Working with theorists in the University of Chicago’s Pritzker School of Molecular Engineering, researchers in the U.S. Department of Energy’s (DOE) Argonne National Laboratory have achieved a scientific control that is a first of its kind. They demonstrated a novel approach that allows real-time control of the interactions between microwave photons and magnons, potentially leading to advances in electronic devices and quantum signal processing.
Tuned photon-magnon interactions. The team’s device is in the center. Arrow indicates direction of spin excitation for magnons. The purplish shroud represents reflectance measurements. The separated darker lines on each side that intersect at the top indicate tunable strong photon-magnon coupling. (Image by Argonne National Laboratory.)
Microwave photons are elementary particles forming the electromagnetic waves that we use for wireless communications. On the other hand, magnons are the elementary particles forming what scientists call “spin waves” — wave-like disturbances in an ordered array of microscopic aligned spins that can occur in certain magnetic materials.
“Before our discovery, controlling the photon-magnon interaction was like shooting an arrow into the air. One has no control at all over that arrow once in flight.”
— Xufeng Zhang, assistant scientist in Argonne’s Center for Nanoscale Materials
Microwave photon-magnon interaction has emerged in recent years as a promising platform for both classical and quantum information processing. Yet, this interaction had proved impossible to manipulate in real time, until now.
“Before our discovery, controlling the photon-magnon interaction was like shooting an arrow into the air,” said Xufeng Zhang, an assistant scientist in the Center for Nanoscale Materials, a DOE User Facility at Argonne, and the corresponding author of this work. “One has no control at all over that arrow once in flight.”
The team’s discovery has changed that. “Now, it is more like flying a drone, where we can guide and control its flight electronically,” said Zhang.
By smart engineering, the team employs an electrical signal to periodically alter the magnon vibrational frequency and thereby induce effective magnon-photon interaction. The result is a first-ever microwave-magnonic device with on-demand tunability.
The team’s device can control the strength of the photon-magnon interaction at any point as information is being transferred between photons and magnons. It can even completely turn the interaction on and off. With this tuning capability, scientists can process and manipulate information in ways that far surpass present-day hybrid magnonic devices.
“Researchers have been searching for a way to control this interaction for the past few years,” noted Zhang. The team’s discovery opens a new direction for magnon-based signal processing and should lead to electronic devices with new capabilities. It may also enable important applications for quantum signal processing, where microwave-magnonic interactions are being explored as a promising candidate for transferring information between different quantum systems.
The DOE Office of Basic Energy Sciences supported this research, which was published in Physical Review Letters. Aside from Zhang, authors include Jing Xu, Changchun Zhong (University of Chicago), Xu Han, Dafei Jin and Liang Jiang (University of Chicago).
About Argonne’s Center for Nanoscale Materials The Center for Nanoscale Materials is one of the five DOE Nanoscale Science Research Centers, premier national user facilities for interdisciplinary research at the nanoscale supported by the DOE Office of Science. Together the NSRCs comprise a suite of complementary facilities that provide researchers with state-of-the-art capabilities to fabricate, process, characterize and model nanoscale materials, and constitute the largest infrastructure investment of the National Nanotechnology Initiative. The NSRCs are located at DOE’s Argonne, Brookhaven, Lawrence Berkeley, Oak Ridge, Sandia and Los Alamos National Laboratories. For more information about the DOE NSRCs, please visit https://science.osti.gov/User-Facilities/User-Facilities-at-a-Glance.
Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation’s first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America’s scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science.
The U.S. Department of Energy’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science.
A remarkable prediction of Einstein’s theory of general relativity—the theory that connects space, time, and gravity—is that rotating black holes have enormous amounts of energy available to be tapped.
For the last 50 years, scientists have tried to come up with methods to unleash this power. Nobel physicist Roger Penrose theorized that a particle disintegration could draw energy from a black hole; Stephen Hawking proposed that black holes could release energy through quantum mechanical emission; while Roger Blandford and Roman Znajek suggested electromagnetic torque as a main agent of energy extraction.
Now, in a study published in the journal Physical Review D, physicists Luca Comisso from Columbia University and Felipe Asenjo from Universidad Adolfo Ibáñez in Chile, found a new way to extract energy from black holes by breaking and rejoining magnetic field lines near the event horizon, the point from which nothing, not even light, can escape the black hole’s gravitational pull.
“Black holes are commonly surrounded by a hot ‘soup’ of plasma particles that carry a magnetic field,” said Luca Comisso, research scientist at Columbia University and first author on the study. “Our theory shows that when magnetic field lines disconnect and reconnect, in just the right way, they can accelerate plasma particles to negative energies and large amounts of black hole energy can be extracted.”
This finding could allow astronomers to better estimate the spin of black holes, drive black hole energy emissions, and might even provide a source of energy for the needs of an advanced civilization, Comisso said.
Why Reconnection Works
Comisso and Asenjo built their theory on the premise that reconnecting magnetic fields accelerate plasma particles in two different directions. One plasma flow is pushed against the black hole’s spin, while the other is propelled in the spin’s direction and can escape the clutches of the black hole, which releases power if the plasma swallowed by the black hole has negative energy.
“It is like a person could lose weight by eating candy with negative calories,” said Comisso, who explained that essentially a black hole loses energy by eating negative-energy particles. “This might sound weird,” he said, “but it can happen in a region called the ergosphere, where the spacetime continuum rotates so fast that every object spins in the same direction as the black hole.”
