Tech

Diagnostics, meet CRISPR

image: The lateral flow strips show three patient samples that are negative for BK virus (13,14,15) and three patient samples that are positive (16,17,18). Presence of the upper band indicates a positive test result.

Image: 
Michael Kaminski, MDC

The simplicity of urine sampling has been combined with the excellent sensing abilities of CRISPR to improve diagnostic testing for kidney transplant patients, an international research team reports in the journal Nature Biomedical Engineering.

The new test screens for two common opportunistic viruses infecting kidney transplant patients, cytomegalovirus (CMV) and BK polyomavirus (BKV), and CXCL9 mRNA, whose expression increases during acute cellular kidney transplant rejection.

"Most people think of gene editing when they think of CRISPR, but this tool has great potential for other applications, especially cheaper and faster diagnostics," said Dr. Michael Kaminski, who heads the Kidney Cell Engineering and CRISPR Diagnostics Lab at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and Charité - Universitätsmedizin Berlin. He spearheaded the test's development while at the Collins lab at the Massachusetts Institute of Technology (MIT). Since 2020 Kaminski, who is a medical doctor at Charité's Medical Department, Division of Nephrology and Internal Intensive Care Medicine, started a new lab at the Berlin Institute for Molecular Systems Biology (BIMSB) from MDC.

Critical need

Kidney transplant patients are on medications suppressing their immune systems to reduce the chance the organ will be rejected. But this increases their risk of getting sick from infections. Closely monitoring patients for both infection and rejection is critical and guides the delicate balance of care. Usually this is done via blood tests and kidney biopsies, which are time-consuming, more invasive and expensive.

While affordable urine-based diagnostic tests are available for a variety of biomarkers, from diabetes to pregnancy, they have not been widely adapted for nucleic acids, such as DNA or RNA. That's where CRISPR comes in.

CRISPR technology is able to find very small segments of a DNA or RNA sequence guided by a complimentary piece of RNA. It works in tandem with certain types of Cas proteins, which cut the target sequence, as well as a fluorescent reporter molecule. This so-called collateral cleavage releases fluorescence, indicating presence of a target. Many labs have been investigating CRISPR's diagnostic potential on synthetic material, but few have tested real clinical samples.

"The challenge is getting down to concentrations that are clinically meaningful," Kaminski said. "It really makes a huge difference if you are aiming for a ton of synthetic target in your test tube, versus if you want to get to the single molecule level in a patient fluid."

Positive or negative

The test kit, formally called an assay, uses a two-step process. First, viral target DNA in a urine sample must be amplified - copied enough times so CRISPR can detect it even if there is just one target molecule present. The team used a specific CRISPR-Cas13 protocol known as SHERLOCK to optimize the process for viral DNA. The results are conveyed much like a home pregnancy test. When a paper strip is dipped in the prepared sample, if only one line appears on the strip, the result is negative, while two lines indicates a virus is present. "It's exciting to see the results appear on the test strips," said Robert Greensmith, a first-year PhD student in Kaminiski's Lab and paper co-author. "As someone new to working with CRISPR, I'm impressed by how it makes for a such a robust testing platform."

For very low target concentrations, often a pale second line appears on the test strip, which could cause confusion. So, the team developed a smartphone app that unbiasedly analyzes pictures of the test strip and renders the final call based on the line's intensity.

The researchers used a similar process for the rejection marker CXCL9. There, mRNA was isolated and amplified, followed by CRISPR-Cas13 mediated target detection.

After a lot of work to optimize the technique, the researchers used their assay to analyze more than 100 samples from kidney transplant patients. The assay was very accurate even with low levels of BKV or CMV infection, and correctly detected signs of acute cellular transplant rejection.

Next steps

While a patent application is pending, Kaminski, who is a medical doctor and clinical researcher, is interested in larger clinical studies comparing the assay to conventional monitoring methods. He would also like to investigate ways to make the test even more streamlined. Right now, samples must be heated for preparation and the test requires multiple steps. While it could be used in a hospital setting, it's not quite ready for at-home testing. The ultimate goal is a one-step process that can quantitatively measure multiple parameters. That way, patients can measure specific changes against their individual baselines.

Kaminski notes this test could also be useful for other immunocompromised people at risk for viral infections, while the CRISPR-based diagnostic approach could potentially be adapted for other organ transplants.

Credit: 
Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Structural protein may be new marker of depression

image: The brains of depressed people contain less modified tubulin in the plasma membrane.

Image: 
Singh et al., JNeurosci 2020

Scientists have zeroed in on a structural protein as a new target for the diagnosis and treatment of depression, according to research recently published in JNeurosci.

The protein tubulin provides structure to cells and assists in many cellular processes, but it also plays a role in depression. A modified form of tubulin anchors the protein Gαs to lipid rafts, fatty structures floating in the cell membrane. In depressed people, Gαs gets stuck in lipid rafts and cannot trigger the production of cAMP, a molecule necessary for quick messaging in the brain. Imaging studies have shown that people with depression have less cAMP in their brains, which is remedied after successful treatment.

Singh et al. examined the amount of modified tubulin in the brains from people who were not depressed as well as those from people with depression who died by suicide and by other causes. All the brains contained the same amount of modified tubulin, but the brains of people with depression had less modified tubulin in the lipid rafts. This could allow more tubulin to trap Gαs in the lipid rafts, preventing cAMP production. Tubulin could provide a diagnostic marker of depression and a target of antidepressant treatment.

Credit: 
Society for Neuroscience

New handle for controlling electromagnetic properties could enable spintronic computing

image: A large, perfect crystal of iron sulfide that was painstakingly grown for the research experiments probing the change of atomic vibrations across magnetic transition.

