Tech

A step forward in wearable robotics: Exosuit assists with both walking and running

A soft robotic exosuit - worn like a pair of shorts - can make both walking and running easier for the wearer, a new study reports. The self-contained, portable device, which weighs only 11 pounds, is capable of detecting the wearer's gait to provide the appropriate assistance, even in complex outdoor environments (see related video). It can reduce the metabolic cost of walking and running by 9.3% and 4.0%, respectively, the authors say - a range of improvement that has shown to be meaningful in athletic performance. While the biomechanics of walking and running are fundamentally different, the natural human body can rapidly switch between the two, resulting in a near-seamless transition between the gaits. However, developing robotic assistive devices that can provide benefits for both walking and running has been challenging, largely limiting research to augmentation of one or the other gait. Robotic exoskeletons, which mechanically augment the wearer's movement, have been shown to reduce the metabolic cost of walking to rates below normal biological levels. However, similar devices designed for assisted running have not been as successful, increasing metabolic cost in some cases due to the devices' weights. Jinsoo Kim and colleagues developed a functional robotic exosuit, consisting of a waist belt and two thigh wraps, and demonstrated its ability to reduce metabolic costs in both walking and running at different speeds and on challenging terrain. According to the authors, the observed metabolic reductions from wearing the suit are comparable to removing between 12 and 17 pounds from the wearer's waist. In a related Perspective, José Pons discusses how advancements like Kim et al.'s are paving the way for implantable, neurologically controlled assistive robotics of the future.

Credit: 
American Association for the Advancement of Science (AAAS)

Adults with mild cognitive impairment can learn and benefit from mindfulness meditation

There's currently no known way to prevent older adults with mild cognitive impairment (MCI) from developing Alzheimer's disease.

But there may be a safe and feasible non-pharmacological treatment that may help patients living with MCI, according to a small pilot study in the current issue of the Journal of Alzheimer's Disease led by a neurologist and researcher with Wake Forest Baptist Health.

"Until treatment options that can prevent the progression to Alzheimer's are found, mindfulness meditation may help patients living with MCI," said Rebecca Erwin Wells, M.D., M.P.H., associate professor of neurology at Wake Forest School of Medicine, a practicing neurologist at Wake Forest Baptist Medical Center and associate director of clinical research for its Center for Integrative Medicine. "Our study showed promising evidence that adults with MCI can learn to practice mindfulness meditation, and by doing so may boost their cognitive reserve."

Mindfulness means maintaining a moment-by-moment, non-judgemental awareness of thoughts, feelings, bodily sensations, and surrounding environment.

"While the concept of mindfulness meditation is simple, the practice itself requires complex cognitive processes, discipline and commitment," Wells explained. "This study suggests that the cognitive impairment in MCI is not prohibitive of what is required to learn this new skill."

Research has demonstrated that high levels of chronic stress negatively impact the hippocampus, a part of the brain involved in memory and learning, and are associated with increased incidence of MCI and Alzheimer's. Other studies have indicated that non-drug interventions such as aerobic exercise can have positive effects on cognition, stress levels and the brain.

To test whether a mindfulness-based stress-reduction (MBSR) program could benefit adults with MCI, the study team enlisted 14 men and women between the ages of 55 and 90 with clinically diagnosed MCI and randomized them to either an eight-week course involving mindfulness meditation and yoga or a "waiting list" control group.

The researchers previously reported that the nine participants who completed the MBSR program showed trends toward improvements on measures of cognition and well-being and indications of positive impacts on the hippocampus as well as other areas of the brain associated with cognitive decline.

The newly published study adds context to those quantitative findings with a qualitative analysis of the MBSR participants' responses in interviews conducted at the end of the eight-week course.

"While the MBSR course was not developed or structured to directly address MCI, the qualitative interviews revealed new and important findings specific to MCI," Wells said. "The participants' comments and ratings showed that most of them were able to learn the key tenets of mindfulness, demonstrating that the memory impairment of MCI does not preclude learning such skills."

Those participants who practiced at least 20 minutes a day were most likely to have understood the underlying concepts of mindfulness, Wells noted.

The limitations of the study include the small sample size and that the results may not generalize to all patients with MCI, as two-thirds of the participants in this study had a college education or more. Additional research is needed to further test the preliminary hypotheses contained in this study.

Credit: 
Atrium Health Wake Forest Baptist

TGen team links gene to children with physical and intellectual disabilities

PHOENIX, Ariz. -- Aug. 15, 2019 -- Modern science and data sharing converged to underpin a study led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, that identified a gene associated with a rare condition that results in physical and intellectual disabilities of children.

The results, published today in the American Journal of Human Genetics, suggest that rare variants in the gene DDX6 are associated with a significant disruption in the development of the central nervous system, governing such basic skills as the ability to walk and talk.

"One of the most powerful revelations of this study is the identification of pathogenic mutations in DDX6; a gene not previously linked to childhood disorders and one which appears to play a key role in early brain development," said Chris Balak, a research associate in TGen's Neurogenomics Division, and the study's lead author.

Balak zeroed in on DDX6 by comparing the sequencing results from a 5-year-old Arizona girl who was seen at TGen's Center for Rare Childhood Disorders (the Center) with those identified in large population databases and to the genomes of her parents, who are healthy. Following this revelation, and preliminary findings posted on a website shared by investigators worldwide, TGen identified four similar cases: two in the U.S., and one each in France and the Netherlands.

