Culture

Like all metals, silver, copper, and gold are conductors. Electrons flow across them, carrying heat and electricity. While gold is a good conductor under any conditions, some materials have the property of behaving like metal conductors only if temperatures are high enough; at low temperatures, they act like insulators and do not do a good job of carrying electricity. In other words, these unusual materials go from acting like a chunk of gold to acting like a piece of wood as temperatures are lowered. Physicists have developed theories to explain this so-called metal-insulator transition, but the mechanisms behind the transitions are not always clear.

"In some cases, it is not easy to predict whether a material is a metal or an insulator," explains Caltech visiting associate Yejun Feng of the Okinawa Institute for Science and Technology Graduate University. "Metals are always good conductors no matter what, but some other so-called apparent metals are insulators for reasons that are not well understood." Feng has puzzled over this question for at least five years; others on his team, such as collaborator David Mandrus at the University of Tennessee, have thought about the problem for more than two decades.

Now, a new study from Feng and colleagues, published in Nature Communications, offers the cleanest experimental proof yet of a metal-insulator transition theory proposed 70 years ago by physicist John Slater. According to that theory, magnetism, which results when the so-called "spins" of electrons in a material are organized in an orderly fashion, can solely drive the metal-insulator transition; in other previous experiments, changes in the lattice structure of a material or electron interactions based on their charges have been deemed responsible.

"This is a problem that goes back to a theory introduced in 1951, but until now it has been very hard to find an experimental system that actually demonstrates the spin-spin interactions as the driving force because of confounding factors," explains co-author Thomas Rosenbaum, a professor of physics at Caltech who is also the Institute's president and the Sonja and William Davidow Presidential Chair.

"Slater proposed that, as the temperature is lowered, an ordered magnetic state would prevent electrons from flowing through the material," Rosenbaum explains. "Although his idea is theoretically sound, it turns out that for the vast majority of materials, the way that electrons interact with each other electronically has a much stronger effect than the magnetic interactions, which made the task of proving the Slater mechanism challenging."

The research will help answer fundamental questions about how different materials behave, and may also have applications in technology, for example in the field of spintronics, in which the spins of electrons would form the basis of electrical devices instead of the electron charges as is routine now. "Fundamental questions about metal and insulators will be relevant in the upcoming technological revolution," says Feng.

Interacting Neighbors

Typically, when something is a good conductor, such as a metal, the electrons can zip around largely unimpeded. Conversely, with insulators, the electrons get stuck and cannot travel freely. The situation is comparable to communities of people, explains Feng. If you think of materials as communities and electrons as members of the households, then "insulators are communities with people who don't want their neighbors to visit because it makes them feel uncomfortable." Conductive metals, however, represent "close-knit communities, like in a college dorm, where neighbors visit each other freely and frequently," he says.

Likewise, Feng uses this metaphor to explain what happens when some metals become insulators as temperatures drop. "It's like winter time, in that people--or the electrons--stay home and don't go out and interact."

In the 1940s, physicist Sir Nevill Francis Mott figured out how some metals can become insulators. His theory, which garnered the 1977 Nobel Prize in Physics, described how "certain metals can become insulators when the electronic density decreases by separating the atoms from each other in some convenient way," according to the Nobel Prize press release. In this case, the repulsion between the electrons is behind the transition.

In 1951, Slater proposed an alternate mechanism based on spin-spin interactions, but this idea has been hard to prove experimentally because the other processes of the metal-insulator transition, including those proposed by Mott, can swamp the Slater mechanism, making it hard to isolate.

Challenges of Real Materials

In the new study, the researchers were able at last to experimentally demonstrate the Slater mechanism using a compound that has been studied since 1974, called pyrochlore oxide or Cd2Os2O7. This compound is not affected by other metal-insulator transition mechanisms. However, within this material, the Slater mechanism is overshadowed by an unforeseen experimental challenge, namely the presence of "domain walls" that divide the material into sections.

"The domain walls are like the highways or bigger roads between communities," says Feng. In pyrochlore oxide, the domain walls are conductive, even though the bulk of the material is insulating. Although the domain walls started out as an experimental challenge, they turned out to be essential to the team's development of a new measurement procedure and technique to prove the Slater mechanism.

"Previous efforts to prove the Slater metal-insulator transition theory did not account for the fact that the domain walls were masking the magnetism-driven effects," says Yishu Wang (PhD '18), a co-author at the Johns Hopkins University who has continuously worked on this study since her graduate work at Caltech. "By isolating the domain walls from the bulk of the insulating materials, we were able to develop a more complete understanding of the Slater mechanism." Wang had previously worked with Patrick Lee, a visiting professor at Caltech from MIT, to lay the basic understanding of conductive domain walls using symmetry arguments, which describe how and if electrons in materials respond to changes in the direction of a magnetic field.

"By challenging the conventional assumptions about how electrical conductivity measurements are made in magnetic materials through fundamental symmetry arguments, we have developed new tools to probe spintronic devices, many of which depend on transport across domain walls," says Rosenbaum.

"We developed a methodology to set apart the domain-wall influence, and only then could the Slater mechanism be revealed," says Feng. "It's a bit like discovering a diamond in the rough."

A new drug reduced tumor size in patients who have lung cancer patients with a specific, disease-causing change in the gene KRAS, a study found.

The results of the CODEBREAK 100 phase 2 clinical trial were presented June 4, 2021, at the American Society of Clinical Oncology (ASCO) annual meeting and published simultaneously in the New England Journal of Medicine. The efficacy and safety of the drug sotorasib, developed by Amgen Inc., was tested in patients with non-small-cell lung cancer (NSCLC) harboring a specific change, or mutation, in the DNA code for KRAS.

The KRAS mutant protein targeted in the study was p.G12C, in which a glycine building block has been mistakenly replaced a cysteine at position 12 in the protein's structure. This change is present in about 13 percent of the more than 200,000 patients diagnosed with lung cancer each year in the United States. KRAS encodes a protein switch that regulates growth but becomes "stuck in the "on" mode" when mutated, signaling cells to continually multiply in tumors.