Inside the ergosphere, magnetic reconnection is so extreme that the plasma particles are accelerated to velocities approaching the speed of light.
Asenjo, professor of physics at the Universidad Adolfo Ibáñez and coauthor on the study, explained that the high relative velocity between captured and escaping plasma streams is what allows the proposed process to extract massive amounts of energy from the black hole.
“We calculated that the process of plasma energization can reach an efficiency of 150 percent, much higher than any power plant operating on Earth,” Asenjo said. “Achieving an efficiency greater than 100 percent is possible because black holes leak energy, which is given away for free to the plasma escaping from the black hole.”
An Energy Source for the Future?
The process of energy extraction envisioned by Comisso and Asenjo might be already operating in a large number of black holes. That may be what is driving black hole flares—powerful bursts of radiation that can be detected from Earth.
“Our increased knowledge of how magnetic reconnection occurs in the vicinity of the black hole might be crucial for guiding our interpretation of current and future telescope observations of black holes, such as the ones by the Event Horizon Telescope,” Asenjo said.
While it may sound like the stuff of science fiction, mining energy from black holes could be the answer to our future power needs.
“Thousands or millions of years from now, humanity might be able to survive around a black hole without harnessing energy from stars,” Comisso said. “It is essentially a technological problem. If we look at the physics, there is nothing that prevents it.”
The study, Magnetic reconnection as a mechanism for energy extraction from rotating black holes, was funded by the National Science Foundation’s Windows on the Universe initiative, NASA, and Chile’s National Fund for Scientific and Technological Development.
“The ideas and concepts discussed in this work are truly fascinating,” said Vyacheslav Lukin, a program director at the National Science Foundation, which aims to bring theoretical physics and observational astronomy under one roof. “We look forward to the potential translation of seemingly esoteric studies of black hole astrophysics into the practical realm.”
Robotics researchers at the University of Zurich show how onboard cameras can be used to keep damaged quadcopters in the air and flying stably – even without GPS.
When one rotor fails, the drone begins to spin on itself like a ballerina. (Picture: UZH)
As anxious passengers are often reassured, commercial aircrafts can easily continue to fly even if one of the engines stops working. But for drones with four propellers – also known as quadcopters – the failure of one motor is a bigger problem. With only three rotors working, the drone loses stability and inevitably crashes unless an emergency control strategy sets in.
Researchers at the University of Zurich and the Delft University of Technology have now found a solution to this problem: They show that information from onboard cameras can be used to stabilize the drone and keep it flying autonomously after one rotor suddenly gives out.
Spinning like a ballerina
“When one rotor fails, the drone begins to spin on itself like a ballerina,” explains Davide Scaramuzza, head of the Robotics and Perception Group at UZH and of the Rescue Robotics grand challenge at NCCR Robotics, which funded the research. “This high-speed rotational motion causes standard controllers to fail unless the drone has access to very accurate position measurements.” In other words, once it starts spinning, the drone is no longer able to estimate its position in space and eventually crashes.
The algorithms combine the information from the sensors to track the quadrotor’s position in the environment. (Image: UZH)
One way to solve this problem is to provide the drone with a reference position through GPS. But there are many places where GPS signals are unavailable. In their study, the researchers solved this issue for the first time without relying on GPS, instead using visual information from different types of onboard cameras.
Event cameras work well in low light
The researchers equipped their quadcopters with two types of cameras: standard ones, which record images several times per second at a fixed rate, and event cameras, which are based on independent pixels that are only activated when they detect a change in the light that reaches them.
The research team developed algorithms that combine information from the two sensors and use it to track the quadrotor’s position relative to its surroundings. This enables the onboard computer to control the drone as it flies – and spins – with only three rotors. The researchers found that both types of cameras perform well in normal light conditions. “When illumination decreases, however, standard cameras begin to experience motion blur that ultimately disorients the drone and crashes it, whereas event cameras also work well in very low light,” says first author Sihao Sun, a postdoc in Scaramuzza’s lab.
Increased safety to avoid accidents
The problem addressed by this study is a relevant one, because quadcopters are becoming widespread and rotor failure may cause accidents. The researchers believe that this work can improve quadrotor flight safety in all areas where GPS signal is weak or absent.
Reference: Sihao Sun, Giovanni Cioffi, Coen de Visser, Davide Scaramuzza: Autonomous Quadrotor Flight despite Rotor Failure with Onboard Vision Sensors: Frames vs. Events. 5. January 2021, IEEE Robotics and Automation Letter. DOI: 10.1109/LRA.2020.3048875
What if the degenerative eye conditions that lead to glaucoma, corneal dystrophy, and cataracts could be detected and treated before vision is impaired? Recent findings from the lab of Investigator Ting Xie, PhD, at the Stowers Institute for Medical Research point to the ciliary body as a key to unlocking this possibility.
Adult mouse eye Morphology. Image: Courtesy of Xie Lab.
Previous work from the lab showed that when mouse stem cells were differentiated into light-sensing photoreceptor cells in vitro, and then transplanted back into mice with a degenerative condition of the retina, they could partially restore vision. However, the transplanted photoreceptors only lasted three to four months.
