Tech

It is safe to say that 3D displays do not necessarily occur in nature - unless one considers the cephalopod, which includes the squid and octopus, as a living 3D display which can morph its structure and create complex shapes and textures for camouflage purposes or drag control (see video). Now, a research team from the University of Iowa and the University of Illinois at Urbana-Champaign is developing a smart skin inspired by the cephalopod which can be used in 3D displays, as interfaces for the visually impaired, and to help reduce drag on marine vehicles.

In a study published in Advanced Materials Technologies, the team, led by Caterina Lamuta, assistant professor of mechanical engineering at the University of Iowa, as well as Sameh Tawfick and Nancy Sottos, professors at the University of Illinois at Urbana-Champaign, found that using twisted and coiled polymer fibers to create artificial muscles could produce lightweight smart skins that are capable of fine motion and shape modulation.

In cephalopods, voxels are controlled by the animal's papillae muscles which allow their skin to take numerous forms, protrude outward, and take new shapes in fractions of seconds (see video, see video). The team took inspiration from the cephalopods' papillae to reproduce digital texture voxels (DTVs) from twisted spiral artificial muscles (TSAMs). With an input voltage of only 0.2 V/cm, TSAMs provide a stroke of 2000% and a roughness profile ranging from a few microns to one centimeter. "These lightweight twisted spiral artificial muscles hold the potential to replace heavy and bulky devices based on conventional electric and pneumatic actuators," said Lamuta. "We actuate this skin using small electrical impulses instead of heavy power sources and noisy air compressors, which allows for more precise movement and general ease of use."

An array of individually controlled TSAMs is embedded into a soft material to reproduce a soft, stretchable, and smart skin, able to perform a potentially unlimited number of output textures and shapes (see video). "The DTVs provide what we call on-demand textures and patterns," said Lamuta. "Because our DTVs are so lightweight and flexible, we believe that their use can pave the way for several applications, ranging from the hydrodynamic drag control of underwater vehicles and robots, to the development of 3D displays and haptic feedback devices for virtual reality and robotic surgery".

Lamuta and her team's work was supported by the Beckman Institute for Advanced Science and Technologies at the University of Illinois Urbana?Champaign, the United States Office of Naval Research, the National Science Foundation, and United States Air Force.

The paper, "Digital Texture Voxels for Stretchable Morphing Skin Applications" can be found here.

How our brain cells, or neurons, use electrical signals to communicate and coordinate for higher brain function is one of the biggest questions in all of science.

For decades, researchers have used electrodes to listen in on and record these signals. The patch clamp electrode, an electrode in a thin glass tube, revolutionized neurobiology in the 1970's with its ability to penetrate a neuron and to record quiet but telltale synaptic signals from inside the cell. But this tool lacks the ability to record a neuronal network; it can measure only about 10 cells in parallel.

Now, researchers from Harvard University have developed an electronic chip that can perform high-sensitivity intracellular recording from thousands of connected neurons simultaneously. This breakthrough allowed them to map synaptic connectivity at an unprecedented level, identifying hundreds of synaptic connections.

"Our combination of the sensitivity and parallelism can benefit fundamental and applied neurobiology alike, including functional connectome construction and high-throughput electrophysiological screening," said Hongkun Park, Mark Hyman Jr. Professor of Chemistry and Professor of Physics, and co-senior author of the paper.

"The mapping of the biological synaptic network enabled by this long sought-after parallelization of intracellular recording also can provide a new strategy for machine intelligence to build next-generation artificial neural network and neuromorphic processors," said Donhee Ham, Gordon McKay Professor of Applied Physics and Electrical Engineering at the John A. Paulson School of Engineering and Applied Sciences (SEAS), and co-senior author of the paper.

The research is described in Nature Biomedical Engineering.

The researchers developed the electronic chip using the same fabrication technology as computer microprocessors. The chip features a dense array of vertically-standing nanometer-scale electrodes on its surface, which are operated by the underlying high-precision integrated circuit. Coated with platinum powder, each nanoelectrode has a rough surface texture, which improves its ability to pass signals.

Neurons are cultured directly on the chip. The integrated circuit sends a current to each coupled neuron through the nanoelectrode to open tiny holes in its membrane, creating an intracellular access. Simultaneously, the same integrated circuit also amplifies the voltage signals from the neuron picked up by the nanoelectrode through the holes.

"In this way we combined the high sensitivity of intracellular recording and the parallelism of the modern electronic chip," said Jeffrey Abbott, a postdoctoral fellow in the Department of Chemistry and Chemical Biology and SEAS, and the first author of the paper.

In experiments, the array intracellularly recorded more than 1,700 rat neurons. Just 20 minutes of recording gave researchers a never-before-seen look at the neuronal network and allowed them to map more than 300 synaptic connections.

"We also used this high-throughput, high-precision chip to measure the effects of drugs on synaptic connections across the rat neuronal network, and now we are developing a wafer-scale system for high-throughput drug screening for neurological disorders such as schizophrenia, Parkinson's disease, autism, Alzheimer's disease, and addiction," said Abbott.

Satellite imagery can be used to peer inside a storm as well as assess the storm's outside shape to give forecasters understanding of what's happening to it. NASA-NOAA's Suomi NPP satellite provided forecasters with a visible image of a less-organized Karen after it moved into the Caribbean Sea and encountered wind shear.

On Sunday, Sept. 22 at 5 a.m. EDT, NOAA's National Hurricane Center said that Tropical Storm Karen formed just east of the Windward Islands. Twelve hours later, it had moved into the Caribbean Sea.

The shape of a tropical cyclone provides forecasters with an idea of its organization and strength. Imagery from Suomi NPP showed Karen had become less organized after it moved west from the Atlantic Ocean into the southeastern Caribbean Sea.

When outside winds batter a storm, it can change the shape of it and push much of the associated clouds and rain to one side of it. That's what wind shear does. Karen encountered northeasterly wind shear when it moved into the Caribbean Sea and those winds continued to affect Karen on Sept. 23.

