Tech

Researchers at the University of Illinois at Urbana-Champaign in collaboration with a Purdue team have discovered that certain crystals are more flexible and stretchable compared to current materials used for electronic applications. These new materials
could therefore be used for making sensors and in robotics.

The study “Super‐ and Ferro‐elastic Organic Semiconductors for Ultraflexible Single Crystal Electronics” was published in Angewandte Chemie, the journal of the German Chemical Society.

Typically, silicon and germanium are used for making electronics. However, these materials are challenging to use on human skin or in robotics because they break apart when they are stretched too much. “Researchers use two ways to make stretchable electronics,” said Ying Diao, an assistant professor of chemical and biomolecular engineering and a faculty member at the Beckman Institute for Advanced Science and Technology. “Either they carve intricate patterns out of silicon or they design new polymer materials. However,
these approaches either involve complicated processes or they compromise the perfect order of the molecules.”

To overcome this limitation, the Diao group looked for single crystal materials that could be stretched easily. The researchers were inspired by nature in their search. “This mechanism is found in a virus called the bacteriophage T4 virus. The tail
of this virus is a single crystal of protein molecules and it is compressed over 60% when the virus injects its DNA into the bacteria. The compression occurs without losing structural integrity,” Diao said.

“We discovered that bis(triisopropylsilylethynyl)pentacene crystals can be stretched over 10%, which is ten-fold that of the elastic limit of most single crystals.” said Sang Kyu Park, a postdoctoral researcher in the Diao group.

“The molecules in the single crystals can cooperatively glide and rotate to accommodate mechanical strain beyond their elastic limit.” said Hong Sun, a graduate student in the Kejie Zhao group at Purdue University.

"This mechanism also is found in shape memory alloys that are available in retail stores,” Park said. “You can distort the wire and then restore it back into its original shape by heating it. However, we are the first to discover this phenomenon
in organic electronic crystals.”

This work was supported by the Sloan Research Fellowship in Chemistry, the 3M Nontenured Faculty Award, and the National Science Foundation.

The paper “Super‐ and Ferro‐elastic Organic Semiconductors for Ultraflexible Single Crystal Electronics” can be found at https://doi.org/10.1002/anie.202004083

Journal

Angewandte Chemie

DOI

10.1002/anie.202004083

Every summer (November-April), the Magellan Strait in the southwestern part of Chile becomes a popular feeding area for migrating humpback whales (Megaptera novaeangliae). The narrow strait is also a heavily used shipping route. A new study by scientists at the Smithsonian Tropical Research Institute (STRI) and collaborating institutions tracked and modelled the movement of individual whales in order to evaluate the potential of vessel collisions and provide policy recommendations for the protection of whale species.

Humpback whales have the longest migratory journeys of any mammal on Earth. The Southern Hemisphere population spends its summer months feeding in the Antarctic and Chile and their winters in the warmer tropical Pacific waters of northern South America and Central America, as far as Nicaragua. Their movements often overlap with boat traffic and may put them at risk of collision, leading to injury or death. Years ago, STRI researcher Héctor M. Guzmán led a study that resulted in international regulations to separate vessel traffic from whale routes near the Panama Canal and in southern Costa Rica, which drastically reduced collision rates in the breeding areas.

"Designing and implementing traffic-separation schemes for Panama and Costa Rica was difficult, because any measures had to be adopted by the International Maritime Organization," said Guzmán, also lead author of the new study in Chile. "It was achieved by having the scientific information explain the whale movements and thanks to the unconditional support of both governments."

The new study, published in Marine Policy, took place in southern Chile, where about 100 humpback whales feed each summer: a population small enough for occasional ship strikes to have important consequences. By tagging and tracking 25 individuals over different years and comparing their movements with available records of vessels traversing the Strait, the team found that, on average, each whale was near a ship about seven times per season. Due to the detailed tracking records of multiple whales, the researchers were able to show that individual animals differed enormously in how often they encountered ships: from less than one to as many as 18 encounters per season.

"Studying variation among whales is a novel feature," said Richard Condit, co-author and modeler of the study. "Other studies I know only considered the average risk of all whales, but the whales most likely to suffer in collisions are those with higher than average risk. This is a major plus of tracking individuals. During the study period, the tagged whale with the highest encounter rate was found dead."

They also noted that a majority of the vessels, large cargos and tankers exceeded the recommended speed limit near the whale feeding sites.

"The Strait humpback population increased nearly 300% in 17 years, reaching between 110 and 100 individuals in 2016 and 2017 and then gradually decreasing to 65 individuals in 2019," said Juan Capella, co-author and researcher from Whalesound (an ecotourism and science project in Chile). "In addition, we report the death of six humpbacks in 10 years, including one young female during our study. If we consider that half of this population is female, a single death represents 3% of the female population in full reproductive age."

Although international recommendations have already been developed to help reduce the risk of ship collisions with whales worldwide, the results of this study allowed scientists to come up with additional policy suggestions that are aligned with the local circumstances. These include proposed speed limits within the Strait of Magellan and a mandatory observer onboard all commercial vessels.

Researchers with the ECOG-ACRIN Cancer Research Group will present a wide range of research findings at the annual meeting of the American Society of Clinical Oncology (ASCO), occurring virtually May 29-31. The presentations include late-breaking data in two plenary sessions and several oral abstract presentations. National Cancer Institute, part of the National Institutes of Health, funded these studies.

Late-Breaking Abstracts

Breast cancer and myeloma

In LBA2 of the plenary session, first author Seema A. Khan, MD (Northwestern University), will present the results of the randomized phase three trial E2108 (NCT01242800), evaluated the use of surgery after initial systemic therapy in patients with newly diagnosed metastatic breast cancer.

In LBA3, first author Shaji K. Kumar, MD (Mayo Clinic), will present the results of myeloma study E1A11 or ENDURANCE (NCT01863550). This randomized phase three trial compared bortezomib, lenalidomide, and dexamethasone with carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma.