“You cannot cure the condition in a diseased eye if you don’t know what causes the disease,” says Xie. “This has been a major hurdle for stem cell therapy in treating degenerative diseases.”
To this end, Xie’s group began to study the eye tissue microenvironment, specifically a specialized tissue in the eye called the ciliary body. Located at the posterior edge of the iris, it is known to maintain ocular pressure by secreting aqueous humor, the clear fluid between the lens and the cornea. It has a similar function in mice and in humans, and defects in the ciliary body manifest in similar ways in the mouse and human eye.
“People think the ciliary body is boring,” says Xie. This might be because the ciliary body was once thought to have a reserve of retinal stem cells, Xie explains, which turned out not to be true. However, its role in eye biology turns out to be quite broad, and “without a functioning ciliary body, the eye degenerates,” Xie adds.
When the Notch signaling pathway—an important cell signaling system found across the animal kingdom—is defective in the ciliary bodies of newly born mice, they fail to develop folds, and secretions decrease, leading to shrunken vitreous bodies. In adult mice, defects in Notch signaling cause low eye pressure, a shrunken vitreous, and eye degeneration. Inactivation of the downstream transcription factor RBPJ in the ciliary body also leads to the same effects. Before now, the underlying molecular mechanism for this outcome was unclear.
In a paper published in Cell Reports on January 12, 2021, first author Ji Pang, a visiting PhD student from Shanghai Jiao Tong University, China, and others describe a signaling pathway wherein Notch and Nectin proteins in the ciliary body function in the development and maintenance of eye tissue and structure.
In this report, the researchers describe the roles of adhesion protein Nectin1 and gap junction protein Connexin43 in the ciliary body of mice. They found that Notch2/3-Rbpj signaling in the outer ciliary epithelium controls the expression of Nectin1, which works with Nectin3 in the inner ciliary epithelium to keep the two tissue layers together, which promotes proper folding of the ciliary body. They found that Notch signaling also maintains the expression of Connexin43 in the outer ciliary epithelium, while Nectin1 localizes and stabilizes Connexin43 on the lateral surface, which maintains the vitreous body and intraocular pressure.
Graphical abstract by Xie Lab.
Lastly, the researchers found that in addition to maintaining ocular pressure and directing ciliary body morphogenesis, Notch2/3-Rbpj signaling in the inner ciliary epithelium also regulates the secretion of various proteins such as Opticin and collagens into the vitreous body, providing nutritive support for the cornea, the lens, and the retina.
“We propose the ciliary body could be a niche for the eye tissues,” explains Xie, in the sense that it can behave like a stem cell niche, by providing signals that affect cellular morphogenesis and function. “The next important question is what other protein factors secreted by the ciliary body are important for maintaining the cornea, the lens, and the retina, respectively. Some of these factors could be involved directly in eye diseases.”
Other coauthors of the study included Liang Le, PhD, Yi Zhou, PhD, Renjun Tu, PhD, Qiang Hou, PhD, Dai Tsuchiya, PhD, Nancy Thomas, Yongfu Wang, PhD, Zulin Yu, PhD, Richard Alexander, Marina Thexton, Brandy Lewis, Timothy Corbin, Michael Durnin, and Hua Li, PhD, from Stowers; Ruth Ashery-Padan, PhD, from Tel Aviv University, Israel; and Deyue Yan, PhD, from Shanghai Jiao Tong University, China.
This work was supported by the Stowers Institute for Medical Research, the National Eye Institute of the National Institutes of Health (award R01EY027441 to TX), and a China National Scholarship (JP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Lay Summary of Findings
One of the leading causes of glaucoma is high intraocular pressure, which can cause blindness due to damage of the optic nerve. Intraocular pressure is largely maintained by the ciliary body, a specialized tissue in the eye of animals that secretes fluids. It also functions to maintain structural integrity of the eye, but detailed mechanisms of how it does so had not yet been described.
In a study published online January 12, 2021, in Cell Reports, researchers at the Stowers Institute for Medical Research from the laboratory of Ting Xie, PhD, and collaborators describe how the Notch pathway regulates the secretion of proteins important for supporting eye structure, and also controls the expression of adhesion proteins Nectin1 and Nectin3 to promote the normal structural development of the ciliary body. They find that Nectin proteins ensure expression of the gap junction protein Connexin43, which functions to ensure proper fluid secretion. This work highlights the broad role of the ciliary body in maintenance of eye health and implicates the ciliary body in various eye diseases.
The Stowers Institute for Medical Research is a non-profit, basic biomedical research organization dedicated to basic research – the critical first step in the quest for new medical diagnostics, therapies and treatments. Jim Stowers, founder of American Century Investments, and his wife, Virginia, opened the Institute in 2000. Since then, the Institute has spent over one billion dollars in pursuit of its mission.
Currently, the Institute is home to about 500 researchers and support personnel, over 20 independent research programs, and more than a dozen technology development and core facilities. Learn more about the Institute at www.stowers.org and about its graduate program at www.stowers.org/gradschool.
DNA usually forms the classic double helix shape of two strands wound around each other. While DNA can form some more exotic shapes in test tubes, few are seen in real living cells.
G-quadruplexes play an important role in a wide variety of processes vital for life, and in a range of diseases, but the missing link has been imaging this structure directly in living cells.
