Tech

Table salt is a commonplace ingredient in the kitchen, but a different kind of salt is at the forefront of chemistry innovation. Low-temperature molten salts known as ionic liquids are said to be "greener" and safer than traditional solvents. According to an article in Chemical & Engineering News, the weekly newsmagazine of the American Chemical Society, ionic liquids are on the cusp of transforming how fibers, fuels and other industrial materials are made.

Ionic liquids are salts that contain an organic cation, and an organic or inorganic anion. Their irregular structure gives them a lower melting point than other salts, making them easier to work with in an industrial capacity. In addition, they are less flammable than other solvents and can be implemented in a variety of applications. In particular, they have been used as solvents in chemical processes and biomass refining, catalysts in chemical synthesis and electrolytes in lithium-ion batteries. Notably, in 2018 the First Lady of Finland wore a dress made of birch fibers processed using ionic liquids. The simple, closed-loop process of making the garment had no chemical discharge, providing an alternative to fossil fuel-based fibers, such as polyester.

The biggest challenge for widespread implementation of ionic liquids is economics. Although some companies are working to reduce the cost of producing ionic liquids by scaling up production, the many potential uses for the molten salts has prevented focused investment in large-scale, profitable solutions. However, industrial giants are getting into the game: Chevron is implementing ionic liquid-based technology in a new refinery in Salt Lake City, where it will replace traditional hydrofluoric acid catalysts for simpler and safer handling. While there is still much work to be done in this area, chemists are optimistic that liquid salts will usher in a new wave of scientific innovation.

EAST LANSING, Mich. - If we understood the humans behind hacking incidents - and their intent - could we stop them? Research from Michigan State University reveals the importance of factoring in a hacker's motive for predicting, identifying and preventing cyberattacks.

Most people tend to focus on how to minimize the risk of a hack, from antivirus software to regularly updating computer software. While these defenses against attacks are helpful, study author and MSU criminal justice professor Thomas Holt believes it's just as important to have a strong offense.

"The more we start thinking like an attacker, the more we can better secure systems and move away from this perspective that everything can be solved through a piece of software," Holt said. "Any good attacker, no matter what their motivation is, can get around a security tool."

Holt found that the targeting practices of a specific kind of hack called a web defacement - where the attacker changes the original content of a webpage to images or content of their choosing - vary based on the self-identified motivation of the attacker.

"Their decision-making process can be modeled, and it can help us to understand how to better secure systems and think like a hacker," Holt said.

While considered a simple form of hacking, web defacements are a timely concern, Holt said.

"Earlier in January, hackers claiming ties to Iran defaced a U.S. government website. The page for the Federal Depository Library Program was replaced with pro-Iran messaging and an image of a bloodied President Donald Trump," Holt said. "The defacement demonstrates hackers are motivated by more than money, and that they may engage in future cyberattacks."

Holt collaborated with Rutger Leukfeldt and Steve Van De Weijer from the Netherlands Institute for the Study of Crime and Law Enforcement to analyze more than 100,000 web defacements against websites from January 2011 to April 2017. The researchers wanted to see if the targets of defacements were associated with attacker motivation, and how they actually performed the hack as well.

The findings revealed that web defacements - one of the more public forms of hacking - can be inspired by a variety of motives. The ways a defacement can be performed also vary, though defacers often attempt to compromise as many sites as possible as quickly as possible. Targeting thousands of web pages simultaneously demonstrates more skill as a hacker than if only one is targeted, unless it is a high level, recognizable site.

"If you can demonstrate to others your capacity, or expertise, that has value," Holt said. "So people will begin to realize and connect the handle or online nickname you use with some type of skill. It can net you clout within the hacker subculture. When you use more sophisticated methods or do things in a novel way, that lends an air of credibility to your identity."

Due to the overall threat they pose, hackers engaging in data breaches or using ransomware garner more attention than those acting out of subcultural or ideological motivations. Still, examining all types of hacks - and the hackers behind them - will help researchers predict and defend against cyberattacks.

"We can't just say we're only concerned about the economic stuff," Holt said. "We have to be concerned about political, ideological and subcultural at the same time."

While a piece of paper is usually flat and floppy, the same piece of paper crumpled into a wad is stiff and round. This demonstrates that scrunching changes the texture and behavior of precisely the same material -- paper.

A new Tel Aviv University study shows how induced defects in metamaterials -- artificial materials the properties of which are different from those in nature -- also produce radically different consistencies and behaviors. The research has far-reaching applications: for the protection of fragile components in systems that undergo mechanical traumas, like passengers in car crashes; for the protection of delicate equipment launched to space; and even for grabbing and manipulating distant objects using a small set of localized manipulations, like minimally invasive surgery.

"We've seen non-symmetric effects of a topological imperfection before. But we've now found a way to create these imperfections in a controlled way," explains Prof. Yair Shokef of TAU's School of Mechanical Engineering, co-author of the new study. "It's a new way of looking at mechanical metamaterials, to borrow concepts from condensed-matter physics and mathematics to study the mechanics of materials."

