the nerve corresponds to what sensation, so the electrodes don't always land in exactly the location in the nerve that would match the location of the sensors in the prosthetic hand," said lead author and developer of the neuromusculoskeletal prostheses, Max Ortiz Catalan, PhD, an associate professor of bionics at Chalmers University of Technology and Director of the Center for Bionics and Pain Research in Gothenburg, Sweden.

"We hoped that because the patients were grabbing objects and feeling the sensation somewhere else in the hand, all day and every day for several months, the brain would resolve the mismatch by shifting the perceived sensation to the thumb," he continued.

Despite being able to observe their hand while interacting with objects, none of the users ever reported that they felt the sensation on their thumb, but rather that the sensation persisted in the same area where it was originally felt.

"Every day, for a year, these subjects saw their prosthetic thumb touching things and felt it in a different location - sometimes close to the thumb, but not on it - and the sensation never budged. Not even a smidge," said senior author Sliman Bensmaia, PhD, the James and Karen Frank Family Professor of Organismal Biology and Anatomy at UChicago.

These results challenge prevailing dogma regarding brain plasticity following limb loss. Many have believed that the brain has a high capacity to reorganize itself after losing sensory input, co-opting existing, unused brain tissue for other purposes.

"There's been this idea that the nervous system is really plastic, so if you see a mismatch between what you see and what you feel, it's a great opportunity for neural remapping," said Bensmaia. "For example, if you sew two fingers together and look at how that's represented in the brain, they seem to have merged."

"But I think that this idea has been vastly overstated. It's less like you're reorganizing a room and more like you're just hearing echoes bouncing around an empty chamber," he continued. "You might get some overlapping sensation from adjacent limbs, but it's just because the area of the brain that used to respond to sensation is empty, and activating the neurons around it leads to an echo through the emptiness."

This study highlights the importance of knowing exactly where to place electrodes when implanting sensory arrays for patients using these types of neuroprosthetic devices, as it appears unlikely that the brain is capable of making substantial adjustments in how it perceives that sensory input. "This means that you really have to get it right," said Bensmaia. "There are no do-overs here."

Credit: 
University of Chicago Medical Center

Reliable anti-counterfeit checks under extreme conditions

image: NUS researchers invent anti-counterfeiting technology for reliable AI authentication under extreme conditions.

Image: 
National University of Singapore

Researchers from the National University of Singapore (NUS) have invented a new method of anti-counterfeiting called DeepKey. Developed in just eight months, this security innovation uses two dimensional (2D)-material tags and artificial intelligence (AI)-enabled authentication software.

Compared to conventional anti-counterfeiting technologies, DeepKey works faster, achieves highly accurate results, and uses durable identification tags that are not easily damaged by environmental conditions such as extreme temperatures, chemical spills, UV exposure, and moisture. This new authentication technology can be applied to different high-value products, ranging from drugs, jewelry, and electronics. For example, DeepKey is suitable for tagging COVID-19 vaccines to enable rapid and reliable authentication, as some of such vaccines need to be stored at the ultra-cold temperature of -70°C.

Led by Asst Prof Chen Po-Yen and Asst Prof Wang Xiaonan from the Department of Chemical and Biomolecular Engineering at NUS Faculty of Engineering, the team's 2D-material secure tags exhibit Physically Unclonable Function patterns (PUF patterns), which are randomly generated by systematically crumpling the 2D-material thin films. The complex 2D-material patterns with multi-scale features can then be classified and validated by a well-trained deep learning model, enabling reliable (100 per cent accurate) authentication in less than 3.5 minutes.

Current anti-counterfeiting technologies using PUF patterns normally face several bottlenecks, including complicated manufacturing, specialised and tedious readout process, long authentication time, insufficient environmental stability, as well as being costly to make.

"With this research, we have tackled several bottlenecks that other techniques encounter," said Asst Prof Wang. "Our 2D-material PUF tags are environmentally stable, easy to read, simple and inexpensive to make. In particular, the adoption of deep learning accelerated the overall authentication significantly, pushing our invention one step further to practical application."

The researchers published their results in scientific journal Matter on 2 December 2020. This study was conducted in collaboration with researchers from Anhui University of Technology and Nanyang Technological University.

A stable, simple and scalable process to create PUF tags

Remarkably, the researchers do not need any special equipment to create the secure tags. They can simply be made with a balloon, a bottle of 2D-material dispersion, and a brush.