-Ben Lewis
However, four-stranded DNA, known as G-quadruplex, has recently been seen forming naturally in human cells. Now, in new research published today in Nature Communications, a team led by Imperial College London scientists have created new probes that can see how G-quadruplexes are interacting with other molecules inside living cells.
G-quadruplexes are found in higher concentrations in cancer cells, so are thought to play a role in the disease. The probes reveal how G-quadruplexes are ‘unwound’ by certain proteins, and can also help identify molecules that bind to G-quadruplexes, leading to potential new drug targets that can disrupt their activity.
Needle in a haystack
One of the lead authors, Ben Lewis, from the Department of Chemistry at Imperial, said: “A different DNA shape will have an enormous impact on all processes involving it – such as reading, copying, or expressing genetic information.
“Evidence has been mounting that G-quadruplexes play an important role in a wide variety of processes vital for life, and in a range of diseases, but the missing link has been imaging this structure directly in living cells.”
G-quadruplexes are rare inside cells, meaning standard techniques for detecting such molecules have difficulty detecting them specifically. Ben Lewis describes the problem as “like finding a needle in a haystack, but the needle is also made of hay”.
To solve the problem, researchers from the Vilar and Kuimova groups in the Department of Chemistry at Imperial teamed up with the Vannier group from the Medical Research Council’s London Institute of Medical Sciences.
They used a chemical probe called DAOTA-M2, which fluoresces (lights up) in the presence of G-quadruplexes, but instead of monitoring the brightness of fluorescence, they monitored how long this fluorescence lasts. This signal does not depend on the concentration of the probe or of G-quadruplexes, meaning it can be used to unequivocally visualise these rare molecules.
Dr Marina Kuimova, from the Department of Chemistry at Imperial, said: “By applying this more sophisticated approach we can remove the difficulties which have prevented the development of reliable probes for this DNA structure.”
Looking directly in live cells
The team used their probes to study the interaction of G-quadruplexes with two helicase proteins – molecules that ‘unwind’ DNA structures. They showed that if these helicase proteins were removed, more G-quadruplexes were present, showing that the helicases play a role in unwinding and thus breaking down G-quadruplexes.
Many researchers have been interested in the potential of G-quadruplex binding molecules as potential drugs for diseases such as cancers. Our method will help to progress our understanding of these potential new drugs.
– Professor Ramon Vilar
Dr Jean-Baptiste Vannier, from the MRC London Institute of Medical Sciences and the Institute of Clinical Sciences at Imperial, said: “In the past we have had to rely on looking at indirect signs of the effect of these helicases, but now we take a look at them directly inside live cells.”
They also examined the ability of other molecules to interact with G-quadruplexes in living cells. If a molecule introduced to a cell binds to this DNA structure, it will displace the DAOTA-M2 probe and reduce its lifetime, i.e. how long the fluorescence lasts.
This allows interactions to be studied inside the nucleus of living cells, and for more molecules, such as those which are not fluorescent and can’t be seen under the microscope, to be better understood.
Professor Ramon Vilar, from the Department of Chemistry at Imperial, explained: “Many researchers have been interested in the potential of G-quadruplex binding molecules as potential drugs for diseases such as cancers. Our method will help to progress our understanding of these potential new drugs.”
Peter Summers, another lead author from the Department of Chemistry at Imperial, said: “This project has been a fantastic opportunity to work at the intersection of chemistry, biology and physics. It would not have been possible without the expertise and close working relationship of all three research groups.”
The three groups intend to continue working together to improve the properties of their probe and to explore new biological problems and shine further light on the roles G-quadruplexes play inside our living cells. The research was funded by Imperial’s Excellence Fund for Frontier Research.
On April 15, 2020, a brief burst of high-energy light swept through the solar system, triggering instruments on several NASA and European spacecraft. Now, multiple international science teams conclude that the blast came from a supermagnetized stellar remnant known as a magnetar located in a neighboring galaxy.
This finding confirms long-held suspicions that some gamma-ray bursts (GRBs) – cosmic eruptions detected in the sky almost daily – are in fact powerful flares from magnetars relatively close to home.
Video: A pulse of X-rays and gamma rays lasting just 140 milliseconds swept across the solar system on April 15, 2020. The event was a giant flare from a magnetar, a type of city-sized stellar remnant that boasts the strongest magnetic fields known. Watch to learn more.Credits: NASA’s Goddard Space Flight Center
“This has always been regarded as a possibility, and several GRBs observed since 2005 have provided tantalizing evidence,” said Kevin Hurley, a Senior Space Fellow with the Space Sciences Laboratory at the University of California, Berkeley, who joined several scientists to discuss the burst at the virtual 237th meeting of the American Astronomical Society. “The April 15 event is a game changer because we found that the burst almost certainly lies within the disk of the nearby galaxy NGC 253.”
Papers analyzing different aspects of the event and its implications were published on Jan. 13 in the journals Nature and Nature Astronomy.
GRBs, the most powerful explosions in the cosmos, can be detected across billions of light-years. Those lasting less than about two seconds, called short GRBs, occur when a pair of orbiting neutron stars – both the crushed remnants of exploded stars – spiral into each other and merge. Astronomers confirmed this scenario for at least some short GRBs in 2017, when a burst followed the arrival of gravitational waves – ripples in space-time – produced when neutron stars merged 130 million light-years away.