Sponsored by Amgen - and led by researchers from Perlmutter Cancer Center at NYU Langone Health, Washington University School of Medicine, MD Anderson Cancer Center, and Memorial Sloan Kettering - the global trial included 126 patients that received daily, oral sotorasib. This KRASG12C inhibitor was recently approved by the U.S. Food and Drug Administration for the treatment of adult patients with KRAS G12C-mutated NSCLC.

The researchers found that 37.1 percent of patients in the study saw their tumors shrink by at least 30 percent, termed an "objective response." About 82 percent of those treated experienced some slowing of tumor growth or "disease control."

All patients in the study had been treated previously with either immunotherapy (PD1-inhibitors) or platinum-based combination chemotherapy, but those treatments were no longer effective for them, and their cancers had begun to regrow. With no targeted options, such patients typically do poorly, with response rates to standard treatments between 6 and 20 percent, according to previous studies.

"The excitement surrounding this trial result is that sotorasib, just approved for clinical use, becomes the first targeted therapy for lung cancer patients with KRAS mutations," says co-corresponding study author Vamsidhar Velcheti, MD, associate professor of Medicine at NYU Grossman of Medicine, and director of thoracic medical oncology at Perlmutter Cancer Center. "KRAS-targeted treatments, decades in the making, are urgently needed for these patients with limited therapeutic options."

The average duration of responses to sotorasib in the current trial was 11.1 months, with a median period during which disease did not worsen (progression-free survival) of 6.8 months, say the study authors. With currently available treatments, median progression-free survival for these patients is between two and four months.

"Sotorasib showed clinically significant benefit without any new safety concerns in patients with this specific form of KRAS mutant lung cancer," says co-corresponding author Ramaswamy Govindan MD, the Anheuser Busch Chair in Medicine at Washington University School of Medicine. "Moving forward, our team will seek to inform the development of combination therapies featuring sotorasib and other emerging drugs, and to determine which best fit the mix of mutations in each patient's cancer cells."

First of Its Kind

The RAS gene family is among the most frequently mutated in human cancers, with one member of the group, KRAS, the most commonly occurring mutant in solid tumors. KRAS has considered "undruggable" for decades because its active form does not include a suitable pocket to which drugs can attach.

Sotorasib is a novel covalent inhibitor that, thanks to recent advances in medical chemistry, can target a specific building block (cysteine residue) only present in the inactive form of KRAS. When the mutated KRAS switch toggles into its inactive state, sotorasib can attach to a structural feature called the switch II pocket and react with the mutant cysteine at position 12, freezing KRAS in the inactive state.

The phase 2 trial CodeBreak 100 study also focused on safety, finding that, while nearly 70 percent of patients had treatment-related adverse events, only about 20 percent had more severe events that required reduction of the dose of sotorasib. About 7 percent of patients had to stop treatment because of severe side effects. The most frequent of these were diarrhea, nausea, fatigue, and an increase in liver enzyme levels. There were no life-threatening side effects, and no treatment-related deaths in the study.

All patients in the single-arm CodeBreak 100 trial were treated with sotorasib, and none with placebo, as is standard in early studies of this type. The ongoing phase 3 CodeBreak 200 trial (NCT04303780), which is comparing the effect of sotorasib against a chemotherapy, docetaxel, will seek to confirm the current results in 345 patients with NSCLC harboring the KRAS p.G12C mutation.

Oak Brook, IL - The June edition of SLAS Discovery features the cover article, "A Perspective on Synthetic Biology in Drug Discovery and Development--Current Impact and Future Opportunities" by Florian David, Ph.D. (Chalmers University of Technology, Gothenburg, Sweden), Andrew M. Davis, Ph.D. (AstraZeneca, Cambridge, England, UK). Michael Gossing, Ph.D., Martin A. Hayes, Ph.D., and Elvira Romero, Ph.D., and Louis H. Scott, Ph.D. (AstraZeneca, Gothenburg, Sweden), and Mark J. Wigglesworth, Ph.D. (AstraZeneca, London, England, UK).

In January 2021, a survey of immunologists, infectious-disease researchers and virologists found that 90% of respondents believe SARS-CoV-2 will become endemic, continuing to circulate in pockets of the global population for years to come. Even as vaccines are becoming more widely available, there are people who either do not respond to the treatment or are not suitable for vaccination. There is a critical need to develop small molecule inhibitors for this pathogen.
The cover article highlights the work of the Drug Discovery Unit at the University of Dundee (Dundee, Scotland, UK) reporting on the development of a high-throughput biochemical assay to assess the impact of small molecules on the methyltransferase activity of SARS-CoV-2 nonstructural protein 14 (nsp14). This enzyme is responsible for the N7-methylation of the cap at the 5' end of viral RNA and is critical in helping coronaviruses evade host defenses. The label-free MS-based assay developed was used to screen a library of 1771 FDA-approved drugs. The chemical hits that were identified may serve as starting points for drug discovery programs aimed at delivering therapeutics for the SARS-CoV-2 virus.

The June issue of SLAS Discovery includes nine articles of original research.

