Amazing Science

A research team led by Professor Hongzhe SUN, Norman & Cecilia Yip Professor in Bioinorganic Chemistry, Department of Chemistry, Faculty of Science, and Professor Kwok Yung YUEN, Henry Fok Professor in Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine of the University of Hong Kong (HKU), has discovered a novel antiviral strategy for treatment of COVID-19.

They discovered that a class of metallodrugs currently used in the treatment of other infectious diseases is showing efficacy to potently suppress SARS-CoV-2 replication and relieve viral-associated symptoms in an animal model.

The findings provide a new and readily available therapeutic option with high clinical potential for infection with SARS-CoV-2. This ground-breaking work has been published online in a top-class scientific journal Nature Microbiology. A related patent has been filed in the US.

Generally, metal compounds are used as anti-microbial agents; their antiviral activities have rarely been explored. After screening a series of metallodrugs and related compounds, the research team identified ranitidine bismuth citrate (RBC), a commonly used anti-ulcer drug which contains the metal Bismuth for treatment of Helicobacter pylori-associated infection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo.

RBC targets the vital non-structural protein 13 (Nsp13), a viral helicase essential for SARS-CoV-2 to replicate, by displacing the crucial zinc(II) ions in the zinc-binding with Bismuth-ions, to potently suppress the activity of the helicase.

RBC has been demonstrated to greatly reduce viral loads by over 1,000-folds in SARS-CoV-2-infected cells. In particular, in a golden Syrian hamster model, RBC suppresses SARS-CoV-2 replications to reduce viral loads by ~100 folds in both the upper and lower respiratory tracts, and mitigates virus-associated pneumonia. RBC remarkably diminishes the level of prognostic markers and other major pro-inflammatory cytokines and chemokines in severe COVID-19 cases of infected hamsters, compared to the Remdesivir-treated group and control group.

RBC exhibits a low cytotoxicity with a high selectivity index at 975 (the larger the number the safer the drug), as compared to Remdesivir which has a low selectivity index at 129. The finding indicates a wide window between the drug's cytotoxicity and antiviral activity, which allows a great flexibility in adjusting its dosages for treatment.

A research team has used novel single-cell sequencing methods to analyze the expression of transposons in the brains of Drosophila melanogaster fruit flies. Their findings suggest that these "jumping" genes may rewire neuronal function in these somatic cells.

The impact of transposons, or "jumping" genes, depends largely on where they land. They can be an important source of genetic mutations, the potential adverse effects of which has led to them often being referred to as "DNA parasites". However, they are also considered to be key drivers of evolution as they contribute to heritable genetic variation, which diversifies species.

Emerging research has also proposed that transposons are able to introduce non-heritable genetic changes in somatic cells, specifically neurons.5 In the brain, transposon insertions could drive the physiology of a specific group of neurons, contributing to specific brain functions such as behavior or cognition – effectively "rewiring" the brain. It also opens the possibility that transposons could be implicated in pathologies such as neurodegeneration or age-associated cognitive decline.

This is Treiber's research focus at the University of Oxford, and the subject of his latest paper published in Genome Research in collaboration with Professor Scott Waddell.7 The research team used novel single-cell sequencing methods to analyze the expression of transposons in the brains of Drosophila melanogaster fruit flies. The Drosophila fly is a commonly adopted model that has been used in the fields of genetics and neuroscience for the last century.

Advances in single-cell sequencing

In the past, somatic transposons have been extremely difficult to analyze as they occur in single DNA molecules, but single-cell sequencing has proven to be a real game changer according to Treiber.

"Being able to access the transcriptome of 10,000s of cells from the brain in a single experiment enables us to analyze many cell types in parallel. And it enables us to shed light on the complex expression patterns of transposons," he told Technology Networks, adding, "In our research group, we have pioneered the application of these new tools in the fly brain."

An important role for transposons in the brain?
Analysis of the Drosophila brain at the single-cell level revealed that transposon expression was not random – it occurred in a pattern. "Amazingly, when we looked at the “junk” sections of the genomes in the brain, a clear pattern started to emerge," Treiber commented. "Our key finding is that transposons are not expressed randomly in the brain. Instead, we found their expression is driven by the genes that surround them."

In addition, the scientists found a range of neural genes for which a substantial amount of their mature mRNA transcript pool contained transposon sequences. They would sometimes occur in the open reading frame, in addition to a location where it could impact the translocation of the gene, known as the untranslated region, or UTR. "We show that many transposons are spliced into cellular genes and thereby potentially change the structure and function of proteins in the brain," Trebier said.

The ever-increasing production and use of plastics over the last half century has created a huge environmental problem for the world.  Currently, most of the 4.9 billion tonnes of plastics ever produced will end up in landfills or the natural environment, and this number is expected to increase to around 12 billion tonnes by 2050.

A druggable pocket in the SARS-CoV-2 Spike protein that could be used to stop the virus from infecting human cells has been discovered by an international team of scientists led by the University of Bristol. The researchers say their findings, published on 21 September, 2020 in the journal Science, are a potential 'game changer' in defeating the current pandemic and add that small molecule anti-viral drugs developed to target the pocket they discovered could help eliminate COVID-19.

SARS-CoV-2 is decorated by multiple copies of a glycoprotein, known as the 'Spike protein', which plays an essential role in viral infectivity. Spike binds to the human cell surface, allowing the virus to penetrate the cells and start replicating, causing widespread damage.

In this ground-breaking study, the team headed by Professor Christiane Schaffitzel from Bristol’s School of Biochemistry and Professor Imre Berger from the Max Planck-Bristol Centre for Minimal Biology, used a powerful imaging technique, electron cryo-microscopy (cryo-EM), to analyze SARS-CoV-2 Spike at near atomic resolution. Enabled by Oracle high-performance cloud computing, a 3D structure of SARS CoV-2 Spike protein was generated allowing the researchers to peer deep inside the Spike identifying its molecular composition.