TAILORx

Largest ever breast cancer treatment trial

Abstract 7004: Previous studies suggest that up to 50% of women with breast cancer do not adhere to the full five years of recommended adjuvant hormone therapy. A subgroup of 954 TAILORx (NCT00310180) women was assessed by clinical report for early discontinuation of hormone therapy, less than four years from initiation, for reasons other than death or recurrence. The study found that women below the age of 40 are at risk for early discontinuation, and modifiable characteristics (health-related quality of life and history of depression) are potential risk factors.

First author, Betina R. Yanez, PhD (Northwestern University): "These results support systematic screening for health-related quality of life and depressive symptoms to identify women at risk for discontinuation of hormone therapy."

Abstract 7041: Cancer patients often face unpredictable or unmanageable costs that may lead to care nonadherence. This study sought to identify correlations between insurance status and early discontinuation of hormone therapy, less than four years from initiation, for reasons other than death recurrence, in 9,475 TAILORx women (mean age: 55.6; 84% white; 9% Hispanic). Early discontinuation rates were highest among self-pay (18.7%) and Medicaid patients (18%).

First author, Gelareh Sadigh, MD (Emory University): "Insurance status plays an important role in adherence to adjuvant hormone therapy, with high rates among uninsured and underinsured patients. Early identification of patients at risk and enrollment in insurance optimization programs may improve adherence to therapy."

Head and Neck Cancer

The first presentation in the Head and Neck Oral Abstract Session

Abstract 6500: E3311 (NCT01898494) is a randomized phase two trial that examined transoral robotic surgery followed by low-dose or standard-dose intensity-modulated radiation therapy (IMRT) in patients with human papillomavirus (HPV) positive, stage III to IVA, oropharynx cancer. The primary endpoint was progression-free survival (PFS). For patients with low-risk disease, two-year PFS was favorable without post-operative therapy. Reduced-dose (50Gy) radiation therapy without chemotherapy appears sufficient for those patients with uninvolved surgical margins,

First author, Robert L. Ferris, MD (University of Pittsburgh): "Transoral resection followed by low-dose radiation is safe in patients with intermediate-risk locally advanced oropharynx cancer, with very good oncologic outcomes. These results present a promising de-intensification approach."

Lung Cancer

The first presentation in the Lung Cancer-Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers Oral Abstract Session

Abstract 9000: Immune checkpoint inhibition with chemotherapy is a first-line treatment for extensive-stage small-cell lung cancer. The randomized phase two study, EA5161 (NCT03382561), evaluated nivolumab (anti-PD1) in combination with platinum-etoposide (CE) as first-line treatment in these patients. Nivolumab plus CE significantly improved progression-free survival, the primary endpoint, compared with CE alone. The secondary endpoint of overall survival was also improved with nivolumab plus CE versus CE alone.

First author, Ticiana Leal, MD (University of Wisconsin): "EA5161 demonstrated improved progression-free survival and overall survival with the addition of nivolumab to chemotherapy for small-cell lung cancer. These results support the role of immune-chemotherapy in front line treatment of patients with small-cell lung cancer."

NCI-MATCH

Latest data from the largest precision medicine cancer trial

Abstract 3506: NCI-MATCH (EAY131) is a platform trial that enrolls patients with solid tumors, lymphomas, or multiple myeloma to single-arm phase two studies of targeted therapies based on matching genomic alterations of interest (NCT02465060). Arm Z1F evaluated copanlisib, a highly selective, pan-Class 1 PI3K inhibitor with predominant activity against PIK3CA mutations (PTEN loss allowed), in 28 patients. The overall response rate, the primary endpoint, was 11%. Partial responses were seen in uterine cancer, clear cell carcinoma of anterior abdominal wall, and liposarcoma. Six patients had more than six months of stable disease, and the clinical benefit rate was 32% (9/28). Two patients remained on treatment at the time of abstract submission.

First author, Senthil Damodaran, MD, PhD (MD Anderson Cancer Center): "While the study did not meet its primary endpoint, copanlisib showed meaningful clinical activity in select tumors with PIK3CA mutation in the late-line refractory setting, warranting further study either alone or in combinations."

Web-based Genetic Education

Care Delivery and Regulatory Policy Oral Abstract Session

Abstract 2008: The COMET (COMunication and Education in Tumor Profiling) trial (NCT02823652) evaluated a web-based intervention to increase genetic knowledge and decrease distress among patients with advanced cancer about to undergo tumor genetic testing. The majority of the 594 patients in this study were being treated at hospitals and cancer centers participating in the NCI Community Oncology Research Program. They were randomized to web-intervention versus usual care. Those randomized to the web intervention had better knowledge improvement than those randomized to usual care (conversations with physicians and staff and information from typical resources).

First author, Angela R. Bradbury, MD (University of Pennsylvania): "Web-based education before receipt of tumor genetic test results increases patient understanding of tumor genetic testing. While the intervention did not significantly reduce distress, results suggest that women who received the intervention had lower cancer-specific distress than those with usual care."

Nuclear bomb tests during the Cold War may have changed rainfall patterns thousands of miles from the detonation sites, new research has revealed.

Scientists at the University of Reading have researched how the electric charge released by radiation from the test detonations, carried out predominantly by the US and Soviet Union in the 1950s and 1960s, affected rainclouds at the time.

The study, published in Physical Review Letters, used historic records between 1962-64 from a research station in Scotland. Scientists compared days with high and low radioactively-generated charge, finding that clouds were visibly thicker, and there was 24% more rain on average on the days with more radioactivity.

Professor Giles Harrison, lead author and Professor of Atmospheric Physics at the University of Reading, said: "By studying the radioactivity released from Cold War weapons tests, scientists at the time learnt about atmospheric circulation patterns. We have now reused this data to examine the effect on rainfall.

"The politically charged atmosphere of the Cold War led to a nuclear arms race and worldwide anxiety. Decades later, that global cloud has yielded a silver lining, in giving us a unique way to study how electric charge affects rain."

It has long been thought that electric charge modifies how water droplets in clouds collide and combine, potentially affecting the size of droplets and influencing rainfall, but this is difficult to observe in the atmosphere. By combining the bomb test data with weather records, the scientists were able to retrospectively investigate this.