The new research is the fruit of a collaboration between Prof. Shokef and Dr. Erdal O?uz of TAU and Prof. Martin van Hecke and Anne Meeussen of Leiden University and AMOLF in Amsterdam. The study was published in Nature Physics on January 27. "Since we've developed general design rules, anyone can use our ideas," Prof. Shokef adds.

"We were inspired by LCD-screens that produce different colors through tiny, ordered liquid crystals," Prof. Shokef says. "When you create a defect -- when, for example, you press your thumb against a screen -- you disrupt the order and get a rainbow of colors. The mechanical imperfection changes how your screen functions. That was our jumping off point."

The scientists designed a complex mechanical metamaterial using three-dimensional printing, inserted defects into its structure and showing how such localized defects influenced the mechanical response. The material invented was flat, made out of triangular puzzle pieces with sides that moved by bulging out or dimpling in. When "perfect," the material is soft when squeezed from two sides, but in an imperfect material, one side of the material is soft and the other stiff. This effect flips when the structure is expanded at one side and squeezed at the other: stiff parts become soft, and soft parts stiff.

"That's what we call a global, topological imperfection," Prof. Shokef explains. "It's an irregularity that you can't just remove by locally flipping one puzzle piece. Specifically, we demonstrated how we can use such defects to steer mechanical forces and deformations to desired regions in the system."

The new research advances the understanding of structural defects and their topological properties in condensed-matter physics systems. It also establishes a bridge between periodic, crystal-like metamaterials and disordered mechanical networks, which are often found in biomaterials.

The research team plans to continue their research into three-dimensional complex metamaterials, and to study the richer geometry of imperfections there.

UPTON, NY--Engineers strive to design smartphones with longer-lasting batteries, electric vehicles that can drive for hundreds of miles on a single charge, and a reliable power grid that can store renewable energy for future use. Each of these technologies is within reach--that is, if scientists can build better cathode materials.

To date, the typical strategy for enhancing cathode materials has been to alter their chemical composition. But now, chemists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory have made a new finding about battery performance that points to a different strategy for optimizing cathode materials. Their research, published in Chemistry of Materials and featured in ACS Editors' Choice, focuses on controlling the amount of structural defects in the cathode material.

"Instead of changing the chemical composition of the cathode, we can alter the arrangement of its atoms," said corresponding author Peter Khalifah, a chemist at Brookhaven Lab and Stony Brook University.

Today, most cathode materials are comprised of alternating layers of lithium ions and transition metals, such as nickel. Within that layered structure, a small number of defects can usually be found. That means atoms from a transition metal can be found where a lithium ion is supposed to be and vice versa.

"You can think of a defect as a 'mistake' in the perfection of the material's structure," Khalifah said. "It is known that a lot of defects will lead to poor battery performance, but what we've come to learn is that a small number of defects should actually improve key properties."

Khalifah says there are two properties that a good cathode material will have: ionic conductivity (the lithium ions can move well) and electronic conductivity (the electrons can move well).

"The presence of a defect is like poking a hole between the lithium ion and transition metal layers in the cathode," he said. "Instead of being confined to two dimensions, the lithium ions and electrons can move in three dimensions across the layers."

To make this conclusion, the scientists needed to conduct high-precision experiments that measured the concentration of defects in a cathode material with far greater accuracy than has ever been done before.

"The concentration of defects in a cathode material can vary between two and five percent," Khalifah said. "Before, defects could only be measured with a sensitivity of about one percent. In this study, we measured defect concentration with exquisite accuracy--a sensitivity of a tenth of a percent."

To achieve this precision, the scientists conducted powder diffraction analyses using data from two DOE Office of Science User Facilities, the Advanced Photon Source (APS) at DOE's Argonne National Laboratory and the Spallation Neutron Source (SNS) at DOE's Oak Ridge National Laboratory.

Powder diffraction is a powerful research technique that reveals the location of individual atoms within a material by directing beams of x-rays, neutrons, or electrons at the material and studying how the beams diffract. In this study, the scientists conducted x-ray measurements at APS and neutron measurements at SNS.

"This work has developed a new way of visualizing structural defects and their relationship to diffraction and scattering strength," said Saul Lapidus, a physicist in the X-ray Science Division at APS. "I expect in the future for this technique to be used commonly in the battery community to understand defects and structural characterizations of cathode materials."

Khalifah added, "the ability to measure the concentration of weakly scattering elements with the sensitivity of a tenth of a percent will also be useful for many other areas of research, such as measuring oxygen vacancies in superconducting materials or catalysts."

With such accurate measurements of defect concentrations, the scientists could then study the relationship between defects and cathode material chemistry.

Ultimately, they developed a "recipe" for achieving any defect concentration, which, in the future, could guide scientists to synthesize cathodes from more affordable and environmentally friendly materials and then tune their defect concentrations for optimal battery performance.