Unexpectedly, the research team’s analysis revealed the presence of a small molecule, linoleic acid (LA), buried in a tailor-made pocket within the Spike protein.  LA is a free fatty acid, which is indispensable for many cellular functions. The human body cannot produce LA. Instead, the body absorbs this essential molecule through diet. Intriguingly, LA plays a vital role in inflammation and immune modulation, which are both key elements of COVID-19 disease progression. LA is also needed to maintain cell membranes in the lungs so that we can breathe properly.

Prof Berger said: "We were truly puzzled by our discovery, and its implications. So here we have LA, a molecule which is at the centre of those functions that go haywire in COVID-19 patients, with terrible consequences. And the virus that is causing all this chaos, according to our data, grabs and holds on to exactly this molecule – basically disarming much of the body's defenses."

Prof Schaffitzel explained: "From other diseases we know that tinkering with LA metabolic pathways can trigger systemic inflammation, acute respiratory distress syndrome and pneumonia. These pathologies are all observed in patients suffering from severe COVID-19.  A recent study of COVID-19 patients showed markedly reduced LA levels in their sera."

Gauging whether or not we dwell inside someone’s computer may come down to advanced AI research—or measurements at the frontiers of cosmology. If posthuman civilizations eventually have both the capability and desire to generate such highest level AI-like simulations, then the number of simulated realities would greatly exceed the one base reality, ostensibly indicating a high probability that we do not live in said base reality.

Recently, it has been argued that since the hypothesis that such simulations are technically possible remains unproven, statistical calculations need to consider not just the number of state spaces, but the intrinsic model uncertainty. This is achievable through a Bayesian treatment of the problem. Using Bayesian model averaging, it is shown that the probability that we are sims is in fact less than 50%, tending towards that value in the limit of an infinite number of simulations. This result is broadly indifferent as to whether one conditions upon the fact that humanity has not yet birthed such simulations, or ignore it. As argued elsewhere, it is found that if humanity does start producing such simulations, then this would radically shift the odds and make it very probably we are in fact indeed simulated.

NASA’s telescope on an airplane, the Stratospheric Observatory for Infrared Astronomy, has provided a new glimpse of the chemistry in the inner region surrounding massive young stars where future planets could begin to form. It found massive quantities of water and organic molecules in these swirling, disk-shaped clouds, offering new insights into how some of the key ingredients of life get incorporated into planets during the earliest stages of formation.

A similar process likely happened during the formation of the Sun and the inner rocky planets of our solar system, including Earth. The results are published in the Astrophysical Journal.

“We’re seeing many more molecular signatures than were ever seen before at these wavelengths,” said Andrew Barr, the lead author of the study and a doctoral candidate at Leiden University in the Netherlands. “It turns out that these stars are like chemical factories churning out molecules important for life as we know it and we just needed the right kind of observations to see them.”

SOFIA’s infrared observations offer an unparalleled view of star chemistry. When visible light is spread into its component colors, a rainbow appears. When infrared light is broken into its components, it reveals a series of bright lines, called spectra. Each element creates a unique line, so the lines act as chemical fingerprints. Scientists use them to identify which substances are in and around stars. SOFIA’s instruments can detect small details in the chemical fingerprints from the cores of massive young stars, similar to how high-resolution images reveal tiny features. This information about massive stars, more than 40 times the mass of our Sun, can be a reference for NASA’s James Webb Space Telescope, which will study the formation of Sun-sized stars, among other types of targets.

“This study is very exciting as it demonstrates the power of infrared observatories to sense the presence of simple organic compounds that were important for the origin of life on Earth, and possibly other planets,” said Klaus Pontoppidan, project scientist for the Webb telescope at the Space Telescope Science Institute. “One of the most important goals of both Webb and SOFIA is to understand the origins of stars and planets — and ultimately ourselves.”

Stars form when celestial clouds collapse, feeding a rotating disc of gas and dust into a central core. SOFIA looked at this process happening around two massive stars, AFGL 2591 and AFGL 2136, each about 3,000 light years away in the constellation Cygnus and the Juggler Nebula respectively. The observatory found the inner regions of these discs are heated from the inside out, transforming the gas surrounding the core into an entirely different composition. Within the same areas of the disc where planets would form were a chemical soup of organic molecules, including water, ammonia, methane, and acetylene — which is a chemical building block of larger and more complex organic molecules.

 Further studies of other massive young stars by SOFIA will deepen our understanding of the processes creating organic molecules. As SOFIA’s observations indicate that massive star formation is a scaled-up version of what is occurring in smaller, Sun-sized stars, these new studies can be of benefit to Webb. While Webb’s extremely sensitive telescope will be able to detect some of the weakest signals from molecules present around Sun-like stars, SOFIA can unambiguously identify the chemical compositions of molecules glowing brightly around more massive stars. This will help scientists using Webb interpret the weaker signals.

Remdesivir, the only antiviral drug authorized for treatment of COVID-19 in the United States, fails to prevent deaths among patients, according to a study of more than 11,000 people in 30 countries sponsored by the World Health Organization.

The data, which were posted online just recently, have not yet been peer-reviewed or published in a scientific journal. “This puts the issue to rest — there is certainly no mortality benefit,” said Dr. Ilan Schwartz, an infectious-disease physician at the University of Alberta in Canada.

But Dr. Peter Chin-Hong, an infectious-disease expert at the University of California, San Francisco, was more circumspect.

A huge trial like this one, conducted in various countries with various health care systems, can lead to inconsistent treatment protocols whose effects can be difficult to analyze, he said.

Remdesivir, which was originally developed as a treatment for Ebola and hepatitis C, interferes with the reproduction of viruses by jamming itself into new viral genes. The drug was granted emergency authorization by the Food and Drug Administration on May 1 following a trial by the National Institutes of Health, which found that remdesivir modestly reduced the time to recovery in severely ill patients.

That study, too, did not find that remdesivir prevented deaths in patients with COVID-19. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, acknowledged at the time that remdesivir was not a “knockout” drug.