"First, we inflate the balloon and brush over its surface with viscous 2D-material ink. After air drying overnight, we deflate the balloon. Because of the interfacial mechanical mismatch between the 2D-material and latex substrate, large-area, crumpled PUF patterns are generated during the contraction. These PUF patterns can be cut to the required size afterwards, and normally, hundreds of them can be made at one time," said Dr Jing Lin, a member of the research team.

Next, the researchers take a quick image of the PUF tag with an electron microscope, which is then synced to their innovative software to go through the deep learning "classification and validation" process. "The whole process takes less than 3.5 minutes, most of which is spent waiting for the readout from the electron microscope. The authentication itself is very fast, in less than 20 seconds," explained Dr Jing.

Fast authentication using AI deep learning algorithms

All PUF key-based technologies have ultra-high encoding capacities because of the huge numbers of distinct patterns that can be theoretically produced. However, the high encoding capacity also leads to long authentication time, as the "search and compare" pattern validation has to be conducted within a huge database. This trade-off between high encoding capacity and long authentication time often restricts such PUF-based anti-counterfeiting tags from practical applications.

"With our new technology, we are breaking this long-lasting trade-off between high encoding capacity and long authentication time by using classifiable 2D-material PUF tags and deep learning algorithms," said Asst Prof Wang.

First, the researchers used various 2D materials to fabricate PUF tags with AI recognisable features. Second, they trained a deep learning model to conduct a two-step authentication mechanism. "We used the deep learning model to pre-categorise the PUF patterns into subgroups, and so the search-and-compare algorithm is conducted in a much smaller database, which shortens the overall authentication time," Asst Prof Wang explained.

Currently, the only available technologies similar to this NUS innovation, are polymer wrinkle-based tags. Wrinkled polymer tags are authenticated based on the surface patterns just like the novel 2D-material tags. However, their authentication presently requires one-by-one feature extraction and matching, which is slow and shows only 80 per cent reliability. The NUS team's authentication is boosted by deep learning, and is therefore much faster, and reaches nearly 100 per cent validation precision.

In addition, compared to the wet chemistry preparation of polymer wrinkle-based tags, which involves the use of harmful organic chemicals and UV light, the NUS researchers' fabrication technique is significantly faster and safer.

Next steps

The NUS team has filed a patent for their invention and is now planning to push this technology one step further. "We are searching for better, faster, and more robust readout and authentication approaches for our PUF tags," said Asst Prof Wang.

The team has already begun to conduct research on other readout techniques to further shorten the processing time. "In addition, such naturally encoded information by the PUF tags could be further secured by being kept on blockchain, so that the whole supply chain and quality control can be transparently tracked," Asst Prof Wang added.

Credit: 
National University of Singapore

Astigmatism measures and corneal power obtained with different devices

As the recently published article in the journal Open Ophthalmology Journal shows, there are significant differences among the measures of corneal parameters obtained by the three most commonly used ophthalmic devices, called topographers.

This is a critical issue for doctors seeking to achieve the best patient outcomes for eyesight recovery after cataract surgery. The calculation of the astigmatic power required for the intraocular lens (IOL) that is to be implanted after cataract surgery is based on the magnitude and axis of corneal astigmatism considered, which can be measured and calculated using different topographers. The accuracy when calculating the appropriate IOL determines the quantity and quality of vision of the post-operative cataract patients and also defines their need for spectacles after the surgery.

This work, published by a team of ophthalmologists from Spain compares the measures obtained from Pentacam system (Oculus Optikgera?te GmbH, Wetzlar, Germany), Cassini (i-Optics, The Hague, The Netherlands, distributed by Ophtec) and IOL-master 700 system (Carl Zeiss Meditec AG, Jena, Germany). These three devices measure corneal parameters using different technologies.

The prospective comparative study reviews data from 94 eyes from 53 patients ranging in age from 29 to 77 years old, recruited from the anterior segment consultation at Vithas Eurocanarias Instituto Oftalmológico in Las Palmas de Gran Canaria (Spain).

"Standard and total keratometric readings and astigmatism measures obtained with these devices cannot be used interchangeably, as there are statistically significant and clinically relevant differences among the results obtained," notes Dr. Humberto Carreras, one of the three co-authors of the paper. "Therefore, if the data of these three systems are used for toric IOL power calculations, significant differences can be expected, what will affect the post-op vision in the cataract patients?" The authors recommend that refractive predictability studies hold the answer to this question, and this needs to be investigated further for each type of optometric device.