This study was supported by DOE's Office of Energy Efficiency and Renewable Energy, Vehicle Technologies Office. Operations at APS and SNS are supported by DOE's Office of Science.

Brookhaven National Laboratory is supported by the U.S. Department of Energy's Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science.

Follow @BrookhavenLab on Twitter or find us on Facebook.

University of Texas at Dallas researchers are breathing new life into an old MRI contrast agent by attaching it to a plant virus and wrapping it in a protective chemical cage.

The novel strategy is aimed at developing a completely organic and biodegradable compound that would eliminate the need to use heavy metals such as gadolinium in contrast agents, said Dr. Jeremiah Gassensmith, associate professor of chemistry and biochemistry in the School of Natural Sciences and Mathematics and corresponding author of a study published online Feb. 5 in the journal Chemical Science, a publication of the Royal Society of Chemistry.

MRI is a commonly used medical imaging technology that allows physicians to see soft tissues in the body. Some tissues, like cancer, are better seen when a patient is given a contrast agent, which makes diseased parts of the body show up brightly in an MRI scan. The only class of contrast agents approved for use with MRI in the U.S. is based on the heavy metal gadolinium, which is typically excreted through a patient's urine after an MRI is completed.

Because of its widespread use, gadolinium -- which is able to sneak through wastewater treatment plants -- is increasingly showing up in watersheds in and around large metropolitan areas.

"Gadolinium-based contrast agents are used so much and so often that, just from patients excreting it in their urine, the metal is being released into water resources and sediments," Gassensmith said. "The observed concentrations are still very low, but, nonetheless, it's not exactly clear what effects long-term accumulation of gadolinium might have on the body."

In addition, for patients with compromised kidneys who have difficulty excreting these contrast agents, gadolinium can increase the risk of further kidney damage.

"For these reasons, we wanted to come up with something that was biocompatible and biodegradable, something completely organic with no heavy metals," Gassensmith said.
Gassensmith and his colleagues revisited a type of organic radical contrast agent, or ORCA, that had been previously considered as an MRI contrast agent but was abandoned in part because it is not bright enough, and it is broken down too quickly in the body by ascorbate -- vitamin C.

"This ORCA is a metal-free agent that is compatible with current MRI techniques, is less toxic to the body and is highly biodegradable. Unfortunately, on its own, it's not very bright, and it's so biodegradable that it's impractical to use," Gassensmith said.

Gassensmith's research group repurposed the agent by first attaching the ORCA molecules to thousands of docking sites on a tobacco mosaic virus.

"Since this is a plant virus, it can't infect people or animals, and it's easily broken down by the liver. Because the virus is so large, it also allows us to put thousands of the ORCA molecules right next to each other," Gassensmith said. "It's the difference between having one Christmas tree light, which is pretty dim, and a whole string of them together, which is quite bright."

The researchers also had to protect the agent so that it would last long enough in the body to be practical for MRI use.

"We put the ORCA in a cage, which no one had done before," Gassensmith said.

Specifically, they fabricated hollow chemical structures called cucurbiturils, so named because they're shaped a bit like a pumpkin (from the plant family Cucurbitaceae), and wrapped them around each ORCA molecule.

"The cage and the contrast agent just sort of stick together -- they don't form a chemical bond with one another," Gassensmith said. "It's similar to the relationship between a key and a lock. Because there is no chemical bond, but the molecules stick together nonetheless, this approach is called 'supramolecular' chemistry, which makes the agent we created a smORCA -- supramolecular macromolecular organic radical contrast agent."

The cage is constructed like a sieve so that water can reach the ORCA. This is necessary because MRIs use the water in the body to create an image. At the same time, the cage blocks larger molecules, like ascorbate, that can inactivate the ORCA.

In mice, the unprotected ORCA broke down within about 30 minutes, while the protected version provided more than two hours of visible contrast.

"Everything we are using has been tested or part of medical research for decades. We just put them all together in a new way," Gassensmith said. "We have some more work to do to show that our material is stable in the complex environment of the human body, and we'd like to see whether we can target it to specific diseases such as cancer and other abnormalities in tissues.

"But I think our results are a promising step toward developing smORCAs into clinically viable contrast agents."

A regulator of gene expression, retinoid X receptor (RXR), can boost scavenging cells in their mission to clear the brain of dead cells and debris after a stroke, thus limiting inflammation and improving recovery, according to preclinical research led by Jarek Aronowski, MD, PhD, of The University of Texas Health Science Center at Houston (UTHealth).

The discovery of RXR as a cleanup booster suggests that the molecule activating RXR could lead to discovery of a promising new therapeutic target. The study was published online this month in Stroke.

"RXR could enhance the cleanup and reduce the injury to brain tissue caused by the toxic byproducts created by an ischemic stroke," said Aronowski, professor in the Department of Neurology at McGovern Medical School at UTHealth. "This could be a clinically relevant target for improving recovery."