Through learning more about how charge affects non-thunderstorm clouds, it is thought that scientists will now have a better understanding of important weather processes.

The race to develop nuclear weapons was a key feature of the Cold War, as the world's superpowers sought to demonstrate their military capabilities during heightened tensions following the Second World War.

Although detonations were carried out in remote parts of the world, such as the Nevada Desert in the US, and on Pacific and Arctic islands, radioactive pollution spread widely throughout the atmosphere. Radioactivity ionises the air, releasing electric charge.

The researchers, from the Universities of Reading, Bath and Bristol, studied records from well-equipped Met Office research weather stations at Kew near London and Lerwick in the Shetland Isles.

Located 300 miles north west of Scotland, the Shetland site was relatively unaffected by other sources of anthropogenic pollution. This made it well suited as a test site to observe rainfall effects which, although likely to have occurred elsewhere too, would be much more difficult to detect.

Atmospheric electricity is most easily measured on fine days, so the Kew measurements were used to identify nearly 150 days where there was high or low charge generation over the UK while it was cloudy in Lerwick. The Shetland rainfall on these days showed differences which vanished after the major radioactivity episode was over.

The findings may be helpful for cloud-related geoengineering research, which is exploring how electric charge could influence rain, relieve droughts or prevent floods, without the use of chemicals.

Professor Harrison is leading a project investigating electrical effects on dusts and clouds in the United Arab Emirates, as part of their national programme in Rain Enhancement Science. These new findings will help to show the typical charges possible in natural non-thunderstorm clouds.

DALLAS, May 13, 2020 -- Drinking one or more sugary beverages a day was associated with a nearly 20% greater likelihood of women having a cardiovascular disease compared to women who rarely or never drank sugary beverages, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.

In the large, ongoing California Teacher's Study, which began in 1995, drinking one or more of any type of sugary beverage daily was associated with a 26% higher likelihood of needing a revascularization procedure, such as angioplasty to open clogged arteries, and a 21% higher likelihood of having a stroke compared to women who rarely or never drank sugary beverages. Sugary beverages in this study were defined as caloric soft drinks, sweetened bottled waters or teas and sugar-added fruit drinks, not 100% fruit juices.

There were also differences based on the type of beverage women consumed. Drinking one or more sugar-added fruit drinks daily was associated with a 42% greater likelihood of having cardiovascular disease. Drinking soft drinks such as sodas daily was associated with a 23% higher risk of cardiovascular disease overall, compared to those who rarely or never drank sugary beverages.

The study included more than 106,000 women, with an average age of 52, who had not been diagnosed with heart disease, stroke or diabetes when they enrolled in the study.

The women reported how much and what they drank via a food questionnaire. Statewide inpatient hospitalization records were used to determine whether a woman had experienced a heart attack, stroke or surgery to open clogged arteries. Women with the highest sugar-sweetened beverage intake were younger, more likely to be current smokers, obese and less likely to eat healthy foods, among other things.

"Although the study is observational and does not prove cause and effect, we hypothesize that sugar may increase the risk of cardiovascular diseases in several ways. It raises glucose levels and insulin concentrations in the blood, which may increase appetite and lead to obesity, a major risk factor for cardiovascular disease," said lead study author Cheryl Anderson, Ph.D., M.P.H., M.S., professor and interim chair of Family and Public Health, University of California San Diego, and chair of the American Heart Association's Nutrition Committee.

"In addition, too much sugar in the blood is associated with oxidative stress and inflammation, insulin resistance, unhealthy cholesterol profiles and type 2 diabetes, conditions that are strongly linked to the development of atherosclerosis, the slow narrowing of the arteries that underlies most cardiovascular disease," said Anderson.

Strengths of the study included its large sample size, extensive follow-up time and prospective data collection on sugar-sweetened beverages and lifestyle characteristics. In addition, the ability to annually link to statewide hospitalization and procedure records resulted in accurate endpoints.

Limitations of the study included having only one measurement of sugar-sweetened beverage intake. The study was also unable to evaluate consumption of artificially sweetened beverages and/or sweetened hot beverages.

The American Heart Association recommends limiting added sugar to no more than 100 calories a day (6 teaspoons of sugar or 25 grams) for most women, and no more than 150 calories a day (9 teaspoons of sugar or 38 grams) for most men. Sugar-sweetened beverages are the biggest source of added sugars in the American diet; a typical 12-ounce can of regular soda has 130 calories and 8 teaspoons (34 grams) of sugar.

Although diet soda may provide an alternative for some people who are trying to reduce the amount of sugary drinks in their diet, they do include artificial sweeteners such as saccharin, aspartame, sucralose and others. Water remains the most accessible and healthy beverage to drink regularly - water has no sugar, no artificial sweeteners and no calories.

Perovskite solar cells (pero-SCs) show great potential in the photoelectric fields due to high power conversion efficiency (PCE), simple processing technology, low fabrication cost, etc.. Recently, the highest certificated PCE of pero-SC has reached 25.2%, which shows great promise for the commercialization. Thus, the next research will focus on the fabrication of efficient and modular pero-SCs to further promote the commercialization of pero-SCs.

In p-i-n planar pero-SCs, the hole-transporting layers (HTLs) have an important influence on the growth of perovskite crystals, the hole transporting ability and the device stability. Therefore, developing efficient and stable HTL materials suitable for large-area processing will play a crucial role in large-area modular pero-SCs. In addition to the matched energy levels, stable chemical properties and good reproducibility, the HTL materials suitable for large-area processing should also have high hole-mobility and good wettability with the perovskite precursor solution.

Although the device based on poly(bis(4-phenyl)(2,4,6-trimethylphenyl)amine) (PTAA) as organic HTLs can achieve a PCE exceeding 22%, the poor wettability of the perovskite precursor solution will hinder the preparation of large-area modules. Up to now, new organic HTL materials in large-area devices have been rarely reported. Therefore, it is urgent to develop high-efficient and high-hole-mobility HTL materials that are compatible with large-area processing in p-i-n planar pero-SCs.

