Culture

PHILADELPHIA - For years, researchers have been trying to target a gene called MYC that is known to drive tumor growth in multiple cancer types when it is mutated or over-expressed, but hitting that target successfully has proven difficult. Now researchers in the Perelman School of Medicine of the University of Pennsylvania have identified a new pathway that works as a partner to MYC and may be its Achilles' Heel. The pathway involves a protein called ATF4, and when it's blocked, it can cause cancer cells to produce too much protein and die. These findings in cell lines and mouse models could point the way toward a new therapeutic approach as inhibitors that can block synthesis of ATF4 already exist. The journal Nature Cell Biology published the findings today.

MYC is a gene that controls normal cell growth, but when it is mutated or amplified in cancer, it sets off a chain reaction that helps tumors grow uncontrollably. While there is currently no specific way to target it, previous research has focused on blocking other steps in the chain as a workaround to impede tumor growth. The team, led by Constantinos Koumenis, PhD, the Richard Chamberlain Professor of Radiation Oncology and vice chair and research division director of Radiation Oncology, have previously shown that in certain tumors, one of these steps is regulated by a kinase called PERK, which activates ATF4. However, in this new study, they've shown that blocking PERK does not always stop tumor growth because MYC actually controls a second process that can work in parallel as a redundancy in the system. This study identified this second kinase, which is called GCN2.

"What we've learned is that we need to go further downstream to block tumor growth in a way that cancer cells can't easily escape, and our study identifies the target to do just that," said Koumenis, who is the co-senior author on this study along with Davide Ruggero, PhD, a professor of Urology in the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco (UCSF).

This study shows the alternative approach is to target ATF4 itself, since it's the point where both signal pathways converge, meaning there's less redundancy built in to allow cancer to survive. The findings also show that ATF4 turns on the genes MYC needs for growth and also controls the rate at which cells make specific proteins called 4E-BP. When the researchers knocked out ATF4 in cells or mice, they found tumor cells continued to build up those proteins and eventually died as a result of stress. This blocked tumor growth in mice with lymphomas and colorectal cancer. This study also found that when tumors in humans are driven by MYC, ATF4 and its protein partner 4E-BP are also overly expressed, which is further evidence that these findings may point to an approach that could work for humans.

"This shows us the potential impacts of targeting ATF4 in MYC-dependent tumors, something we're already studying. We're also working to confirm this approach will not cause any serious off-target effects," said lead author Feven Tameire, PhD, who conducted this research while she was a doctoral candidate at Penn.

Researchers say future studies will also focus on continuing to investigate why ATF4 works the way it does, which may help their understanding of whether there are other potential targets in the chain.

Researchers using the radio telescope ALMA (Atacama Large Millimeter/submillimeter Array) observed signals of oxygen, carbon, and dust from a galaxy in the early Universe 13 billion years ago. This is the earliest galaxy where this useful combination of three signals has been detected. By comparing the different signals, the team determined that the galaxy is actually two galaxies merging together, making it the earliest example of merging galaxies yet discovered.

Takuya Hashimoto, a postdoctoral researcher at the Japan Society for the Promotion of Science and Waseda University, Japan, and his team used ALMA to observe B14-65666, an object located 13 billion light-years away in the constellation Sextans. Because of the finite speed of light, the signals we receive from B14-65666 today had to travel for 13 billion years to reach us. In other words they show us the image of what the galaxy looked like 13 billion years ago, less than 1 billion years after the Big Bang.

ALMA detected radio emissions from oxygen, carbon, and dust in B14-65666. This is the earliest galaxy where all three of these signals have been detected. The detection of multiple signals is important because they carry complementary information.

Data analysis showed that the emissions are divided into two blobs. Previous observations with the Hubble Space Telescope (HST) had revealed two star clusters in B14-65666. Now with the three emission signals detected by ALMA, the team was able to show that the two blobs do in-fact form a single system, but they have different speeds. This indicates that the blobs are two galaxies in the process of merging. This is the earliest known example of merging galaxies. The research team estimated that the total stellar mass of B14-65666 is less than 10% that of the Milky Way. This means that B14-65666 is in the earliest phases of its evolution. Despite its youth, B14-65666 is producing stars 100 times more actively than the Milky Way. Such active star-formation is another important signature of galactic mergers, because the gas compression in colliding galaxies naturally leads to bursty star-formation.

"With rich data from ALMA and HST, combined with advanced data analysis, we could put the pieces together to show that B14-65666 is a pair of merging galaxies in the earliest era of the Universe," explains Hashimoto. "Detection of radio waves from three components in such a distant object clearly demonstrates ALMA's high capability to investigate the distant Universe."