After a stroke, there is a buildup of dead cells and debris in the brain, a toxic environment that leads to damaging inflammation. Phagocytic immune cells, such as microglia and blood-derived macrophages, occur naturally in the body and act as toxic cleanup warriors. RXR appears to work by increasing potency of these warriors in combating the damaging effect of dead tissue while helping to boost brain repair.

In the trial, mice with an RXR gene selectively deleted in these immune cells had worsened late neurological recovery and developed larger brain atrophy compared to control mice. But mice who received bexarotene, a retinoid medication that activates RXR, showed improved neurological recovery and had reduced atrophy volume.

In papers published in the most recent issues of The Leadership Quarterly and Harvard Business Review, the professors write that traditional leadership development efforts overlook this specific developmental attribute that is foundational to how leaders think, learn and behave.

“Mindsets are leaders’ mental lenses that selectively organize and process information in unique ways, guiding them toward corresponding actions and responses,” Reina said. “In other words, mindsets dictate what information leaders take in and use to make sense of and navigate the situations they encounter. Simply, mindsets drive why and what leaders do.” 

The authors identified four distinct series of mindsets that affect leaders’ ability to engage, navigate change and lead more effectively: growth vs. fixed mindsets, learning vs. performance mindsets, deliberative vs. implemental mindsets, and promotion vs. prevention mindsets. 

“If organizations want their investment in leadership development to more fully pay off, it is essential that they prioritize mindset development, specifically by targeting growth, learning, deliberative and promotion leader mindsets,” Reina said. “If organizations focus on and help leaders hone these mindsets, they are much more likely to give their leaders and their organization the gift of lasting and meaningful development.” 

A growth mindset is the belief that people, including oneself, can change their talents, abilities and intelligence, while those with a fixed mindset do not believe that people can change.

A learning mindset involves being motivated toward increasing one’s competence and mastering something new. A performance mindset involves being motivated toward gaining favorable judgments — or avoiding negative judgments — about one’s competence.

Leaders with a deliberative mindset have a heightened receptiveness to all kinds of information as a way to ensure that they think and act optimally. Leaders with an implemental mindset are more focused on implementing decisions, which closes them off to new and different ideas and information.

Those with a promotion mindset focus on winning and gains. They identify a specific purpose, goal or destination and prioritize making progress toward it. Conversely, leaders with a prevention mindset focus on avoiding losses and preventing problems at all costs.

The research has a variety of important implications that include enhancing leaders' self-awareness, improving leaders' meta-cognition and mindfulness, improving leadership effectiveness and improving leadership development.

About VCU and VCU Health

Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 217 degree and certificate programs in the arts, sciences and humanities. Thirty-eight of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 11 schools and three colleges. The VCU Health brand represents the VCU health sciences academic programs, the VCU Massey Cancer Center and the VCU Health System, which comprises VCU Medical Center (the only academic medical center in the region), Community Memorial Hospital, Children’s Hospital of Richmond at VCU, MCV Physicians and Virginia Premier Health Plan. For more, please visit www.vcu.edu and vcuhealth.org.

Journal

The Leadership Quarterly

DOI

10.1016/j.leaqua.2019.101373

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Tourists today spend thousands of dollars to explore and enjoy the lush and thriving rainforests of Guatemala.

It's hard to believe the landscape ever looked any different. But according to new research by UNLV climate scientists, the locations where those jungles exist today likely looked very different less than 9,000 years ago - a blink of an eye by geologic standards.

"We often think of ecosystems as being unchangeable -- that a tropical rainforest is there, and has always been there," said Matthew Lachniet, professor and chair of the geoscience department at UNLV. "But that's not true. Any ecosystem responds to climate changes."

In a study published today in the journal Nature Communications, Lachniet and colleagues at Indiana State University, the University of Venice, and other institutions examined the rainfall history of Central America over the last 11,000 years. The results provide context for the development of tropical rainforest ecosystems in the region, and long-sought answers to what has been controlling rainfall in Central America for several millennia.

"Our results suggest that the rainforest as we know it today must have responded to those climate changes, and must be less than 9,000 years old in terms of its functioning and its structure, because the region was too dry before then to sustain it," Lachniet said.

Stalagmite specimens gathered from a tourist cave in Cobán, Guatemala, provided this insight and other historical data about the climate history of the region.

Researchers found:

Solar radiation, or insolation, is widely known to control rainfall amounts in the tropics. Guatemalan cave records, however, tell a different story for the Central American region of the tropics.

In Central America, rainfall was weak 11,000 years ago, strengthened to modern levels at 9,000 years ago, and showed only a very weak decrease to today, unlike the history of insolation.

When ice sheets from the last Ice Age melted mostly away -- about 9,000 to 7,000 years ago -- temperature rose and Central American rainfall responded in turn.

The Central America rainfall record has the same time evolution as ocean and land temperatures over the last 11,000 years; therefore, ocean surface temperatures were more important than the sun's rays in driving rainfall in the region.