In general, wind shear is a measure of how the speed and direction of winds change with altitude. Tropical cyclones are like rotating cylinders of winds. Each level needs to be stacked on top each other vertically in order for the storm to maintain strength or intensify. Wind shear occurs when winds at different levels of the atmosphere push against the rotating cylinder of winds, weakening the rotation by pushing it apart at different levels.

The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard Suomi NPP provided a visible image of Karen on Sept. 22. The Suomi NPP image revealed that the structure of Karen's thunderstorms continued to lose organization during the afternoon hours and that the center become exposed to the north and northwest of the band of thunderstorms.

NOAA's National Hurricane Center or NHC noted on Sept. 23 that despite Karen's disorganized appearance, it is expected to bring heavy rains and gusty winds to Puerto Rico and the Virgin Islands. A Tropical Storm Warning is in effect for the U.S. Virgin Islands, Puerto Rico, including Vieques and Culebra, and British Virgin Islands.

At 11 a.m. EDT (1500 UTC), the center of Tropical Storm Karen was located near latitude 14.9 degrees north, and longitude 64.8 degrees west. Karen was about 255 miles (415 km) south-southeast of San Juan, Puerto Rico. Karen is moving toward the north-northwest near 12 mph (19 km/h), and this general motion is forecast to continue today. A turn toward the north is expected by Tuesday. Maximum sustained winds are near 40 mph (65 kph) with higher gusts. Little overall change in strength is forecast during the next 48 hours. Tropical-storm-force winds extend outward up to 105 miles (165 km) from the center. The estimated minimum central pressure is 1007 millibars.

On the forecast track, the center of Karen will pass near or over Puerto Rico and the Virgin Islands Tuesday morning, Sept. 24. Karen will move over the western Atlantic to the north of Puerto Rico on Tuesday night and Wednesday.

Hurricanes are the most powerful weather event on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

For updated forecasts. visit: http://www.nhc.noaa.gov

NASA-NOAA's Suomi NPP satellite imagery revealed that Tropical Storm Kiko had a tight circulation center.

The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard Suomi NPP provided a visible image of Kiko on Sept. 22 that revealed the storm consisted of a tight circulation of low clouds with intermittent bursts of deep convection. The VIIRS image showed some powerful storms circled the low-level center and a large band of thunderstorms were located over the northern quadrant of the storm.

By early on Sept. 23, Kiko's structure had improved on satellite imagery.

NOAA's National Hurricane Center or NHC said, "At 11 a.m. EDT (1500 UTC) on Sept. 23 the center of Tropical Storm Kiko was located near latitude 15.7 north, longitude 135.8 west.

That is about 1,755 miles (2,825 km) west-southwest of the southern tip of Baja California, Mexico.  Kiko is moving toward the west-northwest at near 8 mph (13 km/h). This general motion is expected today, followed by a turn toward the northwest on Tuesday. Kiko could begin to turn back toward the west in a few days as it weakens. Maximum sustained winds are near 50 mph (85 kph) with higher gusts. The estimated minimum central pressure is 1002 millibars.

NHC said some additional strengthening is possible today, but weakening is forecast to begin by Tuesday and Kiko is forecast to become a remnant low later this week.

Hurricanes are the most powerful weather event on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

For updated forecasts. visit: http://www.nhc.noaa.gov

As scientists observe the force of nature through a satellite weather tracker, they only see the day's events. To observe the long-term atmospheric influence, University of Cincinnati geologists are taking research a step further by tracking and measuring the distribution of sulfur in plants in the Caribbean island of Trinidad.

A new study out of the University of Cincinnati suggests that coastal proximity, rain and prevailing wind direction can all influence the distribution of marine sulfur on land. While science has known for decades that sulfur is a useful method for tracking diet and mobility, UC researchers say the combined effects of wind and precipitation like rain and ocean spray hasn't been fully investigated before.

Their results, also aligning closely with patterns reported for soils and precipitation in the Mediterranean and Pacific Islands, demonstrate that plants in coastal settings are utilizing marine-derived sulfur.

"What makes our study unique is that we were able to show quite clearly how the spatial distribution of sulfur isotopes in vegetation is related to not just coastal proximity, but also wind and rain," says Brooke Crowley, UC associate professor of geology and anthropology. "And we have shown that these spatial patterns are detectable in vegetation.

"This information may aid researchers in tracking not only the origin of human resources and the movement of animals but also sulfur emissions from human activities within the Caribbean."

Chemical sleuths

Crowley and Janine Sparks, a UC doctoral student in geology at the time and first author on the study's publication, joined researchers at the University of the West Indies to measure sulfur isotope levels from wind-blown ocean spray on Trinidad's weedy native plants.

"We looked at the sulfur content in plants found across the island of Trinidad to see how windward coastal locations compared to inland and leeward wind coastal areas," says Crowley.

The study, published in Applied Geochemistry, described some interesting findings. Along windward coastlines with the most torrential rain and strongest winds blowing off the ocean, the chemical detectives found what they expected -- the highest concentrations of marine-derived sulfur.

"But in the middle of the island, there was not as much as we thought we would see," says Sparks, now a laboratory manager in the Department of Earth, Atmospheric and Planetary Sciences at Purdue University. "Levels started dropping off between 1.5 to 10 kilometers inland.

"We based our expectations on a previous study other researchers performed on sheep's wool in Ireland. There they found a higher content of marine sulfur on sheep near the coast but almost as high a content level for sheep who lived 100 kilometers inland from the windy coast."

While sheep obvously travel more than plants, Sparks says the high content of marine-derived sulfur on inland sheep stems more from the environment than their movement. Unlike Trinidad's dense terrain, Ireland's lack of a diverse variety of plants, especially tall vegetation, and much stronger winds tend to carry the sulfur further inland in a very steady direction. This would enable the sea spray to travel farther without any windbreak.

The UC researchers' results were more similar to patterns reported for soils and precipitation in Japan and Hawaii. Like Trinidad, these islands are peppered with a lot of diverse vegetation and mountains, and marine-derived sulfur is only found up to 16 kilometers inland, "so we were not completely unique," Sparks adds.