A final analysis, published in The New England Journal of Medicine on Oct. 8, 2020, suggested “a trend toward reduced mortality” in certain patients receiving remdesivir, according to the drug’s maker, Gilead. In response, Gilead disputed the conclusions of the WHO study, noting that a variety of drugs and drug combinations had been evaluated under a wide range of circumstances and that more rigorous studies had found a benefit. Because of its design, there was “significant heterogeneity” in the way the trial was conducted. “Consequently, it is unclear if any conclusive findings can be drawn from the study results,” the company said in a prepared statement.

Blocking Immune System Pathway May Stop COVID-19 Infection, Prevent Severe Organ Damage
10/08/2020

Colorized scanning electron micrograph of a cell (purple) heavily infected with SARS-CoV-2 virus particles (yellow). A recent study by Johns Hopkins Medicine shows that blocking a specific protein in a biological pathway may prevent SARS-CoV-2 infection and keep the virus from misdirecting the immune system against healthy cells and organs. Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health

While the world waits eagerly for a safe and effective vaccine to prevent infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus behind the COVID-19 pandemic, researchers also are focusing on better understanding how SARS-CoV-2 attacks the body in the search for other means of stopping its devastating impact. The key to one possibility — blocking a protein that enables the virus to turn the immune system against healthy cells — has been identified in a recent study by a team of Johns Hopkins Medicine researchers.

Based on their findings, the researchers believe that inhibiting the protein, known as factor D, also will curtail the potentially deadly inflammatory reactions that many patients have to the virus.

Making the discovery even more exciting is that there may already be drugs in development and testing for other diseases that can do the required blocking. The study is published in the Sept. 2, 2020, issue of the journal Blood.

Scientists already know that spike proteins on the surface of the SARS-CoV-2 virus — making the pathogen look like the spiny ball from a medieval mace — are the means by which it attaches to cells targeted for infection. To do this, the spikes first grab hold of heparan sulfate, a large, complex sugar molecule found on the surface of cells in the lungs, blood vessels and smooth muscle making up most organs. Facilitated by its initial binding with heparan sulfate, SARS-CoV-2 then uses another cell-surface component, the protein known as angiotensin-converting enzyme 2 (ACE2), as its doorway into the attacked cell.

The Johns Hopkins Medicine team discovered that when SARS-CoV-2 ties up heparan sulfate, it prevents factor H from using the sugar molecule to bind with cells. Factor H’s normal function is to regulate the chemical signals that trigger inflammation and keep the immune system from harming healthy cells. Without this protection, cells in the lungs, heart, kidneys and other organs can be destroyed by the defense mechanism nature intended to safeguard them.

“Previous research has suggested that along with tying up heparan sulfate, SARS-CoV-2 activates a cascading series of biological reactions — what we call the alternative pathway of complement, or APC — that can lead to inflammation and cell destruction if misdirected by the immune system at healthy organs,” says study senior author Robert Brodsky, M.D., director of the hematology division at the Johns Hopkins University School of Medicine. “The goal of our study was to discover how the virus activates this pathway and to find a way to inhibit it before the damage happens.”

Stephen Wolfram uses his fundamental physics model to analyze how to go faster than light as an engineering problem & discusses the structure of space & nature of time for the NASA Innovative Advanced Concepts Program keynote address.

Stephen Wolfram explains: "People ask - you might think you have a fundamental theory of physics. Well, then tell us if warp drive is possible!” Despite the hopes and assumptions of science fiction, real physics has for at least a century almost universally assumed that no genuine effect can ever propagate through physical space any faster than light. But is this actually true? We’re now in a position to analyze this in the context of our model for fundamental physics. And I’ll say at the outset that it’s a subtle and complicated question, and I don’t know the full answer yet.

But I increasingly suspect that going faster than light is not a physical impossibility; instead, in a sense, doing it is “just” an engineering problem. But it may well be an irreducibly hard engineering problem. And one that can’t be solved with the computational resources available to us in our universe. But it’s also conceivable that there may be some clever “engineering solution”, as there have been to so many seemingly insuperable engineering problems in the past. And that in fact there is a way to “move through space” faster than light.

It’s a little tricky even to define what it means to “go faster than light”. Do we allow an existing “space tunnel” (like the wormholes of general relativity)? Perhaps a space tunnel that has been there since the beginning of the universe. Or even if no space tunnel already exists, do we allow the possibility of building one—that we can then travel through? I’ll discuss these possibilities later. But the most dramatic possibility is that even if one’s going where “no one has gone before”, it might still be possible to traverse space faster than light to get there.

To give a preview of why doing this might devolve into an “engineering problem”, let’s consider a loose (but, in the end, not quite so loose) analogy. Imagine you’ve got molecules of gas in a room, all bouncing around and colliding with each other. Now imagine there’s a special molecule—or even a tiny speck of dust or a virus particle—somewhere in the room. Normally the special molecule will be buffeted by the molecules in the air, and will move in some kind of random walk, gradually diffusing across the room. But imagine that the special molecule somehow knows enough about the motion of the air molecules that it can compute exactly where to go to avoid being buffeted. Then that special molecule can travel much faster than diffusion—and effectively make a beeline from one side of the room to the other.

Of course this requires more knowledge and more computation than we currently imagine something like a molecule can muster (though it’s not clear this is true when we start thinking about explicitly constructing molecule-scale computers). But the point is that the limit on the speed of the molecule is less a question of what’s physically possible, and more a question of what’s “engineerable”. And so, I suspect, it is with space, and motion through space. Like our room full of air molecules, space in our theory of physics has a complex structure with many component parts that act in seemingly (but not actually) random ways. And in our theory the question of whether we can “move through space” faster than light can then be thought of as becoming a question of whether there can exist a “space demon” that can find ways to do computations fast enough to be able to successfully “hack space”."

Gravitational wave detectors have opened a new window to the universe by measuring the ripples in spacetime produced by colliding black holes and neutron stars, but they are ultimately limited by quantum fluctuations induced by light reflecting off of mirrors. LSU Ph.D. physics alumnus Jonathan Cripe and his team of LSU researchers have conducted a new experiment with scientists from Caltech and Thorlabs to explore a way to cancel this quantum backaction and improve detector sensitivity.