Image: 
Haidong Zhou, University of Tennessee

DURHAM, N.C. -- Materials scientists at Duke University have shown the first clear example that a material's transition into a magnet can control instabilities in its crystalline structure that cause it to change from a conductor to an insulator.

If researchers can learn to control this unique connection between physical properties identified in hexagonal iron sulfide, it could enable new technologies such as spintronic computing. The results appear April 13 in the journal Nature Physics.

Commonly known as troilite, hexagonal iron sulfide can be found natively on Earth but is more abundant in meteorites, particularly those originating from the Moon and Mars. Rarely encountered in the Earth's crust, most troilite on Earth is believed to have originated from space.

Despite its relative rarity, troilite has been studied since 1862 without much fanfare. A recent theoretical paper, however, suggested that there might be novel physics at play between the temperatures of 289 and 602 degrees Fahrenheit -- the temperature range at which troilite becomes both magnetic and an insulator.

"The paper theorized that the way the atoms shift in their crystalline structure is impacting the mineral's properties through a pretty complicated effect that hasn't been seen before," said Olivier Delaire, associate professor of mechanical engineering and materials science, physics and chemistry at Duke. "The most important aspect is this interaction between magnetic properties and atomic dynamics, which is a subject that has not been investigated a lot before but is opening up new possibilities in computing technologies."

To get to the heart of the material's odd behavior, Delaire and his colleagues turned to Haidong Zhou, assistant professor of experimental condensed matter physics at the University of Tennessee, for the difficult task of growing perfect crystals of troilite. The researchers then took samples to Oak Ridge National Laboratory and Argonne National Laboratory to blast them with neutrons and x-rays, respectively.

When particles such as neutrons or x-rays bounce off the atoms inside a material, researchers can take this scattering information to reconstruct its atomic structure and dynamics. Because neutrons have their own internal magnetic moment, they can also reveal the direction of each atom's magnetic spin. But because neutrons interact weakly with atoms, x-rays are also very handy for resolving a material's atomic structure and atomic vibrations in tiny crystals. The researchers compared results from the two different scans using quantum mechanical models created on a supercomputer at Lawrence Berkeley National Laboratory to make sure they understood what was happening.

After watching the changes that occur through troilite's phase transformations, the researchers discovered previously unseen mechanisms at work. At high temperatures, the magnetic spins of troilite atoms point in random directions, making the material non-magnetic. But once the temperature drops below 602 degrees Fahrenheit, the magnetic moments naturally align and a magnet is born.

The alignment of those magnetic spins shifts the vibration dynamics of the atoms. That shift causes the entire crystalline atomic structure to deform slightly, which in turn creates a band gap that electrons cannot jump across. This causes the troilite to lose its ability to conduct electricity.

"This is the first clear example that the alignment of magnetic spins can control the instabilities of a material's crystal structure," said Delaire. "And because these instabilities lead to a connection between the crystal's magnetic and conductivity properties, this is the type of material that's exciting in terms of enabling new types of devices."

The ability to tune a material's magnetic state by applying electrical currents, and vice versa, would be essential for the realization of technologies such as spin electronics, Delaire said. Known as spintronics for short, this emerging field seeks to use an electron's intrinsic spin and associated magnetic moment to store and manipulate data. Combined with an electron's traditional role in computing, this would allow computer processors to become denser and more efficient.

Through this paper, Delaire and his colleagues have identified the magnetic controls of the distortion mechanisms of the crystal structure, giving researchers a handle to manipulate one with the other. While that handle is currently based in temperature changes, the next step for researchers is to look at applying external magnetic fields to see how they might affect the material's atomic dynamics.

Whether or not troilite becomes the new silicon for the next generation of computing technology, Delaire says finding this unique mechanism in such a well-known material is a good lesson for the entire field.

"It's surprising that, even though you have a compound that is relatively simple, you can have this fancy mechanism that could end up enabling new technologies," said Delaire. "In a sense, it's a wakeup call that we need to reconsider some of the simpler materials to look for similar effects elsewhere."

Credit: 
Duke University

Scientists discover supernova that outshines all others

image: This is an artist's impression of a supernova.

Image: 
Aaron Geller (Northwestern University)

A supernova at least twice as bright and energetic, and likely much more massive than any yet recorded has been identified by an international team of astronomers, led by the University of Birmingham.

The team, which included experts from Harvard, Northwestern University and Ohio University, believe the supernova, dubbed SN2016aps, could be an example of an extremely rare 'pulsational pair-instability' supernova, possibly formed from two massive stars that merged before the explosion. Their findings are published today in Nature Astronomy.

Such an event so far only exists in theory and has never been confirmed through astronomical observations.

Dr Matt Nicholl, of the School of Physics and Astronomy and the Institute of Gravitational Wave Astronomy at the University of Birmingham, is lead author of the study. He explains: "We can measure supernovae using two scales - the total energy of the explosion, and the amount of that energy that is emitted as observable light, or radiation.

"In a typical supernova, the radiation is less than 1 per cent of the total energy. But in SN2016aps, we found the radiation was five times the explosion energy of a normal-sized supernova. This is the most light we have ever seen emitted by a supernova."

In order to become this bright, the explosion must have been much more energetic than usual. By examining the light spectrum, the team were able to show that the explosion was powered by a collision between the supernova and a massive shell of gas, shed by the star in the years before it exploded.