'Reigning' sea spray

The results of this study, the researchers say, helped establish clear spatial patterns in the Carribbean because, although there have been other papers looking at sulfur isotopes in other parts of the planet, they may not be globally relevant. The researchers needed a baseline for what was going on regionally.

While focusing on wind direction and precipitation patterns across Trinidad's diverse terrain, they found differing oceanic sulfur signals between windward coasts blowing sea spray directly in from the ocean compared to coasts that are more leeward where wind is coming from across the island.

"If you travel from the east windward coast of Trinidad to the west coast there are obvious gradients. Within about 1.5 kilometers from the east coast, we see plant sulfur values that look just like marine sulfur," says Crowley. "The plants are using sulfur spray being blown in off the ocean, but there's also more rain there so we can't completely disentangle the influence of wind and rain -- they work in concert.

"On the leeward west coast, we don't see that. Coastal plants resemble plants further inland."

Human activities may be affecting these patterns, specifically. Emissions from oil refineries and vehicles appear to have a measurable influence, they found.

"Sulfur isotope values of plants near busy roads or urban centers are clearly affected by modern human influences," says Sparks. "Using these results and other modern datasets for reconstructions of the past, we need to acknowledge what sources would and would not have been present."

Faunal impact

In an associated study published prior to this one, Crowley and Sparks looked at carbon, nitrogen and sulfur isotope values in modern vegetation as well as land animal remains from three coastal archaeological sites in southwestern Trinidad.

Through a thorough understanding of the uneven distribution of sulfur isotope levels across the island, values found in vegetation can be used to track resource use, geographical origin and mobility of animals or people, says Crowley.

"After establishing what spatial variability is like for each of these isotope systems using plants, we can look at the mobility of organisms or where things are sourced," says Crowley. "For example, if the remains of a deer are recovered from a coastal location -- but have a low sulfur isotope value -- we know the deer must have come from further inland.

"It could have moved to its current location and died here or it may have been brought to the location by people. The important thing is that we can confirm it did not originate or live at the location where it was recovered. We can use this approach to investigate where people obtained their food in the past," she adds.

"We hope our studies will be of use for future ecological and archaeological research, not only for Trinidad but for the Greater Caribbean and other coastal or island systems around the world."

Many aspects of modern energy systems necessitate access to reliable water resources. The findings of a new study involving IIASA researchers shows that Developing Asia's long-term electricity generation plans - which relies heavily on coal power generation - could be significantly impacted by regional changes in the availability of water under climate change.

Thermal power plants that run on natural gas, nuclear power, and coal accounted for 75% of global electricity generation in 2017. Asia in particular, is highly dependent on coal power for electricity supply, and demand is expected to grow in coming years. These plants, however, generally need water for cooling, which is increasingly constraining their electricity output because of low water availability or high intake water temperatures - sometimes both. Although some regional regulations attempt to address the environmental impacts of current and future coal-fired power plants by banning the use of groundwater for cooling, limiting the construction of new power plants, and mandating the use of wet cooling towers, there are still a large number of coal power plants in the region's planning pipeline. This presents a problem, as population growth and economic development continue to drive both water scarcity and electricity demand in Asia. The effects of climate change are further exacerbating water shortages and increasing air and water temperatures, which has led experts to suggest that the usable capacity of thermal power generation could decrease globally by around 8-16% on average by the middle of the 21st century.

In their study published in the journal Energy and Environmental Science, researchers from IIASA, Ohio State University, the Institute for Integrated Energy Systems, and Utrecht University explored the extent to which current and future coal power plants in the region will be impacted by expected changes in the hydroclimate. This is the first study of this type and scale for the Asia region to use ultra-high-resolution hydrology to consider not only current, but also planned power plant capacity.

"We investigated the electricity planning problem in Developing Asia, where the rapid expansion of coal-fired power plants and low water availability co-exist with interdependencies that evolve with the makeup of the energy system and the climate. We used high-resolution hydro-climate simulations and datasets of the existing and planned power plants to quantify the water constraints on coal-fired electricity generation at the power-plant level under various climate and energy planning scenarios," explains Yaoping Wang, who started her work on the topic as part of the 2017 IIASA Young Scientists Summer Program. Wang received a Peccei award for her work at IIASA and is currently an assistant research professor at the University of Tennessee.

To simulate future hydrological conditions, the study employed climate scenarios that correspond to a 1.5°C, 2°C, and 3°C increase in global temperature above pre-industrial levels. The 1.5°C and 2°C warming scenarios are consistent with the temperature and mitigation targets of the Paris Agreement, while 3°C (or higher) warming is likely to happen if the current trajectory of greenhouse gas emissions continues. The researchers further implemented different scenarios of cooling system choice, evolution of the power generation fleet, and the deployment of CO2 capture and storage (CCS) technologies, that are consistent with 1.5°C, 2°C, and 3°C warming to understand the potential impacts of adaptation to water scarcity and CO2 emissions mitigation.

The results revealed local and daily variations in water constraints on thermal power generation. Coal-fired power plants in Mongolia, Southeast Asia, and parts of India and China, for instance, are projected to confront substantially greater water constraints under current electricity sector expansion plans, regardless of the implementation of CO2 capture technology that requires even more water.

The analysis further shows that the planned electricity generation capacity is inconsistent with current international climate policy of limiting warming to 2.0°C. Ironically, large numbers of these plants, and subsequently parts of the entire electricity grid, have their reliability impacted due to changing water availability and air temperatures in a warming climate. Although not covered in this study, power plant outages, due to cooling water unavailability at large units such as coal power plants, are known to have serious implications for grid stability and can increase electricity prices. Climate-adaptation options to reduce reliance on water can also increase costs, which would ultimately be passed on to consumers.

According to the researchers, development and climate change pressures in Asia are immense in terms of the scale of development required for a third of the world's population, who are mostly very vulnerable, and the severity of climate hazards that can be expected across Asia. This necessitates energy and water resource systems planning that can help mitigate the CO2 emissions from electricity generation that cause climate change and is also resilient to the already inevitable impacts of global warming that will occur at 1.5°C or 2.0°C of warming. The study highlights three possible strategies to mitigate water limitations namely, selectively reducing the existing/planned power plants in water-scarce regions; integrating electricity markets so that interregional electricity transmission can compensate for local water stress; and widely adopting dry cooling in northern Asia where the technology does not incur high losses in thermal efficiency.