These include:

Development and Validation of High-Content Analysis for Screening HDAC6-Selective Inhibitors

In Vitro Pharmacokinetic/Pharmacodynamic Modeling of HIV Latency Reversal by Novel HDAC Inhibitors Using an Automated Platform

Identification and Kinetic Characterization of Serum- and Glucocorticoid-Regulated Kinase Inhibitors Using a Fluorescence Polarization-Based Assay

Reducing False Positives through the Application of Fluorescence Lifetime Technology: A Comparative Study Using TYK2 Kinase as a Model System

Biochemical and Cellular Profile of NIK Inhibitors with Long Residence Times

A Novel High-Throughput FLIPR Tetra-Based Method for Capturing Highly Confluent Kinetic Data for Structure-Kinetic Relationship Guided Early Drug Discovery

A Multipronged Screening Approach Targeting Inhibition of ETV6 PNT Domain Polymerization

Unbiased High-Throughput Drug Combination Pilot Screening Identifies Synergistic Drug Combinations Effective against Patient-Derived and Drug-Resistant Melanoma Cell Lines

Regenerable Biosensors for Small-Molecule Kinetic Characterization Using SPR

Other articles include:

A Perspective on Synthetic Biology in Drug Discovery and Development--Current Impact and Future Opportunities

Public-Private Partnerships: Compound and Data Sharing in Drug Discovery and Development

A High-Throughput RNA Displacement Assay for Screening SARS-CoV-2 nsp10-nsp16 Complex Toward Developing Therapeutics for COVID-19

Development of a High-Throughput Assay to Identify Inhibitors of ENPP1

Access to June's SLAS Discovery issue is available at https://journals.sagepub.com/toc/jbxb/current. For more information about SLAS and its journals, visit https://www.slas.org/publications/slas-discovery/ Access a "behind the scenes" look at the latest issue with SLAS Discovery Author Insights podcast. Tune in by visiting https://www.buzzsprout.com/1099559.

Oak Brook, IL - The June edition of SLAS Technology is a Special Issue entitled, "Emerging Trends in 3D Cell Culture: High-Throughput Screening, Disease Modeling and Translational Medicine." Free online access to the articles in this collection is courtesy of Corning Life Sciences, the issue's sponsor.

Precision medicine is becoming an increasingly popular and powerful way to target and treat human diseases. Patient-derived cellular models ushered in high-throughput screenings (HTS) in laboratory automation. While the upkeep and expansion of cells for HTS is predominantly manual, this special issue explores an automated avenue for HTS in research settings that considers the expansion of cells. This design is flexible for research and development of various cell types. The June issue analyzes protocols for controlled cell seeding, splitting and expansion of human fibroblasts, induced pluripotent stem cells (iPSCs), and neural progenitor cells (NPCs). These multiple platforms lend themselves well for research on patient-derived cellular models for precision medicine. "Significant improvements have been made in formation of complex 3D structures, but challenges remain in automating assay protocols with these models. The flowchips described in the issue contain protected sample chambers to allow media exchange, sample staining, wash steps, and supernatant sampling to occur without disruption to or loss of 3D sample," says SLAS Technology author Evan F. Cromwell, Ph.D. (Protein Fluidics, Inc.).

The June issue of SLAS Technology includes six articles of original research including:

Toxicity of Combinations of Kinase Pathway Inhibitors to Normal Human Cells in a Three-Dimensional Culture

Spheroid Trapping and Calcium Spike Estimation Techniques toward Automation of 3D Culture

Miniaturized Drug Sensitivity and Resistance Test on Patient-Derived Cells Using Droplet-Microarray

Automating Human Induced Pluripotent Stem Cell Culture and Differentiation of iPSC-Derived Retinal Pigment Epithelium for Personalized Drug Testing

Creating an Affordable, User-Friendly Electronic Inventory System for Lab Samples

Adapting a Low-Cost and Open-Source Commercial Pipetting 311 Robot for Nanoliter Liquid Handling

Other articles include:

Disease Modeling with 3D Cell-Based Assays Using a Novel Flowchip System and High-Content Imaging

Three-Dimensional Macroporous Sponge for the Culture of Hepatocellular Carcinoma Patient-Derived Xenograft Organoids

Automated Device for Uncapping Multiple-Size Bioanalytical Sample Tubes Designed to Reduce Technician Strain and Increase Productivity

Literature Highlights Column: Life Sciences Discovery and Technology Highlights

Access to June's SLAS Technology issue is available at https://journals.sagepub.com/toc/jlad/26/2. For more information about SLAS and its journals, visit https://www.slas.org/publications/slas-technology/.

Bottom Line: The majority of surveyed Americans had an inadequate understanding of palliative care, and frequency of health care utilization was one determinant of knowledge.

Journal in Which the Study was Published: Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research

Author: Motolani Ogunsanya, PhD, an assistant professor at The University of Oklahoma Health Sciences Center

Background: Palliative care aims to improve the quality of life for patients and caretakers by addressing the physical, psychological, and logistical challenges associated with a disease or its treatment. In contrast to hospice, which provides comfort care for patients who have stopped treatment and are near the end of life, palliative care serves as an adjunct to life-sustaining treatments by addressing the side effects of treatment or symptoms of the disease.

"Despite the known benefits of palliative care and its endorsement by the American Society of Clinical Oncology and the National Comprehensive Cancer Network, we have not seen an increased uptake of palliative care by those who need it most," said Ogunsanya. "A common misconception is that palliative care is only for end-of-life care when, in fact, it can begin at any point in the disease course."

How the Study was Conducted: To study the extent of people's knowledge about palliative care and understand how various factors impact knowledge of palliative care across the American population, Ogunsanya and colleagues analyzed data from a National Cancer Institute's Health Information National Trends Survey (HINTS) from 2018. The dataset included self-reported demographic and clinical information, such as sex, age, education level, current health status, cancer history, and frequency of health care utilization, among others. Respondents self-reported their knowledge of palliative care by selecting between: "I've never heard of it," "I know a little bit about palliative care," and "I know what palliative care is, and I could explain it to someone else." The first two responses were grouped together as inadequate knowledge, and the final response was considered adequate knowledge.

Results: Among the 3,450 survey respondents, approximately 65 percent identified as non-Hispanic white, at least 90 percent had health insurance, about 60 percent had utilized the health care system more than twice in the past year, and about 10 percent had been previously diagnosed with cancer.

Overall, only 11 percent of the respondents reported adequate knowledge of palliative care. Women and married individuals were twice as likely to have adequate knowledge when compared with men and single respondents, respectively. Those who had a college degree were over 13-times more likely to have adequate knowledge of palliative care compared with respondents without a high school degree.

