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As if black holes weren't mysterious enough, astronomers using NASA's Hubble Space Telescope have found an unexpected thin disk of material furiously whirling around a supermassive black hole at the heart of the magnificent spiral galaxy NGC 3147, located 130 million light-years away.

The conundrum is that the disk shouldn't be there, based on current astronomical theories. However, the unexpected presence of a disk so close to a black hole offers a unique opportunity to test Albert Einstein's theories of relativity. General relativity describes gravity as the curvature of space and special relativity describes the relationship between time and space.

"We've never seen the effects of both general and special relativity in visible light with this much clarity," said Marco Chiaberge of the European Space Agency, and the Space Telescope Science Institute and Johns Hopkins University, both in Baltimore, Maryland, a member of the team that conducted the Hubble study.

"This is an intriguing peek at a disk very close to a black hole, so close that the velocities and the intensity of the gravitational pull are affecting how the photons of light look," added the study's first author, Stefano Bianchi of Università degli Studi Roma Tre, in Rome, Italy. "We cannot understand the data unless we include the theories of relativity."

Black holes in certain types of galaxies like NGC 3147 are malnourished because there is not enough gravitationally captured material to feed them regularly. So, the thin haze of infalling material puffs up like a donut rather than flattening out in a pancake-shaped disk. Therefore, it is very puzzling why there is a thin disk encircling a starving black hole in NGC 3147 that mimics much more powerful disks found in extremely active galaxies with engorged, monster black holes.

"We thought this was the best candidate to confirm that below certain luminosities, the accretion disk doesn't exist anymore," explained Ari Laor of the Technion-Israel Institute of Technology located in Haifa, Israel. "What we saw was something completely unexpected. We found gas in motion producing features we can explain only as being produced by material rotating in a thin disk very close to the black hole."

The astronomers initially selected this galaxy to validate accepted models about lower-luminosity active galaxies--those with black holes that are on a meager diet of material. Models predict that an accretion disk forms when ample amounts of gas are trapped by a black hole's strong gravitational pull. This infalling matter emits lots of light, producing a brilliant beacon called a quasar, in the case of the most well-fed black holes. Once less material is pulled into the disk, it begins to break down, becomes fainter, and changes structure.

"The type of disk we see is a scaled-down quasar that we did not expect to exist," Bianchi said. "It's the same type of disk we see in objects that are 1,000 or even 100,000 times more luminous. The predictions of current models for gas dynamics in very faint active galaxies clearly failed."

The disk is so deeply embedded in the black hole's intense gravitational field that the light from the gas disk is modified, according to Einstein's theories of relativity, giving astronomers a unique look at the dynamic processes close to a black hole.

Hubble clocked material whirling around the black hole as moving at more than 10% of the speed of light. At those extreme velocities, the gas appears to brighten as it travels toward Earth on one side, and dims as it speeds away from our planet on the other side (an effect called relativistic beaming). Hubble's observations also show that the gas is so entrenched in the gravitational well the light is struggling to climb out, and therefore appears stretched to redder wavelengths. The black hole's mass is around 250 million Suns.

The researchers used Hubble's Space Telescope Imaging Spectrograph (STIS) to observe matter swirling deep inside the disk. A spectrograph is a diagnostic tool that divides light from an object into its many individual wavelengths to determine its speed, temperature, and other characteristics at a very high precision. The astronomers needed STIS's sharp resolution to isolate the faint light from the black-hole region and block out contaminating starlight.

"Without Hubble, we wouldn't have been able to see this because the black-hole region has a low luminosity," Chiaberge said. "The luminosities of the stars in the galaxy outshine anything in the nucleus. So if you observe it from the ground, you're dominated by the brightness of the stars, which drowns the feeble emission from the nucleus."

The team hopes to use Hubble to hunt for other very compact disks around low-wattage black holes in similar active galaxies.

NASA's Aqua satellite passed over the Gulf of Mexico and took the temperature of Potential Tropical Cyclone 2 as it moved westward through the Gulf of Mexico. NASA found the very cold cloud tops indicating the storm had potential for dropping heavy rain.

Infrared light enables NASA to take the temperatures of clouds and thunderstorms that make up tropical cyclones. The stronger the storms are indicate that they extend high into the troposphere and have cold cloud top temperatures.

An infrared look by NASA's Aqua satellite on July 10, 2019 at 3:23 p.m. EDT (1923 UTC) revealed where the strongest storms were located within Potential Tropical Cyclone 2. The Atmospheric Infrared Sounder or AIRS instrument aboard NASA's Aqua satellite analyzed cloud top temperatures and found cloud top temperatures of strongest thunderstorms as cold as or colder than minus 63 degrees Fahrenheit (minus 53 degrees Celsius) circling the center (which is still not well-defined) and in thunderstorms northwest of the center, extending over southern Louisiana. Cloud top temperatures that cold indicate strong storms that have the capability to create heavy rain.