Credit: 
Bentham Science Publishers

Pandemic and forthcoming stimulus funds could bring climate targets in sight -- or not

image: This is Dr. Yuli Shan, Faculty Research Fellow at ESRIG, the Energy and Sustainability Research Institute Groningen, Faculty of Science and Engineering, University of Groningen. He is the first author of the study published in Nature Climate Change.

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ESRIG, University of Groningen.

The lockdowns that resulted from the COVID-19 pandemic have reduced greenhouse gas emissions. However, in the recovery phase, emissions could rise to levels above those projected before the pandemic. It all depends on how the stimulus money that governments inject into their economies is spent. A team of scientists, led by Dr Yuli Shan and Professor Klaus Hubacek from the University of Groningen, has quantified how different recovery scenarios may affect global emissions and climate change. Their results were published in Nature Climate Change on 22 December. Hubacek: 'A crisis is a terrible thing to waste.'

The worldwide recession caused by the coronavirus has had a profound impact on greenhouse gas emissions that is likely to continue in the coming years. 'The decline in 2020 might bring us back to the levels of 2006-2007', says Yuli Shan, an environmental scientist at the University of Groningen and first author of the paper. The CO2 emissions from industrial sectors over the course of 2020 to 2024 might be 3.9 to 5.6 per cent lower than the emissions that were expected if there had not been a pandemic. 'This drop in emissions will help us to achieve the goals that were set by the Paris Climate Agreement, although it is not yet enough.' However, countries are now developing stimulus packages to boost their economies and that will affect emissions.

Supply chains

Shan and his colleagues from the Netherlands, the UK and China used a recently developed economic impact model to calculate the direct and indirect effects from the lockdowns, but also the effects of stimuli in different scenarios. These calculations were performed for economies in 41 countries, representing some 90 per cent of the global economy. 'We did this for entire global supply chains,' explains Shan. 'For example, if China has to stop producing certain goods, this could also impact production in the US or in Europe.'

The calculations were performed for allocation of the stimuli to five different economic categories (construction, manufacturing, service sector, health sector and households) and for different policy aims. 'These vary in the amount of carbon emissions that they will produce,' explains Shan. The results of the different scenarios were then quantified in terms of greenhouse gas emissions.

Innovations

'The models show that without structural change, we will see a V-shaped response,' says Hubacek. In that case, the emissions will quickly increase to pre-crisis levels and perhaps even exceed those levels. 'Our results show how far apart the different scenarios can bring us.' Emissions could drop by 6.6 gigatons of carbon (-4.7 per cent) or increase by 23.2 gigatons (+12.1 per cent). 'There is plenty of room to go the wrong way,' says Hubacek. 'And a crisis is a terrible thing to waste.'

Stimulus packages should target innovations, support the energy transition and help households to invest in the adoption of renewable energy. 'Spending this money to bail out carbon-intensive sectors such as airlines is heading in the wrong direction. It is much better to improve public transport and railways.' Hubacek's message is that the COVID-19 crisis has made a big dent in greenhouse gas emissions and that we should use this for our benefit. 'This crisis is awful, but it is also a wake-up call for action against climate change. We are now in a position to really do something about it.'

Choices

However, there is also a big risk: governments must borrow billions for the stimulus packages. The increases in national debts leave little space for further investments in the next few decades. 'So, if we do not invest in low-carbon alternatives now, it will not happen for a long time.' This would mean that greenhouse gas emissions could increase beyond what was predicted before the pandemic.

'Our next project is to study the EU economy in greater detail, but still embedded in the global model. So, we will look at entire production chains.' Hubacek hopes that governments will make the right choices. 'At the moment, it can go either way: we can increase global warming or slow it down substantially.'

Simple Science Summary

The corona crisis has brought the world's economies to a standstill. This reduced the amount of greenhouse gas emissions that were produced by power plants, the industry, transport, etc. Lower greenhouse gas emissions lead to less global warming. However, governments are currently spending a huge amount of money on stimulating the economy. Environmental scientists and economists have now shown how important it is where governments target their stimulus money. Investing in renewables and public transport would slow down global warming but investing in parts of the economy that rely on fossil fuels could make it much worse.