Very recently, Prof. Yaowen Li in Soochow University and co-authors designed a π-conjugated small-molecule HTL material BDT-TPA-sTh with a symmetric structure by rationally selecting the planar BDT core, TPA terminal groups, as well as conjugated 2-ethylhexyl-thienyl side chains.

The conformation and stacking model of the resultant BDT-TPA-sTh was directly observed by X-ray crystallography measurements from its single crystals. The pronounced planarity with parallel-displaced π-π and additional S-π supramolecular interactions between neighboring molecules contributed to an improved hole-mobility. In addition, the marginal solubility of BDT-TPA-sTh in the perovskite solution enabled inverse diffusion into the perovskite films, which could be used to further passivate the uncoordinated Pb2+ ion defects by Lewis-base S-atoms in BDT-TPA-sTh without damaging the under-layer HTLs.

The p-i-n planar pero-SCs (Figure 1) using BDT-TPA-sTh without dopant as the HTL not only realized a high PCE (20.5%) and improved moisture stability, but also demonstrated its feasibility for fabricating large area devices through the blade-coated technology. They believe that this HTL design concept through supramolecular interactions and inverse diffusion will pave a way for designing HTL materials of perovskite-based optoelectronic devices. Their work would provide a significant progress in designing interface materials toward high performance, large area and printing p-i-n planar pero-SCs, and thus would be interesting to a wide readership for the perovskite-based opto-electronic community.

Frequently, promising cancer therapies fail when applied to patients in the real clinical setting. This occurs despite many of these new treatments demonstrating promising results at the preclinical stage in the lab. One explanation is that many of the tumor models used in early research phases are established cell lines that have been growing for many decades and in two-dimension (2D) culture flasks. These cancer cells might not completely resemble the features of real tumors from patients that expand into three dimensions (3D).

Very recently, it has been possible to grow "organoids" in the laboratories, cancer models respecting their 3D structure. We know very little about these cells, and if they actually mimic the conformation of the tumor within the body, particularly the chemical modifications of DNA that are "beyond genetics," epigenetics, that don't change genes but control their expression, such as DNA methylation. An article published in the Journal Epigenetics from Taylor & Francis by the group of Manel Esteller, M.D., Ph.D., Director of the Josep Carreras Leukaemia Research Institute (IJC), ICREA Research Professor and Chairman of Genetics in the University of Barcelona, describes the first comprehensive study of the epigenetic landscape of human tumor organoids, validating the use of these samples for cancer research, that could deliver new oncology treatments.

"Our article solves an unmet biomedical need in the cancer research field: the characterization of the epigenetic fingerprint of human cancer organoids. Our study shows that these tumor models can be very useful for the biomedical research community and the pharmaceutical companies developing anti-cancer drugs". Says Manel Esteller, and explains: "First, we show that every cancer organoid retains the properties of the tissue of origin: if the samples were obtained from the surgery of a colon or pancreatic cancer, the organoid closely resembles the original primary tumor. Second, there is no contamination of normal cells; thus, the malignant pure transformed cells can be analyzed without interferences. And finally, the 3D organoid cancers are closer to the patient tumors than the commonly used 2D cell lines."

Two of the most relevant consequences is the open nature of the data obtained with these studies: a large amount of data has been generated to be analyzed with Big Data and made available to the research community. On the other hand, the exchange of samples between researchers is offered to promote more collaborative studies.

"We have deposited all the obtained results in easily accessible public databases, and, in this manner, everyone can perform further data mining to produce new cancer discoveries using different biometric approaches or focusing on particular genes. And most importantly, the characterized cancer organoids can be readily obtainable from a reliable provider (the American Type Culture Collection, ATCC), so researchers around the world can use the epigenetic information of these sharable samples to develop their investigations." Concludes the researcher.

Three hundred-year-old administrative documents from the Roman government, granting residents permission to repair damage to their buildings, can help modern-day seismologists calculate intensities for a notable sequence of earthquakes that struck central Italy in 1703.

Details gleaned from these "Lettere Patenti" offer a unique glimpse at the geographical spread and types of building damage caused by the 1703 earthquakes, according to the report in Seismological Research Letters by Andrea Tertulliani of the Istituto Nazionale di Geofisica e Vulcanologia and colleagues.

Seismic intensity--a way to describe an earthquake's severity through its effects on humans and structures--is assessed with reference to statistically representative buildings. Using information from the historical documents, the three main earthquakes in the 1703 sequence were likely between intensity V and VI, as measured by the European Macroseismic Scale-98.

Intensity V or "strong" means that the earthquake was felt indoors by most people, trembling buildings and tipping over top-heavy objects. Intensity VI or "slightly damaging" earthquakes can cause minor to moderate damage to buildings, like cracking and falling pieces of plaster.

The administrative documents provide a more realistic view into the earthquakes' impact than historical reports of damage to monumental buildings such as churches and Rome's Colosseum, the researchers conclude.

The new study's "fundamental contribution-- information about residential housing-- is crucial for assessing intensity, especially when using the EMS-98," said Tertulliani. "This macroseismic scale suggests, if possible, to not consider monumental buildings in the intensity evaluation because they are not statistically significant. The Lettere Patenti are a source of information on the residential building stock of Rome."

The 1703 sequence, including earthquakes on 14 January, 16 January and 2 February, were widely felt and feared by people in central Italy. The January earthquakes were located in the Umbria region, which at the time was part of the Papal State, and the February earthquake struck the Abrutium region in the Kingdom of Naples.

They are among the few earthquakes to have produced significant damage to monumental structures in the city of Rome, Tertulliani and colleagues noted. The damage included toppled chimneys, falling rubble and cracks in the domes and vaults of several churches, including St. Peter's and St. Paul's Basilicas, and the church of St. Andrea della Valle. Two or three arches at The Colosseum collapsed, and parts of the Aurelian Walls were damaged.

The researchers point out, however, that churches and towers are often the structures that are damaged the most during earthquakes, due to their structural complexity. To expand their view of the earthquakes' impact, Tertulliani and colleagues built on a previous study looking at administrative documents from the time period, called Lettere Patenti or literally, "letter of permission or license." The documents issued by the Roman government authorize individuals to complete maintenance on the external parts of their buildings.