Modern galaxies like our Milky Way have experienced countless, often violent, mergers. Sometimes a larger galaxy swallowed a smaller one. In rare cases, galaxies with similar sizes merged to form a new, larger galaxy. Mergers are essential for galaxy evolution, so many astronomers are eager to trace back the history of mergers.

"Our next step is to search for nitrogen, another major chemical element, and even the carbon monoxide molecule," said Akio Inoue, a professor at Waseda University. "Ultimately, we hope to observationally understand the circulation and accumulation of elements and material in the context of galaxy formation and evolution."

Even on the scale of everyday life, nature is governed by the laws of quantum physics. These laws explain common phenomena like light, sound, heat, or even the trajectories of balls on a pool table. But when applied to a large number of interacting particles, the laws of quantum physics actually predict a variety of phenomena that defy intuition.

In order to study quantum systems made of many particles, physicists must first be able to simulate them. This can be done by solving the equations describing their inner workings on supercomputers. But while Moore's Law predicts that the processing power of computers doubles every couple of years, this is a far cry from the power needed to tackle the challenges of quantum physics.

The reason is that predicting the properties of a quantum system is enormously complex, demanding a computational power that grows exponentially with the size of the quantum system - an "intrinsically complex" task, according to Professor Vincenzo Savona, who directs the Laboratory of Theoretical Physics of Nanosystems at EPFL.

"Things become even more complicated when the quantum system is open, meaning that it is subject to the disturbances of its surrounding environment," Savona adds. And yet, tools to efficiently simulate open quantum systems are much needed, as most modern experimental platforms for quantum science and technology are open systems, and physicists are constantly in search of new ways to simulate and benchmark them.

But significant progress has been made thanks to a new computational method that simulates quantum systems with neural networks. The method was developed by Savona and his PhD student Alexandra Nagy at EPFL - and independently by scientists at Université Paris Diderot, the Heriot-Watt University in Edinburgh, and the Flatiron Institute in New York. The total body of work is being published across three papers in Physical Review Letters.

"We basically combined advances in neural networks and machine-learning with quantum Monte Carlo tools," says Savona, referring to a large toolkit of computational methods that physicists use to study complex quantum systems. The scientists trained a neural network to represent simultaneously the many quantum states in which a quantum system can be cast by the influence of its environment.

The neural-network approach allowed the physicists to predict the properties of quantum systems of considerable size and arbitrary geometry. "This is a novel computational approach that addresses the problem of open quantum systems with versatility and a lot of potential for scaling up," says Savona. The method is set to become a tool of choice for the study of complex quantum systems, and, looking a bit more into the future, for assessing the effects of noise on quantum hardware.

Millions of patients all over the world undergo surgical procedures related to bone defect repair every year. With an ever-increasing life expectancy and the issues that come with a decaying skeleton, the number of interventions can only increase in the coming years. This is why orthopaedic surgeons are constantly looking for improved medical implants for the treatment of bone repair.

Following certain surgeries and traumatic experiences, like traffic accidents, patients often suffer from significant fractures and losses to the bone, referred to as bone defects. Bone scaffolds are porous implants that are used in order to fill significantly large defects. While the currently available solutions are suitable when implanted in non-load bearing areas, like the face, using a stronger material could result in a more attractive option when filling defects in load-bearing areas, like the bones found in legs.

The University of Malta has teamed up with Mater Dei Hospital to address the shortcomings of current bone scaffolds on the market in a project entitled Biodegradable Iron for Orthopaedic Scaffold Applications - BioSA. The project is being led by Prof. Ing. Joseph Buhagiar, from the Department of Metallurgy and Materials Engineering, and also involves members from the surgical team at the Department of Orthopaedic, Trauma and Sports Medicine at Mater Dei Hospital under the coordination of Mr Ray Gatt M.D., as well as academics from various departments at the University of Malta. The team members are pooling their expertise to develop an improved bone regeneration scaffold design with optimised characteristics.

Despite the fact that ceramic scaffolds are widely used, their tendency to break due to their brittle nature, has made them inadequate for use in bones that are subjected to sudden loading, while polymeric scaffolds lack the mechanical strength to be used in load-bearing applications. Metals, on the other hand, have the potential to exhibit the perfect balance between strength and toughness. The BioSA scaffold is being designed such that it corrodes at a controlled rate within the body, to match the rate at which the bone is healing. This aspect could result in reducing the necessity of a second surgical intervention to remove the implant after bone has healed.

The BioSA team is focused on understanding the corrosion behaviour of such an implant while also studying the effect that such an implant has on cells found in the bone. Through an innovative processing technique, based on the use of metal powders, the team also aims to gain control over the shape of the final scaffold. Accidents can happen to everyone and defects can be bigger than the body can heal naturally. So ideally scaffolds are not designed as one-size-fits-all but can also be custom-made for a specific patient.