"While many supernovae are discovered every night, most are in massive galaxies," said Dr Peter Blanchard, from Northwestern University and a coauthor on the study. "This one immediately stood out for further observations because it seemed to be in the middle of nowhere. We weren't able to see the galaxy where this star was born until after the supernova light had faded."

The team observed the explosion for two years, until it faded to 1 per cent of its peak brightness. Using these measurements, they calculated the mass of the supernova was between 50 to 100 times greater than our sun (solar masses). Typically supernovae have masses of between 8 and 15 solar masses.

"Stars with extremely large mass undergo violent pulsations before they die, shaking off a giant gas shell. This can be powered by a process called the pair instability, which has been a topic of speculation for physicists for the last 50 years," says Dr Nicholl. "If the supernova gets the timing right, it can catch up to this shell and release a huge amount of energy in the collision. We think this is one of the most compelling candidates for this process yet observed, and probably the most massive."

"SN2016aps also contained another puzzle," added Dr Nicholl. "The gas we detected was mostly hydrogen - but such a massive star would usually have lost all of its hydrogen via stellar winds long before it started pulsating. One explanation is that two slightly less massive stars of around, say 60 solar masses, had merged before the explosion. The lower mass stars hold onto their hydrogen for longer, while their combined mass is high enough to trigger the pair instability."

"Finding this extraordinary supernova couldn't have come at a better time," according to Professor Edo Berger, a coauthor from Harvard University. "Now that we know such energetic explosions occur in nature, NASA's new James Webb Space Telescope will be able to see similar events so far away that we can look back in time to the deaths of the very first stars in the Universe."

Supernova 2016aps was first detected in data from the Panoramic Survey Telescope and Rapid Response System (Pan-STARRS), a large-scale astronomical survey programme. The team also used data from the Hubble Space Telescope, the Keck and Gemini Observatories, in Hawaii, and the MDM and MMT Observatories in Arizona. Other collaborating institutions included Stockholm University, Copenhagen University, California Institute of Technology, and Space Telescope Science Institute.

Credit: 
University of Birmingham

Deadliest malaria strain protects itself from the immune system

The parasite causing the most severe form of human malaria uses proteins to make red blood cells sticky, making it harder for the immune system to destroy it and leading to potentially fatal blood clots. New research at the Crick has identified how the parasite may control this process.

The Nature Microbiology study looked into how the parasite, Plasmodium falciparum, evades the immune system. This parasite causes more than 95% of the 400,000 deaths caused by malaria each year.

Once it enters the human bloodstream, the parasite releases proteins into the host's red blood cell which are then presented on the outside surface of the cell. These proteins stick to other blood cells and blood vessel walls so that the infected cells no longer circulate around the body and pass through the spleen. This protects the parasite as the spleen and the immune cells inside it would destroy these infected cells.

This stickiness can also lead to blood cells lumping together into blood clots. By blocking the blood flow to vital organs, these clots can have fatal consequences, especially if they form in the brain or placenta.

Heledd Davies, co-lead author and postdoc in the Signalling in Apicomplexan Parasites Laboratory at the Crick, says: "This malaria parasite species is able to use a number of different variants of the same protein to make red blood cells sticky. So, if the body develops antibodies that stop one variant working, the parasite can simply switch to another one, leading to a constant arms race."

A potentially more effective route for therapies could be to target the mechanism malaria uses to transport the proteins to the cell's surface, as blocking it would reduce symptoms and allow the body to clear the parasites."

In this study, the authors identified proteins, so-called kinases, which are involved in getting the sticky proteins to the cell surface. Kinases are enzymes that can turn many other proteins on or off, and often regulate important processes in cells.

"These kinases are not released by other strains of malaria that infect humans, so we predicted that they are some of the factors that makes this species deadlier," says Hugo Belda, co-lead author and PhD student in the Signalling in Apicomplexan Parasites Laboratory at the Crick.

"In our research, we tested what happened when we removed different protein kinases from the parasite, while it is living in human blood. One protein played an important role in controlling cell stickiness, while others may be required for yet unknown aspects of the parasite's biology. This is very exciting and will help to better understand the disease mechanism," explains Moritz Treeck, group leader in the Signalling in Apicomplexan Parasites Laboratory at the Crick.

Credit: 
The Francis Crick Institute

Making big data processing more energy efficient using magnetic circuits

The rapid progression of technology has led to a huge increase in energy usage to process the massive troves of data generated by devices. But researchers in the Cockrell School of Engineering at The University of Texas at Austin have found a way to make the new generation of smart computers more energy efficient.

Traditionally, silicon chips have formed the building blocks of the infrastructure that powers computers. But this research uses magnetic components instead of silicon and discovers new information about how the physics of the magnetic components can cut energy costs and requirements of training algorithms -- neural networks that can think like humans and do things like recognize images and patterns.

"Right now, the methods for training your neural networks are very energy-intensive," said Jean Anne Incorvia, an assistant professor in the Cockrell School's Department of Electrical and Computer Engineering. "What our work can do is help reduce the training effort and energy costs."

The researchers' findings were published this week in IOP Nanotechnology. Incorvia led the study with first author and second-year graduate student Can Cui. Incorvia and Cui discovered that spacing magnetic nanowires, acting as artificial neurons, in certain ways naturally increases the ability for the artificial neurons to compete against each other, with the most activated ones winning out. Achieving this effect, known as "lateral inhibition," traditionally requires extra circuitry within computers, which increases costs and takes more energy and space.

Incorvia said their method provides an energy reduction of 20 to 30 times the amount used by a standard back-propagation algorithm when performing the same learning tasks.