These children's conditions were characterized by intellectual disability, developmental delay, speech and feeding difficulties, low muscle strength with difficulties walking, mild-to-moderate cardiac anomalies, and specific facial features.

"Something we are quite proud of with this work is our combined effort with other physicians and scientists in Europe to demonstrate that changes in this gene cause this rare syndrome in multiple patients," said Dr. Matt Huentelman, TGen Professor of Neruogenomics, Scientific Director of the Center, and one of the study's senior authors. "Collectively, our clinical and laboratory data describe a new brain development syndrome caused by genetic changes in DDX6."

Since opening in 2012, the Center has sequenced the genomes of hundreds of children and their families.

"Through an international collaboration, by combining genomic methods with detailed molecular studies using cells and tissues from our patients, we were led to the discovery of a new neurodevelopmental syndrome caused by mutation of DDX6," said Dr. Vinodh Narayanan, Medical Director of the Center, and another of the study's senior authors. "We expect that the insight into disease mechanisms gained from our studies will lead to a better understanding of an entire group of neurodevelopmental disorders, and eventually guide us to specific treatments."

Credit: 
The Translational Genomics Research Institute

Deep-earth diamonds reveal primordial rock source in Earth's mantle

An analysis of helium isotopes locked inside “super-deep” diamonds hundreds of kilometers below Earth’s surface suggests that vast reservoirs of molten primordial source rock, perhaps nearly as old as the Earth, are present. The helium-bearing diamonds studied as part of the analysis provide the first and most direct record of the variation of helium isotope compositions below Earth’s lithosphere, the authors say. Isotope compositions of volcanic rocks formed from magma once stored deep in the mantle are important; these compositions provide crucial information about the chemical reservoirs of Earth’s interior. Of these, helium isotopes are one of the best tools for understanding the nature of the very deepest and oldest parts of Earth’s mantle. Previous studies of helium isotopes have suggested that regions below the upper mantle may hold pristine reservoirs of primordial rock material. However, the preservation of such long-standing reservoirs has repeatedly been questioned based on disruptive deep-Earth dynamics. As well, there have been difficulties in accurately determining the provenance of isotopic signals from below the upper mantle using erupted basalts. Suzette Timmerman and colleagues located a set of diamonds that formed deep beneath the Earth in an area of Brazil known for its super-deep diamonds. As these diamonds formed in the transition zone of the mantle, a depth spanning 410 to 660 kilometers, helium and other elements became trapped in tiny fluid inclusions within the minerals. Timmerman et al. measured the isotopes of the captured elements and found extreme isotope variability, but also high 3He/4He ratios. The results indicate the existence of a deep, primordial source of helium that occasionally infiltrates the transition zone and mixes with subducting material from above, creating diverse isotopic compositions recorded in basalts.

Credit: 
American Association for the Advancement of Science (AAAS)

New pain organ discovered in the skin

image: Patrik Ernfors, PhD, Professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Sweden.

Image: 
Gunnar Ask

Researchers at Karolinska Institutet in Sweden have discovered a new sensory organ that is able to detect painful mechanical damage, such as pricks and impacts. The discovery is being published in the journal 'Science'.

Pain causes suffering and results in substantial costs for society. Almost one person in every five experiences constant pain and there is a considerable need to find new painkilling drugs. However, sensitivity to pain is also required for survival and it has a protective function. It prompts reflex reactions that prevent damage to tissue, such as pulling your hand away when you feel a jab from a sharp object or when you burn yourself.

Researchers at Karolinska Institutet have now discovered a new sensory organ in the skin that is sensitive to hazardous environmental irritation. It is comprised of glia cells with multiple long protrusions and which collectively go to make up a mesh-like organ within the skin. This organ is sensitive to painful mechanical damage such as pricks and pressure.

The study describes what the new pain-sensitive organ looks like, how it is organised together with pain-sensitive nerves in the skin and how activation of the organ results in electrical impulses in the nervous system that result in reflex reactions and an experience of pain. The cells that make up the organ are highly sensitive to mechanical stimuli, which explain how they can participate in the detection of painful pinpricks and pressure. In experiments, the researchers also blocked the organ and saw a resultant decreased ability to feel mechanical pain.

"Our study shows that sensitivity to pain does not occur only in the skin's nerve fibres, but also in this recently-discovered pain-sensitive organ. The discovery changes our understanding of the cellular mechanisms of physical sensation and it may be of significance in the understanding of chronic pain," says Patrik Ernfors, professor at Karolinska Institutet's Department of Medical Biochemistry and Biophysics and chief investigator for the study.

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Karolinska Institutet

Immune cells drive gallstone formation

image: This figure shows neutrophil elastase (green) and DNA (red) co-localize on the surfaces of human gallstones (yellow). Scale bar 4mm.

Image: 
Munoz et al./Immunity

Sticky meshworks of DNA and proteins extruded by white blood cells called neutrophils act as the glue that binds together calcium and cholesterol crystals during gallstone formation, researchers in Germany report August 15 in the journal Immunity. Both genetic and pharmacological approaches that inhibited the formation of these so-called neutrophil extracellular traps (NETs) reduced the formation and growth of gallstones in mice.

"Neutrophils have long been considered the first line of defense against infection and have been shown to generate NETs that entangle and kill pathogens," says senior study author Martin Herrmann, an immunologist at Universitätsklinikum Erlangen. "Here, we provide additional evidence for the double-edged-sword nature of these NETs by showing that they play an important role in the assembly and growth of gallstones. Targeting neutrophils and NET formation may become an attractive instrument to prevent gallstones in high-risk populations."