1 July 2019

Period pain significantly impacts young women’s academic performance worldwide, according to new Australian-led research – and women are ‘putting up with it’ rather than seeking treatment.

New research from Western Sydney University published in the Journal of Women’s Health(opens in a new window) has found that, regardless of geographical location or economic status, more than two thirds (71%) of young women globally suffer from painful periods.

Furthermore, one in five young women (20%) reported being absent from class due to period pain, while 41% reported that their concentration or performance in class was negatively affected.

Researchers led by NICM Health Research Institute’s Dr Mike Armour examined the results of thirty-eight studies including 21,573 young women. Twenty-three of the studies were from low, lower middle, or upper middle-income countries, and 15 were from high-income countries.

Despite the common held belief women ‘grow out’ of period pain, rates of dysmenorrhea (period pain) were found to be similar between students at school and university.

Dr Armour said the research highlights the need for better education around period pain, and has implications for the self-care and treatment of the disorder.

“Young women, whether they were at school or university, experienced significant negative impact on their education as a result of their menstrual symptoms,” Dr Armour said.

“This lowered classroom efficiency during the period is something women often feel they must put up with, meaning that both adolescent girls and young women may be significantly disadvantaged in their studies by the impact of period pain.

“This often occurs at a crucial time in their academic lives during their final schooling years when academic results can have long term consequences.”

Women also reported they had to restrict social, sporting, and other school activities due to menstrual symptoms, negatively affecting health outcomes.

According to Dr Armour the belief that period pain is a normal part of becoming a woman and the inability of many women to identify the symptoms of period pain are barriers to women seeking help.

“Improving women’s education about menstruation may help women make better choices about self-care and when to seek medical treatment,” Dr Armour said.

This research formed part of the groundwork that led to a 12-month national project from Western Sydney University to change the way young women learn about and deal with menstrual symptoms like period pain. The two-part project supported by U by Kotex.® (UbK) (opens in a new window) aims to reduce the incidence of undiagnosed menstrual disorders, and improve the levels of knowledge and understanding (‘health literacy’) relating to the menstrual cycle and its management among young women. The results of this study will be published separately and are expected in 2020.

The paper, The Prevalence and Academic Impact of Dysmenorrhea in 21,573 Young Women: A Systematic Review and Meta-Analysis, can be accessed online at https://doi.org/10.1089/jwh.2018.7615(opens in a new window)

Amyotrophic lateral sclerosis (ALS) is a neurological condition that affects motor neurons -- the nerve cells that control breathing and muscles. Under a microscope, researchers have noticed that the motor neurons of patients with ALS contain excessive aggregation of a protein called TDP-43. Since TDP-43 proteins stuck in these aggregates can't perform their normal function, the scientists believe this build-up contributes to motor neuron degeneration, the hallmark of ALS.

In a study publishing July 1, 2019 in Neuron, UC San Diego School of Medicine researchers discovered that prolonged cellular stress, such as exposure to toxins, triggers TDP-43 clumping in the cytoplasm of human motor neurons grown in a laboratory dish. Even after the stress is relieved, TDP-43 clumping persists in ALS motor neurons, but not in healthy neurons.

The team then screened and identified chemical compounds (potential precursors to therapeutic drugs) that prevent this stress-induced, persistent TDP-43 accumulation. These compounds also increased the survival time of neurons with TDP-43 proteins containing an ALS-associated mutation.

"These compounds could provide a starting point for new ALS therapeutics," said senior author Gene Yeo, PhD, professor at UC San Diego School of Medicine and faculty member in the Sanford Consortium for Regenerative Medicine.

Yeo and team, including first author Mark Fang, PhD, who was a graduate student in Yeo's lab at the time, generated motor neurons from induced pluripotent stem cells (iPSCs) that had been converted from human skin cells. To mimic cellular aspects of ALS, they exposed these laboratory motor neurons to toxins such as puromycin, which stressed the cells and led to TDP-43 clumps.

Normally, TDP-43 proteins help process molecules called messenger RNA, which serve as the genetic blueprints for making proteins. But when they clump outside the nucleus, TDP-43 proteins can't perform their normal duty, and that can have a profound effect on many cellular functions.

The researchers tested thousands of chemical compounds for their effects on RNA-protein aggregation. They were surprised to find compounds that not only reduced the overall amount of clumping by up to 75 percent, but also varied clump size and number per cell.