Magnetars are neutron stars with the strongest-known magnetic fields, with up to a thousand times the intensity of typical neutron stars and up to 10 trillion times the strength of a refrigerator magnet. Modest disturbances to the magnetic field can cause magnetars to erupt with sporadic X-ray bursts for weeks or longer.
Rarely, magnetars produce enormous eruptions called giant flares that produce gamma rays, the highest-energy form of light.
Most of the 29 magnetars now cataloged in our Milky Way galaxy exhibit occasional X-ray activity, but only two have produced giant flares. The most recent event, detected on Dec. 27, 2004, produced measurable changes in Earth’s upper atmosphere despite erupting from a magnetar located about 28,000 light-years away.
Shortly before 4:42 a.m. EDT on April 15, 2020, a brief, powerful burst of X-rays and gamma rays swept past Mars, triggering the Russian High Energy Neutron Detector aboard NASA’s Mars Odyssey spacecraft, which has been orbiting the Red Planet since 2001. About 6.6 minutes later, the burst triggered the Russian Konus instrument aboard NASA’s Wind satellite, which orbits a point between Earth and the Sun located about 930,000 miles (1.5 million kilometers) away. After another 4.5 seconds, the radiation passed Earth, triggering instruments on NASA’s Fermi Gamma-ray Space Telescope, as well as on the European Space Agency’s INTEGRAL satellite and Atmosphere-Space Interactions Monitor (ASIM) aboard the International Space Station.
The eruption occurred beyond the field of view of the Burst Alert Telescope (BAT) on NASA’s Neil Gehrels Swift Observatory, so its onboard computer did not alert astronomers on the ground. However, thanks to a new capability called the Gamma-ray Urgent Archiver for Novel Opportunities (GUANO), the Swift team can beam back BAT data when other satellites trigger on a burst. Analysis of this data provided additional insight into the event.
The pulse of radiation lasted just 140 milliseconds – as fast as the blink of an eye or a finger snap.
The giant flare, cataloged as GRB 200415A, reached detectors on different NASA spacecraft at different times. Each instrument pair established its possible location in different swaths of the sky, but the bands intersect in the central part of the bright spiral galaxy NGC 253. This is the most precise position yet established for a magnetar located well beyond our galaxy. Credits: NASA’s Goddard Space Flight Center and Adam Block/Mount Lemmon SkyCenter/University of Arizona
The Fermi, Swift, Wind, Mars Odyssey and INTEGRAL missions all participate in a GRB-locating system called the InterPlanetary Network (IPN). Now funded by the Fermi project, the IPN has operated since the late 1970s using different spacecraft located throughout the solar system. Because the signal reached each detector at different times, any pair of them can help narrow down a burst’s location in the sky. The greater the distances between spacecraft, the better the technique’s precision.
The IPN placed the April 15 burst, called GRB 200415A, squarely in the central region of NGC 253, a bright spiral galaxy located about 11.4 million light-years away in the constellation Sculptor. This is the most precise sky position yet determined for a magnetar located beyond the Large Magellanic Cloud, a satellite of our galaxy and host to a giant flare in 1979, the first ever detected.
Giant flares from magnetars in the Milky Way and its satellites evolve in a distinct way, with a rapid rise to peak brightness followed by a more gradual tail of fluctuating emission. These variations result from the magnetar’s rotation, which repeatedly brings the flare location in and out of view from Earth, much like a lighthouse.
Observing this fluctuating tail is conclusive evidence of a giant flare. Seen from millions of light-years away, though, this emission is too dim to detect with today’s instruments. Because these signatures are missing, giant flares in our galactic neighborhood may be masquerading as much more distant and powerful merger-type GRBs.
A detailed analysis of data from Fermi’s Gamma-ray Burst Monitor (GBM) and Swift’s BAT provides strong evidence that the April 15 event was unlike any burst associated with mergers, noted Oliver Roberts, an associate scientist at Universities Space Research Association’s Science and Technology Institute in Huntsville, Alabama, who led the study.
In particular, this was the first giant flare known to occur since Fermi’s 2008 launch, and the GBM’s ability to resolve changes at microsecond timescales proved critical. The observations reveal multiple pulses, with the first one appearing in just 77 microseconds – about 13 times the speed of a camera flash and nearly 100 times faster than the rise of the fastest GRBs produced by mergers. The GBM also detected rapid variations in energy over the course of the flare that have never been observed before.
“Giant flares within our galaxy are so brilliant that they overwhelm our instruments, leaving them to hang onto their secrets,” Roberts said. “For the first time, GRB 200415A and distant flares like it allow our instruments to capture every feature and explore these powerful eruptions in unparalleled depth.”
Giant flares are poorly understood, but astronomers think they result from a sudden rearrangement of the magnetic field. One possibility is that the field high above the surface of the magnetar may become too twisted, suddenly releasing energy as it settles into a more stable configuration. Alternatively, a mechanical failure of the magnetar’s crust – a starquake – may trigger the sudden reconfiguration.
Roberts and his colleagues say the data show some evidence of seismic vibrations during the eruption. The highest-energy X-rays recorded by Fermi’s GBM reached 3 million electron volts (MeV), or about a million times the energy of blue light, itself a record for giant flares. The researchers say this emission arose from a cloud of ejected electrons and positrons moving at about 99% the speed of light. The short duration of the emission and its changing brightness and energy reflect the magnetar’s rotation, ramping up and down like the headlights of a car making a turn. Roberts describes it as starting off as an opaque blob – he pictures it as resembling a photon torpedo from the “Star Trek” franchise – that expands and diffuses as it travels.