Credit: 
University of Groningen

Voluntary or compulsory? New evidence on motivation for anti-COVID-19 policies

Policies to contain the Covid-19 pandemic require widespread cooperation in order to be successful. Is the German population more likely to follow these measures when they are voluntary or when they are enforced? Dr Katrin Schmelz, a behavioural economist and psychologist at the University of Konstanz and the Thurgau Institute of Economics, investigated this question. To do so, she relied on a large-scale, representative survey program conducted as part of the Cluster of Excellence "The Politics of Inequality" at the University of Konstanz at the end of the first lockdown in Germany (spring of 2020). The results are published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), online on December 21, 2020.

Close to 5,000 Germans were asked how much they agreed with limiting their contacts and travel activities, wearing a face mask, using a contact tracing app and getting vaccinated, if these measures were either strongly recommended by the government but remained voluntary, or if they were made mandatory and checked by the government.

The existing literature points in two directions: On the one hand, enforced policies might increase support since individuals could rely on others following the law as well. On the other hand, enforced policies might also undermine the intrinsic motivation of those who take responsibility and are willing to cooperate voluntarily.

Voluntary support for policies is relatively high but may be crowded out

The result: Overall support for voluntary policies is relatively high. However, at least 25 percent of respondents express control aversion - i.e. lower agreement with a policy in case it is enforced than in case it is strongly recommended but remains voluntary. Especially for a contact tracing app and vaccinations, average agreement to follow those measures was higher if implemented on a voluntary than on a mandatory basis. This was also true to a smaller extent for limiting contacts. By contrast, average agreement with wearing a mask and limiting travel was the same under both conditions, regardless of whether these measures were voluntary or compulsory.

What determines whether individuals react negatively to government control and compulsory measures? "Trust in the government and the truthfulness of its information plays an important role in the coronavirus pandemic", summarizes Katrin Schmelz. The less people trust, the more can compulsory policies destroy voluntary motivation.

People who grew up in the GDR are less control averse

The researcher identified one particular segment of the population that expresses less resistance to compulsory measures and state control: individuals who grew up in the former GDR. Dr Schmelz's conjecture that there could be an "East-West difference" was her motivation for conducting the study. In the past, her dissertation used an online experiment to examine how individuals who have experienced different governmental systems (in East and West Germany) react to control. The results of that work were confirmed in the current representative survey focusing on anti-Covid-19 policies: Individuals (like the author herself) who grew up in the former GDR respond differently to enforcement than individuals who grew up in West Germany.

The difference between East and West was especially evident for measures that paralleled GDR experiences: East Germans who had experienced the GDR government expressed less opposition to mandatory policies than their peers from the West with respect to vaccinations, travel restrictions and contact restrictions. Similarly, in the case of the contact tracing app, enforcement undermines voluntary motivation less among respondents who grew up in the GDR and are familiar with other surveillance measures. However, there is no East-West difference with respect to masks - neither East nor West Germans have any past experience with such a restriction of personal freedom. The East-West difference disappears in the younger generation that grew up in a unified Germany.

Recommendations for policymakers

The findings of this study provide another building block as a basis for policy decision on the design of anti-Covid-19 measures, namely the share of citizens who are motivated to comply with a policy voluntarily and the extent to which enforcement may crowd out this motivation and provoke resistance. These findings need to be assessed in relation to other aspects, especially the level of compliance required for a policy to be successful and the extent to which a policy is actually enforceable.

For example, the 60% of the population that would wear a face mask voluntarily would not suffice to ensure the success of this policy. Moreover, the study does not provide much evidence for an enforced mandate on masks to crowd out voluntary motivation. This along with the feasibility of enforcement indicates that enforcement can be quite effective. Similar considerations apply to policies limiting travel.

The picture looks quite different for a contact tracing app: Enforcement would evoke strong opposition among a substantial share of 40 percent. At the same time, it is difficult to control whether people actually use the app. "A contact tracing app is one of the measures that evoke considerable control aversion and that cannot fully be enforced in Germany. Thus, it makes little sense to have it compulsory", Katrin Schmelz says.