Some of the compounds tested were molecules with extended planar aromatic moieties -- arms that allow them to insert themselves in nucleic acids, such as DNA and RNA. TDP-43 must bind RNA in order to join ALS-associated clumps. Thus, according to Yeo, it makes sense that a compound that interacts with RNA would prevent TDP-43 from clumping.

"While these findings still need to be tested in model organisms and there is more work to do before a potential therapy could one day be tested in patients," Fang said, "these compounds already expand our toolbox for unraveling the relationship between RNA-protein aggregations and neurological disease."

ALS, also known as Lou Gehrig's disease, affects more than 20,000 Americans. Currently, there are no effective treatments for ALS, largely due to poor understanding of how the disease initiates and progresses at the molecular level. The disease is invariably fatal.

A major 2009 revision to a federal nutrition program for low-income pregnant women and children improved recipients' health on several key measures, researchers at UC San Francisco have found.

The study is the first to analyze the health effects of the changes to the U.S. Special Supplemental Nutrition Program for Women, Infants and Children (WIC), which serves half of all infants and more than a quarter of all pregnant and postpartum women in the U.S. It comes amid renewed attention to poor maternal health outcomes for low-income women, as well as an opposing push to cut social welfare programs like WIC.

WIC was introduced in the mid-1970s but remained unchanged until 2009, when it was revamped to address rising rates of obesity and diabetes. The revisions added a monthly food allotment of $10 to allow women to purchase fresh fruits and vegetables, instead of only providing fruit juice. The revisions also required purchases of whole grain bread and low-fat milk.

Previous research showed these changes improved maternal and child nutrition by decreasing purchases of refined grains and whole milk, but the effects on health have gone unexamined until the current paper, published Monday, July 1, in JAMA Pediatrics.

Researchers used a "quasi-experimental" framework to examine the effects on more than 2 million babies born between 2007 and 2012 to California mothers who received WIC. These babies' birth certificates were linked to hospital discharge records for mothers and infants, providing information on their health.

To account for forces that may have been affecting women's health generally and did not come from the changes to the WIC program, the researchers also included a control group of women who were not receiving WIC to see how their health changed during the period under study. Then they subtracted these trends from the trends for WIC recipients.

In all, they examined data for nearly 3 million babies born to nearly 2.5 million mothers, concluding that many, though not all, of the health indicators under review improved.

"This shows that there are social policy levers that can affect millions of people at once," said Rita Hamad, MD, PhD, an assistant professor of family and community medicine affiliated with the Philip R. Lee Institute for Health Policy Studies at UCSF, and first author of the paper. "We saw these improvements in high-risk moms and babies, even with these relatively modest improvements in the nutritional content of the WIC food packages."

After the revisions, pregnant women receiving WIC were less likely to get preeclampsia, an often dangerous complication involving high blood pressure, and they were more likely to gain the recommended amount of weight. But some women gained less weight than recommended, and there was no change in gestational diabetes or preterm birth.

The effects were smaller for the infants, but still mostly positive. Babies were more likely to be born later, and at an appropriate weight and size, although there was no reduction in very low birth weight, the length of admission at birth, or readmission in the first year of life.

"Despite improvements in programs like WIC, our country still has large health disparities between rich and poor," Hamad said. "The 2009 revisions were modest, and there is still a lot of room for improvement. Our society values families and kids, so this is a policy people can get behind."

PROVIDENCE, R.I. [Brown University] -- Most of the well-studied proteins in our bodies are like metal; some can change shape easily, like aluminum foil, and others are rigid, like steel beams, but they typically have a solid, well-defined structure. Many other essential proteins are more like water -- able to change phase from liquid to solid ice.

One of these important phase-changing proteins is called FUS. In healthy cells, FUS switches between floating diffusely and condensing into liquid droplets with other proteins to make, edit and deliver the blueprints for protein production. However, FUS also has a "solid" or aggregate phase that has been found in some people with severe cases of amyotrophic lateral sclerosis (ALS) and a type of dementia called frontotemporal dementia.

A team of researchers led by Nicolas Fawzi, an associate professor in the Department of Molecular Pharmacology, Physiology and Biotechnology at Brown University, used a combination of techniques to determine the atomic interactions that stabilize the liquid, yet "condensed" phase of FUS.

"What we want to understand is the atomic details of these interactions so that we know what kind of treatments would be important for ALS and other diseases," said Fawzi, a co-corresponding author on the paper who is also affiliated with the Carney Institute for Brain Science. "First we need to know the structural differences between the normal form and the disease form, so we know where to put in a wrench to stop it. We can't design a drug to bind to something when we don't know what it looks like."

The findings were published on Monday, July 1, in the journal Nature Structural and Molecular Biology.