"We found that as the oceans warm up, rainfall increases over Central America," Lachniet said.

The team also found that the rainfall variations over the last 3,000 years, during which time the famed Maya civilization reached its maximum urban development and subsequent collapse, were relatively small compared to the total range of rainfall variation captured by the cave deposits.

Lachniet and collaborators spent several days completing field work underground in Rey Marcos Cave, Guatemala for this research, which is a subterranean wonder of stalactites, stalagmites, and a disappearing river.

According to Lachniet, the next phase of the team's research in the region will continue to examine the impacts of climate on the Maya civilization throughout its history. In previous research, Lachniet and an international team of researchers used stalagmite specimens to link the rise and fall of ancient Mesoamerican civilizations to changing rainfall.

DURHAM, N.C. - The water filter on your refrigerator door, the pitcher-style filter you keep inside the fridge and the whole-house filtration system you installed last year may function differently and have vastly different price tags, but they have one thing in common.

They may not remove all of the drinking water contaminants you're most concerned about.

A new study by scientists at Duke University and North Carolina State University finds that - while using any filter is better than using none - many household filters are only partially effective at removing toxic perfluoroalkyl substances, commonly known as PFAS, from drinking water. A few, if not properly maintained, can even make the situation worse.

"We tested 76 point-of-use filters and 13 point-of-entry or whole-house systems and found their effectiveness varied widely," said Heather Stapleton, the Dan and Bunny Gabel Associate Professor of Environmental Health at Duke's Nicholas School of the Environment.

"All of the under-sink reverse osmosis and two-stage filters achieved near-complete removal of the PFAS chemicals we were testing for," Stapleton said. "In contrast, the effectiveness of activated-carbon filters used in many pitcher, countertop, refrigerator and faucet-mounted styles was inconsistent and unpredictable. The whole-house systems were also widely variable and in some cases actually increased PFAS levels in the water."

"Home filters are really only a stopgap," said Detlef Knappe, the S. James Ellen Distinguished Professor of Civil, Construction and Environmental Engineering at NC State, whose lab teamed with Stapleton's to conduct the study. "The real goal should be control of PFAS contaminants at their source."

PFAS have come under scrutiny in recent years due to their potential health impacts and widespread presence in the environment, especially drinking water. Exposure to the chemicals, used widely in fire-fighting foams and stain- and water-repellants, is associated with various cancers, low birth weight in babies, thyroid disease, impaired immune function and other health disorders. Mothers and young children may be most vulnerable to the chemicals, which can affect reproductive and developmental health.

Some scientists call PFAS "forever chemicals" because they persist in the environment indefinitely and accumulate in the human body. They are now nearly ubiquitous in human blood serum samples, Stapleton noted.

The researchers published their peer-reviewed findings Feb. 5 in Environmental Science & Technology Letters. It's the first study to examine the PFAS-removal efficiencies of point-of-use filters in a residential setting.

They analyzed filtered water samples from homes in Chatham, Orange, Durham and Wake counties in central North Carolina and New Hanover and Brunswick counties in southeastern N.C. Samples were tested for a suite of PFAS contaminants, including three perfluoroalkal sulfonic acids (PFSAs), seven perfluoroalkyl carboxylic acids (PFCAs) and six per- and poly-fluoroalkyl ether acids (PFEAs). GenX, which has been found in high levels in water in the Wilmington area of southeastern N.C., was among the PFEAs for which they tested.

Key takeaways include:

Reverse osmosis filters and two-stage filters reduced PFAS levels, including GenX, by 94% or more in water, though the small number of two-stage filters tested necessitates further testing to determine why they performed so well.

Activated-carbon filters removed 73% of PFAS contaminants, on average, but results varied greatly. In some cases, the chemicals were completely removed; in other cases they were not reduced at all. Researchers saw no clear trends between removal efficiency and filter brand, age or source water chemical levels. Changing out filters regularly is probably a very good idea, nonetheless, researchers said.

The PFAS-removal efficiency of whole-house systems using activated carbon filters varied widely. In four of the six systems tested, PFSA and PFCA levels actually increased after filtration. Because the systems remove disinfectants used in city water treatment, they can also leave home pipes susceptible to bacterial growth.

"The under-sink reverse osmosis filter is the most efficient system for removing both the PFAS contaminants prevalent in central N.C. and the PFEAs, including GenX, found in Wilmington," Knappe said. "Unfortunately, they also cost much more than other point-of-use filters. This raises concerns about environmental justice, since PFAS pollution affects more households that struggle financially than those that do not struggle."

The physical properties of clusters - systems of a relatively small number of interacting particles - are qualitatively different from that of infinite systems.

In 2004, UTMN scientists discovered world's first clusters of levitating water microdrops. The properties of such droplet clusters make them suitable for in situ analysis of the contents and processes occurring in bioaerosols.

Today, scientists at X-BIO of UTMN have proposed a new general approach to the problem of clustering, both in natural and in artificial objects.