Health care utilization was also associated with knowledge of palliative care, as those with a regular source of medical care were 2.67 times more likely to have adequate knowledge of palliative care than those without regular medical care. In addition, respondents with a prior cancer diagnosis were 51 percent more likely to have adequate knowledge of palliative care than those who had never been diagnosed with cancer. Ogunsanya noted that this might be due to the increased engagement patients with cancer have with the health care system.

Author's Comments: "We found that in addition to personal factors, such as education level or marital status, the frequency of health care utilization had a significant impact on an individual's understanding of palliative care," said Ogunsanya. "This is a novel finding for the palliative care field and provides important insight into how we might be able to improve knowledge of this service.

"Since health care providers are often the first and most trusted source of health care information, educating physicians on palliative care and encouraging them to discuss it with their patients and caretakers is one potential strategy to increase understanding of palliative care," Ogunsanya noted. She added that addressing additional barriers to palliative care, such as misconceptions and lack of resources or time, are also important approaches to increasing awareness.

Study Limitations: A limitation of the study was that knowledge of palliative care was self-reported; however, Ogunsanya noted that this mode of data collection also provided an important perspective. "How someone perceives their own knowledge of palliative care may reveal more about their likelihood to pursue palliative care than a more objective measure," she explained. "If someone is not confident in their knowledge of palliative care, they may be less inclined to ask for it, regardless of how well they do understand it."

Additional limitations of the study included the exclusion of individuals who did not speak English or Spanish and those without a permanent address.

Dogs may have earned the title "man's best friend" because of how good they are at interacting with people. Those social skills may be present shortly after birth rather than learned, a new study by University of Arizona researchers suggests.

Published today in the journal Current Biology, the study also finds that genetics may help explain why some dogs perform better than others on social tasks such as following pointing gestures.

"There was evidence that these sorts of social skills were present in adulthood, but here we find evidence that puppies - sort of like humans - are biologically prepared to interact in these social ways," said lead study author Emily Bray, a postdoctoral research associate in the UArizona School of Anthropology in the College of Social and Behavioral Sciences.

Bray has spent the last decade conducting research with dogs in collaboration with California-based Canine Companions, a service dog organization serving clients with physical disabilities. She and her colleagues hope to better understand how dogs think and solve problems, which could have implications for identifying dogs that would make good service animals.

To better understand biology's role in dogs' abilities to communicate with humans, Bray and her collaborators looked at how 375 of the organization's 8-week-old budding service dogs, which had little previous one-on-one interaction with humans, performed on a series of tasks designed to measure their social communication skills.

Because the researchers knew each puppy's pedigree - and therefore how related they were to one another - they were also able to look at whether inherited genes explain differences in dogs' abilities. Genetics explained more than 40% of the variation in puppies' abilities to follow human pointing gestures, as well as variation in how long they engaged in eye contact with humans during a task designed to measure their interest in people.

"People have been interested in dogs' abilities to do these kinds of things for a long time, but there's always been debate about to what extent is this really in the biology of dogs, versus something they learn by palling around with humans," said study co-author Evan MacLean, assistant professor of anthropology and director of the Arizona Canine Cognition Center at the University of Arizona. "We found that there's definitely a strong genetic component, and they're definitely doing it from the get-go."

At the time of the study, the puppies were still living with their littermates and had not yet been sent to live with a volunteer puppy raiser. Therefore, their interactions with humans had been limited, making it unlikely that the behaviors were learned, Bray said.

The researchers engaged the puppies in four different tasks. In one task, an experimenter hid a treat beneath one of two overturned cups and pointed to it to see if the puppy could follow the gesture. To ensure that the pups weren't just following their noses, a treat was also taped to the inside of both cups. In another version of the task, puppies watched as the researchers placed a yellow block next to the correct cup, instead of pointing, to indicate where the puppy should look for the food.

The other two tasks were designed to observe puppies' propensity to look at human faces. In one task, the researchers spoke to the puppies in "dog-directed speech," reciting a script in the sort of high-pitched voice people sometimes use when talking to a baby. They then measured how long the puppy held a gaze with the human. In the final task - a so-called "unsolvable task" - researchers sealed a treat inside a closed container and presented it to the puppy, then measured how often the puppy looked to the human for help opening the container.

While many of the puppies were responsive to humans' physical and verbal cues, very few looked to humans for help with the unsolvable task. That suggests that while puppies may be born knowing how to respond to human-initiated communication, the ability to initiate communication on their own may come later.

"In studies of adult dogs, we find a tendency for them to look to humans for help, especially when you look at adult dogs versus wolves. Wolves are going to persist and try to independently problem solve, whereas dogs are more likely to look to the social partner for help," Bray said. "In puppies, this help-seeking behavior didn't really seem to be part of their repertoire yet."

In many ways, that mirrors what we see in human children's development, Bray said.

"If you think about language learning, children can understand what we're saying to them before they can physically produce the words," she said. "It's potentially a similar story with puppies; they are understanding what is being socially conveyed to them, but the production of it on their end is probably going to take a little bit longer, developmentally."

MacLean said the next step will be to see if researchers can identify the specific genes that may contribute to dogs' capacity to communicate with humans.

"We've done some previous studies that show that dogs who tend to be successful as service dogs respond to people in different ways than dogs who aren't successful," MacLean said. "If you could identify a potential genetic basis for these traits, you might be able to predict, even before the puppy is born, if they are part of a litter that would be good service dog candidates, because they have the right genetic background. It's a long way down the road, but there is potential to start applying this."

WASHINGTON (June 3, 2021) - Nearly three-quarters of breast cancer patients (73%) report using at least one type of complementary medicine after cancer diagnosis, while oncologists believe that less than half (43%) of patients are using these approaches during cancer care. These and other findings from a national survey of oncologists and breast cancer patients were released in conjunction with the 2021 ASCO Annual Meeting. The study found that doctors report discussing integrative health with only about half of patients, leading patients to seek information outside the clinic.