The torpedo also factors into one of the event’s biggest surprises. Fermi’s main instrument, the Large Area Telescope (LAT), also detected three gamma rays, with energies of 480 MeV, 1.3 billion electron volts (GeV), and 1.7 GeV – the highest-energy light ever detected from a magnetar giant flare. What’s surprising is that all of these gamma rays appeared long after the flare had diminished in other instruments.
Nicola Omodei, a senior research scientist at Stanford University in California, led the LAT team investigating these gamma rays, which arrived between 19 seconds and 4.7 minutes after the main event. The scientists conclude that this signal most likely comes from the magnetar flare. “For the LAT to detect a random short GRB in the same region of the sky and at nearly the same time as the flare, we would have to wait, on average, at least 6 million years,” he explained.
Video: Astronomers explain the observations of GRB 200415A with the sequence of events illustrated here. A sudden reconfiguration of the magnetar’s magnetic field produced a quick, powerful pulse of X-rays and gamma rays. The event also ejected a blob of matter, which followed the pulse traveling at about 99% the speed of light. After a few days, they both reached the boundary, called a bow shock, where a steady outflow from the magnetar causes a pile-up of interstellar gas. Light from the flare passed through, followed many seconds later by the ejected cloud. The fast-moving matter interacted with gas at the bow shock, creating shock waves that accelerated particles and produced high-energy gamma rays. This accounts for the delay in the arrival of the most energetic gamma rays detected by NASA’s Fermi spacecraft.Credits: NASA’s Goddard Space Flight Center/Chris Smith (USRA/GESTAR)
A magnetar produces a steady outflow of fast-moving particles. As it moves through space, this outflow plows into, slows, and diverts interstellar gas. The gas piles up, becomes heated and compressed, and forms a type of shock wave called a bow shock.
In the model proposed by the LAT team, the flare’s initial pulse of gamma rays travels outward at the speed of light, followed by the cloud of ejected matter, which is moving nearly as fast. After several days, they both reach the bow shock. The gamma rays pass through. Seconds later, the cloud of particles – now expanded into a vast, thin shell – collides with accumulated gas at the bow shock. This interaction creates shock waves that accelerate particles, producing the highest-energy gamma rays after the main burst.
The April 15 flare proves that these events constitute their own class of GRBs. Eric Burns, an assistant professor of physics and astronomy at Louisiana State University in Baton Rouge, led a study investigating additional suspects using data from numerous missions. The findings will appear in The Astrophysical Journal Letters. Bursts near the galaxy M81 in 2005 and the Andromeda galaxy (M31) in 2007 had already been suggested to be giant flares, and the team additionally identified a flare in M83, also seen in 2007 but newly reported. Add to these the giant flare from 1979 and those observed in our Milky Way in 1998 and 2004.
“It’s a small sample, but we now have a better idea of their true energies, and how far we can detect them,” Burns said. “A few percent of short GRBs may really be magnetar giant flares. In fact, they may be the most common high-energy outbursts we’ve detected so far beyond our galaxy – about five times more frequent than supernovae.”
Primary amoebic meningoencephalitis (PAM), a deadly disease caused by the “brain-eating amoeba” Naegleria fowleri, is becoming more common in some areas of the world, and it has no effective treatment. Now, researchers reporting in ACS Chemical Neuroscience have found that a compound isolated from the leaves of a traditional medicinal plant, Inula viscosa or “false yellowhead,” kills the amoebae by causing them to commit cell suicide in lab studies, which could lead to new treatments.
Leaves from Inula viscosa, a Mediterranean perennial shrub, contain a compound that kills brain-eating amoebae. Credit: Adapted from ACS Chemical Neuroscience 2020, DOI: 10.1021/acschemneuro.0c00685
PAM, characterized by headache, fever, vomiting, hallucinations and seizures, is almost always fatal within a couple of weeks of developing symptoms. Although the disease, which is usually contracted by swimming in contaminated freshwater, is rare, increasing cases have been reported recently in the U.S., the Philippines, southern Brazil and some Asian countries. Amphotericin B is the most common therapy given to those with the infection. It can kill N. fowleri in the lab, but it isn’t very effective when given to patients, likely because it cannot cross the blood-brain barrier. Ikrame Zeouk, José Piñero, Jacob Lorenzo-Morales and colleagues wanted to explore whether compounds isolated from I. viscosa, a strong-smelling plant that has long been used for traditional medicine in the Mediterranean region, could effectively treat PAM.
The researchers first made an ethanol extract from the herb’s leaves, finding that it could kill N. fowleri amoebae. Then, they isolated and tested specific compounds from the extract. The most potent compound, inuloxin A, killed amoebae in the lab by disrupting membranes and causing mitochondrial changes, chromatin condensation and oxidative damage, ultimately forcing the parasites to undergo programmed cell death, or apoptosis. Although inuloxin A was much less potent than amphotericin B in the lab, the structure of the plant-derived compound suggests that it might be better able to cross the blood-brain barrier. More studies are needed to confirm this hypothesis, the researchers say.