Gallstones are hard, pebble-like pieces of material that may be as small as a grain of sand or as large as a golf ball. They form in a pear-shaped organ called the gallbladder, which releases bile to the small intestine through the bile ducts during meals to help break down fat. Although most people with gallstones do not have symptoms, they can cause abdominal pain, nausea and vomiting, and they are a leading cause of hospital admissions worldwide. Surgery to remove the gallbladder is one of the most common operations performed on adults in the United States. Although medicines do exist, they may require months or years of treatment to break up all gallstones.

One hurdle limiting the development of new treatments is that scientists do not yet fully understand exactly how gallstones form. It has been known for decades that the precipitation of cholesterol and calcium salts in the bile is a prerequisite for gallstone formation. But it has not been clear what causes calcium and cholesterol crystals to stick together during gallstone assembly and growth.

A clue to this mystery came while Herrmann, co-first author Luis Muñoz of Universitätsklinikum Erlangen, and their team were examining biliary sludge--small stones in the bile--extracted from human patients receiving stents. They observed large aggregates of DNA, as well as robust activity of neutrophil elastase--a secreted enzyme that helps break down proteins. The researchers also observed DNA patches and high neutrophil elastase activity on the surfaces of larger human gallstones. Together, these molecules are telltale signs of NETs--web-like structures extruded by neutrophils that help protect against infection but have also been implicated in autoimmune and inflammatory disorders. To determine what triggered NET formation, the investigators cultured cholesterol crystals with human neutrophils and observed the release of DNA from these cells.

To test whether NETs play a role in gallstone growth, the researchers mounted human gallstones to rotating and shaking devices and spun them in the presence or absence of neutrophil suspensions. In the presence of neutrophils, the gallstones rapidly collected DNA patches and neutrophil elastase on their surfaces. Additional experiments showed that NETs aggregated cholesterol and calcium crystals to form gallstones, and the DNA wrapped around the crystals and pulled them together to form larger stones.

To further examine the role of NETs and neutrophils in gallstone development, the researchers fed mice a cholesterol-rich diet that induced gallstone formation. The number and size of gallstones were smaller in mice with genetic defects that inhibited NET formation, and the size of gallstones was also smaller in mice with fewer neutrophils. In addition, the number and size of gallstones were reduced in mice whose diets were supplemented with either a compound that inhibits protein-arginine deiminase 4 (PAD4) --an enzyme involved in NET formation--or a beta blocker called metoprolol, which interferes with neutrophil migration and is also widely used for the treatment of high blood pressure and chest pain. Treatment with the PAD4-inhibiting compound or metoprolol also completely blocked the additional growth of pre-existing gallstones.

The authors say that the identification of neutrophils and NETs as culprits in gallstone formation and growth opens new avenues for therapeutic interventions. "The possibility of stopping these processes with new PAD4 inhibitors or with metoprolol--an established beta-blocker--may introduce new therapeutic strategies that avoid surgery," Muñoz says. "However, human studies are required to establish new therapies for gallstone disease. Hopefully, we can convince pharmaceutical companies to perform a clinical study with inhibitors of NET formation or NET aggregation."

Credit: 
Cell Press

One in five awaiting new hip suffering extreme pain, study shows

Almost 20 per cent of people awaiting hip replacements are experiencing extreme pain or discomfort, a study shows.

Researchers also found that 12 per cent of patients on waiting lists for knee replacements considered themselves to be in a similarly acute state of health.

The figures are worse than for many other chronic health conditions, such as diabetes, heart failure or lung diseases.

Researchers at the University of Edinburgh say the findings disprove the perception that hip and knee arthritis only causes mild discomfort and that surgery is considered optional.

They measured more than 4000 Scottish patients' health conditions using an internationally approved score called the EQ-5D - the first time this has been done.

This rating measures a patients' ability to perform routine activities and look after themselves, as well as their levels of mobility, discomfort and anxiety.

The researchers measured the health states of more than 2000 people waiting for a total hip replacement and found that 19 per cent were in extreme pain or discomfort - a state defined as "worse than death" by the EQ-5D.

Some 12 per cent of the 2000-plus patients waiting for knee replacements said they were in a similar condition.

These scores improved dramatically following joint replacement, experts say.

The study is published in the Bone and Joint Journal.

Hip and knee replacements are highly cost-effective treatments with long lasting and almost immediate benefit from the pain and disability from arthritis, according to the study's authors.

Despite this, patients receiving these procedures are the first to have their treatment limited or cancelled.

Chloe Scott, Consultant Orthopaedic Surgeon and honorary senior clinical lecturer at the University of Edinburgh, said: "Patients with the most extreme EQ-5D scores should be a priority for health care delivery. Indeed, given the overall high levels of pain and disability described by all patients awaiting joint replacement compared with most other illnesses, access to appropriate treatment should be free and available to all at the time of need not limited by cost or bed availability."

Credit: 
University of Edinburgh

Modified lactides promise new implementations in pharmacology and catalysis

image: Applications of PLA functionalized with macrocyclic structures [β-cyclodextrins (A), tetrapyrroles (B), calixarenes (C), R1, R2 indicate possible modification by PLA fragments].