In a new paper inPhysical Review X, the investigators present a method for removing quantum backaction in a simplified system using a mirror the size of a human hair and show the motion of the mirror is reduced in agreement with theoretical predictions. The research was supported by the National Science Foundation.

Despite using 40-kilogram mirrors for detecting passing gravitational waves, quantum fluctuations of light disturb the position of the mirrors when the light is reflected. As gravitational wave detectors continue to grow more sensitive with incremental upgrades, this quantum backaction will become a fundamental limit to the detectors' sensitivity, hampering their ability to extract astrophysical information from gravitational waves.

"We present an experimental testbed for studying and eliminating quantum backaction," Cripe said. "We perform two measurements of the position of a macroscopic object whose motion is dominated by quantum backaction and show that by making a simple change in the measurement scheme, we can remove the quantum effects from the displacement measurement. By exploiting correlations between the phase and intensity of an optical field, quantum backaction is eliminated."

Garrett Cole, technology manager at Thorlabs Crystalline Solutions (Crystalline Mirror Solutions was acquired by Thorlabs Inc. last year), and his team constructed the micromechanical mirrors from an epitaxial multilayer consisting of alternating GaAs and AlGaAs. An outside foundry, IQE North Carolina, grew the crystal structure while Cole and his team, including process engineers Paula Heu and David Follman, manufactured the devices at the University of California Santa Barbara nanofabrication facility.

"By performing this measurement on a mirror visible to the naked eye—at room temperature and at frequencies audible to the human ear—we bring the subtle effects of quantum mechanics closer to the realm of human experience," said LSU Ph.D. candidate Torrey Cullen. "By quieting the quantum whisper, we can now listen to the more subtle notes of the cosmic symphony."

Ingesting more data than ever, exascale model will simulate the impact of climate change on humans

The European Union is finalizing plans for an ambitious “digital twin” of planet Earth that would simulate the atmosphere, ocean, ice, and land with unrivaled precision, providing forecasts of floods, droughts, and fires from days to years in advance.

Destination Earth, as the effort is called, won’t stop there: It will also attempt to capture human behavior, enabling leaders to see the impacts of weather events and climate change on society and gauge the effects of different climate policies.

"It’s a really bold mission, I like it a lot,” says Ruby Leung, a climate scientist at the U.S. Department of Energy’s (DOE’s) Pacific Northwest National Laboratory. By rendering the planet’s atmosphere in boxes only 1 kilometer across, a scale many times finer than existing climate models, Destination Earth can base its forecasts on far more detailed real-time data than ever before. The project, which will be described in detail in two workshops later this month, will start next year and run on one of the three supercomputers that Europe will deploy in Finland, Italy, and Spain.

Destination Earth rose out of the ashes of Extreme Earth, a proposal led by the European Centre for Medium-Range Weather Forecasts (ECMWF) for a billion-euro flagship research program. The European Union ultimately canceled the flagship program, but retained interest in the idea. Fears that Europe was falling behind China, Japan, and the United States in supercomputing led to the European High-Performance Computing Joint Undertaking, an €8 billion investment to lay the groundwork for eventual “exascale” machines capable of 1 billion billion calculations per second. The dormant Extreme Earth proposal offered a perfect use for such capacity. “This blows a soul into your digital infrastructure,” says Peter Bauer, ECMWF’s deputy director of research, who coordinated Extreme Earth and has been advising the European Union on the new program.

Vanderbilt University engineers have determined that their back-assist exosuit, a clothing-like device that supports human movement and posture, can reduce fatigue by an average of 29-47 percent in lower back muscles. The exosuit's functionality presents a promising new development for individuals who work in physically demanding fields and are at risk for back pain, including medical professionals and frontline workers.

The article describing the experiment and findings, "Low-Profile Elastic Exosuit Reduces Back Muscle Fatigue," was published in the Nature journal Scientific Reports on September 29, 2020. The research, led by Assistant Professor of Mechanical Engineering Karl Zelik and recent Ph.D. graduate and primary author Erik Lamers, used surface electromyography techniques to measure changes in low back muscle fatigue in male and female participants, who were given physical tasks to perform both with and without the exosuit.

The wearable technology developed by Zelik's team may conjure images of Iron Man's suit, but it does not rely on motors or batteries. Instead, the low-profile, elastic exosuit applies assistive forces that cooperate with the low back extensor muscles, to relieve strain on the muscles and spine, and to help reduce injury risks.

This study showed that wearing the exosuit made holding a 35-pound weight (the average weight of a 4-year-old child) less tiring on the back than holding a 24-pound weight (the average weight of an 18-month-old baby) without the exosuit. "These findings show how exosuits could provide valuable back relief to frontline and essential workers who have been taking a physical toll and supporting all of us throughout this pandemic. What we learned has the potential to shape the biomechanical and industrial standards of future wearable technologies," said Zelik, who holds secondary appointments in biomedical engineering and in physical medicine and rehabilitation.

The work also demonstrated a sharpened understanding of how the latissimus dorsi muscles (the "lats") -- those that adduct, extend and medially rotate the shoulder joint -- affect low back mechanics. While previous research has shown that the lats generally do not contribute much to supporting the low back, the investigators discovered that, as people get tired, they may suddenly recruit the lats to offload the main back extensor muscles to a significant degree.

"The lats act sort of like an exosuit. When a person's low back muscles become over-strained and fatigued, they summon extra assistance from their lats to relieve this back strain and fatigue. The elastic bands in our exosuit work the same way to help sustain endurance and strength," said Lamers, a National Science Foundation Graduate Research Fellow who worked in Vanderbilt's Center for Rehabilitation Engineering and Assistive Technology.

Zelik, a former collegiate athlete who competed in the long jump and triple jump, knows firsthand how intensive physical activity can fatigue the body. He also understands the importance of ensuring that the exosuit and its utility are built with inclusive design practices. "Wearables are going to change the way we work and live, and we want to improve safety, health and well-being for everyone. One of the critical challenges moving forward will be to ensure that all wearable technology is developed to serve and protect both women and men. We are thrilled that this research helped lead to the first commercial exosuit or exoskeleton designed with both male- and female-fits," Zelik said.