The same way human brains contain neurons, new-era computers have artificial versions of these integral nerve cells. Lateral inhibition occurs when the neurons firing the fastest are able to prevent slower neurons from firing. In computing, this cuts down on energy use in processing data.

Incorvia explains that the way computers operate is fundamentally changing. A major trend is the concept of neuromorphic computing, which is essentially designing computers to think like human brains. Instead of processing tasks one at a time, these smarter devices are meant to analyze huge amounts of data simultaneously. These innovations have powered the revolution in machine learning and artificial intelligence that has dominated the technology landscape in recent years.

This research focused on interactions between two magnetic neurons and initial results on interactions of multiple neurons. The next step involves applying the findings to larger sets of multiple neurons as well as experimental verification of their findings.

Credit: 
University of Texas at Austin

Cybersecurity, tech infrastructure requires international trust

ITHACA, N.Y. - In new research published in the journal Technology and Culture, Rebecca Slayton, professor of science and technology studies at Cornell University, uses the field of incident response to shed light on how experts - and nations - can more effectively combat cyberwarfare when they foster trust and transcend politics.

"People often think of infrastructure as a set of technologies just sitting there, but in fact they're living technologies - socio-technical systems that are constantly being maintained by people, and trust is central to that," Slayton said.

Most experts agree that state-sponsored hackers in Russia are trying to use the internet to infiltrate the U.S. electrical grid and sabotage elections, yet internet security teams in the U.S. and Europe actively seek to cooperate with their Russian counterparts, focusing on the issues where they can establish mutual trust.

"Even though they recognize that there are actors in the shadows in those countries whom they don't trust, they have a shared goal of keeping the infrastructure running," Slayton said.

The field of incident response began after the internet was struck by "an attack from within" in November 1988. A self-replicating program - a "worm" - infected thousands of connected computers, causing them to stop processing and communicating normally.

Although computer scientists realized that the connected nature of the internet required international cooperation, global participation in these efforts was initially limited. But that began to change in the early 1990s, with the formation of the Forum of Incident Response and Security Teams (FIRST), which remains the leading global organization of security experts.

"Teams in the U.S. and in Europe very much want to cooperate with teams in Russia, and they see that as a way of having influence they might otherwise not have in that space," Slayton said.

Previous research on the history of computer and network security focused largely on development of new technology, rather than repair or maintenance. However, Slayton wrote in the new paper "Trusting Infrastructure: The Emergence of Computer Security and Incident Response, 1989-2005," that without the efforts of incident responders, the internet as we know it wouldn't exist.

"It's one thing to come up with a new algorithm or a new technique for, say, intrusion detection, but actually making it work and operate requires people to implement and maintain it on an ongoing basis," Slayton said. "It's nice to think some innovative technology will fix everything. But in practice, people have to keep things up to date, particularly when you're dealing with an intelligent adversary. You have to stay ahead of that."

Credit: 
Cornell University

Tight spaces tip presence of petrochemicals

image: Rice University researchers used large-scale simulations to eliminate the role of paramagnetism in NMR characterization of oil and shale deposits in nanoporous shale formations. Under strong confinement, they found the volume fraction of heptane in a model polymer is low, as though the light hydrocarbon is being dissolved in the confining matrix. The figure shows measurements (open circles) and simulation results (filled circles) of the T1/T2 ratio for surface relaxation for one applied magnetic-field strength.

Image: 
Arjun Valiya Parambathu/Rice University

HOUSTON - (April 13, 2020) - Rice University engineers have put to rest a long-held theory about the detection of oil and gas that hides inside the nanoscale pores of shale formations.

The Rice researchers determined that puzzling indicators from nuclear magnetic resonance (NMR) tools are not due, as thought, to the paramagnetic properties of the rock but solely to the size of the space that traps the petrochemicals.

The team expects the discovery will lead to better interpretation of NMR logs by the oil and gas industry, especially in unconventional shale formations.

The study's authors -- senior investigators Dilip Asthagiri, Philip Singer, George Hirasaki and Walter Chapman and graduate student Arjun Valiya Parambathu, all of the Brown School of Engineering's Department of Chemical and Biomolecular Engineering -- have been at the forefront in using atomistic simulations to refine how to interpret NMR relaxation behavior.

Their paper in the Journal of Physical Chemistry B builds on earlier work from the same group and elucidates the critical role of molecular confinement on NMR relaxation response.

NMR relaxation is an important tool to nondestructively measure the dynamics of molecules in porous materials. NMR is commonly used to detect diseased tissues in the human body, but is also employed to help extract oil and gas safely and economically by characterizing sedimentary rocks to see if they contain hydrocarbons.

NMR manipulates the nuclear magnetic moments of hydrogen nuclei by applying external magnetic fields and measuring the time it takes for the moments to "relax" back to equilibrium. Because relaxation times differ depending on the molecule and its environment, the information gathered by NMR, specifically the relaxation times known as T1 and T2, can help identify whether a molecule is gas, oil or water and the size of the pores that contain them.

A puzzle in the field has been to explain the large T1/T2 ratio of light hydrocarbons confined in such nanoporous material as kerogen or bitumen (aka asphalt) and the mechanism behind NMR surface relaxation, a phenomenon that emerges when formerly free molecules are adjacent to the surfaces that confine them.

Specifically, the researchers note, the T1/T2 ratio of hydrocarbons in kerogen is found to be much larger than the T1/T2 ratio of water in clays. While this contrast in T1/T2 has potential for predicting hydrocarbon reserves in unconventional shale formations, the fundamental mechanism behind it remained elusive.

The conventional explanation of the large T1/T2 ratio in kerogen invoked the physics of paramagnetism that dictate how materials respond to magnetic fields.