Image: 
Kazan Federal University

The project concerning modification of oligo- and polylactic acids with thiacalix[4]arene derivatives was launched at Kazan Federal University three years ago. The main idea of the study was to improve physical and chemical properties of polymers by introducing macrocyclic rigid structures which determine spatial arrangement of linear chains of lactides in their microenvironment.

During this time, as the team leader, Professor Ivan Stoikov, comments, new synthetic approaches have been developed. The scientists have managed not only to obtain various oligomeric structures with variable length of the polymer fragments but also implement macrocycles with different arrangements of the functional groups in the product composition. Such macrocycles were called "macrocyclic knots" because of their likeness to fishing nets. As the research went on, it became clear that the introduction of the macrocycle solved problems that were above and beyond those stated in the initial plans.

In particular, regulation of the chain flexibility, internal space, and ability to self-assemble made it possible to obtain hybrids with inclusion of biopolymers, in which nucleic acids and proteins retained their native structure and biochemical functions, but also were separated in accordance with their effect on the polymer aggregation. As a result, such hybrids were successfully applied in prototypes of chemical and biochemical sensors, and it seems that they offer good prospects in creating new "smart" drugs and systems for targeted drug delivers. The team that works on this topic comprises two laboratories, i.e., it unites chemists who obtain new modified oligo- and polylactides and analysts who develop new enzyme and DNA sensors based on the compounds described above. Dr. Stoikov is in charge of the work.

Polycondensation products of lactic acid have been previously used in various products due to their low cost, chemical and biological inertness, non-toxicity and biodegradability. The project diversified these properties by imparting reception properties related to the modification of polylactides by macrocycles.

Modification products retain their advantages mentioned in the initial polymers, primarily biological inertness and chemical resistance, but are able to recognize some important specimens interesting for biomedicine and pharmacy, mostly proteins and nucleic acids. In turn, the hybrids formed in binding biopolymers become sensitive to biochemical interactions with drugs, toxins, etc. To achieve this, it was necessary to develop new methods for the synthesis of modified oligolactides. Polylactic acids are usually synthesized in three ways: condensation/binding of lactic acid, azeotropic distillation of water, and polymerization of lactide with the opening of its cycle. The macrocycles introduced into the reaction medium played the role of improving agent. Besides, they provide products with additional binding sites, control fixed orientation for the spatial arrangement of the polymer chains and al­ter hydrophilic-lipophilic balance. All these properties make it possible to implement the principles of molecular and supramolecular recognition, when functional groups and binding sites of the modified polylactide specifically bind functional groups of biopolymers and response on such interaction by changing the structure and aggregation properties detected by optical and other signal transducers.

When deposited on the surface of a sensor, modified polylactides form films whose permeability, charge and sorption properties are determined by the "macrocyclic knot" of the polymer. By varying the thiacalixarene conformation, it is possible to selectively "tune" the properties of the coating so that it binds biopolymers but retains high permeability for small ions. Such properties made it possible to obtain a kind of universal sensors that respond to analyte molecules bonded to a bioreceptor on the sensor interface. The signal might be a change in the flow of ions added to the sample. It is decreased in the analyte binding or increased in the introduction of compounds charged oppositely to a probe ion. This approach was implemented in a family of electrochemical sensors, which, depending on the nature of the bioreceptor, made it possible to detect the presence of a wide variety of compounds - from toxins (aflatoxins, organophosphorus pesticides) to biological additives - antioxidants and vitamins. In this case, it did not matter whether analyte molecules were able to oxidize at the electrode as required by "ordinary" electrochemical sensors, or not.

By varying the nature of the modified polylactide, first of all, the conformation of the "macrocyclic knot", it is possible to select the conditions for the inclusion of the receptor, either synthetic or natural, and record its interactions with molecules with high sensitivity. Different composite materials based on oligolactides as matrices for such redox probes, approaches to their synthesis, and examples of sensors based on them were described in this mini-review.

"Polylactic acid modified by "macrocyclic knots" gives a wide variety of materials characterized by high chemical stability, biocompatibility, ease of synthesis and the possibility of directional binding to a wide range of compounds demanded in clinical analysis, biomedicine in general, and the manufacture of portable biosensors for point-of -care diagnostics," says Professor Stoikov. "Prospects for programming properties that are promising for assembling of drug delivery systems, photosensitizers in photodynamic therapy, and protein binding are also obvious. It is also important that the mentioned achievements require implementation of very simple algorithms, the elucidation of which is an important part of the project, no less than the synthesis of individual polymers. This includes the choice of the type of macrocyclic block, stoichiometry of the polycondensation reaction, method of introducing the polymer into the sensitive layer of a sensor and the process of membrane formation with the inclusion of biocomponents. It sounds trivial, but the confirmation of these laws required the use of all modern tools of physical organic chemistry and electrochemical methods of analysis. Some of the described advantages have already been shown by the examples of electrochemical sensors and biosensors with advanced characteristics of the determination of drugs, metabolites, antioxidants, aflatoxins, Alzheimer's disease medications, assessment of total antioxidant activity, etc."

The derivatives of macrocyclic compounds are already used in pharmacology as antibacterial and catalytic systems, components of drug delivery and release agents, and as materials for biosensors. The introduction of such polyfunctional fragments into the structure of synthetic polymers allows modeling active sites of various enzymes depriving them of their main drawback, i.e., instability, but maintaining high selectivity of a substrate binding. DNA sensors are a promising tool required in personalized medicine to provide diagnostic information outside the hospital. Thus, potential directions for further work include development of new chemical (electrochemical) sensors and biosensors based on poly- and oligolactic acids modified with macrocyclic fragments (porphyrin, cyclodextrin, and cyclophane).