Scientists have estimated that the age of an individual does not indicate how likely they are to be infected by SARS-CoV-2. However, development of symptoms, progression of  the disease, and mortality are age-dependent.

There have been a large number of deaths due to the ongoing COVID-19 pandemic, and it has been shown that elderly individuals disproportionately develop severe symptoms and show higher mortality. 

A team of scientists, including Associate Professor Ryosuke Omori from the Research Center for Zoonoses Control at Hokkaido University, have modeled available data from Japan, Spain and Italy to show that susceptibility to COVID-19 is independent of age, while occurrence of symptomatic COVID-19, severity and mortality is likely dependent on age. Their results were published in the journal Scientific Reports on October 6, 2020.

Causes of mortality in elderly individuals may be due to two factors: how likely they are to be infected due to their advanced age (age-dependent susceptibility), which is reflected in the number of cases; and, how likely they will be affected by a severe form of the disease due to their advanced age (age-dependent severity), which is reflected in the mortality rate. These factors are not fully understood for COVID-19.

The scientists chose to analyse data from Italy, Spain and Japan to determine if any relationship between age, susceptibility and severity. These three countries were chosen as they have well recorded, publicly available data. As of May 2020, the mortality rate (number of deaths per 100,000) was 382.3 for Italy, 507.2 for Spain and 13.2 for Japan. However, despite the wide disparity in mortality rates, the age distribution of mortality (the proportional number of deaths per age group) was similar for these countries.

Modern beam shaping techniques have enabled the generation of optical fields displaying a wealth of structural features, which include three-dimensional topologies such as Möbius, ribbon strips and knots. However, unlike simpler types of structured light, the topological properties of these optical fields have hitherto remained more of a fundamental curiosity as opposed to a feature that can be applied in modern technologies. Due to their robustness against external perturbations, topological invariants in physical systems are increasingly being considered as a means to encode information. Hence, structured light with topological properties could potentially be used for such purposes.

Now, a team of scientists introduce the experimental realization of structures known as framed knots within optical polarization fields. They further develop a protocol in which the topological properties of framed knots are used in conjunction with prime factorization to encode information. Beam shaping methods can generate optical fields with nontrivial topologies, which are invariant against perturbations and thus interesting for information encoding. Here, the authors introduce the realization of framed optical knots to encode programs with the conjoined use of prime factorization.

While building a muscle damage model in a cultured system, a research collaboration between Kumamoto University and Nagasaki University in Japan has found that components leaking from broken muscle fibers activate "satellite” muscle stem cells. While attempting to identify the proteins that activate satellite cells, they found that metabolic enzymes, such as GAPDH, rapidly activated dormant satellite cells and accelerated muscle injury regeneration. This is a highly rational and efficient regeneration mechanism in which the damaged muscle itself activates the satellite cells that begin the regeneration process.
 
Skeletal muscle is made up of bundles of contracting muscle fibers and each muscle fiber is surrounded by satellite cells—muscle stem cells that can produce new muscle fibers. Thanks to the work of these satellite cells, muscle fibers can be regenerated even after being bruised or torn during intense exercise. Satellite cells also play essential roles in muscle growth during developmental stages and muscle hypertrophy during strength training. However, in refractory muscle diseases like muscular dystrophy and age-related muscular fragility (sarcopenia), the number and function of satellite cells decreases. It is therefore important to understand the regulatory mechanism of satellite cells in muscle regeneration therapy.
 
In mature skeletal muscle, satellite cells are usually present in a dormant state. Upon stimulation after muscle injury, satellite cells are rapidly activated and proliferate repeatedly. During the subsequent myogenesis, they differentiate and regenerate muscle fibers by fusing with existing muscle fibers or with together. Of these three steps (satellite cell activation, proliferation, and muscle differentiation), little is known about how the first step, activation, is induced.
 
Since satellite cells are activated when muscle fibers are damaged, researchers hypothesized that muscle damage itself could trigger activation. However, this is difficult to prove in animal models of muscle injury so they constructed a cell culture model in which single muscle fibers, isolated from mouse muscle tissue, were physically damaged and destroyed. Using this injury model, they found that components leaking from the injured muscle fibers activated satellite cells, and the activated cells entered the G1 preparatory phase of cell division. Further, the activated cells returned to a dormant state when the damaged components were removed, thereby suggesting that the damaged components act as the activation switch.
 
The research team named the leaking components "Damaged myofiber-derived factors” (DMDFs), after the broken muscle fibers, and identified them using mass spectrometry. Most of the identified proteins were metabolic enzymes, including glycolytic enzymes such as GAPDH, and muscle deviation enzymes that are used as biomarkers for muscle disorders and diseases. GAPDH is known as a "moonlighting protein" that has other roles in addition to its original function in glycolysis, such as cell death control and immune response mediation.

The researchers therefore analyzed the effects of DMDFs, including GAPDH, on satellite cell activation and confirmed that exposure resulted in their entry into the G1 phase. Furthermore, the researchers injected GAPDH into mouse skeletal muscle and observed accelerated satellite cell proliferation after subsequent drug-induced muscle damage. These results suggest that DMDFs have the ability to activate dormant satellite cells and induce rapid muscle regeneration after injury. The mechanism by which broken muscle activates satellite cells is a highly effective and efficient tissue regeneration mechanism.

In the global race to measure ever shorter time spans, physicists from Goethe University Frankfurt have now taken the lead: together with colleagues at the accelerator facility DESY in Hamburg and the Fritz-Haber-Institute in Berlin, they have measured a process that lies within the realm of zeptoseconds for the first time: the propagation of light within a molecule. A zeptosecond is a trillionth of a billionth of a second (10-21 seconds).