Through large-scale atomistic simulations by Valiya Parambathu, Chapman and Asthagiri and experiments by Singer and Hirasaki, the Rice team showed that explanation is not correct.

In the study, the team showed instead that the large T1/T2 ratio emerges as a consequence of confining the hydrocarbon in a tight space.

"In physical terms, under strong confinement, the correlation times of the molecular motions get longer," Asthagiri said.

"These longer correlation times result in faster NMR relaxation -- that is shorter T1 and T2 times," Singer added. "This effect is more pronounced for T2 than it is for T1, which results in a large T1/T2 ratio."

Chapman noted the team is also interested in exploring ideas presented in the paper in the context of medical MRI.

Credit: 
Rice University

UofL researchers describe possible mechanism for link between obesity and breast cancer

image: High expression of adipose fatty acid binding protein (FABP4) in mammary glands, shown in red.

Image: 
University of Louisville

LOUISVILLE, Ky. - It is widely accepted that higher levels of body fat increase the risk of developing breast cancer, as well as other cancers. Based on his ongoing research, Bing Li, Ph.D., associate professor in the Department of Microbiology and Immunology and UofL Health - James Graham Brown Cancer Center at the University of Louisville, has published an article which proposes a unique theory that a protein secreted by fat cells drives the development of breast cancer.

Li has been conducting research funded by the National Cancer Institute for the past five years which led him to the connection between activity of a protein expressed in fatty tissue and an increase in breast cancer development. Li and colleagues shared the theory in an invited forum in Trends in Molecular Medicine, a Cell Press journal, published online last week. The article describes Li's theory that adipose fatty acid binding protein (FABP4), expressed in fatty tissue, is responsible for fueling breast cancer tumor growth.

"Many types of cancer are related to obesity, not only breast cancer. More than 13 types of cancer are clearly associated with obesity and I think the list will go on and on once we have more data," Li said. "In our research, we found the fatty acid binding protein family, especially one member, FABP4, plays a very critical role in the association of obesity and cancer, most specifically breast cancer. We theorize that FABP4 is responsible for the underlying molecular mechanism which promotes obesity-associated breast cancer development."

Adipose tissue in the body produces FABP4 within fat cells, where it processes and distributes water-insoluble long-chain fatty acids. A certain amount of FABP4 enters the bloodstream under normal conditions. However, as a higher volume of fat tissue is accumulated, more FABP4 is secreted into circulation.

"When we get obese, this protein is secreted out much more into the circulatory system," Li said. "Normally these molecules are inside the cells, but when people are obese, the molecules are outside."

Li's theory offers two ways in which FABP4 may stimulate growth in breast cancer tumors.

First, within the cells, FABP4 increases in certain tumor-associated macrophages, which accumulate in tumors to promote tumor growth. Li's research also revealed that when FABP4 is inhibited, tumor growth is reduced in animal models even though the adipose tissue remained.

Second, when elevated levels of FABP4 circulate outside the fat cells in obesity, the protein promotes breast cancer development through direct interaction with breast cancer cells. In animal research, mammary tumor development and growth were reduced in obese animals in which FABP4 was controlled.

In addition, FABP4 in the bloodstream appears to work in multiple mechanisms to fuel interactions between tumor components and fat cells, thereby promoting cancer development.

Moreover, Li's research group recently published findings in Cancer Research showing that different types of high-fat diets have different effects on tumor development. High-fat diets of either cocoa butter or fish oil both result in fat-induced obesity. However, the cocoa butter diet results in increased mammary tumor growth, while the fish oil diet does not. This study not only confirms the critical role of FABP4 in obesity-associated cancer, but reveals that not all obesity promotes the development of tumors.

Li and his team believe a better understanding of how FABP4 works both within macrophages and in circulation could provide opportunities to prevent certain breast cancers from progressing. It may also lead to the development of treatment methods that target FABP4 with drugs or specific antibodies.

"Now we are trying to generate some antibodies for this protein, which could be a very effective therapy strategy for obesity-associated cancer," Li said.

Credit: 
University of Louisville

Observing the atmosphere at high altitudes using unmanned aeria vehicles

image: Sounding observations using UAVs in the Southern Ocean: (a) launch of a UAV mission; (b) example of a typical flight pattern of the UAV. The colors indicate the ground speed of the aircraft given in m s?1.

Image: 
Qizhen Sun

Severe weather conditions such as low air temperatures and strong winds often bring difficulties to scientific expeditions in Antarctica. Thus, monitoring and forecasting the weather is critical. Soundings constitute one important way to observe the high-altitude atmosphere. This kind of observational data helps with analyzing and studying the atmospheric circulation and improving the accuracy of weather forecasts. In recent years, unmanned aerial vehicles (UAVs) have become ideal atmospheric sounding observation platforms. European and American countries have already tried to carry out drone sounding activities over the Arctic Svalbard Islands and the Antarctic Terra Nova Bay.

"UAVs have many advantages for Antarctic atmospheric sounding observations." Said Dr. Qizhen Sun of the National Marine Environmental Forecasting Center (NMEFC) of China, "First of all, UAVs have good motility and can be used to observe specific weather systems at any time as needed; secondly, the single observation time of a UAV is generally around 20 minutes, making it particularly favorable for observing rapidly changing weather situations."

Other advantages of a UAV include: UAV observation data have high vertical resolution with a sampling interval of fewer than five meters and the horizontal movement of UAV sounding observations is usually less than 200 meters--much smaller than traditional radiosondes.