"The work of the historical seismologist has something of both the archaeologist and the detective, so it is necessary to look for a wide typology of documents," Tertulliani explained. "Before the end of 18th century, most of the reports or chronicles that were written after a natural phenomenon were not conceived with the primary aim of describing its effects, so the seismologist has to search for administrative documents."

With the help of the Lettere Patenti and a 1748 property map, the researchers were able to pinpoint 93 new damage points on civil buildings spread throughout the historic center of Rome. Most of the repairs authorized by the documents involved demolition and reconstructions of walls or parts of buildings after moderate structure damage.
Tertulliani hopes to study other historical Italian earthquakes using these document-based methods, especially as new archival material becomes available. But he cautioned that "this kind of research is extremely time-consuming, and it does not always lead to appreciable results."

Death from sudden cardiac arrest makes headlines when it strikes athletes. But it also causes the most deaths by natural causes in the U.S. estimated at 325,000 per year.

The heart's bioelectrical system goes haywire during arrest. The malfunction can send heartbeats racing out of control, cutting off blood to the body and brain. This differs from a heart attack, which is caused by a blockage of the heart's arteries. The leading risk factors for sudden cardiac arrest are a past attack and the presence of disease. Another risk factor is the side effects from medications, which can cause deadly arrhythmias.

Using supercomputers, scientists have developed for the first time a way to screen drugs through their chemical structures for induced arrhythmias.

Up until the early 2000s, the reason most drugs were removed from the market following FDA approval was cardiotoxicity in the form of deadly arrhythmia. In 2005, the FDA required a separate test for all drugs. It measured the average time between the Q and T waves on an electrocardiogram, a record of the heartbeat. QT prolongation became a red flag for drug cardiotoxicity. But one problem is that some harmless substances, like grapefruit juice, also prolong QT interval, and using it as a proxy for heart arrhythmia could mean the loss of potentially useful and safe drugs.

"What we set out to do was to try to solve that problem by building a computer-based pipeline for screening," said Colleen Clancy, a professor in the Department of Physiology and Membrane Biology and the Department of Pharmacology at the UC Davis School of Medicine. Clancy co-authored a study on the computational cardiotoxicity drug screening pipeline in the journal Circulation Research in April 2020.

"The major novelty of the pipeline is that we found a way to connect the atomistic scale to higher level function scales, like protein function, cell function, and in our simulated tissue-level models we can calculate the spatial and temporal gradients of electrical activity in those simulated pieces of tissue," Clancy said. "That is an approximation of the electrocardiogram that's measured in the clinic. We can do a direct comparison between the electrocardiogram in the simulated tissue, and electrocardiograms from patients that have taken those drugs."

The two drugs chosen in the study both prolonged the QT interval. One of them, dofetilide, is a known proarrhythmic agent. The other, moxifloxacin, has a strong safety profile in healthy humans.

"There's been no way to distinguish between those two classes," Clancy said. "That's what we were able to show in the computational pipeline." Starting from the chemistry of the drug interactions with a target, the scientists used that information to predict proarrhythmia vulnerability through a machine learning approach based on multi-scale computer simulation data.

Clancy and colleagues chose the hERG (human Ether-à-go-go-Related Gene) potassium channel in the heart as the drug target in the first step of their computational pipeline. The hERG mediates the electrical activity of the heart, and drug companies usually screen for whether a drug blocks it.

"The big challenge computationally is the system that we studied is pretty large," said study co-author Igor Vorobyov, an assistant professor in the Department of Physiology and Membrane Biology and the Department of Pharmacology at the UC Davis School of Medicine. "It's on the atomistic scale. We have around 130,000 atoms in our system. This includes the hERG protein embedded in the lipid membrane surrounded in a salt aqueous solution in water."

The calculations involved billions of individual time steps to achieve an all-atom simulation of several microseconds, enough to get detailed information on how the drug binds to the target.

"Here is where supercomputers come in very handy," Vorobyov said. He was awarded allocations on the Stampede2 system of the Texas Advanced Computing Center (TACC) by XSEDE, the Extreme Science and Engineering Discovery Environment funded by the National Science Foundation (NSF). XSEDE also provided supercomputing time on Comet at the San Diego Supercomputer Center, making use of Comet's GPU and CPU nodes. The National Center for Supercomputing Applications allocated use of its NSF-funded Blue Waters system. And the scientists made use of the Anton2 system at the Pittsburgh Supercomputing Center.

"Stampede 2 offered a large array of powerful multi-core CPU nodes, which we were able to efficiently use for dozens of molecular dynamics runs we had to do in parallel. Such efficiency and scalability rivaled and even exceeded other resources we used for those simulations including even GPU equipped nodes," Vorobyov added.

The team uses enhanced sampling simulations, called umbrella sampling, to facilitate the molecular dynamics simulations and yield quantitative determination of the binding affinities and rates of reaction needed for linking scales and feeding parameters further up the pipeline to the functional model.

"That was the novel linkage between our scales that we've both worked on for many years," Clancy added. "But until now, there was no way to really connect those scales in a meaningful way."

"This is a very novel link," Vorobyov said, "because pretty much no one has done it before. We were able to successfully predict the outcome of the models. Just to take the parameters from the atomistic molecular dynamics simulation and predict how the cardiac cells and tissues respond to the drug application, we were able to predict the experimental prolongation of the QT interval."

Clancy explained the key pieces of the study. "The first is connecting atomistic scale simulations to cardiac tissue simulations on the order of milliseconds, second, minutes That's the first novelty," she explained. "The second novelty is building a pipeline to predict cardiotoxicity, which hadn't been done before. But the third piece is to move beyond QT interval as the surrogate, or proxy indicator for proarrhythmia."

The researchers are taking the next steps in their computational pipeline to expand the set of drugs screened for cardiotoxicity, looking at a variety of agents that have been part of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) safety pharmacology testing group. They're also working with the biopharmaceutical company Amgen to get blinded compounds for their screening.

"The idea is that Amgen would give us the chemical structures of the drugs, but we wouldn't know whether they were proarrhythmic or not," Clancy said. "Then we'll use the pipeline to make some predictions about those drugs, and send those results back where they will reveal if our model was accurate in predicting what they've seen."