"We know that coal power contributes significantly to global warming - more than almost any other electricity source, and what this study shows is that coal power development can expect reduced reliability in many locations across Asia. In addition to the other known negative impacts such as on air and water quality, this is further evidence of coal power's increasingly recognized incompatibility with current international and national climate and sustainable development policy," concludes study coauthor Edward Byers, a researcher with the IIASA Energy Program.

Versions of an antibiotic drug called DON first isolated from soil bacteria more than 60 years ago have shown promising signs of extending survival in mice models of especially lethal pediatric brain tumors marked by the high expression of a cancer-causing gene known as the MYC oncogene, according to results of two studies from researchers at the Johns Hopkins Kimmel Cancer Center.

The MYC-expressing subgroups of atypical teratoid/rhabdoid tumors and medulloblastoma, while rare, are especially aggressive, with a minority of patients surviving their disease, even with the use of intensive chemotherapy and radiation. The poor outcomes for patients have brought urgency, scientists say, to the search for new ways to treat the cancers in conjunction with current therapies such as surgery, chemotherapy and radiation therapy. The new findings, they say, suggest that the altered metabolism of an amino acid in these tumors needed to make proteins and energy for the cancer cell could be a productive target for clinicians.

Tumors with high MYC expression have increased metabolism of the key amino acid glutamine, the scientists say. By inhibiting glutamine metabolism with DON or a so-called "prodrug" version of it that converts to DON in the brain, the researchers were able to extend survival times by more than 30% in mice transplanted with these human cancer cells. DON was first isolated in 1956 from bacteria in soil found in Peru, and its ability to block glutamine has long made it a candidate for cancer therapy, but it was never systematically tested against high-MYC-expressing cancers.

For the current experiments, the Johns Hopkins scientists gave a weekly DON injection to mice bearing high-MYC-expressing AT/RT cell lines and extended the animals' median survival times from 21 to 36 days, and to 45 days when DON was combined with the chemotherapy drug carboplatin. The scientists performed metabolic experiments that showed that DON blocked glutamine from being made into glutathione, one of major detoxifying substances that cancer cells use to thwart carboplatin chemotherapy. DON depleted the cancer cells of glutathione, making carboplatin chemotherapy more effective.

In mice with MYC-expressing medulloblastoma who were treated twice weekly with JHU-083 by mouth, an experimental DON version designed to be better metabolized and less toxic in the brain and in development at Johns Hopkins Drug Discovery, median survival rose from 21 to 28 days in immune-deficient mice and 16 to 25 days in immune-competent mice.

Disrupting abnormal metabolism is targeting "an Achilles' heel that would hurt the cancer cells but not hurt the normal cells in the brain or body," said Eric Raabe, M.D., Ph.D., an associate professor of oncology at the Johns Hopkins University School of Medicine, who was a co-author on both papers and lead author of the paper on medulloblastoma published July 21 in Translational Oncology.

AT/RT, the most common malignant brain tumors in infancy, are usually treated with intensive chemotherapy and radiation. The median survival time is less than one year after diagnosis. Medulloblastoma is the most common malignant brain tumor of childhood, and is treated with surgical removal of the tumor, radiation and chemotherapy. The MYC subgroup of medulloblastoma (also known as "Group 3") has a particularly poor outcome, with fewer than 50% of the patients surviving more than five years after diagnosis. Similarly, the MYC subgroup of AT/RT is also associated with worse outcome. "They are the baddest of the bad players," says Jeffrey Rubens, M.D., an assistant professor of oncology and pediatrics at the Johns Hopkins University School of Medicine who led the study on AT/RT and DON published July 12 in Clinical Cancer Research. "They seem to be more aggressive, more resistant to chemotherapy, and lead to worse survival rates than other subgroups."

MYC is difficult to target directly with a drug, however. Its protein-binding site is "flat and featureless," says Rubens, "and it's hard to design a small molecule that will fit into it. We're trying to identify a drug that we can use to treat kids relatively soon."

To look for other vulnerabilities of MYC-driven tumors, Rubens and his colleagues analyzed the metabolic profiles of MYC-expressing AT/RT cell lines derived from patients, discovering that the cells were dependent on increased levels of glutamine metabolism for their survival.

To inhibit this metabolic pathway in the cancer, they turned to DON, not only because of its well-known characteristics, but also because it has already been tested for safety in a phase 1 pediatric cancer clinical trial in the 1980s.

"Our hope would be to someday add this drug to the standard therapy for AT/RT to decrease some of the chemotherapy resistance that we see and to help improve survival," says Rubens.

Rubens says this metabolic approach might also be used to identify tumors that are sensitive to DON therapy even before the tumor is biopsied. A technique called MRI spectroscopy can pinpoint peaks of glutamine production and its metabolic byproduct glutamate in brain tissue. When the MRI scans show a high ratio of glutamine to glutamate in tumors, they indicate that the cancer might be sensitive to DON, he says. "This could be important to know in patients who have relapsed," says Rubens, "where you might not want to perform another surgery."

In the Translational Oncology study, Raabe and colleagues used a twice-weekly oral dose of JHU-083, developed by Barbara Slusher, Ph.D., director of Johns Hopkins Drug Discovery, and colleagues at Johns Hopkins, in mice with MYC-driven medulloblastoma.

"The rationale for the development of so-called 'prodrugs' is to maximize the brain penetration of DON to the brain tumor and to minimize the side effects that would come from delivering DON peripherally," such as nausea and a lower white blood cell count, says Raabe.

Raabe says testing JHU-083 in mice with intact immune systems in the study was significant because these mice more closely resemble the immune environment in human patients. "If we can combine JHU-083 or other DON prodrugs with other drugs that we think work with medulloblastoma, or other drugs that we identify through metabolic analysis, we hope to be able to further extend the survival of these mice," Raabe says.