"Last but not the least, UAVs can be reused multiple times, reducing the overall costs." Said Sun.

To test the value of atmospheric sounding observations from UAVs, Dr. Sun, Professor Timo Vihma of the Finnish Meteorological Institute and other meteorologists, evaluated the ability of such sounding data to improve Antarctic weather forecasting. Their findings are published in Advances in Atmospheric Sciences.

They found that UAV sounding data can improve Antarctic weather forecasting to a certain extent, especially the prediction of temperature, wind speed, and humidity. Because the flight altitude of UAVs is generally below two kilometers, the improvement to the accuracy of meteorological prediction is mainly limited to the atmospheric boundary layer. Based on these experiments and studies, NMEFC plans to conduct more atmospheric sounding observation activities with UAVs in Antarctica, including aircraft meteorological observations over the Antarctic ice sheet and vertical structure observations of katabatic winds across the Ross Sea, Antarctica.

Credit: 
Institute of Atmospheric Physics, Chinese Academy of Sciences

Simple method for ceramic-based flexible electrolyte sheets for lithium metal batteries

video: Researchers at Tokyo Metropolitan University have developed a new method to make ceramic-based flexible electrolyte sheets for lithium metal batteries. They combined a garnet-type ceramic, a polymer binder, and an ionic liquid, producing a quasi-solid-state sheet electrolyte. The synthesis is carried out at room temperature, requiring significantly less energy than existing high-temperature (> 1000°C) processes. It functions over a wide range of temperatures, making it a promising electrolyte for batteries in e.g. electric vehicles.

Image: 
Tokyo Metropolitan University

Tokyo, Japan - Researchers at Tokyo Metropolitan University have developed a new method to make ceramic-based flexible electrolyte sheets for lithium metal batteries. They combined a garnet-type ceramic, a polymer binder, and an ionic liquid, producing a quasi-solid-state sheet electrolyte. The synthesis is carried out at room temperature, requiring significantly less energy than existing high-temperature (> 1000°C) processes. It functions over a wide range of temperatures, making it a promising electrolyte for batteries in e.g. electric vehicles.

Fossil fuels account for most of the world's energy needs, including the electricity we use. But fossil fuels are running out, and burning them also leads to the direct emission of carbon dioxide and other pollutants like toxic nitrogen oxides into the atmosphere. There is a global demand to shift to cleaner renewable energy sources. But major sources of renewable energy like wind and solar power are often intermittent - the wind does not blow all the time and the sun does not shine at night. Advanced energy storage systems are thus required to use renewable, intermittent sources more effectively. Lithium ion batteries have had a profound impact on modern society, powering a wide range of portable electronics and appliances like cordless vacuum cleaners since their commercialization by Sony in 1991. But using these batteries in electric vehicles (EVs) still requires a substantial improvement in the capacity and safety of state-of-the-art Li-ion technology.

This has led to a renaissance of research interest in lithium metal batteries: lithium metal anodes have a much higher theoretical capacity than the graphite anodes in commercial use now. There are still technological hurdles associated with lithium metal anodes. In liquid-based batteries, for example, lithium dendrites (or arms) can grow which might short-circuit the battery and even lead to fires and explosions. That's where solid-state inorganic electrolytes have come in: they are significantly safer, and a garnet-type (type of structure) ceramic Li7La3Zr2O12, better known as LLZO, is now widely regarded as a promising solid-state electrolyte material for its high ionic conductivity and compatibility with Li metal. However, producing high-density LLZO electrolytes requires very high sintering temperatures, as high as 1200 °C. This is both energy inefficient and time-consuming, making large-scale production of LLZO electrolytes difficult. In addition, the poor physical contact between brittle LLZO electrolytes and the electrode materials usually results in high interfacial resistance, greatly limiting their application in all-solid-state Li-metal batteries.

Thus, a team led by Professor Kiyoshi Kanamura at Tokyo Metropolitan University set out to develop a flexible composite LLZO sheet electrolyte which can be made at room temperature. They cast a LLZO ceramic slurry onto a thin polymer substrate, like spreading butter on toast. After drying in a vacuum oven, the 75-micron thick sheet electrolyte was soaked in an ionic liquid (IL) to improve its ionic conductivity. ILs are salts which are liquid at room temperature, known to be highly conductive while being almost non-flammable and non-volatile. Inside the sheets, the IL successfully filled the microscopic gaps in the structure and bridged the LLZO particles, forming an efficient pathway for Li-ions. They also effectively reduced interfacial resistance at the cathode. On further investigation, they found that Li-ions diffused through both the IL and the LLZO particles in the structure, highlighting the role played by both. The synthesis is simple and suitable for industrial production: the whole process is carried out at room temperature without any need for high-temperature sintering.

Though challenges remain, the team say that the mechanical robustness and operability of the flexible composite sheet at a wide range of temperatures makes it a promising electrolyte for Li-metal batteries. The simplicity of this new synthesis method may mean that we will see high capacity lithium metal batteries on the market sooner than we think.

Credit: 
Tokyo Metropolitan University

A new strategy to create 2D magnetic order

image: (a) The transport measurements. (b) An atomically resolved electron microscopy image showing the anionic and cationic configuration of SrRuO3 grain boundary. The first principles calculations bridge the structure-property relation.

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©Science China Press

Grain boundaries, which are consist of periodic arrangement of structural units and generally recognized as a two-dimensional "phase", can exhibit novel properties that are not existed in the intrinsic bulk crystal. The altered continuity of atomic bonding at grain boundaries cause local chemical environment dramatically change at a few unit cells, subsequently alter local electrical activity, magnetic order or other physical properties. The effects of grain boundary on properties is even more significant in the complex oxides due to the substantial interactions between lattice and other order parameters. Therefore, such an inhomogeneity of materials with grain boundary may dominate the entire response in nanoscale devices and have garnered particular interest in designing novel functional devices.