"Cancer is a complex disease that affects every component of a patient's life. While conventional medicine is effective for curing disease, it can fall short in helping patients heal," said Wayne Jonas, MD, report co-author and executive director for Integrative Health Programs at the Samueli Foundation. "Patients are turning to these therapies to looking for hope and to improve their quality of life and wellbeing after diagnosis, but they are looking for more guidance from their oncologists."

A national survey of 115 clinical oncologists who treat breast cancer was conducted in late 2020 alongside a similar survey of 164 breast cancer patients who had been diagnosed within two years of the survey. The poll was conducted by IQVIA, a global provider of advanced analytics, technology solutions, and clinical research services to the life sciences industry, to understand awareness, usage, and attitudes toward the use of complementary and lifestyle therapies in addition to medical treatment.

In the study, the researchers found that two-thirds of oncologists (66%) and patients (65%) believe using complementary and lifestyle therapies improve patients' quality of life. Many patients (60%) also believe these treatments lead to better health outcomes. Interestingly, patient use of tai chi/chi gong or acupuncture had the strongest correlation with positive impact on quality of life among the 12 modalities tested.

The survey also gauged patients' and physicians' awareness of complementary and lifestyle therapies and sources of information for patients. Most oncologists reported familiarity with at least one therapy. These physicians saw nutrition consultation, support groups, psycho-oncology support, and exercise consultation as the most important integrative services. However, they gave relatively low marks to spiritual services and meditation or mindfulness--two approaches that patients see as important. Patients also recall their care teams providing fewer recommendations about these two modalities than the others.

While oncologists and patients agree that an oncologist, oncology nurse, or patient navigator is a good source of information for complementary medicine and lifestyle therapies, patients have a slight preference to hear directly from the oncologists.

"Many oncologists are generally supportive of integrating complementary and lifestyle therapies with conventional medical treatment, but the education and guidance given to patients varies widely," said Terri Crudup, Senior Principal of Primary Intelligence at IQVIA. "Oncologists and the institutions at which they practice should look for methods to educate and expose patients to a variety of safe and effective complementary and lifestyle therapies to find the ones that will help their patients most."

Astronomers studying the fast-moving jet of material ejected by a still-forming, massive young star found a major difference between that jet and those ejected by less-massive young stars. The scientists made the discovery by using the U.S. National Science Foundation's Karl G. Jansky Very Large Array (VLA) to make the most detailed image yet of the inner region of such a jet coming from a massive young star.

Both low- and high-mass young stars, or protostars, propel jets outward perpendicular to a disk of material closely orbiting the star. In stars with masses similar to the Sun, these jets are narrowed, or focused, relatively tightly near to the star in a process called collimation. Because most high-mass protostars are more distant, studying the regions close to them has been more difficult, so astronomers were unclear if this was the case with them.

A team of scientists observed a massive protostar called Cep A HW2, located about 2,300 light-years from Earth in the constellation Cepheus. Cep A HW2 is expected to develop into a new star about 10 times more massive than the Sun. The new VLA images showed the finest detail yet seen in such an object, giving the astronomers their first view of the innermost portion of the jet, a portion roughly as long as the diameter of the Solar System.

"What we saw is very different from what usually is seen in the jets from low-mass stars," said Adriana Rodriguez-Kamenetzky, of the National Autonomous University of Mexico (UNAM).

In lower-mass protostars, observations have shown the jets to be collimated as close to the star as only a few times the Earth-Sun distance.

In Cep A HW2, however, "We see not a single jet, but two things -- a wide-angle wind originating close to the star, then a highly-collimated jet some distance away," said Alberto Sanna, of the Osservatorio Astronomico di Cagliari (INAF) in Italy. The collimated jet starts at a distance from the star comparable to the distance from the Sun to Uranus or Neptune.

The discovery raises two main possibilities, the astronomers said.

First, the same mechanism could be at work in both high-mass and low-mass protostars, but the collimation distance could be determined by the mass, occurring farther away in more-massive systems. The second possibility is that high-mass stars might produce only the wide-angle wind seen in Cep A HW2, with collimation only coming when physical conditions around the star restrict the flow.

"That case would point to a major difference in the mechanisms at work in protostars of different masses," said Carlos Carrasco-Gonzalez, also of UNAM, leader of the work. "Answering this question is important to understanding how stars of all masses form," he added.

(SACRAMENTO, Calif.) - An international team of researchers, led by UC Davis Health, has developed a new therapeutic approach to treating psoriatic arthritis, a chronic inflammatory disease affecting the joints.

Using a novel chemical blocker targeting chemokine proteins, the researchers were able to significantly reduce skin and joint inflammation in a mouse model with psoriasis and psoriatic arthritis.

What is psoriatic arthritis?

Psoriatic arthritis affects up to a third of patients with psoriasis, an auto-immune skin inflammation. It creates mobility and functional changes that make it painful for patients to use their hands or walk. Some of these changes are irreversible.

Psoriatic arthritis is tough to treat.

"There is a clear need for better treatments using alternative approaches to joint inflammation," said Sam T. Hwang, professor and chair of dermatology at UC Davis and senior author of the study.

Understanding the mechanism behind joint inflammation

Chemokines are small molecules with a critical role in the body's response to inflammation and infection. They help guide the migration of immune cells to the site of injury or trauma. Chemokines need receptors to function. One specific chemokine receptor is CCR6.

The researchers assessed the role of CCR6 and its binding partner CC chemokine ligand 20 (CCL20) in inflammation linked to psoriatic arthritis and psoriasis. They looked at the potential of the CCR6/CCL20 combo as an effective therapeutic target.

They measured the CCR6 and the CCL20 levels in the joint fluid and tendon tissues of patients with psoriatic arthritis. CCR6 is a critical agent for the migration of T cells - a type of white blood cells - in skin psoriasis. The new study showed that CCR6 plays a similar role in joint inflammation. The team also found that CCL20 is present at very high levels in inflamed joint fluid.