Credit: 
Kazan Federal University

Discovery could pave the way for disease-resistant rice crops

image: Protein crystals and a rice panicle depicted against a backdrop of rice grains represent the structural biology and plant pathology aspects of a study by Varden et al., which unveiled a new way to combat rice blast disease.

Image: 
Marina Franceshetti and Phil Robinson

Researchers have uncovered an unusual protein activity in rice that can be exploited to give crops an edge in the evolutionary arms race against rice blast disease, a major threat to rice production around the world.

Magnaporthe oryzae, the fungus that leads to rice blast disease, creates lesions on rice plants that reduce the yield and quality of grain. The fungus causes a loss of up to a third of the global rice harvest, roughly enough to feed more than 60 million people each year.

Various strategies to ward off the fungus have been employed, but a sustainable approach has not yet been developed. Cost and environmental concerns have limited the success of toxic fungicides. And a phenomena called linkage drag, where undesirable genes are transferred along with desired ones, has made it difficult for breeders to produce varieties of rice that exhibit improved disease resistance but still produce grain at a desired rate.

Gene-editing technologies could eventually be used to precisely insert genes in rice plants, overcoming the issue of linkage drag, but first, genes that boost rice immunity need to be identified or engineered.

A team of researchers in Japan and the U.K. report in the Journal of Biological Chemistry that a particular rice immune receptor--from a class of receptors that typically recognize only single pathogenic proteins--pulls double duty by triggering immune reactions in response to two separate fungal proteins. The genes that encode this receptor could become a template for engineering new receptors that can each detect multiple fungal proteins, and thereby improve disease resistance in rice crops.

Rice blast fungus deploys a multitude of proteins, known as effectors, inside of rice cells. In response, rice plants have evolved genes encoding nucleotide binding-leucine-rich repeat proteins, or NLRs, which are intracellular immune receptors that bait specific fungal effectors. After an NLR receptor's specific fungal effector binds to the bait, signaling pathways are initiated that cause cell death.

"(The cells) die in a very localized area so the rest of the plant is able to survive. It's almost like sacrificing your finger to save the rest of your body," said Mark Banfield, professor and group leader at John Innes Centre in Norwich, England, and senior author of the study.

After learning from previous work that the fungal effectors AVR-Pia and AVR-Pik have similar structures, the researchers sought to find out whether any rice NLRs known to bind to one of these effectors could perhaps also bind to the other, Banfield said.

The scientists introduced different combinations of rice NLRs and fungal effectors into tobacco (a model system for studying plant immunity) and also used rice plants to show if any unusual pairs could come together and elicit immune responses. An AVR-Pik-binding rice NLR called Pikp triggered cell-death in response to AVR-Pik as expected, but surprisingly, the experiments showed that plants expressing this NLR also partially reacted to AVR-Pia.

The authors took a close look at the unexpected pairing using X-ray crystallography and noticed that the rice NLR possessed two separate docking sites for AVR-Pia and AVR-Pik.

In its current form, Pikp causes meager immune reactions after binding AVR-Pia, however, the receptor's DNA could be modified to improve its affinity for mismatched effectors, Banfield said.

"If we can find a way to harness that capability, we could produce a super NLR that's able to bind multiple pathogen effectors," Banfield said.

As an ultimate endgame, gene-editing technologies could be used to insert enhanced versions of NLRs--like Pikp--into plants, Banfield said, which could tip the scale in favor of rice crops in the face of rice blast disease.

Credit: 
American Society for Biochemistry and Molecular Biology

Data assimilation method offers improved hurricane forecasting

image: The top row shows actual GOES-16 satellite observations in six-hour intervals. The bottom row shows a weather model developed by the National Center for Atmospheric Research and the middle row shows how that model is improved by the use of Penn State's all-sky radiance method.

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Penn State

Operational models for severe weather forecasting predicted Hurricane Harvey would become a Category 1 hurricane in 2017, according to the University Corporation for Atmospheric Research. Instead, it became a massive Category 4 just before it made landfall, tying Hurricane Katrina for the costliest hurricane on record.

Now a new approach developed at Penn State's Center for Advanced Data Assimilation and Predictability Techniques can forecast the intensity and trajectory of Hurricane Harvey, according to researchers at Penn State and the National Oceanographic and Atmospheric Administration.

The approach used data from the GOES-16 satellite, coupled with Penn State's all-sky radiance method, which more accurately modeled Hurricane Harvey. The data is called "all-sky" because it captures data in all weather conditions, including clouds and rain.

The work, led by Fuqing Zhang, distinguished professor of meteorology and atmospheric science at Penn State, now deceased, is the first time GOES-16 satellite data was used to forecast hurricanes. Hurricane Harvey was the first major hurricane captured by GOES-16, which became fully operational in 2017. Zhang died in July not long after being diagnosed with cancer.

When he discussed the research in June, Zhang said, "This is still experimental. We have demonstrated that we can improve the track, position, intensity and structure of this particular event. We still need to study all other hurricane events with new satellite data but this gives us a lot of promises for the future of hurricane forecasting."

Zhang added that this study, published in the Bulletin of the American Meteorological Society, suggested that all-sky radiance data could greatly benefit hurricane forecasting in general.