"We analyzed data on a wide spectrum of, at first glance, completely different systems of interacting particles, and tried to find out what is common in these systems, what distinguishes a simple set of particles from a particle cluster, regardless of the nature of interaction," Alexander Fedorets, Head of the microhydrodynamic technologies laboratory at X-BIO Institute of UTMN, said.

The authors noted that the properties of clusters are never intense: they always depend on a cluster's size and the number of particles. This has made studying cluster systems extremely difficult.

In biological systems, clustering leads to nonequilibrium multiscale assembling, with autonomous components of each scale coming together. To form a hierarchical structure, such clusters should be energized from without.

Radionuclide therapy has proven successful in delaying the growth of disseminated tumor cells (DTCs) in early-stage breast cancer in a small animal model, suggesting its use as a potential adjuvant therapy for retarding the proliferation of DTCs. As reported in the January issue of the Journal of Nuclear Medicine, the alpha-particle-emitting radiopharmaceutical 223RaCl2 not only impacts cells directly hit by radiation but also has significant effects on cells outside of the radiation field (i.e., bystander cells).

Breast cancer is the most common cancer diagnosed in women in the United States. While survival rates for women are high, approximately 20 percent of five-year survivors ultimately develop metastatic disease five to ten years after treatment. The formation of metastases involves circulating tumor cells that shed from the primary tumor and gain access to the circulatory system. These DTCs may sustain active proliferation and develop into macrometastases or may remain dormant for years before becoming active.

"With a renewed interest in therapy with alpha-particle emitters and their potential for sterilizing DTCs, our study sought to determine whether bystander effects play a role in 223RaCl2 therapy and, if so, whether they can be leveraged to treat DTCs before disease progression," noted Roger W. Howell, PhD, and co-authors at Rutgers New Jersey Medical School, University of Florida and University of Gothenburg.

In the study, female mice were administered 0, 50 or 600 kBq/kg of 223RaCl2 to create bystander conditions prior to tumor cell inoculation. After 24 hours, mice were inoculated with either estrogen receptor-positive human breast cancer cells or triple-negative (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative) human breast cancer cells into the tibial marrow compartment. Bioluminescence intensity of the inoculated tumor cell populations was measured on day one and weekly thereafter.

Tumor burden analysis revealed that DTCs were present both within and beyond the range of the alpha particles emitted from 223RaCl2 in both types of breast cancer cells. Growth delays were then tracked for each group of breast cancer cells. Estrogen receptor-positive breast cancer cells responded to the 50 and 600 kBq/kg treatments with seven-day and 65-day growth delays, respectively. In contrast, the triple negative breast cancer cells demonstrated a 10-day growth delay in tumor progression for the 600 kBq/kg group. No significant difference was noted for the triple negative breast cancer cell group administered 50 kBq/kg when compared to the control group.

"The increased magnitude of the bystander effect in this study suggests that higher injected activities may better sterilize undetected dormant or slow-growing DTCs in the bone marrow micro-environment.," said Howell and co-authors. "Thus, 223RaCl2 may potentially be an adjuvant treatment option for select patients at early stages of breast cancer.

They continued, "This study adds to the mounting evidence that radiation-induced bystander effects can play a role in in the design of future treatment plans for radiopharmaceuticals alone or combined with external-beam therapy. Furthermore, the capacity to target specific cells or tissues in a systemic manner may offer advantages over the use of external beams of radiation for eliciting therapeutic bystander responses."

The authors of "Dose-Dependent Growth Delay of Breast Cancer Xenografts in the Bone Marrow of Mice Treated with 223Ra: The Role of Bystander Effects and Their Potential for Therapy" include Calvin N. Leung, Edouard I. Azzam and Roger W. Howell, Department of Radiology, New Jersey Medical School, Rutgers University, Newark, New Jersey; Brian S. Canter, Department of Radiology, New Jersey Medical School, Rutgers University, Newark, New Jersey, and Department of Orthopedics, New Jersey Medical School, Rutgers University, Newark, New Jersey; J. Christopher Fritton, Department of Orthopedics, New Jersey Medical School, Rutgers University, Newark, New Jersey; Didier Rajon, Department of Neurosurgery, University of Florida, Gainesville, Florida; and Tom A. Bäck, Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

This study was made available online in September 2019 ahead of final publication in print in January 2020.

Most bioinformatics software used for genomic analysis is experimental in nature and has a relatively high failure rate. In addition, cloud infrastructure itself, when run at scale, is prone to system crashes. These setbacks mean that big biomedical data analysis can take a long time and incur huge costs. To solve these problems, Sergei Yakneen, Jan Korbel, and colleagues at EMBL developed a system that identifies and fixes crashes efficiently.

Researchers performing analysis on the cloud need a number of technological skills, from configuring large clusters of machines and loading them with software, to handling networking, data security, and efficiently recovering from crashes. Butler helps researchers master these new domains by serving up appropriate tools that overcome all these challenges.