Fawzi said you can think of the condensed liquid droplets FUS can form within cells as somewhat like the condensation that forms on a cold glass on a humid day. Both the water droplets and the humid air contain water molecules, but they are in distinct phases.

In addition to its implication in ALS -- commonly called Lou Gehrig's disease -- the disordered region of FUS is known to be associated with some types of cancer including Ewing's sarcoma, Fawzi said. In fact, the acronym FUS stands for FUsed in Sarcoma.

Using a combination of nuclear magnetic resonance (NMR) spectroscopy, Raman spectroscopy and computational modeling, Fawzi's team including Brown doctoral student Anastasia Murthy, the lead author on the study, found that the interactions between a disordered region of FUS in the condensed liquid droplets are quite varied and dynamic, he said. FUS does not form any traditional structural elements. However, multiple atomic interactions -- including those formed by specific amino acids within the protein, namely glutamine and tyrosine -- maintain the condensed yet disordered nature of FUS.

The knowledge of these molecular interactions -- which are distinct from the interactions in the neurodegeneration-associated aggregate phase -- might someday be used to guide the development of therapeutics that hinder disease-associated aggregation or support the normal condensed phase interactions.

Additionally, the combination of techniques Fawzi's team used to uncover FUS's atomic interactions could be used by other scientists studying intrinsically disordered proteins that also form liquid or solid condensed forms, such as Huntington's, Parkinson's, prion diseases and Type II diabetes in addition to ALS.

"We did these NMR experiments in a new way that allowed us to explicitly look at which atoms in one protein are interacting with atoms in another FUS protein," Fawzi said. "I expect that people will start doing experiments like this because it provides more assurance and detail on the contacts between intrinsically disordered proteins. Disordered proteins do all kinds of important things, and we don't really know how they normally work. When they go wrong, we really don't know what's going on."

Fawzi plans to continue studying FUS. Specifically, he wants to study the entire protein, not just the intrinsically disordered region that was the primary focus of this paper, in test tubes as well as in living cells. He also plans to apply this combination of techniques to continue studying the molecular interactions of other neurodegeneration-associated disordered proteins such as hnRNPA2 and TDP-43.

Some young adults who were bullied as a child could have a greater risk of ongoing depression due to a mix of genetic and environmental factors according to a new study from the University of Bristol.

Researchers wanted to find out what factors influenced depression in young adults between the ages of 10 and 24 and why some people responded differently to risk factors such as bullying, maternal postnatal depression, early childhood anxiety and domestic violence.

Using detailed mood and feelings questionnaires and genetic information from 3,325 teenagers who are part of Bristol's Children of the 90s study, alongside evidence of these risk factors at nine points in time they found that childhood bullying was strongly associated with trajectories of depression that rise at an early age. Children who continued to show high depression into adulthood were also more likely to have genetic liability for depression and a mother with postnatal depression. However, Children who were bullied but did not have any genetic liability for depression showed much lower depressive symptoms as they become young adults.

University of Bristol PhD student Alex Kwong commented:

"Although we know that depression can strike first during the teenage years we didn't know how risk factors influenced change over time. Thanks to the Children of the 90s study, we were able to examine at multiple time points the relationships between the strongest risk factors such as bullying and maternal depression, as well as factors such as genetic liability.

"It's important that we know if some children are more at risk of depression long after any childhood bullying has occurred. Our study found that young adults who were bullied as children were eight times more likely to experience depression that was limited to childhood. However, some children who were bullied showed greater patterns of depression that continued into adulthood and this group of children also showed genetic liability and family risk.

"However, just because an individual has genetic liability to depression does not mean they are destined to go on and have depression. There are a number of complex pathways that we still don't fully understand and need to investigate further.

"The next steps should continue to look at both genetic and environmental risk factors to help untangle this complex relationship that would eventually help influence prevention and coping strategies for our health and education services."

Lecturer in Psychiatric Epidemiology at the University of Bristol Dr Rebecca Pearson added:

"The results can help us to identify which groups of children are most likely to suffer ongoing symptoms of depression into adulthood and which children will recover across adolescence. For example, the results suggest that children with multiple risk factors (including family history and bullying) should be targeted for early intervention but that when risk factors such as bullying occur insolation, symptoms of depression may be less likely to persist"

Karen Black, Chief Executive Officer for Bristol's Off the Record added:
"At Off The Record we see a diverse mix of young people presenting with a range of needs, often depression and anxiety. Understanding some of the factors that influence this will further help us to shape services and our offer for young people. I would also hope that studies such as these will help change policy direction and spending so that we start to get upstream of the issues that we know affect mental health including education and family, prevention rather than cure ideally."

Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals. They focussed on the interaction between so-called G-proteins - the "mediators" of signal transmission - and the receptors known as GPCRs, which trigger signal processes. The researchers not only gained a better understanding of GPCR-G-protein interactions; they are now able to predict their functions better than before.

All living systems react to external signals from the environment. In humans and other animals, these signals are primarily detected and processed with biological receptors in the cell membrane that are coupled to the G-protein. These proteins have a key position in signal transmission. The GPCRs, or G-protein coupled receptors, are the largest family of transmembrane receptors which can react to a multitude of extracellular, physico-chemical signals and then trigger specific processes in the cell. One way they do this is by coupling with one or more G-proteins. In collaboration with colleagues from Japan, the team led by Prof. Dr Robert Russell of the Heidelberg University Biochemistry Center has now studied these couplings.

Humans have a total of 16 G-proteins that are coupled to nearly 1,000 different GPCRs. Using biotechnological tools and machine learning, the researchers closely investigated 148 representative receptors and 11 proteins to better understand the full breadth of GPCR-G-protein interactions. They were able to uncover several hundred coupling events, thus adding greatly to our understanding of how GPCRs work. "Thanks to the new data, we can now predict GPCR-G-protein coupling better than ever before. It also allows us to design artificial GPCRs with very specific signalling properties for ultimate use in biomedical studies," explains the study's primary author Dr Francesco Raimondi. He is a member of Prof. Russell's team, whose research group is also located at Heidelberg University's BioQuant Centre. The researchers assume that a better understanding of the interactions between GPCRs and G-proteins could also be important in the development of new drugs.

Bottom Line: Radioactive iodine has been used since the 1940s to treat hyperthyroidism, an overactive thyroid. This study is an extension of one that has followed patients in the United States and the United Kingdom treated for hyperthyroidism for nearly 70 years. Researchers sought to determine the association of doses of radioactive iodine absorbed by organs or tissue with overall and site-specific cancer death. This analysis included 18,805 patients treated with radioactive iodine and with no history of cancer at the time of treatment. Researchers report a modest association between greater organ-absorbed doses of radioactive iodine and risk of death from solid cancer (a mass), including breast cancer. The study has limitations, including uncertainties in the organ dose estimates and a limited ability to detect significant associations for some outcomes because of a small number of cancer deaths and relatively small doses of radioactive iodine to organs other than the thyroid. More studies are needed to compare the risks and advantages of all major treatment options for patients with hyperthyroidism.

Galaxies grow by accumulating gas from their surroundings and converting it to stars, but the details of this process have remained murky. New observations, made using the Keck Cosmic Web Imager (KCWI) at the W. M. Keck Observatory in Hawaii, now provide the clearest, most direct evidence yet that filaments of cool gas spiral into young galaxies, supplying the fuel for stars.

"For the first time, we are seeing filaments of gas directly spiral into a galaxy. It's like a pipeline going straight in," says Christopher Martin, a professor of physics at Caltech and lead author of a new paper appearing in the July 1 issue of the journal Nature Astronomy. "This pipeline of gas sustains star formation, explaining how galaxies can make stars on very fast timescales."

For years, astronomers have debated exactly how gas makes its way to the center of galaxies. Does it heat up dramatically as it collides with the surrounding hot gas? Or does it stream in along thin dense filaments, remaining relatively cold? "Modern theory suggests that the answer is probably a mix of both, but proving the existence of these cold streams of gas had remained a major challenge until now," says co-author Donal O'Sullivan (MS '15), a PhD student in Martin's group who built part of KCWI.

KCWI, designed and built at Caltech, is a state-of-the-art spectral imaging camera. Called an integral-field unit spectrograph, it allows astronomers to take images such that every pixel in the image contains a dispersed spectrum of light. Installed at Keck in early 2017, KCWI is the successor to the Cosmic Web Imager (CWI), an instrument that has operated at Palomar Observatory near San Diego since 2010. KCWI has eight times the spatial resolution and 10 times the sensitivity of CWI.

"The main driver for building KCWI was understanding and characterizing the cosmic web, but the instrument is very flexible, and scientists have used it, among other things, to study the nature of dark matter, to investigate black holes, and to refine our understanding of star formation," says co-author Mateusz (Matt) Matuszewski (MS '02, PhD '12), a senior instrument scientist at Caltech.