In this proof-of-concept study, researchers used hindcasting -- using data collected during the event, but analyzing it afterwards. This allowed researchers to hone in on the most telling data and further refine the model.

The process for creating operational-ready models often takes several years. It begins with hindcasted models before those models are tested alongside existing models to see if any improvements occurred. Because weather forecasting saves lives, the models undergo strict procedures and testing before implementation.

The all-sky radiance approach was paired with a model developed at the National Center for Atmospheric Research with help from members of Penn State's Department of Meteorology and Atmospheric Science. When running the model for a 24-hour period, researchers found assimilating all-sky radiance data better reproduced cloud intensity and patterns when contrasted with the current model. That led to more accurate forecasting in both the eye of the storm and peripherals.

Research shows common inaccuracies in forecasting hurricane intensity and structure days in advance primarily come from poor hurricane vortex generation. Better predicting the eyewall and secondary circulations of a storm could lead to more accurate hurricane prediction, Zhang said.

"We will continue to test our satellite data assimilation system with more hurricanes to see if this method works well with other severe weather events," said Xingchao Chen, an assistant research professor at Penn State who was involved in this research. "In addition to all-sky infrared radiances, we are beginning to look at microwave radiances, which effectively penetrate cloudy regions."

When researchers contrasted images created using models with and without all-sky radiance data included, it not only showed a stark improvement over operational models, it created images nearly identical to actual satellite images during the storm. The operational models that failed to predict the rapid intensification of Harvey included the National Oceanic and Atmospheric Administration's (NOAA) regional-scale Hurricane Weather Research and Forecasting Model, NOAA's Global Forecast System, and the integrated forecast system by the European Center for Medium Range Weather Forecasts.

"That's the beauty of assimilating the GOES-16 satellite," Zhang said. "It looks almost identical to the actual observation. The use of all-sky radiance doesn't just improve existing models. It makes a huge difference."

Credit: 
Penn State

Discovery of how cells override genetic changes

image: Nathan Krah, Charles Murtaugh, Ph.D.; Huntsman Cancer Institute Researchers and co-authors of study.

Image: 
Huntsman Cancer Institute

SALT LAKE CITY-- A discovery by scientists at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) could lead researchers to a more effective way to treat pancreatic cancer. Their findings were published today in Developmental Cell.

Pancreatic cancer is one of the deadliest cancers. It is difficult to diagnose, is often not found until it has spread to other parts of the body, and is mostly untreatable. Like most cancers, pancreatic cancer develops in part because of genetic changes in healthy cells, making those cells grow out of control. These genetic changes can't be reversed and usually don't respond to anti-cancer drugs.

Nathan M. Krah, HCI researcher, MD/PhD candidate at the U of U, and lead author of the study, explained what researchers set out to discover. "All the cells in our body have a specific job to do. Previous work from our laboratory supports the idea that cancer cells lose the ability to do their normal job. In this study, we wanted to understand what would happen if pancreatic cells knew how to do their job, no matter what signals they were receiving."

Charles Murtaugh, PhD, HCI researcher and associate professor of human genetics at the U of U, is the senior author of the study. He and his team conducted studies focused on PTF1A, a protein used by pancreas cells to override genetic changes and remain "differentiated" or healthy. "Differentiated cells are non-dividing and well-behaved. PTF1A maintains this good behavior in differentiated cells of the pancreas," Murtaugh said.

The researchers primarily worked with mouse models. They introduced cancer-causing mutations into normal cells. When pancreatic cancer occurs, PTF1A is always shut down. Researchers were able to prevent that and found keeping PTF1A on was enough to completely block pancreatic cancer cells from forming. They also found early-stage cancer cells reverted back to normal pancreas cells when PTF1A was turned back on. PTF1A also blocked the growth of late-stage cancer cells.

The researchers took their experiment beyond mouse models. They studied human pancreatic cancer cell lines and performed similar experiments on cells grown in culture dishes. They found turning on PTF1A blocked the growth of cancer in about half of these cell lines. Murtaugh said this result was surprising. "PTF1A made pancreas cancer cells behave normally, and this property correlated with its ability to activate differentiation."

Krah says the strength of this research is showing pancreatic differentiation is a powerful way to prevent and reverse cancer initiation in a variety of models and circumstances. "We varied conditions and timing of re-differentiations and always obtained the same result--expression of PTF1A was sufficient to stop cancer initiation and progression."

Krah believes this development is encouraging for pancreatic cancer patients in the long run, but not the immediate future. "I think once we have an idea of how this differentiation state is turned off in early stages of pancreatic cancer, we might have a better idea about how to restore it. But we're probably years away from being able to apply our findings to human patients," he said.

Murtaugh agrees with his colleague, "We can't launch a clinical trial on this tomorrow, but now we have straightforward ways to proceed that might lead to new approaches in the next five to ten years."

Looking more broadly, they would like to learn if factors like PTF1A suppress cancer in any organ where tumor initiation involves loss of differentiation.

Credit: 
Huntsman Cancer Institute

Winning coaches' locker room secret

It's a staple of every sports movie: The team is down at the half, and the coach gives an inspirational locker room speech--think Gene Hackman in Hoosiers, Billy Bob Thornton in Friday Night Lights--leading the team to come roaring back to victory. But do pep talks really work?