"We observed a significant increase of both CCR6 and CCL20 in the connective tissue of mice with psoriasis and psoriatic arthritis," Hwang noted. "This high presence was also confirmed in inflamed human tendon biopsies."

The presence of CCL20 at the site of the inflammation makes it a very attractive target for arthritis therapy.

The connective tissue linking tendons and ligaments with the bones is called the enthesis. It is an important site of inflammation in psoriatic arthritis. The study found that entheses are distinct locations which CCR6+ T cells appear to locate and, therefore, cause inflammation.

"It is critical to identify the specific tissues where inflammation in the joints first occurs before it spreads and damages the cartilage and the bone," Hwang said.

Blocking the function of the CCR6 chemokine

The researchers tested the ability of a novel engineered protein- known as CCL20 locked dimer (CCL20LD)- in blocking the CCR6 function in a mouse model with psoriatic arthritis. The protein profoundly reduced both skin and joint inflammation by shutting the CCR6's power to attract T cells.

"The success of CCL2OLD in blocking CCR6 function in a mouse model shows potential for treating psoriatic arthritis in humans," Hwang said. "Definitely, this requires more testing and clinical trials to explore its effectiveness and safety."

The study was published in the journal Arthritis & Rheumatology.

A recent study by a team of researchers led by Dr Vinod Kumar Saranathan from the Division of Science at Yale-NUS College has discovered a complex, three-dimensional crystal called the single gyroid within feathers of the blue-winged leafbird. Dr Saranathan and his team's breakthrough came from their investigation of the feather colours of leafbirds, an enigmatic group of perching birds endemic to South and Southeast Asia (including Singapore), one species of which has evolved the unique crystals in its plumage.

By comparing the colour-producing nanostructures present in close relatives, the team reported that this species is able to directly synthesise single gyroid photonic crystals, which have highly desirable optical and electronic properties that make them ideal for use in photovoltaic cells to generate solar energy. Use of this crystal - a "crowning achievement" in material science engineering which thus far has been manufactured only with great difficulty - has the potential not only to improve photovoltaic cells, meaning they can be produced more easily and cheaply, but also for use in other industrial applications like catalysis in fuel cells and fibre optics.

Published in Proceedings of the National Academy of Sciences of the United States of America (PNAS), this study is particularly relevant as the search for renewable sources of energy and sustainable manufacturing has taken on a fresh urgency.

Dr Saranathan, who holds a concurrent appointment at the National University of Singapore's Department of Biological Sciences, said, "Currently, we cannot industrially manufacture single gyroid photonic crystals to work in the visible light spectrum, via self-assembly, a process that spontaneously brings together nanoscale chemical 'Lego-blocks'. Larger crystals can be manufactured and then heat-shrunk to work with visible light, but so far this can be done only on a small scale and is not defect-free. Thus, our discovery of the first directly self-assembled single gyroid crystals known to science, found in these leafbirds, we think is revolutionary. The way leafbirds manufacture these crystals is much more straightforward than how butterflies (some of which use the same structure in their wing scales) or material scientists are known to do so."

"Our research provides a clear insight on the class of patchy particles like charged proteins that researchers can investigate in the future, to see if they can be coaxed into forming these crystals at visible light scales. Knowing how leafbirds manufacture these exotic structures can spur novel biomimetic eco-friendly self-assembly strategies for large-scale materials synthesis at these highly challenging optical length-scales, given the urgent ecological need for such materials."

BUFFALO, N.Y. - College students who engaged in four or more high-impact practices such as study abroad or internships have a 70% chance of either enrolling in graduate school or finding a full-time job after graduating with a bachelor's degree, finds a new University at Buffalo study.

Each additional high-impact practice increased a student's chance of attaining a bachelor's degree and a full-time job by 17% or enrolling in graduate school by 30%, according to the study. These practices - such as study abroad, internships, undergraduate research, community service, first-year seminars and capstone courses - have the greatest influence on college success, regardless of student or family background, say the researchers.

The results, published in the International Journal of Educational Research Open, may help universities close the learning gap between immigrant and international college students compared to students whose families were born in the United States, ensuring educational equity and inclusion for marginalized students.

Immigrant students are more likely to be economically disadvantaged, take part in fewer high-impact practices, and lag behind U.S.-born students in graduation rates, graduate school enrollment and job attainment, according to the study.

International students excel in graduation rates and graduate school enrollment but trail in finding full-time employment, despite higher levels of participation in high-impact practices than U.S.-born students. Strict anti-immigration policies that limit employment, internship and research opportunities for international students may contribute to their difficulties in finding employment, says lead investigator Jaekyung Lee, PhD, professor of counseling, school and educational psychology in the UB Graduate School of Education.

"Disadvantaged students are often neglected and stereotyped as not being capable of obtaining success when it is the environments that are at fault," says Lee. "Transforming one's self-trajectory at the individual level is an unfair burden on students whose every day is already fraught with multi-systemic barriers. Intentional, committed action at the institutional level is vital to students' college readiness and success."

"It is important that higher education institutions do not merely state they value inclusion, but provide support services that address key issues such as language difficulties, adjusting to cultural norms, financial concerns and discrimination," says Namsook Kim, PhD, co-author and clinical assistant professor of educational leadership and policy in the UB Graduate School of Education.

The study, funded by the AccessLex Institute, Association for Institutional Research, and UB Baldy Center for Law and Social Policy, sought to compare the performance of immigrant and international college students with U.S.-born students, and understand the factors that improved or impeded their success.

The researchers examined data on student transition from college to career from the National Center for Education Statistics, and interviewed international and immigrant students. Students were considered U.S.-born if their parents were born in the U.S., and regarded as immigrants if their parents were born in another country but reside in the U.S.

Lithium is a vital element in the batteries that power electric vehicles, but soaring lithium demand is expected to exhaust land-based reserves by 2080. KAUST researchers have now developed an economically viable system that can extract high-purity lithium from seawater.