Looking ahead, the researchers plan to learn more about the best time to add DON to a therapeutic regimen and how well JHU-083 and other DON prodrugs might pair with other drugs used to treat pediatric brain cancers.

"The initial efficacy that we show of DON prodrugs in these tumors is encouraging," says Raabe, "and leads us to believe that we will be able to further improve the survival of laboratory mice bearing aggressive MYC medulloblastoma."

Researchers from CRG and IBEC in Barcelona use a technique called high-throughput mutagenesis to study Amyotrophic Lateral Sclerosis (ALS), with unexpected results.

Results showed that aggregation of TDP-43 is not harmful but actually protects cells, changing our understanding of ALS and opening the door to radically new therapeutic approaches.

Amyotrophic lateral sclerosis (ALS) is a devastating and incurable nervous system disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control and normally death within a few years of diagnosis. In ALS, like in other neurodegenerative diseases, specific protein aggregates have long been recogniSed as the pathological hallmarks, but it is not clear whether they represent the actual cause of the disease. Indeed, alleviating aggregation has repeatedly failed as a therapeutic strategy when trying to treat neurodegenerative diseases such as Alzheimer's disease.

In order to cast more light on this issue, researchers at the Center of Genomic Regulation (CRG) and the Institute of Bioengineering of Catalonia (IBEC) have applied a novel approach called deep mutagenesis, with unexpected results. "By studying all possible mutations in a protein, we have a much more reliable way to understand toxicity and we are excited to move on to many more proteins implicated in neurodegenerative diseases", says Benedetta Bolognesi, IBEC researcher, CRG Alumni, and first author of the paper.

In a collaboration between the labs of ICREA research professors Ben Lehner and Gian Tartaglia, Benedetta Bolognesi and Andre J. Faure focused on TDP-43, a protein that aggregates in the motor neurons of nearly all ALS patients. They made over 50,000 mutants of TDP-43 and tracked their toxicity to yeast cells. Researchers found that mutant forms that aggregated were actually less toxic than other versions of the protein which instead were forming unusual liquid species in the cells. "This is the exact opposite of what we expected," Lehner says, and challenges a lot of the assumptions in this field.

It still remains to be established whether aggregation of TDP-43 is also protective in mammalian cells and neurons, something Bolognesi is working on, but if this proves to be the case, it means we will have to entirely change the way we therapeutically address ALS if we want to have significant effects.

Diving seabirds watch each other to work out when to dive, new research shows.

Scientists studied European shags and found they were twice as likely to dive after seeing a fellow bird go underwater.

The study is the first to investigate why large groups (known as "rafts") of shags dive together at sea.

University of Exeter scientists filmed the birds off the Isles of Scilly to examine their behaviour.

"Our results suggest these birds aren't just reacting to underwater cues when deciding where and when to dive," said Dr Julian Evans, who led the study as part of his PhD at the University of Exeter.

"They respond to social cues by watching their fellow birds and copying their behaviour.

"They're essentially using other flock members as sources of information, helping them choose the best place to find fish."

This behaviour might bring various benefits, and more research is needed to fully understand it.

"Watching other birds could help shags save energy by reducing the need for uninformed sample dives," said Dr Evans.

"Diving in the same area as another bird might also be beneficial because the prey might be disorganised, pushed into certain areas or fatigued by previous divers."

Dr Evans said it was important to understand the behaviour of European shags because they - like most seabird species - are under "great pressure" due to declining fish stocks, climate change and habitat loss.

An international research team has observed in real time how football molecules made of carbon atoms burst in the beam of an X-ray laser. The study shows the temporal course of the bursting process, which takes less than a trillionth of a second, and is important for the analysis of sensitive proteins and other biomolecules, which are also frequently studied using bright X-ray laser flashes. The football molecules disintegrate more slowly and differently than expected, as the team around Nora Berrah from the University of Connecticut and Robin Santra from DESY report in the journal Nature Physics. This observation contributes to a more detailed protein analysis with X-ray free-electron lasers (XFEL).

The researchers had experimented with buckminster fullerenes, or buckyballs for short. These spherical molecules consist of 60 carbon atoms arranged in alternating pentagons and hexagons like the leather coat of a football. "Buckyballs are well suited as a simple model system for biomolecules," explains Santra, who is a Lead Scientist at DESY at the Center for Free-Electron Laser Science (CFEL) and a physics professor at the Universität Hamburg. "Since they consist of only one type of atom and have a symmetrical structure, they can be well represented in theory and experiment. This is a first step before the investigation of molecules from different types of atoms."

Using the X-ray laser LCLS (Linac Coherent Light Source) at the SLAC National Accelerator Laboratory in California, the scientists shot short X-ray flashes of about 20 femtoseconds (quadrillionths of a second) duration at individual football molecules and observed their effect in real time with a temporal resolution in the range of about ten femtoseconds. The data show that the X-ray flash knocks electrons out of about one in five of the 60 carbon atoms. "After that, nothing happens for some time. Only after a few dozen femtoseconds do carbon atoms gradually detach from the molecule," reports Santra.

"What follows then is not an actual explosion," explains the scientist. "Instead, the buckyballs disintegrate comparatively slowly. Carbon atoms gradually evaporate - with many more neutral ones than electrically charged ones, which was surprising." Since the fragmentation of the buckyballs on this time scale is not explosive but happens gradually, the researchers speak of the evaporation of the atoms. The experimental data could only be meaningfully interpreted with the help of theoretical modelling of the process.

"Typically, about 25 neutral and only 15 electrically charged carbon atoms fly out of the molecule," Santra explains. "The rest form fragments of several atoms." The whole process takes about 600 femtoseconds. This is still unimaginably short by human standards, but extremely long for structural analysis with X-ray lasers. "In the typically 20 femtoseconds of an X-ray laser flash, the atoms move a maximum of 0.1 nanometers - that is in the range of individual atom diameters and smaller than the measurement accuracy of structural analysis." One nanometer is one millionth of a millimeter.