Clancy and team also want to move the research into a personalized medicine approach, building models of an individual's cellular electrophysiology that include some genetic background. One project cultures heart muscle cells from individuals to develop a model called the "induced pluripotent stem cell derived cardiac myocyte."

"The benefit of a personalized medicine approach is that it includes all of the genetic information in the background, so you can screen drugs and then start to ask, 'Why are some individuals susceptible to drugs and proarrhythmia from drugs and other people aren't?' We may even be able to work towards developing reconstructions of their hearts in silico," Clancy said.

A longtime collaborator of Clancy's at Johns Hopkins, Natalia Trayanova, has developed high resolution three-dimensional models based on CT or MRI imaging of individual hearts. The hope is to use a finite element approach to populate the three-dimensional reconstructions with their own electrophysiology. "That's what we're thinking about in the next five to 10 years," Clancy said.

In the shorter term, Vorobyov was awarded allocations in April 2020 on the NSF-funded Frontera supercomputer at TACC to scale up his calculations. "We want to test this on many more different types of drugs, including the prospective COVID-19 therapeutics. This allocation will help run many of these drugs in parallel. Frontera, on which we recently got 200,000 node hours to use as part of our LRAC award, is one of the world's most powerful supercomputers and offers unprecedented possibilities for improving efficiency and scalability of our simulations. We will be able to run simulations for several hERG blocking drugs in parallel in a matter of few weeks, which will greatly accelerate development of our multi-scale safety pharmacology pipeline."

Women who drink two or three cups of coffee a day have been found to have lower total body and abdominal fat than those who drink less, according to a new study published in The Journal of Nutrition.

Researchers examined data from the National Health and Nutrition Examination Survey, organised by the Center for Disease Control (CDC) in the United States and looked at the relationship between cups of coffee drunk per day, and both total body fat percentage and abdominal or 'trunk' fat (adiposity).

They found that women aged 20-44 who drank two or three cups of coffee per day had the lowest levels of adiposity, 3.4% lower than people who did not consume coffee. Among women aged between 45-69, those who drank four or more cups had an adiposity percentage 4.1% lower.

Overall, the average total body fat percentage was 2.8% lower among women of all ages who drank two or three cups of coffee per day.

The findings were consistent whether the coffee consumed was caffeinated or decaffeinated, and among smokers/non-smokers and those suffering from chronic diseases when compared to those in good health.

In men, the relationship was less significant, although men aged 20-44 who drank two or three cups per day had 1.3% less total fat and 1.8% less trunk fat than those who did not consume coffee.

Around 7 million tons of coffee is consumed globally every year.

Dr Lee Smith, Reader in Public Health at Anglia Ruskin University and senior author of the study, said: "Our research suggests that there may be bioactive compounds in coffee other than caffeine that regulate weight and which could potentially be used as anti-obesity compounds.

"It could be that coffee, or its effective ingredients, could be integrated into a healthy diet strategy to reduce the burden of chronic conditions related to the obesity epidemic.

"It is important to interpret the findings of this study in light of its limitations - the study was at a specific point in time so trends cannot be established. However, we don't believe that someone's weight is likely to influence their coffee consumption."

Photocatalytic water splitting is one of the most promising ways to convert solar energy into the chemical one. Generally, the activity of a photocatalytic system composed of photocatalysts and cocatalysts is integrally determined by the efficiencies of basic processes such as light absorption, charge separation and surface catalysis. Conventionally, the nanoparticles of cocatalysts have been loaded on the surface of nanosized/microsized semiconductors.

However, this conventional configuration of photocatalysts has to confront the competition of light harvesting caused by deposited cocatalysts and ineffective interface contacts between photocatalysts and cocatalysts. This greatly retards the enhancement of photocatalytic performances.

Very recently, Prof. Fuxiang Zhang and his colleagues in Dalian Institute of Chemical Physicals, Chinese Academy of Sciences, introduced a reversed configuration of photocatalysts fabricated by depositing nanosized CdS (semiconductor) on the surface of microsized Mo2N hexagonal rods (cocatalyst).

The as-obtained reversed photocatalyst is denoted as Mo2N@CdS. For comparison, the photocatalyst with conventional configurations was fabricated by depositing nanosized Mo2N (cocatalyst) on the surface of bulk CdS (light harvester, photocatalyst), and the corresponding sample is denoted as Mo2N/CdS. The photocatalytic H2 evolution activity of the Mo2N@CdS sample under visible light irradiation is remarkably superior to that of Mo2N/CdS, during which the basic processes such as light absorption, charge separation and surface catalysis between the conventional and reversed configurations have been discussed and compared.

The reversed configuration of photocatalyst in this work shows advantages in light absorption, charge separation and surface catalysis with respect to the conventional configuration. Specifically, the reversed configuration can ensure the preferential light absorption of the CdS semiconductor to avoid the competition of light harvesting caused by the Mo2N cocatalyst. Secondly, much better charge separation is observed for the reversed configuration with respect to the conventional ones. Finally, the electron interactions between CdS and Mo2N and the pore-confined space of CdS particle stack make an effective confinement effect to promote the surface catalysis of Mo2N.

The novel design concept on the reversed configuration can be extended into more other systems, reactions and the fabrication of composites with inner 1D (or 2D) cocatalysts and outer 0D photocatalysts to promote the solar-to-chemical conversion.

For the first time, using a mouse model of Alzheimer's disease, scientists have documented a link between raised levels of calcium in mitochondria and neuronal death in the living brain. This relationship was previously documented in cell culture, but seeing this phenomenon in living mice makes it more likely that this occurs in people also and could point to a new target for Alzheimer's disease.

"We were able to show mitochondrial calcium dysregulation in the neurons of living mice with Alzheimer's-like symptoms using cutting edge live imaging techniques," says the lead author of the paper, Maria Calvo-Rodriguez, PhD. The senior author is Brian J. Bacskai, PhD. They are both from the Department of Neurology at Massachusetts General Hospital.