The oceans contain about 5,000 times more lithium than the land but at extremely low concentrations of about 0.2 parts per million (ppm). Larger ions, including sodium, magnesium and potassium, are all present in seawater at much higher concentrations; however, previous research efforts to tease lithium from this mixture have yielded little.

The KAUST team solved this problem with an electrochemical cell containing a ceramic membrane made from lithium lanthanum titanium oxide (LLTO). Its crystal structure contains holes just wide enough to let lithium ions pass through while blocking larger metal ions. "LLTO membranes have never been used to extract and concentrate lithium ions before," says postdoc Zhen Li, who developed the cell.

The cell contains three compartments. Seawater flows into a central feed chamber, where positive lithium ions pass through the LLTO membrane into a side compartment that contains a buffer solution and a copper cathode coated with platinum and ruthenium. Meanwhile, negative ions exit the feed chamber through a standard anion exchange membrane, passing into a third compartment containing a sodium chloride solution and a platinum-ruthenium anode.

The researchers tested the system using seawater from the Red Sea. At a voltage of 3.25V, the cell generates hydrogen gas at the cathode and chlorine gas at the anode. This drives the transport of lithium through the LLTO membrane, where it accumulates in the side-chamber. This lithium-enriched water then becomes the feedstock for four more cycles of processing, eventually reaching a concentration of more than 9,000 ppm. Adjusting the pH of this solution delivers solid lithium phosphate that contains mere traces of other metal ions -- pure enough to meet battery manufacturers' requirements.

The researchers estimate that the cell would need only US$5 of electricity to extract 1 kilogram of lithium from seawater. The value of hydrogen and chlorine produced by the cell would more than offset this cost, and residual seawater could also be used in desalination plants to provide freshwater.

"We will continue optimizing the membrane structure and cell design to improve the process efficiency," says group leader Zhiping Lai. His team also hopes to collaborate with the glass industry to produce the LLTO membrane at large scale and affordable cost.

Regular strength and impact-type training may decrease or even prevent age-related bone deterioration in men, new research at the University of Jyväskylä, Finland, shows. The tibial bone properties of middle-aged and older male sprint athletes were followed over 10 years. The study presents novel findings on maintaining the adaptability of the aging skeleton and on the importance of regular intensive training for maintaining bone health.

"Part of the age-related bone loss is probably explained by reduced levels of physical activity. Especially intensive, bone-loading exercise typically decreases with age," says Tuuli Suominen, a doctoral researcher at the Gerontology Research Center, Faculty of Sport and Health Sciences at the University of Jyväskylä.

High-intensity strength, sprint and jumping training have beneficial effects on bone even in old age. However, the ability of such training to prevent or decrease age-related bone deterioration remains unclear, as no longitudinal studies have been conducted on the topic thus far.

Associations of regular strength and sprint training with bone aging were examined in a larger research program by the Gerontology Research Center and Faculty of Sport and Health Sciences at the University of Jyväskylä, Finland. A total of 69 men aged 40 to 85 years participated in the follow-up part of the study. At the beginning of the follow-up, all the men were training and competing actively.

Tibial bone properties of the participants were examined by computed tomography at baseline and after 10 years. The associations of the training status with the longitudinal changes in bone were examined in two groups: in athletes who had continued regular strength and sprint training and in athletes who had reduced their training load.

The study showed that regular strength and sprint training was associated with maintained or even improved tibial bone properties while in those athletes who had reduced their training load the bone properties declined over the 10-year follow-up period. The positive effects of the training were most evident in trabecular bone density and in cross-sectional geometry of the tibial shaft, which supports the benefits of both impact-type training and strength training.

"Although the intensive training of the athletes as such is not possible for all aging people, strength and power training is highly recommended at all ages, regardless of the functional status," Suominen says. "In the present study, the benefits of high-impact training were most evident among middle-aged while strength training may be effective in preserving bone in older populations. Muscle strength and power are highly important also in preventing falls and related fractures."

Affecting more than one in a hundred children, autism spectrum disorder is one of the most common neurodevelopmental disorders. It has a particular impact on social interaction, including difficulties in understanding other people's perspectives, beliefs, desires and emotions, known as 'theory of mind'. Bilingual families with an autistic child often tend - and are sometimes encouraged - to forego the use of one of the home languages, so as not to further complicate the development of their child's communicative skills. A researcher from the University of Geneva (UNIGE, Switzerland), in collaboration with the Universities of Thessaly (Greece) and Cambridge (Great-Britain), has shown that bilingualism allows autistic children to partially compensate for deficits in theory of mind and executive functions, which are at the root of many of their challenges. These results can be read in the journal Autism Research.

Diagnosed in early childhood, autism spectrum disorder has a particular impact on a child's social and communicative abilities. "It is a spectrum, which is why the intensity of the symptoms varies greatly", explains Stéphanie Durrleman, a researcher in the Department of Linguistics at the UNIGE Faculty of Arts and co-author of the study. "But what children with autism have in common is that they have difficulties putting themselves in the place of their interlocutor, focusing on the latter's point of view and thus disengaging their attention from their own perspective." Autism therefore affects not only everything that has to do with the theory of mind - understanding the beliefs, emotions, intentions and desires of others - but also often executive functions, including attentional abilities.

Could benefits of bilingualism be applied to children with autism?

Studies on bilingualism have shown that children without autism who use several languages have increased theory of mind and executive function skills compared to monolingual children. "Bilingualism therefore seems to bring benefits precisely where the autistic child has difficulties", says Stéphanie Durrleman. "We therefore wondered whether bilingual autistic children manage to mitigate the difficulties of their neurodevelopmental disorder by using two languages every day."