For the structural analysis of proteins, researchers usually grow small crystals from the biomolecules. The bright X-ray laser flash is then diffracted at the crystal lattice and generates a typical diffraction pattern from which the crystal structure and with it the spatial structure of the individual proteins can be calculated. The spatial structure of a protein reveals details about its exact function. The protein crystals are very sensitive and evaporate through the X-ray laser flash. However, previous investigations had shown that the crystal remains intact long enough to generate the diffraction image before evaporation and thus to reveal its spatial structure.

The new study now confirms that this is also the case with individual molecules that are not bound in a crystal lattice. "Our findings with buckyballs are likely to play a role in most other molecules," Santra emphasises. Since many biomolecules are notoriously difficult to crystallise, researchers hope to be able to determine the structure of ensembles of non-crystallised proteins or even individual biomolecules with X-ray lasers in the future. The results obtained now lay the foundation for a deeper understanding and quantitative modelling of the radiation damage in biomolecules induced by X-ray laser flashes, the scientists write.

Porto Alegre, Brazil 21 Sept 2019: Encouraging activity and improving diet in children is crucial to cut deaths from cardiovascular disease - and is the focus of an innovative school project in São Paulo, Brazil. The first results are presented today at the Brazilian Congress of Cardiology (SBC 2019).

The annual congress of the Brazilian Society of Cardiology (SBC) is held 20 to 22 September in Porto Alegre. The European Society of Cardiology (ESC) is holding scientific sessions in collaboration with the SBC as part of the ESC Global Activities programme.1

"Atherosclerosis - clogged arteries - starts in childhood and is more likely with a sedentary lifestyle and unhealthy diet," said study author Dr Karine Turke, of ABC Medical School, São Paulo. "Exposure to these behaviours throughout life increases the risk of heart attacks and strokes, so prevention should begin in childhood. Yet children are sitting more, eating processed foods, and obesity is becoming the norm."

Cardiovascular disease is the world's number one killer, causing 17.9 million deaths a year. In Brazil alone, around 370,000 lives are lost to cardiovascular diseases annually. The World Health Organization (WHO) estimates that the number of overweight or obese infants and young children rose from 32 million globally in 1990 to 41 million in 2016.2 Around 3.2 million deaths each year are due to insufficient physical activity.3

The SBC Goes to School project4 is set to enlist 3,000 monitors (teachers and students) to receive cardiovascular education. Monitors will then teach 63,000 students aged 6 to 18 from 210 public schools in the state of São Paulo. The first teaching is on School Heart Day, held 25 September 2019, when students will also have baseline measurements of diet and activity. This will be followed by further education and monitoring of diet and activity levels.

Cardiovascular education will address seven risk factors (physical inactivity, obesity, smoking/other drugs, dyslipidaemia, high blood pressure, diabetes, and stress) and two protective factors: healthy eating and regular physical activity. Schools are expected to promote exercise and good eating habits. Input will be provided by numerous disciplines, including cardiologists, nurses, teachers, and psychologists.

The pilot project presented today shows baseline results in the first 433 students. The median age was 13 years and 51% were male. The median time spent doing mild, moderate and vigorous physical activity over one week was 40, 60 and 60 minutes respectively. The median sitting time was 360 minutes per week.

"Physical activity is well below the level recommended by the WHO, which is 300 minutes per week for children and adolescents," said Dr Turke. "Modern lifestyles promote interaction by mobile phone and video games. There is less security on the streets so children cannot play outside. The programme encourages less sedentary time and finding ways to move around more."

Regarding food, 53% had consumed leafy vegetables the previous day, 69% fruit, 91% carbohydrates like rice or pasta, 70% legumes, 79% meat/chicken, 42% soft drinks/sodas, 39% chocolate, 39% powdered beverage mixes, 42% sausages, and 49% candy including chocolate or any sweets.

"Many had eaten processed foods, which are easier for parents to prepare than cooking from fresh ingredients," said Dr Turke. "Students will learn to classify foods as fresh, minimally processed, processed, and ultra-processed, and to prioritise fresh and minimally processed items."

She concluded: "Advocating the choice of healthy foods and greater activity is essential to halt the obesity crisis in Brazil and worldwide and stop needless deaths from heart attack and stroke."

Professor Dalton Précoma, scientific chair of SBC 2019, said: "The decline in death from cardiovascular disease in Brazil has plateaued, suggesting the need for novel strategies to combat these conditions. More than half of the population is overweight. To prevent cardiovascular disease, children and adolescents are advised to do moderate to vigorous physical activity every day and limit sedentary time.5 Parents should create an environment that promotes these behaviours and be role models. Healthy lifelong eating habits must be encouraged, such as family meals, eating breakfast and limiting fast foods."

Professor Carlos Aguiar, course director of the ESC programme at SBC 2019, said: "Improving lifestyles in children is a collective responsibility. Law makers should restrict marketing of junk foods and sugary drinks to children.6 Schools can provide fresh drinking water and healthy foods in cafeterias and vending machines and hold regular activity breaks. Communities need parks and playgrounds. These efforts and others should go a long way to reducing cardiovascular events in the long run."

The project is being run by the Brazilian Society of Cardiology's Committee of Children and Adolescents, with support from the São Paulo Society of Cardiology, the Department of Education of the state of São Paulo, and the department of cardiology at ABC Medical School. The programme is led by Dr Carla Lantieri, first author of the current abstract and a cardiologist at ABC Medical School.

Phoenix, Arizona, USA: Identifying geological features in a densely vegetated, steep, and rough terrain can be almost impossible. Imagery like LiDAR can help researchers see through the tree cover, but subtle landforms can often be missed by the human eye.

Now, a team of scientists has tapped into the power of machine learning to identify hidden geologic features. Specifically, the scientists are identifying previously unidentified cave entrances that are difficult to see in imagery, and hard to access on the ground.

Leila Donn, a doctoral student at the University of Texas at Austin and lead author of the new research, is presenting the results of her research on Sunday at The Geological Society of America's Annual Meeting in Phoenix.