The nature of structural defects is determined by the atomic arrangements. Correlating the properties of single defect-based device with its specific atomic structure is vital and prerequisite for the device application. However, experimentally revealing such a structure-property relation is very challenging due to the atomic-size and chemical and structural complexity of defects, especially for the perovskite oxides that contain multiple elements.

In a new research article published in the Beijing-based National Science Review, scientists at Peking university, Institute of Physics, Chinese Academy of Sciences, and Tianjin University present atomic mechanism of spin-valve magnetoresistance at the asymmetry SrRuO3 grain boundary. The asymmetry atomic structure is very different from the common assumption based on prototype perovskite SrTiO3. The transport measurements exhibit the spin-valve magnetoresistance for the as fabricated centimeter-size and sub-nm-width Σ5(310) SrRuO3 grain boundary. Advanced scanning transmission electron microscopy and spectroscopy reveal its atomic arrangements based on which the first principles calculations reveal its electronic properties. Scientists find that owing to the Ru-O octahedron distortion near the asymmetric grain boundary, Ru d orbital reconstructs and results in reduction of magnetic moments and change of spin polarization along the grain boundary, forming a magnetic/nonmagnetic/magnetic junction. The calculations bridge the atomic structure with transport properties.

"Our findings can help us to understand the past transport properties such as the negative magnetoresistance and absence of tunneling magnetoresistance at the SrRuO3 grain boundary, and also predict new effects of SrRuO3 grain boundary such as the interfacial magnetoelectric coupling when SrRuO3 is used as a bottom electrode for growth of ferroelectric thin films." Prof. Peng Gao said, "In a broader perspective, control of defect structure at atomic scale can realize peculiar physical properties, providing us a new strategy to design devices with new low-dimensional magnetic properties by using boundary engineering."

This work was supported by the National Key R&D Program of China (2016YFA0300804), National Equipment Program of China (ZDYZ2015-1), National Natural Science Foundation of China (51672007 and 11974023), the Key-Area Research and Development Program of GuangDong Province (No. 2018B030327001?2018B010109009) and "2011 Program" Peking-Tsinghua-IOP Collaborative Innovation Center of Quantum Matter. Project was also supported by State Key Laboratory of Powder Metallurgy, Central South University, Changsha, China

Credit: 
Science China Press

New paper points out flaw in Rubber Hand Illusion raising tough questions for psychology

image: A demonstration of the Rubber Hand Illusion.

Image: 
University of Sussex

A world-famous psychological experiment used to help explain the brain's understanding of the body, as well as scores of clinical disorders, has been dismissed as not fit-for-purpose in a new academic paper from the University of Sussex.

The Rubber Hand Illusion, where synchronous brush strokes on a participant's concealed hand and a visible fake hand can give the impression of illusory sensations of touch and of ownership of the fake hand, has been cited in more than 5,000 articles since it was first documented more than 20 years ago.

In a new research paper Dr Peter Lush, Research Fellow at the Sackler Centre for Consciousness Science at the University of Sussex, demonstrates that the control conditions typically used in the Rubber Hand Illusion do not do they job they need to do.

His results show that the commonly reported effects of the Rubber Hand Illusion can be attributed to imaginative suggestion' - otherwise known as 'hypnosis'.

Dr Lush is calling for the development of valid control methods for the Rubber Hand Illusion while raising the prospect that suggestion effects could confound many other effects throughout psychological science.

He said: "The Rubber Hand Illusion is a cornerstone of contemporary consciousness science. It has been extended to almost any body part imaginable and investigated in just about any clinical disorder you can imagine.

"This paper prompts the reinterpretation of all this work, and other work which uses the same control methods, such as the full body illusion, the out of body illusion and the enfacement illusion. Existing claims that the rubber hand illusion is not a suggestion effect are invalid, and therefore it is possible that existing reports of the rubber hand illusion are entirely attributable to suggestion effects."

Last year Dr Lush and colleagues reported in a paper, currently under peer review but available as a preprint on PsyArxiv, substantial correlations between response to the Rubber Hand Illusion and response to imaginative suggestion , or phenomenological control, in a large sample of 353 participants. This study shows that response to the Rubber Hand Illusion is, partially or entirely a suggestion effect.

Psychologists have long been aware of the dangers of 'demand characteristics' - in which subjects, often without realising it, say what they implicitly think they ought to say.

Dr Lush's work takes these concerns much further by showing that how suggestible someone is can dramatically influence what people report in the Rubber Hand Illusion - and potentially in many other experiments too.

Dr Lush said: "The extent to which phenomenological control confounds psychological science is currently unknown, but may be substantial. If the effects are widespread - and they may well be - psychology will be faced with a new crisis of generalisability."

In the new study, published this week in Collabra: Psychology, an innovative design was employed to test imaginative suggestion in rubber hand illusion reports.

Participants were provided with information about the Rubber Hand Illusion procedure (including a text description and a minute-long video demonstration of the illusion) and then asked to fill out a standard questionnaire on what they would expect to happen if they were a participant in the procedure.

Strikingly, people expect the same pattern of results that is typically found in Rubber Hand Illusion studies, both for the 'experimental' conditions and the 'control' conditions.

According to Dr Lush, this means the control methods that have been used for 22 years of Rubber Hand Iillusion studies, are not fit for purpose because demand characteristics have not been adequately controlled, meaning the illusion may be, partially or entirely, a suggestion effect.