Reference: Ikrame Zeouk, Ines Sifaoui, Aitor Rizo-Liendo, Iñigo Arberas-Jiménez, María Reyes-Batlle, Isabel L. Bazzocchi, Khadija Bekhti, José E. Piñero, Ignacio A. Jiménez, and Jacob Lorenzo-Morales, “Exploring the Anti-Infective Value of Inuloxin A Isolated from Inula viscosa against the Brain-Eating Amoeba (Naegleria fowleri) by Activation of Programmed Cell Death”, ACS Chem. Neurosci. 2021, 12, 1, 195–202. https://doi.org/10.1021/acschemneuro.0c00685https://pubs.acs.org/doi/abs/10.1021/acschemneuro.0c00685
Researchers clean up data to identify the bugs better.
Biomedical engineers at Duke University have devised an algorithm to remove contaminated microbial genetic information from The Cancer Genome Atlas (TCGA). With a clearer picture of the microbiota living in various organs in both healthy and cancerous states, researchers will now be able to find new biomarkers of disease and better understand how numerous cancers affect the human body.
In the first study using the newly decontaminated dataset, the researchers have already discovered that normal and cancerous organ tissues have a slightly different microbiota composition, that bacteria from these diseased sites can enter the bloodstream, and that this bacterial information could help diagnose cancer and predict patient outcomes.
The results appear online on December 30, 2020 in the journal Cell Host & Microbe.
TCGA is a landmark cancer genomics program that molecularly characterized over 20,000 primary cancer and matched healthy samples spanning 33 cancer types. It has produced more than 2.5 million gigabytes of “omic” data. The atlas includes which DNA is present, what epigenetic markers are on the DNA, which DNA is turned on and which proteins are being produced. It is freely available for public use.
One study from the atlas data revealed an abundance of Fusobacterium nucleatum in colorectal cancer, which has since been shown to be indicative of stage, survival, metastasis and even drug responses of this kind of cancer.
Many more studies have searched for such bacterial biomarkers, however few have been discovered. A large reason for this is contamination. When bacteria get introduced into the samples accidentally by the laboratories, it becomes difficult to discern which species were actually in the samples to begin with. While similar microbiome studies using microbe-rich material such as feces can overcome small amounts of contamination, the relatively miniscule samples taken from live human organs and tumor samples cannot.
When examining a subset of TCGA sequencing data, previous analyses found that microbial DNA from a number of species was the result of lab contamination.
“All microbiota studies are plagued by the notion that if you find a microbe, was it really in the tissue or was it contamination introduced during processing?” said Xiling Shen, the Hawkins Family Associate Professor of Biomedical Engineering at Duke. “We’ve invented a method that can extract the microbes that were truly in each sample and used it to build what we’ve called The Cancer Microbiome Atlas, which will be a tremendous resource for the community and allow us to understand how cancer alters an organ’s microbiome.”
The method for removing contamination from TCGA data was invented by Anders Dohlman, a graduate student in Shen’s laboratory. Dohlman first compared the microbiome signatures between cancer tissues from different organs and blood, and ruled out contaminant species that showed up indiscriminately. He then compared the microbiome signatures of identical samples that were processed at separate sites, ranging from Harvard to Baylor. Dohlman concluded that the microbial species that can only be detected from a specific site would be the contaminants, allowing him to assign a unique contamination signature for each site.
“A big challenge in this process was mixed-evidence species, which are bacteria that are both a contaminant and endogenous to the tissue,” said Dohlman. “But because TCGA has so many different types of data, we were able to tease it out. Big data really helps!”
“We’ve invented a method that can extract the microbes that were truly in each sample and used it to build what we’ve called The Cancer Microbiome Atlas, which will be a tremendous resource for the community and allow us to understand how cancer alters an organ’s microbiome.”
– XILING SHEN
The effort is already paying dividends in a variety of ways. After using Dohlman’s decontamination algorithm, the researchers took a close look at the microbiota signatures of samples taken from colorectal cancer patients. They discovered two unique groups of bacteria frequently found together, one of which appears to be associated with patient survival.
The researchers also discovered that some cancers do indeed alter the microbiome of their resident organs. It might be, Shen reasons, that tumors alter an organ’s microenvironment, making it more or less hospitable to different microbial species. And by looking for microbial signatures within patient blood samples, they also found that, despite conventional wisdom to the contrary, some bacteria does find its way into the bloodstream, which could also provide an indication of a cancer’s progress.
“There has been a sort of crisis in the field about whether or not high-profile papers can be reproduced, owing to the challenge of contamination,” said Shen. “For example, while one center would be able to reproduce its results, another center would not. This explains why: Each center has its own very consistent bias. (Its own resident microbe contaminants.) In the future, new studies can use our method to remove this bias and reproduce results, and research centers might be able to use their bias we’ve identified to mitigate their contamination.”
This research was supported by the National Institutes of Health (R35GM122465, DK119795) and the Defense Advanced Research Projects Agency (W911NF1920111).
Reference: “The Cancer Microbiome Atlas: A Pan-Cancer Comparative Analysis to Distinguish Tissue-Resident Microbiota from Contaminants.” Anders B. Dohlman, Diana Arguijo Mendoza, Shengli Ding, Michael Gao, Holly Dressman, Iliyan D. Iliev, Steven M. Lipkin, Xiling Shen. Cell Host & Microbe, 2021. DOI: 10.1016/j.chom.2020.12.001
The research team used the Advanced Photon Source to confirm an effective antibody that prevents the dengue virus from infecting cells in mice, and may lead to treatments for this and similar diseases.