The question of how galaxies and stars form out of a network of wispy filaments in space--what is known as the cosmic web--has fascinated Martin since he was a graduate student. To find answers, he led the teams that built both CWI and KCWI. In 2017, Martin and his team used KCWI to acquire data on two active galaxies known as quasars, named UM 287 and CSO 38, but it was not the quasars themselves they wanted to study. Nearby each of these two quasars is a giant nebula, larger than the Milky Way and visible thanks to the strong illumination of the quasars. By looking at light emitted by hydrogen in the nebulas--specifically an atomic emission line called hydrogen Lyman-alpha--they were able to map the velocity of the gas. From previous observations at Palomar, the team already knew there were signs of rotation in the nebulas, but the Keck data revealed much more.

"When we used Palomar's CWI previously, we were able to see what looked like a rotating disk of gas, but we couldn't make out any filaments," says O'Sullivan. "Now, with the increase in sensitivity and resolution with KCWI, we have more sophisticated models and can see that these objects are being fed by gas flowing in from attached filaments, which is strong evidence that the cosmic web is connected to and fueling this disk."

Martin and colleagues developed a mathematical model to explain the velocities they were seeing in the gas and tested it on UM287 and CSO38 as well as on a simulated galaxy.

"It took us more than a year to come up with the mathematical model to explain the radial flow of the gas," says Martin. "Once we did, we were shocked by how well the model works."

The findings provide the best evidence to date for the cold-flow model of galaxy formation, which basically states that cool gas can flow directly into forming galaxies, where it is converted into stars. Before this model came into popularity, researchers had proposed that galaxies pull in gas and heat it up to extremely high temperatures. From there, the gas was thought to gradually cool, providing a steady but slow supply of fuel for stars. In 1996, research from Caltech's Charles (Chuck) Steidel, the Lee A. DuBridge Professor of Astronomy and a co-author of the new study, threw this model into question. He and his colleagues showed that distant galaxies produce stars at a very high rate--too fast to be accounted for by the slow settling and cooling of hot gas that was a favored model for young galaxy fueling.

"Through the years, we've acquired more and more evidence for the cold-flow model," says Martin. "We have nicknamed our new version of the model the 'cold-flow inspiral,' since we see the spiraling pattern in the gas."

"These type of measurements are exactly the kind of science we want to do with KCWI," says John O'Meara, the Keck Observatory chief scientist. "We combine the power of Keck's telescope size, powerful instrumentation, and an amazing astronomical site to push the boundaries of what's possible to observe. It's very exciting to see this result in particular, since directly observing inflows has been something of a missing link in our ability to test models of galaxy formation and evolution. I can't wait to see what's coming next."

Even if we study them at school, oxidation numbers have so far eluded any rigorous quantum mechanical definition. A new SISSA study, published in Nature Physics, reverses this state of affairs by providing such a definition, based on the theory of topological quantum numbers, which was honoured with the 2016 Nobel prize in Physics awarded to Thouless, Haldane and Kosterlitz. This result, combined with recent advances in the theory of transport achieved at SISSA, paves the way to an accurate, yet tractable, numerical simulation of a broad class of materials that are important in energy-related technologies and planetary sciences.

Every undergraduate student in the natural sciences learns how to associate an integer oxidation number to a chemical species participating in a reaction. Unfortunately, the very concept of oxidation state has thus far eluded a rigorous quantum mechanical definition, so that no method was known until now to compute oxidation numbers from the fundamental laws of nature, let alone demonstrate that their use in the simulation of charge transport does not spoil the quality of numerical simulations. At the same time, the evaluation of electric currents in ionic conductors, which is required to model their transport properties, is presently based on a cumbersome quantum-mechanical approach that severely limits the feasibility of large-scale computer simulations. Scientists have lately noticed that a simplified model where each atom carries a charge equal to its oxidation number may give results in surprising good agreement with rigorous but much more expensive approaches. By combining the new topological definition of oxidation number with the so-called "gauge invariance" of transport coefficients, recently discovered at SISSA, Federico Grasselli and Stefano Baroni proved that what was considered a mere coincidence stands in fact on solid theoretical grounds, and that the simple integer-charge model captures the electrical transport properties of ionic conductors without any approximations.

Besides solving a fundamental conundrum in condensed matter physics, this result, achieved within the framework of the European MAX Centre of Excellence for supercomputing applications, also represents a breakthrough for applications, enabling computationally feasible quantum simulations of charge transport in ionic systems of paramount importance in energy-related technologies, in the automotive and telecommunications sectors, as well as in planetary sciences. Such applications range from the ionic mixtures adopted in electrolytic cells and heat exchangers in power plants, to solid-state-electrolyte batteries for electric cars and electronic devices, and even to the conducting exotic phases of water occurring in the interior of icy giants, which are supposed to be related to the origin of the magnetic fields in these planets.

The best way to protect corals threatened by climate change is to conserve a wide range of their habitats, according to a study in Nature Climate Change. The finding likely applies to conservation efforts for many other species in the ocean and on land, including trees and birds.