Their collaborators included researchers from Harvard School of Public Health and the School of Medicine at Instituto de Investigacion Biomedica de Cadiz (INIBICA) in Spain. This study was recently published in Nature Communications.

One of the defining hallmarks of Alzheimer's disease is the deposition of amyloid beta plaques and loss of neurons. The accumulation of amyloid beta has long been thought to be a trigger of the disease, but the exact means by which neurons die in Alzheimer's remain a mystery, and the amyloid beta theory has become controversial because so many drug candidates targeting amyloid beta have failed in clinical trials.

One of the effects of amyloid beta plaques is that they cause high calcium ion (Ca2+) levels in the brain cells. There is also evidence that, at least in cell culture, exposure to amyloid beta can raise Ca2+ levels within mitochondria and lead to neuronal death.

Mitochondria influence Ca2+ signaling inside neurons through the "mitochondrial calcium uniporter" that takes up Ca2+ into mitochondria. The investigation of this mechanism in living mice has been hampered by the lack of technologies sensitive enough to directly assess Ca2+ levels in mitochondria in the living brain.

To explore the relationship between Ca2+, mitochondria and neuronal death, Calvo-Rodriguez and her colleagues combined multiphoton-microscopy with a ratiometric Ca2+ indicator targeted to mitochondria to asses Ca2+ levels. They applied these technologies to examine the neurons of a transgenic mouse model of Alzheimer's disease that develops amyloid plaques similar to those from human patients.

Their studies demonstrate that increased mitochondrial Ca2+ levels are associated with plaque deposition and neuronal death in this model, indicating that abnormal Ca2+ levels in mitochondria could play a role in neuronal cell death in Alzheimer's disease.

Additionally, they observed that when soluble Aβ is applied to the healthy mouse brain Ca2+ concentration in mitochondria increases. That process can be prevented by blockage of the mitochondrial calcium uniporter with a drug. Soluble amyloid beta is a type of amyloid beta similar to that in the human Alzheimer's brain.

"High calcium levels in the mitochondria cause oxidative stress, and the death of neurons via apoptosis," says Calvo-Rodriguez. "We propose that by blocking the neuronal mitochondrial calcium uniporter we can prevent cell death and impact disease progression." Their work suggests targeting calcium entry to the mitochondria could be a promising new therapeutic approach in Alzheimer's disease.

Journal

Nature Communications

DOI

10.1038/s41467-020-16074-2

WASHINGTON, May 12, 2020 -- In the movie "Transformers," cars morph into robots, jets or a variety of machinery. A similar concept inspired a group of researchers to combine gas foaming, which is a blend of chemicals that induces gas bubbling, and 3D molding technologies to quickly transform electrospun membranes into complex 3D shapes for biomedical applications.

In Applied Physics Reviews, from AIP Publishing, the group reports on its new approach that demonstrates significant improvements in speed and quality compared with other methods. The work is also the first successful demonstration of formation of 3D neural tissue constructs with an ordered structure through differentiation of human neural progenitor/stem cells on these transformed 3D nanofiber scaffolds.

"Electrospinning is a technology to produce nanofiber membranes," said co-author Jingwei Xie, at the University of Nebraska Medical Center. "The physics principle behind it involves applying an electrical force to overcome the surface tension of a solution to elongate a solution jet into continuous and ultrafine fibers after solvent evaporation."

Due to an intrinsic property of electrospinning, nanofibers are often deposited to form 2D membranes or sheets with dense structures and small pore sizes that are less than the size of cells.

"This greatly inhibits the applications of electrospun nanofibers, because cells fail to seed or penetrate throughout the nanofiber membranes, which is undesirable," he explained.

Researchers combined gas foaming and 3D molding concepts to expand nanofiber membranes within a confined space to form predesigned 3D nanofiber objects in cylindrical, cuboid, spherical, and irregular shapes.

"Our 3D objects have the appropriate pore size and controlled fiber alignment for guiding and enhancing cell penetration to form new tissue," Xie said.

The group's work is significant, because it can be done within an hour. Other methods can require up to 12 hours to complete the transformation process.

"Thanks to the ability to mimic the architecture of extracellular matrix, electrospun nanofibers show great potential in applications such as tissue engineering, regenerative medicine and tissue modeling," said Xie.

One of the group's most intriguing findings is that after coating 3D nanofiber objects with gelatin, they exhibit superelasticity and shape recovery.

"Gelatin-coated, cube-shaped scaffolds functionalized with polypyrrole coatings exhibited dynamic electrical conductivity during cyclical compression," he said.

They also demonstrated that cuboid-shaped nanofiber objects were effective for compressible hemorrhage in a pig liver injury model.

In the future, the group's method may help "enable therapeutic-free biomaterials for tissue repair and regeneration, such as using predesigned nanofiber objects to fit irregular tissue defects," Xie said. "Beyond that, superelasticity and shape recovery could allow 3D-nanofiber objects to be applied in a minimally invasive manner."

A study led by Nanyang Technological University, Singapore (NTU Singapore) researchers has revealed how the physical presence of spouses who are co-parenting can alter each other's brain activity.

The researchers analysed how the brain activity of 24 pairs of husband and wife from Singapore changed in response to recordings of infant stimuli such as crying, when they were physically together and when they were separated.

They found that when spouses were physically together, they showed higher similarities in brain responses to the stimuli than when they were separated. This effect was only found in true couples and not in randomly matched study participants.

The area of the brain the researchers monitored is the prefrontal cortex, which is associated with complex behaviour and emotional states.

When similar brain activity in the same area of the brain (i.e. greater synchrony) is observed in two people, it suggests that both are highly attuned to each other's emotions and behaviours.

The senior author of the study, NTU Associate Professor Gianluca Esposito, who holds a joint appointment in the School of Social Sciences and the Lee Kong Chian School of Medicine, said, "Our study indicates that when spouses are physically together, there is greater synchrony in their attentional and cognitive control mechanisms when parenting. Since the brain response of parents may be shaped by the presence of the spouse, then it is likely that spouses who do not spend much time together while attending their children may find it harder to understand each other's viewpoint and have reduced ability to coordinate co-parenting responsibilities. This may undermine the quality of parental care in the long run."