The research was inspired in part by the lush, hard-to-access areas of tropical forests. "We saw the need to get LiDAR coverage for our deep tropical forest areas," says Timothy Beach, co-author of the research. "LiDAR imagery has been showing a lot of archaeology, but we also knew they could show a lot of new geology and a lot of new human-environmental interactions."

The project was also inspired by Donn's own field experiences. While helping a colleague look for cave entrances in Guatemala, they would find a spot that looked promising on the LiDAR imagery, then spend all day hiking to the location. "It was really fun, but really, really labor intensive," says Donn. And sometimes their day-long hike led to a spot that wasn't a cave at all -- a frustrating situation. "While we were out doing this, I thought, 'What if we could do this with machine learning?'" She explains that instead of the researchers picking out possible locations by eye, the computer would do the identification, revealing the most promising locations.

To test if machine learning could help them narrow in on interesting geology sites, Donn and Beach focused on an area in northwestern Belize that was heavily vegetated and difficult to access. They concentrated on finding cave entrances deep in the forest that had yet to be been uncovered.

Using the LiDAR imagery collected from a similar site with mapped caves, Donn plotted the location of known cave entrances, along with points that were not caves. She then collected information on the landscape, including slope, roughness of terrain, and distance to streams. This information was compiled into a spreadsheet and fed into the machine learning as a way to "teach the computer how to predict what is a cave and what isn't," says Donn.

Over the summer, Donn hacked through the jungle to ground-truth the areas where caves had been identified with machine learning. She confirmed that a number of previously unmapped cave entrances did indeed exist in the landscape, including a very large surprise.

"The coolest thing that we found was a sinkhole that was a collapsed cave complex," says Donn. She said that the find came after an incredibly hard hike through dense vegetation. Despite being 60 meters long, 30 meters wide, and 35 meters deep, "You couldn't see it until you were on top of it," she says.

When she was back in the lab, Donn said she went back to the LiDAR with fresh eyes to see if the cave entrance would now pop out of the imagery. "When I went back to the location and looked at the LiDAR, it was visible," she says, but she notes that without knowing it was there, she probably wouldn't have recognized it as a cave entrance. "The program found it for me."

Her machine learning also can pick up much smaller caves, says Donn. "One of them was a small cave with an entrance that was maybe a meter and a half long and just 30 feet deep." And on the LiDAR, she says that smaller cave was invisible to the naked eye.

Donn says her program can be used for geology studies, like finding and studying undiscovered caves. But she also sees applications for other disciplines like archaeology, forest management, urban development, and land management. "I see this having a future outside of academia," she says.

"What Leila is doing is an exciting connection between the history and the future of geosciences," says Beach. A project like this, he says, "comes from this ability to get into very difficult places that most of us can't get into, but also then this creative angle of making the machine learn how to do it too."

Imagine a world in which electricity could flow through the grid without any losses or where all the data in the world could be stored in the cloud without the need for power stations. This seems unimaginable but a path towards such a dream has opened with the discovery of a new family of materials with magical properties.

These materials - magnetic Weyl semi-metals - are innately quantum but bridge the two worlds of topology and spintronics. Topological materials exhibit strange properties including super-fast electrons that travel without any energy loss. On the other hand magnetic materials are essential to our everyday lives from magnets for electric cars to spintronic-devices in every hard disk drive in computers and in the cloud. The concept of a magnetic Weyl semi-metal (WSM) was in the air but a real life material has only just now been realized by the team of Claudia Felser, Director at the MPI CPfS, Dresden, in two very different compounds Co2MnGa and Co3Sn2S2. To find these extraordinary materials, Felser's team scanned the materials database and came up with a list of promising candidates [1-5]. The proof that these materials are magnetic WSMs was obtained via electronic structure investigations of Co2MnGa and Co3Sn2S2 [6-8]. Scientists from Claudia Felser's group at the MPI CPfS and Stuart Parkin's team at the MPI of Microstructure Physics, Halle, in collaboration with M. Zahid Hasan's team from Princeton, Yulin Chen's team from Oxford University, and Haim Beidenkopf's team from the Weizmann Institute of Science, have experimentally confirmed the existence of magnetic Weyl fermions in these two materials in studies that were published in three papers in Science Magazine today.

For the very first time, using angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscope (STM) experiments, time-reversal symmetry broken WSM states were observed, made possible by the high quality single crystals grown at the MPI CPfS. "The discovery of magnetic WSMs is a big step towards the realization of high temperature quantum and spintronic effects. These two materials, that are members of the highly tunable Heusler and Shandite families, respectively, are ideal platforms for various future applications in spintronic and magneto-optic technologies for data storage, and information processing as well as applications in energy conversion systems," says Stuart Parkin, the Managing Director of the Max Planck Institute of Microstructure Physics, Halle.

The magnetic topological states in Co2MnGa and Co3Sn2S2 play a crucial role in the origin of the observed anomalous quantum transport effects, due to the strong Berry curvature associated with their topological states. With Weyl nodal line and nodal point band structures, Co2MnGa and Co3Sn2S2 are the only two currently known examples of materials that host both large anomalous Hall conductivity and anomalous Hall angle [3, 4, 6]. "Our materials have the natural advantages of high order temperature, clear topological band structure, low charge carrier density, and strong electromagnetic response. The design of a material that exhibits a high temperature quantum anomalous Hall effect (QAHE) via quantum confinement of a magnetic WSM, and its integration into quantum devices is our next step," says Claudia Felser. The discovery of magnetic WSMs is a big step to the realization of a room temperature QAHE and is the basis for new energy conversion concepts "A Quantum Anomalous Hall effect enables dissipationless transport via chiral edge states that are innately spin-polarized." realized Yan Sun immediately. Realization of the QAHE at room temperature would be revolutionary by overcoming limitations of many of today's data based technologies, which are affected by large electron scattering-induced power loss. This would pave the way to a new generation of low energy consuming quantum electronic and spintronic devices.