In 1999, the Egyptian chemist Ahmed Zewail received the Nobel Prize for measuring the speed at which molecules change their shape. He founded femtochemistry using ultrashort laser flashes: the formation and breakup of chemical bonds occurs in the realm of femtoseconds. A femtosecond equals 0.000000000000001 seconds, or 10-15 seconds.

Now atomic physicists at Goethe University in Professor Reinhard Dörner's team have for the first time studied a process that is shorter than femtoseconds by magnitudes. They measured how long it takes for a photon to cross a hydrogen molecule: about 247 zeptoseconds for the average bond length of the molecule. This is the shortest timespan that has been successfully measured to date.

The scientists carried out the time measurement on a hydrogen molecule (H2) which they irradiated with X-rays from the synchrotron lightsource PETRA III at the Hamburg accelerator centre DESY. The researchers set the energy of the X-rays so that one photon was sufficient to eject both electrons out of the hydrogen molecule.

Electrons behave like particles and waves simultaneously, and therefore the ejection of the first electron resulted in electron waves launched first in the one, and then in the second hydrogen molecule atom in quick succession, with the waves merging.

The photon behaved here much like a flat pebble that is skimmed twice across the water: when a  wave trough meets a wave crest, the waves of the first and second water contact cancel each other, resulting in what is called an interference pattern.

The scientists measured the interference pattern of the first ejected electron using the COLTRIMS reaction microscope, an apparatus that Dörner helped develop and which makes ultrafast reaction processes in atoms and molecules visible. Simultaneously with the interference pattern, the COLTRIMS reactions microscope also allowed the determination of the orientation of the hydrogen molecule. The researchers here took advantage of the fact that the second electron also left the hydrogen molecule, so that the remaining hydrogen nuclei flew apart and were detected.
 
“Since we knew the spatial orientation of the hydrogen molecule, we used the interference of the two electron waves to precisely calculate when the photon reached the first and when it reached the second hydrogen atom," explains Sven Grundmann whose doctoral dissertation forms the basis of the scientific article in Science. “And this is up to 247 zeptoseconds, depending on how far apart in the molecule the two atoms were from the perspective of light."

Professor Reinhard Dörner adds: “We observed for the first time that the electron shell in a molecule does not react to light everywhere at the same time. The time delay occurs because information within the molecule only spreads at the speed of light. With this finding we have extended our COLTRIMS technology to another application."

Publication: 

• Sven Grundmann, Daniel Trabert, Kilian Fehre, Nico Strenger, Andreas Pier, Leon Kaiser, Max Kircher, Miriam Weller, Sebastian Eckart, Lothar Ph. H. Schmidt, Florian Trinter, Till Jahnke, Markus S. Schöffler, Reinhard Dörner: Zeptosecond Birth Time Delay in Molecular Photoionization. Science https://science.sciencemag.org/cgi/doi/10.1126/science.abb9318

A common genetic deletion boosts the risk for schizophrenia by 30-fold.

Researchers at the National Institute of Standards and Technology (NIST) and their colleagues have proposed a novel method for finding dark matter, the cosmos’s mystery material that has eluded detection for decades. Dark matter makes up about 27% of the universe; ordinary matter, such as the stuff that builds stars and planets, accounts for just 5% of the cosmos. A mysterious entity called dark energy, accounts for the other 68%.

According to cosmologists, all the visible material in the universe is merely floating in a vast sea of dark matter — particles that are invisible but nonetheless have mass and exert a gravitational force. Dark matter’s gravity would provide the missing glue that keeps galaxies from falling apart and account for how matter clumped together to form the universe’s rich galactic tapestry. 

The proposed experiment, in which a billion millimeter-sized pendulums would act as dark matter sensors, would be the first to hunt for dark matter solely through its gravitational interaction with visible matter. The experiment would be one of the few to search for dark matter particles with a mass as great as that of a grain of salt, a scale rarely explored and never studied by sensors capable of recording tiny gravitational forces.

Dark matter, the hidden stuff of our universe, is notoriously difficult to detect. In search of direct evidence, NIST researchers have proposed using a 3D array of pendulums as force detectors, which could detect the gravitational influence of passing dark matter particles. When a dark matter particle is near a suspended pendulum, the pendulum should deflect slightly due to the attraction of both masses. However, this force is very small, and difficult to isolate from environmental noise that causes the pendulum to move. To better isolate the deflections from passing particles, NIST researchers propose using a pendulum array.

Environmental noise affects each pendulum individually, causing them to move independently. However, particles passing through the array will produce correlated deflections of the pendulums. Because these movements are correlated, they can be isolated from the background noise, revealing how much force a particle delivers to each pendulum and the particle’s speed and direction, or velocity.

Previous experiments have sought dark matter by looking for nongravitational signs of interactions between the invisible particles and certain kinds of ordinary matter. That’s been the case for searches for a hypothetical type of dark matter called the WIMP (weakly interacting massive particles), which was a leading candidate for the unseen material for more than two decades. Physicists looked for evidence that when WIMPs occasionally collide with chemical substances in a detector, they emit light or kick out electric charge. 

Researchers hunting for WIMPs in this way have either come up empty-handed or garnered inconclusive results; the particles are too light (theorized to range in mass between that of an electron and a proton) to detect through their gravitational tug. 

With the search for WIMPs seemingly on its last legs, researchers at NIST and their colleagues are now considering a more direct method to look for dark matter particles that have a heftier mass and therefore wield a gravitational force large enough to be detected.

Researchers have detected a group of lakes hidden under the red planet’s icy surface.

Two years ago, planetary scientists reported the discovery of a large saltwater lake under the ice at Mars’s south pole, a finding that was met with excitement and some skepticism. Now, researchers have confirmed the presence of that lake — and found three more.

The discovery, reported on 28 September in Nature Astronomy1, was made using radar data from the European Space Agency’s Mars-orbiting spacecraft, called Mars Express. It follows the detection of a single subsurface lake in the same region in 2018 — which, if confirmed, would be the first body of liquid water ever detected on the red planet and a possible habitat for life. But that finding was based on just 29 observations made from 2012 to 2015, and many researchers said they needed more evidence to support the claim. The latest study used a broader data set comprising 134 observations from 2012 to 2019.