Saving time by checking the system's pulse

Butler differs from other bioinformatics workflow systems because it constantly collects health metrics from all system components, for example the Central Processing Unit (CPU), memory, or disk space. Its self-healing modules use these health metrics to figure out when something has gone wrong, and can take automated action to restart failed services or machines.

When this automated action does not work, a human operator is notified by email or Slack to solve the problem. Previously, a crew of trained people was necessary to check a similar system and detect failures. By automating this process, Butler dramatically reduces the time needed to execute large projects. "It is indeed very rewarding that these large-scale analyses can now take place in a few months instead of years," Korbel says.

Open source

Good solutions are already available for individual challenges associated with scientific computing in the cloud. So instead of reinventing the wheel, the team improved existing technologies. "We built Butler by integrating a large number of established open source projects", says Sergei Yakneen, the paper's first author, currently Chief Operating Officer at SOPHiA GENETICS. "This dramatically improves the ease and cost-effectiveness with which the software can be maintained, and regularly brings new features into the Butler ecosystem without the need for major development efforts."

Besides system stability and maintainability, using the cloud for genomics research is also challenging with respect to data privacy and the way it is regulated in different countries. Bigger projects will need to make simultaneous use of several cloud environments in different institutes and countries in order to meet the diverse data handling requirements of various jurisdictions. Butler addresses this challenge by being able to run on a wide variety of cloud computing platforms, including most major commercial and academic clouds. This allows researchers access to the widest variety of datasets while meeting stringent data protection requirements.

Butler in use

Butler's ability to facilitate such complex analyses was demonstrated in the context of the Pan-Cancer Analysis of the Whole Genome study. Butler processed a 725 terabyte cancer genome dataset in a time-efficient and uniform manner, on 1500 CPU cores, 5.5 terabytes of RAM, and approximately one petabyte of storage. The European Bioinformatics Institute (EMBL-EBI) played a crucial role by providing access and support to their Embassy Cloud, which was used for testing Butler. The system has recently been used in other projects as well, for example in the European Open Science Cloud pilot project (EOSC).

The Pan-Cancer project

The Pan-Cancer Analysis of Whole Genomes project is a collaboration involving more than 1300 scientists and clinicians from 37 countries. It involved analysis of more than 2600 genomes of 38 different tumour types, creating a huge resource of primary cancer genomes. This was the starting point for 16 working groups to study multiple aspects of cancer development, causation, progression, and classification.

Researchers at EMBL's European Bioinformatics Institute (EMBL-EBI) and the Francis Crick Institute have analysed the whole genomes of over 2600 tumours from 38 different cancer types to determine the chronology of genomic changes during cancer development.

Cancer occurs as part of a lifelong process in which our genome changes over time. As we age, our cells cannot maintain the integrity of the genome after cell division without making some errors (mutations). This process can be accelerated by various genetic predispositions and environmental factors, such as smoking. Over our lifetime these mutations build up and cells may be mis-programmed, leading to cancer.

The scientists published their research in Nature as part of an international collaboration of over 1300 scientists known as the Pan-Cancer Analysis of Whole Genomes (PCAWG). The project aims to identify and catalogue the underlying patterns of mutation that give rise to many different cancer types. Access to this resource has significant implications for aiding the understanding of tumour progression, as well as opening up possibilities for early diagnosis and clinical intervention.

Calibrating cancer's molecular clock

"We can map out the point mutations arising throughout normal ageing to create a molecular clock for the human genome, akin to tracking the rings of a tree," says Moritz Gerstung, Group Leader at EMBL-EBI. "This provides us with a yardstick to estimate the age of some alterations seen in cancer, and to measure how far a tumour has progressed."

The researchers used data from the Pan-Cancer project and The Cancer Genome Atlas (ICGC) to create tumour development timelines for several cancer types including glioblastoma, and colorectal and ovarian adenocarcinoma. Their findings suggest that tumour development can span the entire lifetime of an individual, so the mutations that initiate cancer progression may arise decades before diagnosis.

"We've observed that changes in chromosome count within tumour cells typically occur late during tumour evolution. However, in some cases, such as in glioblastoma multiforme tumours, these changes can occur decades before diagnosis," says Stefan Dentro, Postdoctoral Fellow at EMBL-EBI. "Typically, cells don't survive for very long with an odd number of chromosomes, but somehow these cells do; possibly founding a tumour that is detected many years later."

Towards early cancer detection

"We've developed the first timelines of genetic mutations across the spectrum of cancer types," says Peter Van Loo, co-lead author and group leader in the Cancer Genomics Laboratory at the Francis Crick Institute. "For more than 30 cancers, we now know what specific genetic changes are likely to happen, and when these are likely to take place. Unlocking these patterns means it should now be possible to develop new diagnostic tests that pick up signs of cancer much earlier."