They can make tiny cell structures visible: cutting-edge light microscopes offer resolutions of a few tenths of a nanometre--in other words, a millionth of a millimetre. Until now, super-resolution microscopes were much slower than conventional methods, because more or finer image data had to be recorded. Together with partners from Jena, researchers from Bielefeld University have now developed the super-resolution SR-SIM process further. The academics show that SR-SIM is also possible in real time and at a very high imaging rate--and thus suitable for observing movements of very small cell particles, for example. Their findings have been published today (20 September) in the journal "Nature Communications".

"This is what makes this type of microscopy really useful for applications in biology or medicine. The problem so far is that microscopes offering a sufficiently high resolution cannot display information at the corresponding speed," says Professor Dr Thomas Huser, who heads the Biomolecular Physics Working Group at Bielefeld University. The SR-SIM project is funded by the German Research Foundation (DFG) and the European Union through Marie Sk?odowska-Curie Actions.

SR-SIM stands for "super-resolution structured illumination microscopy" and is a fluorescence microscopy procedure. Objects are irradiated with laser light. This light excites special fluorescent molecules in the sample so that they re-emit light at a different wavelength. The microscopic image then shows the re-emitted light. "Unlike other conventional fluorescence microscopy methods, SR-SIM does not illuminate the specimens uniformly, but with a fine, grid-like pattern. This special technology enables much higher resolution," says Huser.

The procedure consists of two steps: the light re-emitted by the specimen is first recorded in several individual images. The finished image is then reconstructed on a computer from these raw data. "The second step, in particular, has cost a great deal of time so far," says Andreas Markwirth, also a member of Bielefeld University's Biomolecular Physics Working Group and lead author of the study. The Bielefeld researchers therefore worked together with Professor Dr Rainer Heintzmann from the Leibniz Institute for Photonic Technologies and the Friedrich Schiller University in Jena to speed up the process. The microscope is now designed to generate the raw data faster. In addition, image reconstruction takes considerably less time thanks to the use of parallel computer processing on modern graphics cards.

For their study, the researchers tested the new method on biological cells and recorded the movements of mitochondria, cell organelles about one micrometre in size. "We have been able to produce about 60 frames per second--a higher frame rate than cinema films. The time between measurement and image is less than 250 milliseconds, so the technology allows real-time recording," says Markwirth.

Up to now, super-resolution methods have often been combined with conventional methods: a conventional fast microscope is used to first find structures. These structures can then be examined in detail using a super-resolution microscope. "However, some structures are so small that they cannot be found with conventional microscopes, for example specific pores in liver cells. Our method is both high-resolution and fast, which enables biologists to explore such structures," says Huser. Another application for the new microscope is the study of viral particles on their way through the cell. "This enables us to understand exactly what happens during infection processes," says Huser. He expects the microscope to be used for such studies at Bielefeld University during the coming year.

Super-resolution microscopes have only been around for about 20 years. In 1873, Ernst Abbe had discovered that the resolution of an optical system for visible light is limited to about 250 nanometres. In recent years, however, several optical methods have been developed to break what has become known as Abbe's diffraction barrier. In 2014, William E. Moerner and Eric Betzig, both from the USA, as well as Stefan Hell from Germany were awarded the Nobel Prize in Chemistry for developing a super-resolution in the range of about 20 to 30 nanometres.

Additive manufacturing (AM), also known as three-dimensional printing, is a process that fabricates parts in a layer-by-layer manner by adding and processing materials. Advancements in AM technology have enabled the processing of a wide range of materials to create products in varying scales which span from medical implants to aircraft engine parts. These products, which can be rich in shape, material, hierarchical and functional complexities, offer high potential to revolutionize existing product development processes.

However, it can be a difficult process to fully realize the potential of AM's unique capabilities for product development as it requires product designers to change their design mindsets.

In conventional manufacturing processes, the main task for designers is tailoring their designs to eliminate manufacturing difficulties and minimize costs. On the contrary, AM has fewer manufacturing constraints while offering designers with much more design freedom to explore. Therefore, designers must search for optimal design solutions out of millions of design alternatives that are different in geometry, topology, structure, and material. This can be a tedious task with current design methods and computer-aided design (CAD) tools due to the lack of ability to rapidly explore and exploit such a high dimensional design space.

To address this issue, researchers from Digital Manufacturing and Design (DManD) Centre from the Singapore University of Technology and Design (SUTD) proposed a holistic approach that applies data-driven methods in design search and optimization at successive stages of a design process for AM products.

First, they used simple and computationally inexpensive surrogate models in the design exploration process to approximate and replace complex high-fidelity engineering analysis models for rapidly narrowing down the high-dimensional design space. Next, they conducted design optimization based on refined surrogate models to obtain a single optimal design. These surrogate models are trained based on an updated dataset using the Markov Chain Monte Carlo resampling method.

This design approach was demonstrated in the design of an AM fabricated ankle brace (refer to image) that has a tunable mechanical performance for facilitating the recovery process of joints. In this design, the researchers selected a metamaterial which has a horseshoe-like structure, where its stiffness can be tailored. The proposed design approach was applied to optimize the orientation and dimensions of the horseshoe-like structure's geometry in different areas to achieve desired stiffness distributions.

Such geometry complexities enabled by AM offer the ankle brace design unique and favorable behaviors. The ankle brace is very soft within the allowable range of motions which provides comfort to patients. However, once the movement is out of the permissible range, it becomes stiff enough to protect the users' joints from extreme load conditions due to its geometrical design.

"Previously, it was hard for designers to imagine a design of such complex geometry due to the limitations in conventional manufacturing, but now this design is easily achievable with AM. Our new approach allows designers to embrace the design freedom in AM that comes with the shift in design paradigm and create more optimal products similar to the ankle brace," said first author Dr. Yi Xiong, Research Fellow from SUTD.

With the design space exploration and exploitation capability developed, the research team is working towards a more ambitious goal - to develop a next-generation CAD system for AM.

"This CAD-AM system will enable designers to design complex geometric and material structures that exhibit behaviors that are unobtainable with conventional design and manufacturing tools. Designers can rapidly examine design alternatives 10 times more compared to what the current methods allow," said SUTD Professor David Rosen, lead of the research team and co-director of the DManD Centre.