“We identified the same body of water, but we also found three other bodies of water around the main one,” says planetary scientist Elena Pettinelli at the University of Rome, who is one of the paper’s co-authors. “It’s a complex system.” The team used a radar instrument on Mars Express called the Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) to probe the planet’s southern polar region. MARSIS sends out radio waves that bounce off layers of material in the planet’s surface and subsurface. The way the signal is reflected back indicates the kind of material that is present at a particular location — rock, ice or water, for example. A similar method is used to identify subsurface glacial lakes on Earth. The team detected some areas of high reflectivity that they say indicate bodies of liquid water trapped under more than one kilometre of Martian ice.

The lakes are spread over about 75,000 square kilometres — an area roughly one-fifth the size of Germany. The largest, central lake measures 30 kilometres across, and is surrounded by 3 smaller lakes, each a few kilometres wide.

Salty lakes

On the surface of Mars, the low pressure that results from the planet’s lack of a substantial atmosphere makes liquid water impossible. But scientists have long thought that there could be water trapped under Mars’s surface, perhaps a remnant of when the planet once had seas and lakes billions of years ago. If such reservoirs exist, they could be potential habitats for Martian life. On Earth, life is able to survive in subglacial lakes in places such as Antarctica.

But the amount of salt present could pose problems. It’s thought that any underground lakes on Mars must have a reasonably high salt content for the water to remain liquid. Although this far beneath the surface there might be a small amount of heat from the interior of Mars, this alone would not be enough to melt the ice into water. “From a thermal point of view, it has to be salty,” says Pettinelli.

Lakes with a salt content that is about 5 times that of sea-water can support life, but as the concentration approaches 20 times that of sea-water, life is no longer present, says John Priscu, an environmental scientist at Montana State University in Bozeman. “There’s not much active life in these briny pools in Antarctica,” says Priscu, whose group studies microbiology in icy environments. “They’re just pickled. And that might be the case [on Mars].”

OmniVision OV6948 enters the Guinness Book of Records as the world's smallest camera.

OmniVision OV6948 measures in super-small at just 0.575 x 0.575 x 0.232mm and is good for 40,000-pixel color images using an RGB Bayer back-side-illuminating chip. This new camera is ridiculosuly small, but it's for specific use cases in surgery.

With the OmniVision OV6948 surgeons can have a camera so small it will fit into the smallest veins inside of the human body.

This technology provides surgeons and doctors that have the OmniVision OV6948 with next-gen camera access for future surgeries. Until now, surgeons do this without any camera -- acting blind. The only cameras capable of anything close to this are very few, but they also have a much lower resolution fiber optic feed. The new OmniVision OV6948 captures images at 30FPS, and can have analog output at over 4mm away with minimal noise.

The OmniVision OV6948 has a 120-degree super-side angle field of view, something that on a regular camera would come up as 14nm on a full-frame sensor. The depth of field for the OmniVision OV6948 spans between 3mm and 30mm.

Two teams at the Wyss Institute have demonstrated the use of NLP and CV techniques to optimize RNA sequences to develop improved sensors for the SARS-CoV-2 genome that is responsible for COVID-19.

A genome is a genetic blueprint that determines an organism's characteristics. Deoxyribonucleic acid (DNA), and usually in the case of viruses, Ribonucleic acid (RNA) are the building blocks of genomic sequences. And manipulating these nucleic acids directly can lead to tangible changes in the organism.

As such, developments in genetic engineering focus on our ability to manipulate genomic sequences. But this is a daunting task. For example, precisely controlling a specific class of engineered RNA molecules called "toehold switches" can lend vital insight into cellular environments and potential diseases. However, previous experiments have shown that toehold switches are not tractable, many don't respond to modifications even though they have been engineered to produce the desired output in response to a given input based on known RNA folding rules.

Considering this, two teams of researchers from the Wyss Institute at Harvard University and MIT have developed a set of machine learning algorithms that can improve this process. Specifically, they used deep learning to analyze a large volume of toehold switch sequences to accurately predict which toeholds perform their intended tasks reliably thereby allowing researchers to identify high-quality toeholds for their experiments. Their findings have been published in Nature in two separate papers today.

With any machine learning problem, the first step is to collect domain-specific data to train the model on. The researchers collected a large dataset composed of toehold switch sequences. Alex Garruss, co-first author and a graduate student working at the Wyss stated: "We designed and synthesized a massive library of toehold switches, nearly 100,000 in total, by systematically sampling short trigger regions along the entire genomes of 23 viruses and 906 human transcription factors."

Since there were two separate teams, the researchers tried their hands with two different techniques to approach the problem. The authors of the first paper decided to analyze toehold switches not as sequences of bases, but as 2D images of base-pair possibilities. This approach, called Visualizing Secondary Structure Saliency Maps, or VIS4Map, successfully identified physical elements of the toehold switches that influenced their performance, providing insight into RNA folding mechanisms that had not been discovered using traditional analysis techniques.

SPARROW, a steam-powered robotic concept, could one day take giant leaps over some of the most hazardous terrains known (and unknown) in the solar system.

Steam locomotion may sound like an antiquated way to get around, but it might be getting a science fiction makeover as we expand our reach into the solar system. A novel robotic concept being investigated at NASA's Jet Propulsion Laboratory in Southern California would use steam propulsion to hop across the sort of icy terrains found on Jupiter's moon Europa and Saturn's moon Enceladus. Both are thought to host vast subsurface oceans of salty water under a thick ice crust. But while that makes them fascinating destinations for scientific study, the little we know about their surfaces could also make navigating them especially challenging.

That's where the Steam Propelled Autonomous Retrieval Robot for Ocean Worlds, or SPARROW, comes in. About the size of a soccer ball, the robot consists of a system of thrusters, avionics and instruments encased in a protective spherical cage. To keep the environment pristine for study, SPARROW would run not on rocket fuel but on steam produced from melted ice, traveling primarily through the air via short thrusts. In the sort of low-gravity environment found on those distant icy moons, there'd be no atmospheric drag to slow it down, enabling hops of many miles over landscapes that other robots would have difficulty navigating.