Understanding the sequence and chronology of mutations leading to cancer may help clarify the mechanisms of cancer development, which otherwise appear convoluted due to the presence of many alterations in the final cancer cells. Being able to determine whether a mutation typically occurs early or late during cancer progression may also help to guide early detection. This would make it possible to define the sets of alterations to screen for, to detect pre-cancerous cells at different stages of transformation.

"To a large extent, cancer development is an unfortunate consequence of the normal ageing of our cells," says Moritz Gerstung. "Fully understanding the molecular progression of the disease is the first step towards identifying targets for early detection and perhaps treatment. The observation that many genetic alterations were already present years before the cancer was diagnosed provides a window of opportunity to detect aberrant cells before they become fully malignant."

The Pan-Cancer project

The Pan-Cancer Analysis of Whole Genomes project is a collaboration involving more than 1300 scientists and clinicians from 37 countries. It involved analysis of more than 2600 genomes of 38 different tumour types, creating a huge resource of primary cancer genomes. This was the starting point for 16 working groups to study multiple aspects of cancer development, causation, progression, and classification.

The United States Census Bureau estimates that by 2060, nearly one in four Americans will be age 65 and older. As America turns increasingly gray, numerous stressors, such as declining health, loss of loved ones or independence, negatively impact the lives of older adults.

Resilience improves the ability to cope with these stressors, but only one-third of older adults score high on resilience measures. In a new study, researchers at University of California San Diego School of Medicine, in collaboration with Mather Institute, described a method to enhance resilience and reduce subjective stress in residents living in senior housing communities.

The multi-site study, published in the February 5, 2019 online issue of International Psychogeriatrics, used an intervention program called Raise Your Resilience (RYR) and found an increase in resilience and wisdom, as well as a significant reduction in the level of daily stress experienced by seniors.

"The increase in the score on a scale to measure wisdom was a pleasant surprise. Psychosocial interventions are beneficial to older adults, but few have been implemented in the senior housing community setting," said senior author Dilip V. Jeste, MD, senior associate dean for the Center of Healthy Aging and Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine. "We found the senior housing communities to be excellent sites for a group intervention. We went directly into the actual environment in which many older adults reside and face their everyday difficulties."

RYR addresses topics like gratitude and ageism, and employs value-based activities emphasizing empathy, compassion and self-compassion.

For example, group members were asked to record one event each day that made them feel happy or grateful and one activity that made them feel proud. "Satisfaction with the intervention was quite high among the participants. Almost all of them completed their diary on most days, which was remarkable," said Danielle Glorioso, LCSW, executive director of the Center for Healthy Aging at UC San Diego.

The study involved a one-month control period and a one-month intervention period. Participants were then followed for three months post-intervention. The study was conducted in five senior housing communities across three states: California, Illinois and Arizona. Eighty-nine participants were recruited for the study, with an average age of 85. Three-fourths were female and almost all the participants were white.

RYR was delivered in three 90-minute sessions by residential staff who were not licensed therapists but were trained by the researchers. Most psychosocial interventions require specialized therapists with advanced education to conduct the intervention, which is often expensive and impractical. "Our intervention can be easily duplicated at a low cost," said Jeste, "which suggests a high potential for its implementation and dissemination across similar communities nationally."

When compared to the control period, RYR participants had significantly lower stress scores and higher wisdom scores during the intervention period with significantly higher scores in resilience post-intervention. "Our results show that something can be done in a practical way to empower seniors," said Jeste.

Lithium-ion batteries are in everything from cell phones to cars. However, recent incidents involving fires or explosions of these devices show there's a need for safer batteries. One option is to replace the flammable liquid electrolyte with a solid-state electrolyte (SSE). But some of the most-studied SSEs are themselves flammable, leaving the original safety concern unaddressed. Researchers now report in ACS' Nano Letters that they have developed an SSE that won't burn up.

Traditional lithium-ion batteries consist of a cathode and anode, separated by a liquid electrolyte and a thin piece of porous plastic. If the battery is damaged -- for example, if it is overcharged or if needlelike lithium projections grow and pierce the plastic separator -- the electrolyte can catch fire. Scientists have experimented with a variety of solutions, such as adding fire retardants to the electrolyte, or replacing the soft and flammable separator and electrolyte with an SSE. However, state-of-the-art SSEs have their own limitations, including brittleness and heaviness. Fragility can be reduced by using a polymer SSE, but lithium needles can still breach these soft materials. Polymer/ceramic composite SSEs get around that problem, but most of these materials are still flammable. Yi Cui and colleagues wanted to design a safer alternative.

The team developed an SSE composed of a porous mechanical support (a polyimide film), fire-retardant additive (decabromodiphenyl ethane), and polymer electrolyte (polyethylene oxide/lithium bis[trifluoromethanesulfonyl]imide). The researchers say this is the first ultralightweight polymer-based SSE that is fireproof. In fact, a battery they made from this SSE continued to function well even when it was exposed to flames. In addition, the new SSE can provide an energy density and performance at least comparable to conventional lithium-ion batteries.