In a new paper published in the Journal of Applied Psychology, Berkeley Haas Prof. Emeritus Barry Staw and two colleagues, Katherine DeCelles and Peter de Goey, test that question where it counts: the basketball court. Their analysis of hundreds of half-time speeches and final scores from high school and college games found that coaches do better when they shelve the happy talk and bring down the hammer.

In fact, the researchers found a significant relationship between how negative a coach was at half-time and how well the team played in the second half: The more negativity, the more the team outscored the opposition. "That was even true if the team was already ahead at halftime," Staw says. "Rather than saying, 'You're doing great, keep it up,' it's better to say, 'I don't care if you're up by 10 points, you can play better than this.'"

This is not the first time Staw has studied basketball. In previous research, he found that NBA coaches were more apt to use expensive draft picks in games--regardless of how well they played--just because they'd paid more for them. Sports, he says, can provide a clear and objective playing field on which to examine behaviors that might not be evident elsewhere.

"In business, there are so many external events and economic factors that it is hard to figure out what is causing organizational performance," Staw says. "For example, one cannot easily study certain things like the effect of CEO emotions, unless you could convince CEOs to let researchers tape their boardroom talks and office interactions--and even then it would be difficult to figure out whether there are effects on organizational performance." In basketball, on the other hand, the outcomes are easier to interpret and more definite: the score of your team vs. the opposition.

The researchers gathered the information for their study by contacting more than 50 coaches for high-school and college basketball teams in Northern California, asking if they could record their half-time locker room talks. Sometimes getting agreement took some doing. "Coaches regard the locker room as their inner sanctum--so it was kind of an achievement just to get the tapes," he says. One coach dropped out halfway through the study, out of superstition: "The coach complained that every time we taped the game, they lost," Staw said.

In the end, Staw and his colleagues were left with speeches for 304 games played by 23 teams. They trained coders to rate each halftime talk on the extent that coaches expressed various emotions, ranging from positive (pleased, excited, relaxed, inspired) to negative (disgusted, angry, frustrated, afraid).

Negative speeches can be motivating--up to a point

The results showed two basic effects of coaches' emotional expression at halftime. First, there was a strong and clear relationship between negative half-time speeches and higher scores in the second half. That is, expressing negative emotion at halftime helped teams perform better in the second half. However, at the most intense end of negative expression, the researchers found somewhat of a reversal of the effect. "We're talking Bobby Knight-level, when you're throwing chairs," Staw says, a reference to the notoriously volatile former Indiana University coach. That is, extremely negative expressions of emotion can impede performance.

The researchers also conducted a controlled laboratory experiment, in which they played selected pep talks for participants, and asked them how motivated or unmotivated they felt after hearing them. Again, Staw, DeCelles, and de Goey found that negative speeches could have a motivating effect, but that the effects of such negativity turned downward rather quickly. In other words, the results showed a more traditional bell curve, where motivation dropped off when the coaches became too angry or too negative.

Staw notes that in the psychology of leadership, the trend has been to emphasize the idea of "positive affect" driving people to greater performance. A smaller strand of research, however, has surmised that at least in the short term, negative emotion might actually push people to greater effort.

Staw and his colleagues conclude that negative emotion can be underrated as a motivational tool. By expressing anger or dissatisfaction, a leader signals to followers that their performance is not at the level where it should be, potentially driving them to greater effort. "We sometimes strip content from emotion, treating it as simply positive or negative expression, but emotion often has a message carried along with it that causes people to listen and pay attention, as leaders try to correct or redirect behavior," Staw says.

In a business context, Staw, DeCelles, and de Goey caution against applying the findings too liberally--prolonged negative feedback can lead to demoralized employees. However, in some short-term instances, getting a boost in performance is critical, and the situation may parallel the do-or-die moment at half-time in a basketball game, where expressing anger and disappointment can lead a team to renewed effort and improved results.

"Our results do not give leaders a license to be a jerk," Staw says, "but when you have a very important project or a merger that needs to get done over the weekend, negative emotions can be a very useful arrow to have in your quiver to drive greater performance."

Credit: 
University of California - Berkeley Haas School of Business

Predictive value of resting pd/pa for fractional flow reserve assessed with monorail pressure microcatheter in real-world practice

In the current issue of Cardiovascular Innovations and Applications volume 4, issue 2, pp. 113-120; DOI https://doi.org/10.15212/CVIA.2017.0078, Keng Tat Koh, Asri Said, Khaw Chee Sin, Oon Yen Yee, Erwin Mulia, Tan Chen Ting, Francis Shu Eng Pbeng , Ho Kian Hui, Voon Chi Yen, Cham Yee Ling, Khiew Ning Zan, Nor Hanim Mohd Amin, Alan Fong Yean Yip, and Ong Tiong Kiam from the Department of Cardiology, Sarawak Heart Centre; Faculty of Medicine and Health Sciences, University Malaysia Sarawak; Clinical Research Centre, Sarawak General Hospital; Sarawak, Malaysia consider predictive value of resting Pd/Pa for fractional flow reserve assessed with monorail pressure microcatheter in real-world practice.

Resting Pd/Pa showed poor agreement with hyper-emic FFR assessed with use of a monorail pressure microcatheter. However, resting Pd/Pa of 0.96 or greater had excellent sensitivity and NPV to predict normal hyperemic FFR, and resting Pd/Pa of 0.82 or less had excellent specificity and PPV to predict abnormal hyperemic FFR.