A team of researchers has discovered an antibody that blocks the ability of the dengue virus to cause disease in mice. The findings open the potential for developing effective treatments and designing a vaccine for dengue and similar diseases.
Researchers have revealed how one antibody (in green) is able to neutralize a protein that is central to the dengue virus’s ability to cause disease, by blocking the protein’s ability to interact with host cells. Image credit: Rajani Arora, U-M Life Sciences Institute
Dengue virus, a member of a group of viruses called flaviviruses, causes 50 to 100 million cases of dengue disease each year, with no effective treatment or vaccine. Other members of this group include the viruses that cause Zika, yellow fever and West Nile fever.
In a new study scheduled to publish Jan. 8 in the journal Science, researchers from the University of California, Berkeley, and the University of Michigan revealed how an antibody called 2B7 neutralizes one specific protein made by the virus—a protein that is key to the dengue virus’s ability to both replicate and cause disease.
The protein, called NS1 (short for “non-structural protein 1”) circulates in the patient’s blood and exacerbates disease by interacting directly with endothelial cells, the cells that form protective barriers around organs. By breaking apart the connections between endothelial cells, NS1 weakens this barrier, increasing permeability and contributing to increased vascular leak, which is the hallmark of severe dengue disease. This endothelial permeability may also enable the virus to more easily cross barriers to infect and damage target organs.
The authors and other researchers had previously demonstrated that this protein itself can cause leaks in the endothelial barrier, even in the absence of infectious viral particles. And in cases of dengue virus infection, the more NS1 found circulating in the host’s blood, the more severe the infection is likely to be.
“We think of bacterial toxins, but this idea of a viral toxin is a new concept,” said Eva Harris, a professor of infectious diseases and vaccinology at UC Berkeley’s School of Public Health and one of the study’s senior authors. “This is really an important protein in terms of creating new paradigms regarding how we think about viral proteins and their functions in disease.”
In this latest study, the researchers identified specific regions of the protein that are responsible for damaging the endothelial cells: a so-called wing region that allows the protein to connect to the host cells, and another region that triggers destructive events within the endothelial cells.
By analyzing the precise way that the 2B7 antibody attaches to the protein, they found that the antibody is able to neutralize both of these regions—simply by getting in the protein’s way. The antibody connects to NS1 in such a way that the wing regions cannot reach the endothelial cells, preventing the protein from latching onto (and thus interacting with and damaging) the endothelial cells.
“This collaborative approach gives us a lot of great insight into understanding the biology of this protein, its interactions with cells and its pathogenesis,” said David Akey, a researcher at the U-M Life Sciences Institute and a lead author of the study. “It’s an example of combining structure and function to open therapeutic avenues.”
One reason no effective therapeutic has been found for dengue is that the disease can be caused by one of four different virus strains (dengue virus 1, 2, 3 or 4). Having antibodies against one strain of the virus can actually increase severity of a subsequent infection from another strain, a phenomenon called antibody-dependent enhancement.
By binding only to the NS1 protein and not to the virus particle itself, however, the 2B7 antibody does not lead to antibody-dependent enhancement of the infection.
“These findings tell us that we can really have an effect on the virus’s pathogenesis by blocking these sites on just the circulating proteins,” said Janet Smith, a professor at the U-M Life Sciences Institute and U-M Medical School. “It offers a strategy not only for a therapy to treat an infection, but also for a vaccine to prevent infection.”
And because the NS1 protein is produced by many flaviviruses, the scientists believe the antibody that targets NS1 may be useful in treating or preventing multiple flaviviruses.
“We were able to show not only the mechanism of how the antibody protects the host cells, but also the actual mechanism of pathogenesis of this protein that is conserved across other flaviviruses,” Harris said.
“I think the fact that this antibody is cross-reactive with other flavivirus NS1 proteins is one of the most exciting elements of this work,” said Scott Biering, a postdoctoral researcher in Harris’s lab and a lead author of the study. “This research is the proof of concept that you can target this one protein for multiple flaviviruses to protect against pathogenesis. It opens a lot of avenues not only for better understanding the mechanics of this virus, but also for developing effective therapeutics.”
The research was supported by the National Institutes of Health.
Study authors are: Scott B. Biering, Marcus P. Wong, Nicholas T.N. Lo, Henry Puerta-Guardo, Francielle Tramontini Gomes de Sousa, Chunling Wang, Diego A. Espinosa, Dustin R. Glasner, Jeffrey Li, Sophie F. Blanc, Evan Y. Juan, P. Robert Beatty and Eva Harris of the University of California, Berkeley; David L. Akey, W. Clay Brown, Jamie R. Konwerski, Nicholas J. Bockhaus and Janet L. Smith of the University of Michigan; Stephen J. Elledge of Brigham and Women’s Hospital, the Howard Hughes Medical Institute and Harvard Medical School; and Michael J. Mina of the Harvard T.H. Chan School of Public Health.
“Structural basis for antibody inhibition of flavivirus NS1-triggered endothelial dysfunction,” Science. DOI: 10.1126/science.abc0476. Once the embargo lifts, the paper will be available at https://science.sciencemag.org/cgi/doi/10.1126/science.abc0476
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