To test this hypothesis, the researchers from the universities of Geneva, Thessaly and Cambridge followed 103 autistic children aged 6 to 15, 43 of whom were bilingual. "In order to observe the real effects of bilingualism on their socio-communicative skills, we grouped them according to their age, gender and the intensity of their autistic disorder", explains Eleni Peristeri, researcher at the Faculty of Medicine of the University of Thessaly and co-author of the study. The participants then performed various tasks to assess their theory of mind and executive function skills. The bilinguals quickly distinguished themselves by scoring higher than their monolingual peers. "On tasks relating to theory of mind, i.e. their ability to understand another person's behaviour by putting themselves in their place, the bilingual children gave 76% correct answers, compared with 57% for the monolingual children", notes the Greek researcher. The same is true for executive functions: the score for correct responses in bilinguals is twice that of monolinguals. But why are the differences so clear?

"Bilingualism requires the child to work first on skills directly related to theory of mind, i.e. he or she must constantly be concerned with the knowledge of others: Does the person I am speaking to speak Greek or Albanian? In what language should I talk to him or her? Then, in a second phase, the child uses his executive functions by focusing his attention on one language, while inhibiting the second", explains Eleni Peristeri. This is a real gymnastics for the brain, which acts precisely on the deficits linked to the autistic disorder.

Encouraging bilingualism instead of giving it up

"From our evaluations, we can clearly see that bilingualism is very beneficial for children with autism spectrum disorders", enthuses Stéphanie Durrleman. In order to certify that the socio-economic level in which the participants grew up did not play a role in the results, this was also recorded and it turned out that the bilingual children were mostly in a lower socio-economic environment than the monolinguals. "We can therefore affirm that benefits in theory of mind and executive functions emerge in bilinguals, even when there is a socio-economic disadvantage", says the Geneva researcher.

These findings are important for the care of children diagnosed with autism. "Indeed, as this neurodevelopmental disorder often affects language acquisition, bilingual families tend to give up the use of one of the two languages, so as not to exacerbate the learning process. However, it is now clear that far from putting autistic children in difficulty bilingualism can, on the contrary, help these children to overcome several aspects of their disorder, serving as a kind of natural therapy", concludes Stéphanie Durrleman.

Paleo researcher Charlotte Prud'homme, who until recently worked at the Max Planck Institute for Chemistry and is now a researcher at the Université Lausanne, explains: "The 80-meter-thick sedimentary sequence we found at Charyn Canyon in southeast Kazakhstan provides us with a virtually continuous record of five million years of climate change. This is a very rare occurrence on land!" The alternating dust and soil layers provide the first reliable evidence, in one place, of long-term interactions between major climate systems on the Eurasian continent. "Over the past five million years, the land surfaces of Eurasia appear to have more actively contributed to the land-atmosphere-ocean water-cycle than previously acknowledged. The sediments preserved at Charyn Canyon acted as a litmus test for the influx of freshwater into the Arctic Ocean, stimulating the transport of moist air masses from the North Atlantic back onto land via westerly air flows," corresponding author Prud'homme says. The results of the research have now been published in the scientific journal Communications Earth and Environment.

The researchers focused their investigation on the Pliocene and Pleistocene periods. The Pliocene, five to 2.6 million years ago, represents the best analogue for the climatic conditions of the Anthropocene: this geologic time period was the last time concentration of carbon dioxide in the atmosphere was comparable to today, around 400 parts per million (ppm). "That's why our insights from the Charyn Canyon sediments are so essential for understanding future climate," Prud'homme says.

Until now, little has been known about the role Central Asia plays in global climate evolution past and present. Earth's climate evolution over the past five million years has been understood mainly from the perspective of marine mechanisms. In contrast, the significance of climate feedbacks that originated on land - rather than in the oceans, lakes or ice cores - has remained largely unexplored. The international research team has filled this gap with their field research in Charyn Canyon.

Interactions between mid- and high-latitude climatic systems

The geographical location of the study site in the middle of Central Asia was of key importance to the team: "We needed to find a place that was inland and as far away from the ocean as possible," Kathryn Fitzsimmons, Group Leader of the Terrestrial Paleoclimate Reconstruction Research Group at the Max Planck Institute for Chemistry, explains. "We could hardly find a more continental situation than at Charyn Canyon in southeastern Kazakhstan." The semi-arid climate of the canyon, and its landscape, was shaped by the interaction between the mid-latitude westerlies and the high-latitude polar fronts, and by sediment transported from the nearby Tien Shan mountains. Charyn Canyon is ideal, according to Kathryn Fitzsimmons, for studying long-term land-climate feedback mechanisms.

The researchers examined the 80-meter-thick sedimentary succession and sampled by abseil to ensure continuous coverage of the record. By measuring the relative concentrations of isotopes within soil carbonates, they reconstructed the changing availability of moisture in the soil through time. A combination of paleomagnetic analyses and absolute uranium-lead dating of soil carbonates established the age and accumulation rates of the sediment record. The soil samples revealed a region characterized by ever-increasing aridity over the last five million years. In the early Pliocene, the soil was significantly wetter than in subsequent epochs or than today's climate. This process of aridification was not linear, however; it was interrupted by short-term climate fluctuations which provide insights into the interaction between the mid-latitude westerly winds and the Siberian high-pressure system.

Interaction between the Siberian high and rain-bringing westerlies

The research at Charyn Canyon enabled the scientists to investigate the long-term interaction of the Siberian high with the rain-bringing westerlies. Kathryn Fitzsimmons says: "We're confident that the changes in soil moisture we found at our site can also be used as a proxy for Siberian river activity further north." The hydroclimate at Charyn Canyon reflects that of the steppe to the north, from where a number of large Siberian rivers, such as the Irtysh and Ob, flow, she says. These are similarly influenced by the dynamics of the Siberian high and westerly air masses. One particular phase where this link is important stands out: a sustained period of wet conditions at Charyn Canyon just prior to the first major global glaciation around 3.3 million years ago. It is likely that these wet conditions extended to the Siberian rivers to the north, whose outflow of fresh water to the Arctic ocean may have breached a tipping point for widespread increased sea ice formation.

The information from this most complete terrestrial climate archive for the past five million years provides a very valuable basis for future climate models. Charlotte Prud'homme literally says, "We have opened a door."