Credit: 
Cardiovascular Innovations and Applications

Enriched environment in aquaculture enhances the survival of fish from bacterial disease

image: In enriched rearing method structures are added to rearing tanks to increase habitat complexity and resemblance to natural conditions.

Image: 
Natural Resources Institute Finland (Luke)

Cooperative study conducted by University of Jyväskylä and Natural Resources institute Finland (Luke), revealed that enriched rearing of juvenile fish significantly enhances the survival of fish from bacterial infection commonly seen in rearing conditions. That may also improve the post release survival of the fish after stocking into the wild. The study has been published in Journal of Applied Ecology.

Importance of aquaculture is increasing worldwide. Along with food production, rearing of endangered fish populations for supportive stocking has become important. In such actions, it is important that the behavior and survival of introduced fish resembles to that of their natural conspecifics.

Traditional stimulus poor rearing environment offers favorable conditions for spread of parasites and diseases, which can significantly reduce the pre- and post-release survival of aquaculture fish. For enhancing the quality of stocked fish, enriched rearing method has been developed in Kainuu Fisheries Research Station of Luke in Paltamo. In this method, structures are added to rearing tanks to increase habitat complexity and resemblance to natural conditions. Earlier, enriched rearing has also been shown to enhance survival of fish during disease epidemics in rearing conditions, but the underlying mechanisms have remained unclear.

New results about the effects of enriched rearing have now been achieved from collaborate study of University of Jyväskylä and Luke. The study showed that enriched rearing enhanced the survival of Atlantic salmon (Salmo salar) and sea migrating brown trout (Salmo trutta) exposed to a common pathogenic fish bacterium, the Flavobacterium.

"Adding enrichments to rearing tanks significantly improved the survival of fish during natural disease outburst. However, there were minor differences between fish species and populations", says PhD student Ville Räihä from University of Jyväskylä.

Benefits of enriched tank can be seen quickly

The beneficial effects of enrichments can be seen very quickly in just few days. One proposed reason may be e.g. the better stress tolerance levels of fish in enriched environment, but this has not been studied yet, Ville Räihä evaluates.

For experimental infection, fish were raised in enriched or standard conditions for six months, after which they were exposed to Flavobacterium in both of these environments.

"The controlled exposure revealed that fish exposed to the disease in enriched environment had higher survival regardless of the rearing background in standard or enriched conditions. This emphasizes the importance of the environment of exposure for severity of the disease", Ville Räihä tells.

The results of the study may advance e.g. the development of natural disease prevention methods in aquaculture.

Credit: 
University of Jyväskylä - Jyväskylän yliopisto

New research could provide better food and faster analysis of blood tests

image: Anne Bech Risum and Rasmus Bro next to the gas chromatograph at the Department of Food Science, at the University of Copenhagen (UCPH FOOD) in Denmark.

Image: 
Morten Vormsborg Christiansen

Gas chromatography is a method of analysis that most people have experienced at one time or another without necessarily knowing it. For example, gas chromatography can be used to reveal food fraud, find out where a particular batch of cocaine was produced or monitor a fermentation of cheese.

"The new interpretive method of gas chromatographic analysis can make this type of analysis accessible to many more, which means that better and cheaper decisions can be made in a number of areas in society," says Professor Rasmus Bro, Department of Food Science at the University of Copenhagen (UCPH FOOD), who is one of the researchers behind the new interpretive method.

The method can also be used to measure flavour and aroma in gastronomy and to examine blood samples taken in the hospital.

"Gas chromatography is one of the most widely used analytical methods and it provides a chemical profile that can reveal thousands of things. The analysis shows most of the chemical components in a sample of biological material in a particular pattern that can then be interpreted in terms of the specific things you want to examine. You could say that you take a chemical "fingerprint" of the material," says Rasmus Bro.

Gas chromatography is generally important when talking about safety and improving the quality of global food production. And monitoring by means of measurements and artificial intelligence is one of the topics at a new major food conference in Copenhagen later this month, Food Day 2019, under the heading "The role of online monitoring and artificial intelligence in sustainable food production".

Use of gas chromatographic analysis in the food industry

It is quite expensive to interpret the analyses, as it requires highly specialised workforce.

"There is a great deal of manual work behind the interpretation of many gas chromatographic analyses and in some cases it takes several weeks to get the results from the measurements. With this research, we show that some of the most time consuming tasks can be done automatically by a computer," says PhD student Anne Bech Risum, who is also one of the researchers behind the method of interpretation.

The computer can make a number of decisions that usually require a chemist.

"The interpretation consumes a great deal of work because you work through the data bit by bit. A computer can do this much more efficiently and reproducibly," explains Anne Bech Risum.

Gas chromatography using mass spectrometry (GC-MS) is widely used in the food industry. For example, all large companies that work with fermentation will use this method of analysis to measure how the microorganisms in a fermentation develop and affect the final product.

"If you, for example, produce a cheese, the taste and aroma develop differently depending on the microbiological culture you add and how you treat the cheese during production. Gas chromatography can be used to measure the chemical elements that together form the aroma profile of the cheese. So if you, for example, want a more fruity or nutty aroma, you could try to change the production and then measure whether you have formed more of the chemicals behind the desired flavour profile," says Anne Bech Risum.

The method of interpretation could also help give smaller food companies access to highly advanced analytical methods that can help companies with product optimisation, quality assurance and raw material identification.

Credit: 
University of Copenhagen - Faculty of Science