Vaccination better voluntary

The situation is similar for vaccinations, where about 50 to 65 percent of respondents fully or somewhat agreed to take this action voluntarily. "Assuming that less than 70 percent of the population needs to be vaccinated in order to achieve herd immunization when vaccinations are targeted to those more likely to get infected, this might suffice", the researcher concludes. By contrast, support in the case of vaccinations being mandatory was significantly lower in the study, with considerable resistance against mandatory vaccination. Provoking this resistance may not be necessary, since a vaccination rate of 100 percent is not required.

While waiting for vaccines, limiting contacts is at the core of fighting the pandemic and requires widespread cooperation. As for the app and vaccinations, enforced contact restrictions provoke control aversion but this negative response is less pronounced. Some degree of enforcement may be necessary and effective - for example, to increase the level of cooperation among healthy people who would have lower incentives to avoid getting infected themselves, but whose cooperation would protect those at higher risk.

The study also shows that, for all policies, trust in the government and the truthfulness of its information about the Covid-19 pandemic positively affect both voluntary cooperation and acceptance of enforced anti-Covid-19 policies.

Samuel Bowles, a famous economist at the Santa Fe Institute in the U.S. called it "a timely and important study showing that ethical values and social norms are essential for the success of policies to address the pandemic, and may be compromised in some cases by governmental attempts to control citizens."

Credit: 
University of Konstanz

It's electrifying! This is how Earth could be entirely powered by sustainable energy

Can you imagine a world powered by 100% renewable electricity and fuels? It may seem fantasy, but a collaborative team of scientists has just shown this dream is theoretically possible - if we can garner global buy-in.

The newly published research, led by Professor James Ward from the University of South Australia and co-authored by a team including Luca Coscieme from Trinity College Dublin, explains how a renewable future is achievable.

The study, published in the international journal, Energies, explores what changes are needed in our energy mix and technologies, as well as in our consumption patterns, if we are to achieve 100% renewability in a way that supports everyone, and the myriad of life on our planet.

The fully renewable energy-powered future envisioned by the team would require a significant "electrification" of our energy mix and raises important questions about the potential conflict between land demands for renewable fuel production.

Explaining the work in some detail, Luca Coscieme, Research Fellow in Trinity's School of Natural Sciences, said:

"Firstly, the high fuel needs of today's high-income countries would have to be reduced as it would require an unsustainably vast amount of land to be covered with biomass plantations if we were to produce enough fuel to satisfy the same levels.

"Additionally, our research shows that we would need to radically 'electrify' the energy supply of such countries - including Ireland - with the assumption that these changes could supply 75% of society's final energy demands. We would also need to adopt technology in which electricity is used to convert atmospheric gases into synthetic fuels.

"We very much hope that the approach designed in this research will inform our vision of sustainable futures and also guide national planning by contextualising energy needs within the broader consumption patterns we see in other countries with energy and forest product consumption profiles that--if adopted worldwide--could theoretically be met by high-tech renewably derived fuels. Countries such as Argentina, Cyprus, Greece, Portugal and Spain are great examples in this regard.

"Even so, the success of this green ideal will be highly dependent on major future technological developments, in the efficiency of electrification and in producing and refining new synthetic fuels. Such a scenario is still likely to require the use of a substantial - albeit hopefully sustainable - fraction of the world's forest areas."

Credit: 
Trinity College Dublin

How roundworms decide the time is right

image: Roundworm embryos (purple ovals) use a master switch protein called BLIMP-1 to prepare the embryo for development. BLMP-1 primes genes needed to develop into a larva and later an adult. Green dots are fluorescent tags on genes for cell growth. The larger green dots are associated with skin cells, indicating preparation for development, and the smaller dots are associated with brain cells, indicating no anticipated growth.

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Natalia Stec/Hammell lab/CSHL, 2020

Transforming a fertilized egg into a fully functional adult is a complicated task. Cells must divide, move, and mature at specific times. Developmental genes control that process, turning on and off in a choreographed way. However, the environment influences development. A team of researchers led by Cold Spring Harbor Laboratory Associate Professor Christopher Hammell reported December 22, 2020 in the journal Current Biology how gene activity matches nutrient levels. They found a master switch developing worms use to pause growth when nutrients are scarce. When the environment improves, animals continue developing. The switch adjusts gene activity to match nutrient levels.

Caenorhabditis elegans is a tiny roundworm. In a lab, this worm develops from an embryo to a 959-cell adult in about three days. Hammell says:

"This always happens the same way. You always get 959 cells, and the patterns of those divisions that give you those cells are always done in the same manner between one animal and the next."