"Rather than conserving just the cold places with corals, we found that the best strategies will conserve a wide diversity of sites," said co-author Malin Pinsky, an associate professor in the Department of Ecology, Evolution, and Natural Resources at Rutgers University-New Brunswick. "Hot reefs are important sources of heat-tolerant corals, while cold sites and those in between are important future refuges and stepping stones for corals as the water heats up."

Worldwide, about 500 million people rely on coral reefs for food and livelihoods, with billions of dollars a year boosting economies, according to the National Oceanic and Atmospheric Administration. Reefs protect coastlines from storms and erosion; provide habitat as well as spawning and nursery grounds for fish; and result in income from fishing, recreation and tourism, among other benefits.

But corals face several threats, including global warming, warm water bleaching episodes, reef destruction, nutrient pollution and ocean acidification from carbon dioxide emitted when fossils fuels burn.

Predictions about the future of corals are generally grim, the study notes, but there is growing recognition that they can adapt rapidly to a changing climate.

Pinsky and scientists at the University of Washington, Utah State University, Coral Reef Alliance, Stanford University and University of Queensland in Australia modeled how different conservation strategies might help coral reefs survive climate change. Previous research addressed where to establish marine protected areas to help corals, but nearly all studies overlooked the fact that corals can also evolve in response to climate change, Pinsky said.

The researchers evaluated a range of potential conservation strategies, including those that: protected sites where existing coral populations appeared to be "preadapted" to future conditions; conserved sites suitable for corals to move to in the future; conserved sites with large populations of certain species; conserved the smallest populations; or protected reef sites chosen at random. The researchers found that conserving many different kinds of reefs would work best.

"Corals are facing a gauntlet over the coming years and decades from warming oceans, but we found that reef conservation in general can really boost corals' ability to evolve and cope with these changes," Pinsky said. "There is strength in diversity, even when it comes to corals. We need to think not only about saving the cooler places, where corals can best survive in the future, but also the hot places that already have heat-resistant corals. It's about protecting a diversity of habitats, which scientists hadn't fully appreciated before."

The researchers are developing regional models to test conservation strategies for the Caribbean Sea, the central Pacific Ocean and the Coral Triangle in the western Pacific, he said. They want to understand how the most effective conservation strategies differ from one region to the next.

"We are working closely with conservation groups that will be applying the guidelines and findings from this study to coral reef conservation around the world," Pinsky said.

In the contract-based demand response, some of the participants may default in providing the scheduled negawatt energy owing to demand-side fluctuations faults. Thus, the detection of defaulting participants is an important function of the aggregator. A group of Japanese researchers has developed a method to detect defaulting participants based on sparse reconstruction. This enables assured detection of defaulting participants with limited information that aggregator can utilize.

The demand response (DR), i.e., the changes in electricity usage of consumers in response to incentive payments, is expected to be one of the solutions to supply-side anomalies, such as fluctuations in wind and solar generation. The DR takes various forms depending on its design, including price/incentives, prearranged contracts, direct load control, and so on. In contract-based DR, the aggregator contracts with individual consumers for their scheduled amounts of negawatt energy. Meanwhile, it is inevitable that some of the participants default in providing the scheduled negawatt energy owing to demand-side fluctuations such as instrument faults. Therefore, the detection of failure sources (i.e., defaulting participants) is an important function of the aggregator.

The detection of defaulting participants may be easily performed if the aggregator can continuously meter their real-time consumption via smart meters. However, such metering is difficult in practice from the viewpoint of communication costs. Moreover, real-time continuous metering will be a barrier to social acceptance for the DR. Thus, it is preferable to detect defaulting participants with more limited information, e.g., by irreversible data compression and intermittent metering.

A group of researchers of Nagoya University, Hokkaido University, and Tokyo University of Science has developed a method to detect defaulting participants in a contract-based DR program with the data of the time series of the total amount of negawatt energy and the data of the actual negawatt energy of a limited number of participants, which are inspected via smart meters. In the development, they have focused on the fact that the DR is prearranged by contracts, i.e., only a few participants are defaulting on providing their scheduled negawatt energy. On the basis of this prior knowledge, they have considered to apply the technique of the so-called sparse reconstruction, i.e., reconstructing a sparse vector from a small number of scalar equations, to the detection problem. However, the exact solution is not always derived by direct application of the standard sparse reconstruction technique to the detection problem. By observing this result, they have developed an iterative method that improves the sparse reconstruction in each iteration by including inspection data from the previous iteration. For the proposed method, it is theoretically guaranteed that the result is exact. Moreover, the method enables the detection with a small number of inspections.