He added: "Few contemporary scientists seem to be aware of the extent to which imaginative suggestion can drive experience, and so haven't been able to control for suggestion effects in the Rubber Hand Illusion.

"Future studies of the Rubber Hand Illusion - and many other similar effects - will need to take individual differences in suggestibility properly into account, if they are to make justifiable claims about how people experience their bodies."

Credit: 
University of Sussex

Development of new photovoltaic commercialization technology

image: Illustration of stable initial PCE under the actual operating environment of PV devices with the deployment of KI.

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DGIST

A technology to further accelerate the commercialization of Colloidal Quantum Dot(CQD) Photovoltaic(PV) devices, which are expected to be next-generation photovoltaic devices, has been developed.

On the 30th (Monday), DGIST announced that a research team of Professor Jongmin Choi from the Department of Energy Science & Engineering and Professor Edward H. Sargent from the University of Toronto has identified the cause of the performance degradation in CQD PV devices and developed a material processing method capable of stabilizing the performance of the devices.

Quantum dots have excellent light absorbance and are capable of absorbing light over a wide range of wavelengths. Hence, they have gained expectation as a key material for the next generation photovoltaic devices. In particular, quantum dots are light, flexible, and involve low processing costs; therefore, they can be replaced by supplementing the drawbacks of silicon solar cells currently in use

In this regard, several studies on photoelectric conversion efficiency (PCE) have been conducted with the aim of improving the performance of CQD PV devices. However, very few studies have focused on improving the stability of these devices, which is necessary for the commercialization process. In particular, few studies have used the CQD PV device at the Maximum Power Point, which is the actual operating environment of PV devices.

For this purpose, the research team investigated the causes of performance degradation by continuously exposing them to illumination and oxygen for long periods of time, similar to the actual operating conditions, in order to improve the stability required for the actual commercialization stage of CQD PV devices. As a result, it was identified that the iodine ions on the surface of the quantum dot solids were removed via oxidation, resulting in the formation of an oxide layer. This oxide layer resulted in the deformation of the quantum dot structure, thereby decreasing the efficiency of the device.

The research team developed a ligand substitution method with potassium(K) to improve the low efficiency of the device. Ligand refers to the ions or molecules that bond to the central atom of a complex similar to a branch. Here, potassium iodide, which prevents the oxidation of iodine, was deployed on the surface of quantum dot solids to undergo a substitution process. As a result of application of the invented method, the device maintained its continuous performance rate of over 80%, which is its initial efficiency rate, for 300 hours. This number is a figure that is higher than premeasured performance thus far.

Professor Jongmin Choi from DGIST said, "The study is to demonstrate that the CQD PV device can operate more stably in the actual operating environment," and further commented, "The results are expected to further accelerate the commercialization of the CQD PV device. "

The results of this study were published on February 20, in a world-leading, international academic journal Advanced Materials (IF = 25.809). Professor Jongmin Choi from the Energy Science & Engineering Department of DGIST participated in this study as the lead author.

Credit: 
DGIST (Daegu Gyeongbuk Institute of Science and Technology)

Light driven proton pump in distant relative

image: Asgard archaea containing schizorhodopsin cannot be cultured so Escherichia coli was used.

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© 2020 IDKlab CC BY-SA 4.0

Researchers investigated the group of microorganisms classified as Asgard archaea, and found a protein in their membrane which acts as a miniature light-activated pump. The schizorhodopsin protein draws protons into the organisms' body. This research could lead to new biomolecular tools to control the pH in cells or microorganisms, and possibly more.

Asgard archaea are relatively new to science, but they are ancient and important to us in more ways than one. They are single-celled organisms and were originally found at the bottom of the ocean. Asgard archaea are what are known as a prokaryote, they do not have a cell nucleus, yet despite this, they are genetically close to single-celled organisms called eukaryotes which do contain a cell nucleus. They are like a modern analogue of an ancient common ancestor.

The race is on to investigate these small but significant organisms. Associate Professor Keiichi Inoue from the Institute for Solid State Physics at the University of Tokyo, Professor Hideki Kandori from Nagoya Institute of Technology and their team chose to study a feature of Asgard archaea that although not unique to them, is especially interesting in their case, and that is light-sensitive or photoreceptive proteins called rhodopsins. The organisms live at the bottom of oceans and lakes so it's surprising they need any kind of sensitivity to light.

"We explored the molecular function of special rhodopsins in Asgard archaea called schizorhodopsins and found that they acted as light-activated microscopic pumps," explained Inoue. "Schizorhodopsin uses sunlight energy to take up a proton into the cell along a pathway inside the protein. Many prokaryotes such as bacteria and other archaea use rhodopsins to pump protons out, but we find this newly characterized form in Asgard archaea particularly interesting."

As the scale this function occurs on is nanoscopic, sophisticated measurement techniques with high sensitivity and high temporal resolution were required. Inoue, Kandori and their team used a method called laser flash photolysis which uses pulsed laser light to stimulate reactions. Color change in the protein affected by laser light was monitored by sensitive sensors. These detected the presence and nature of the short-lived activation of schizorhodopsin.

"These findings will help us better understand proton and other ion transport mechanisms. In addition, schizorhodopsin could be made into a useful molecular tool for researchers," commented Inoue. "For example in optogenetics, which is a new methodology to control various cellular phenomena with light. Schizorhodopsins could also be used to control the pH inside cells or microorganisms with light, as pH can be altered by changing the proton concentration."

Credit: 
University of Tokyo