"The terrain on Europa is likely highly complex," said Gareth Meirion-Griffith, JPL roboticist and the lead researcher of the concept. "It could be porous, it might be riddled with crevasses, there might be meters-high penitentes" — long blades of ice known to form at high latitudes on Earth — "that would stop most robots in their tracks. But SPARROW has total terrain agnosticism; it has complete freedom to travel across an otherwise inhospitable terrain."

The concept depends on a lander serving as the home base for SPARROW. It would mine the ice and melt it down before loading the water onto the hopping robot. SPARROW would then heat the water inside its engines, creating bursts of steam to give a boost off the surface. When low on fuel, the hopping bot would return to the lander for more, also dropping off any scientific samples for further analysis.

To maximize the science investigations that could be done, many SPARROWs could be sent together, swarming around a specific location or splitting up to explore as much alien terrain as possible.

In 2018, SPARROW was awarded Phase I funding by the NASA Innovative Advanced Concepts (NIAC) program, which nurtures visionary ideas that could, someday, be used in future space missions. Phase I studies explore the overall viability and advance the Technology Readiness Level (TRL). Eligible recipients of Phase I awards can propose a follow-on Phase II study.

For SPARROW, the NIAC Phase I funding allowed the development and testing of different water-based propellant systems that could be used to produce steam in the most efficient way. Additionally, the SPARROW team was able to better understand how the spherical robot might tumble when landing on chaotic icy terrain by using computer simulations, thereby identifying the most efficient angle of launch and speed of hop. "From this, and related propulsion calculations, we were able to determine that a single long hop would be more efficient that several smaller hops," added Meirion-Griffith.

Explore the history of computers + micro-electronics technology at the virtual museum called Chips etc. — 1,000 rare parts from the world’s foremost electronics + semi-conductor companies.

People from every generation have a fascination with the evolution of computers: whether it’s chips, computer hardware, or ephemera. Both specialists and amateurs — hobbyist, makers, historians, engineers, and scientists — enjoy vintage computer parts. Since computing first began in the 20th century, the field has been progressing in leaps + bounds — making these historic markers of the past even more interesting. 

It’s always an intriguing and valuable lesson to see how we got from the past to where we are today. This is especially true watching the development of computers. For example: an old Apple II computer made by Apple from years 1977 — 1993. Once ubiquitous in school classrooms in the 1980s, the Apple II is now functionally useless: except for helping us understand Apple’s re-emergence as a huge brand in personal computing. Apple’s early computers sparked trends in design, craftsmanship, and applications that set the stage for modern laptops, desktops, smartphones, and tablets.

What is rare is intriguing. People are fascinated by antiques, it’s a special experience to touch artifacts from the past, and bring history to life. As we approach year 2020, vintage electronic components are becoming rare. Old computer parts continue to be melted down for their scrap gold content by precious metal recyclers. With only a few thousand in the world — collectors and museums are essential to preserving our technological past.

Some dedicated curators manage large collections that are now highly valuable, as vintage electronics items age: from yesterday’s junk — to today’s hard-to-find, coveted antiquities.

Two and a half years ago, MIT entered into a research agreement with startup company Commonwealth Fusion Systems to develop a next-generation fusion research experiment, called SPARC, as a precursor to a practical, emissions-free power plant.

Now, after many months of intensive research and engineering work, the researchers charged with defining and refining the physics behind the ambitious reactor design have published a series of papers summarizing the progress they have made and outlining the key research questions SPARC will enable.

Overall, says Martin Greenwald, deputy director of MIT's Plasma Science and Fusion Center and one of the project's lead scientists, the work is progressing smoothly and on track. This series of papers provides a high level of confidence in the plasma physics and the performance predictions for SPARC, he says. No unexpected impediments or surprises have shown up, and the remaining challenges appear to be manageable. This sets a solid basis for the device's operation once constructed, according to Greenwald.

Greenwald wrote the introduction for a set of seven research papers authored by 47 researchers from 12 institutions and published today in a special issue of the Journal of Plasma Physics. Together, the papers outline the theoretical and empirical physics basis for the new fusion system, which the consortium expects to start building next year.

SPARC is planned to be the first experimental device ever to achieve a "burning plasma" -- that is, a self-sustaining fusion reaction in which different isotopes of the element hydrogen fuse together to form helium, without the need for any further input of energy. Studying the behavior of this burning plasma -- something never before seen on Earth in a controlled fashion -- is seen as crucial information for developing the next step, a working prototype of a practical, power-generating power plant.

Such fusion power plants might significantly reduce greenhouse gas emissions from the power-generation sector, one of the major sources of these emissions globally. The MIT and CFS project is one of the largest privately funded research and development projects ever undertaken in the fusion field.

The SPARC design, though about the twice the size as MIT's now-retired Alcator C-Mod experiment and similar to several other research fusion reactors currently in operation, would be far more powerful, achieving fusion performance comparable to that expected in the much larger ITER reactor being built in France by an international consortium. The high power in a small size is made possible by advances in superconducting magnets that allow for a much stronger magnetic field to confine the hot plasma.

The SPARC project was launched in early 2018, and work on its first stage, the development of the superconducting magnets that would allow smaller fusion systems to be built, has been proceeding apace. The new set of papers represents the first time that the underlying physics basis for the SPARC machine has been outlined in detail in peer-reviewed publications. The seven papers explore the specific areas of the physics that had to be further refined, and that still require ongoing research to pin down the final elements of the machine design and the operating procedures and tests that will be involved as work progresses toward the power plant.

The papers also describe the use of calculations and simulation tools for the design of SPARC, which have been tested against many experiments around the world. The authors used cutting-edge simulations, run on powerful supercomputers, that have been developed to aid the design of ITER. The large multi-institutional team of researchers represented in the new set of papers aimed to bring the best consensus tools to the SPARC machine design to increase confidence it will achieve its mission.