Assoc Prof Esposito who also leads the Social and Affective Neuroscience Lab (SAN-Lab) at NTU said more time together while attending a child may seem a "waste of time". However, it may prove to help the couple with parenting.

"This finding is particularly useful for parents who are working from home during this "circuit breaker" period in Singapore - as families spend more time together at home as part of social distancing measures in the fight against COVID-19. The entire family interacting together for an extended period may be stressful, but parents can take this time to tune into each other's behaviour and emotions while caring for their children."

The study, undertaken in collaboration with researchers from the United States' National Institute of Child Health and Human Development and Italy's University of Trento, was published in the Nature Scientific Reports in May 2020.

How the study was done

The researchers used functional Near-infrared Spectroscopy (fNIRS), a non-invasive optical imaging technique to measure the brain signals based on the level of oxygenated and deoxygenated blood in the brain.

Prior to the experiment, couples answered a questionnaire that aims to measure how often the mother or father takes the lead in co-parenting. The couples were then exposed to infant and adult laughter and cries, as well as a static sound either together (in the same room at the same time) or separately (in different rooms at different times).

The NTU research team compared the couple's brain activity to calculate brain-to-brain synchrony and found that couples showed greater degree of synchrony when they were together than separated. This degree of similar brain activity was found to be unique to real couples and was not observed between randomly matched couples.

The paper's first author Ms Atiqah Azhari, an NTU PhD candidate at the SAN-Lab said, "Our study brings us a step closer in uncovering how the parental brain may be shaped by the physical presence of the co-parenting spousal partner.

To ascertain how synchrony may be beneficial or not for the couple or child, future research should look into how synchrony during positive and negative emotional situations directly affects coordinated caregiving behaviours."

The paper's co-first author Ms Mengyu Lim, who is a Project Officer at the SAN-Lab at NTU, said, "The findings of this study may be empowering for those who experience parenting stress - that we should not think of parenting as an individual task, but a shared responsibility with the spouse. Co-parenting requires active teamwork, communication, and trust in each other."

The study builds on Assoc Prof Esposito's earlier studies on the effects of parenting stress in the brains of both mothers and their children.

Studies of metal complexes with organic ligands at Kazan Federal University were initiated back in the 1970s by Professor Andrey Popel. Current research, headed by Associate Professor Tamara Bychkova and Associate Professor Valery Shtyrlin, concentrates on complex compounds of transition metals in aqueous and aqueous-organic solutions. So far, data has been obtained about the composition and stability of complexes of cobalt (II), nickel (II), copper (II) and vanadium oxide (IV) with mono-, di- and tetrahydrazides of various nature (aliphatic, aromatic, and macrocyclic) in aqueous, aqueous-dimethylsulfide, aqueos-dimethylformamide, aqueous-ethanol, and other media. Special software tools created at the Department of Inorganic Chemistry - CPESSP and STALABS - are used to calculate equilibrium parameters in solutions. In some cases, based on the analysis of stability constants and kinetic characteristics of complex formation, conjectures have been put forth about the structure of complexes; lately, quantum chemistry apparatus is widely used for this purpose.

The article presents the results of a study of complex formation processes in aqueous solutions containing copper (II) as a complexing agent and two ligands - dihydrazide (malonic or adipic) acid and amino acid - L-histidine. Heteroligand complexes of 1: 1: 1 composition with the zwitterionic form of L-histidine and adipic or malonic acid dihydrazide in neutral form were found. Despite the pH restrictions created by the solubility of the ligands (hydrazides are salted out from solution above pH 5), a heteroligand complex with adipic acid and the anionic form of L-histidine was also detected. The stability of the first two heteroligand complexes is consistent with statistics (we always carry out a statistical analysis of equilibrium constants, guided by the generally accepted approach), but for the latter complex there is some extrastabilization. In the general case, this means that the presence of one ligand in the internal sphere of the complexing ion favors the entry of another, that is, one ligand "positively" affects the other. The next question is what is this influence? Unable to isolate the complexes unchanged from the solution, we performed quantum-chemical calculations of the structures. From these calculations, several interesting conclusions follow: 1) copper (II) ions in heteroligand complexes with the indicated ligands are pentacoordinated (a discussion over the coordination number of copper (II) ions in water has been going on for many years), 2) a chain is realized in some isomeric forms of complexes hydrogen bonds between the protonated imidazole group of histidine and the oxygen atom of the hydrazide fragment through an axially coordinated water molecule; 3) the cis-structure of heteroligand complexes with malonic or adipic dihydrazide acid and negatively charged L-histidine are energetically more beneficial than the corresponding trans-structure. This fact is explained by the manifestation of trans-influence in copper (II) complexes, in which the strongest trans-agents (NH2 groups in this case) avoid being located on the same coordinate. Such an effect was previously established for homoligand complexes of copper (II) with L / DL-histidine. The manifestation of transfusion in heteroligand complexes of copper (II) with histidine and dicarboxylic acid hydrazides was established for the first time in this work.

Information on the presence of trans-influence as a type of stereoselectivity, which manifests itself in the formation of copper (II) complex compounds with malonic and adipic acid dihydrazides and L-histidine, contributes to a deeper understanding of the properties of coordination bonds, structural features of complex compounds in general and their existence in solutions in particular.

"The material accumulated to date in coordination chemistry allows us to speak about many aspects of the complex formation of transition metals with confidence, but there are still many unsolved problems. We plan to continue research on heteroligand complex compounds of essential 3d metals with biologically significant organic ligands," explains co-author Nikita Troshanin. Such complexes are interesting both from the point of view of fundamental chemistry (they can serve as models of biological systems, for example, compounds of proteins with metals), and for solving a number of practical problems (primarily in pharmacology). The literature describes many examples of how the biologically active properties of organic substances, mainly bacteriostatic, are enhanced by complex formation. However, not all complexes formed in solution can be isolated in solid form; therefore, biological tests are either impossible or impractical. "We hope that someday we will be able to get at least a few crystals of our heteroligand complexes, and then they will be studied comprehensively," concludes Mr. Troshanin.