The genes that direct this flexible program switch on and off in predictable patterns as an embryo morphs through several larval stages into a fully formed worm.

In the wild, developing worms can't always depend on comfortable temperatures and plentiful food. Sometimes, development must pause until conditions improve. Hammell's team discovered a protein called BLMP-1 that adjusts gene activity (transcription) to keep pace with development. When conditions are good, BLMP-1 levels increase and unravel stretches of DNA, so genes are more accessible. Activators then switch on the genes at the right time. "This is an anticipatory mechanism to say 'everything's okay, make development as robust as possible,'" Hammell explains. If conditions are not optimal, BLMP-1 levels go down, leaving genes packed tightly away, slowing or even stopping development.

The team's experiments revealed BLMP-1 as a master regulator of thousands of genes that cycle on and off during development. Hammell says that was a surprise since his team initially set out to investigate this process in just a handful of developmental genes. BLMP-1 is unique in that it coordinates many different kinds of processes.

Hammell is not the first researcher to call attention to BLMP-1. An analogous gene is known to be overactive in some human blood cancers, where it alters the activity of a large set of genes. Hammell is hopeful that BLMP-1 in C. elegans will provide a model system to study human diseases.

Credit: 
Cold Spring Harbor Laboratory

Brain gene expression patterns predict behavior of individual honey bees

image: Researchers used barcodes to track individual honey bees in a study that looked for parallels between the bees' foraging and egg-laying behavior and patterns of gene expression in their brains.

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Graphic by Michael B. Vincent

CHAMPAIGN, Ill. -- An unusual study that involved bar coding and tracking the behavior of thousands of individual honey bees in six queenless bee hives and analyzing gene expression in their brains offers new insights into how gene regulation contributes to social behavior.

The study, reported in the journal eLife, reveals that the activity profile of regulator genes known as transcription factors in the brain strongly correlates with the behavior of honey bees, the researchers said. A single transcription factor can induce - or reduce - the expression of dozens of other genes.

"If the queen in a colony dies and the workers fail to rear a replacement queen, some worker bees activate their ovaries and begin to lay eggs," said Beryl Jones, a former graduate student at the University of Illinois Urbana-Champaign who led the study with entomology professor Gene Robinson, the director of the Carl R. Woese Institute for Genomic Biology at the U. of I.; and Sriram Chandrasekaran, a professor of biomedical engineering at the University of Michigan. Jones is a postdoctoral researcher at Princeton University.

"This is an example of 'behavioral plasticity,' the ability to change behavior in response to the environment," Jones said. "We know that behavioral plasticity is influenced by the activity of genes in the brain, but we do not know how genes in the brain work together to regulate these behavioral differences."

"We wanted to compare egg-laying and foraging behaviors because they are quintessential examples of selfish and cooperative behaviors," Robinson said.

Under typical conditions, queens lay eggs and workers forage. Studies that focus on differences in the brains and behavior of queens and foragers must contend with the fact that queens are fed and nurtured differently during development than worker bees, making any differences in gene regulation difficult to interpret. By studying queenless colonies, the researchers were able to analyze only worker bees and could therefore avoid this complication.

"Another challenge in studying how genes influence behavior is that behavior varies over time and also between individuals," Robinson said. "Hence, we automatically tracked the behavior of thousands of individual bees, 24/7, using small bar codes and computer vision to generate an unusually large dataset to help answer our questions."

The scientists used computational algorithms to look for patterns of brain gene activity in the bees. They found consistent differences in gene regulation between bees that devoted themselves to foraging and those primarily focused on egg-laying. These patterns of transcription-factor regulation were so distinct that the researchers could use them to predict whether individual bees were foragers or egg-layers.

The analysis revealed that a small number of egg-laying worker bees also engaged in foraging. These "generalist" bees had an intermediate gene-expression profile between the foraging specialists and the egg-laying specialists.

"We identified 15 transcription factors that best explained the behavioral differences in the bees," Jones said. The findings suggest that changes in the activity of a small number of influential transcription factors can lead to strikingly different behavior, she said.

"Some of the transcription factors we identified as important for honey bee behavior were previously identified as influencing the evolution of social behavior in other species," Robinson said. "This suggests our findings will aid in understanding how social behavior evolved and is regulated in multiple species, including, perhaps, humans."

Credit: 
University of Illinois at Urbana-Champaign, News Bureau