On July 10, the National Weather Service Office in New Orleans reported the official rainfall in New Orleans at more than 7 inches, which fell over six hours on the morning of July 10.

On July 11 at 8 a.m. EDT (1200 UTC) NOAA's National Hurricane Center (NHC) continued to post warnings and watches for the Gulf coast states. A Storm Surge Watch is in effect from the mouth of the Pearl River to Intracoastal City, Louisiana. A Hurricane Watch is in effect from the mouth of the Mississippi River to Cameron, and a Tropical Storm Watch is in effect from the mouth of the Mississippi River northward to the mouth of the Pearl River.

At 8 a.m. EDT (1200 UTC), the NHC said the disturbance was centered near latitude

27.6 degrees north and longitude 88.5 degrees west. That puts the center of circulation about 115 miles (185 km) south-southeast of the mouth of the Mississippi River. Reports from a NOAA Hurricane Hunter aircraft indicate that maximum sustained winds are near 35 mph (55 km/h) with higher gusts. Strengthening is forecast during the next couple of days, and the disturbance is forecast to become a tropical depression or a tropical storm later today, and could become a hurricane by late Friday.

NHC noted that the associated thunderstorm activity is gradually becoming better organized, and the disturbance is expected to become a tropical depression or a tropical storm later today or Friday. The chance that the system will become a tropical storm through 48 hours is high at 100 percent.

The system is moving toward the west near 5 mph (7 kph), but the NHC forecasters said a west-northwest motion is expected on Friday, July 12, followed by a northwestward track by early Saturday. On the forecast track, the system is expected to approach the Louisiana coast this weekend.

A research team headed by scientists at University of California San Diego School of Medicine and the Ludwig Institute for Cancer Research at UC San Diego has identified an enzyme involved in remodeling the plasma membrane of multiple cancer cell types that is critical to both survival of tumors and their uncontrolled growth.

The finding, published in the July 11, 2019 issue of Cell Metabolism, suggests a potential target for new drugs.

"Cancers are characterized not only by major changes in their genomes, but also by profound shifts in how they take up and utilize nutrients to propel rapid tumor growth," said senior author Paul S. Mischel, MD, professor in the UC San Diego School of Medicine Department of Pathology and Ludwig member. "How do these diverse aspects fit together and can they be taken advantage of, for the benefit of patients?"

In the new study, conducted in collaboration with Benjamin Cravatt, PhD, professor at Scripps Research, and led by first author Junfeng Bi, PhD, in Mischel's lab, researchers identified an enzyme called LPCAT1, whose levels increase in cancer and which plays a key role in tumor growth by changing the phospholipid composition of the cancer cells' plasma membrane, allowing amplified and mutated growth factor signals to spur tumor growth.

Without LPCAT1, tumors cannot survive. When researchers genetically depleted LPCAT1 in multiple types of cancer in mice, including highly lethal glioblastomas (brain) and an aggressive lung cancer, malignancies shrank dramatically and survival times improved.

The results, wrote the authors, demonstrate that LPCAT1 is an important enzyme that becomes dysregulated in cancer, linking common genetic alterations in tumors with changes in their metabolism to drive aggressive tumor growth."

"Advances in DNA sequencing technologies have reshaped our understanding of the molecular basis of cancer, suggesting a new and more effective way of treating cancer patients," said Mischel. "However, to date, precision oncology has yet to benefit many patients, motivating a deeper search into understanding how genetic alterations in tumors change the way cancer cells behave, and potentially unlocking new ways to more effectively treat patients.

"These results also suggest that LPCAT1 may be a very compelling new drug target in a wide variety of cancer types."

PITTSBURGH (July 11, 2019) -- Glass for technologies like displays, tablets, laptops, smartphones, and solar cells need to pass light through, but could benefit from a surface that repels water, dirt, oil, and other liquids. Researchers from the University of Pittsburgh's Swanson School of Engineering have created a nanostructure glass that takes inspiration from the wings of the glasswing butterfly to create a new type of glass that is not only very clear across a wide variety of wavelengths and angles, but is also antifogging.

The team recently published a paper detailing their findings: "Creating Glasswing-Butterfly Inspired Durable Antifogging Omniphobic Supertransmissive, Superclear Nanostructured Glass Through Bayesian Learning and Optimization" in Materials Horizons (doi:10.1039/C9MH00589G). They recently presented this work at the ICML conference in the "Climate Change: How Can AI Help?" workshop.

The nanostructured glass has random nanostructures, like the glasswing butterfly wing, that are smaller than the wavelengths of visible light. This allows the glass to have a very high transparency of 99.5% when the random nanostructures are on both sides of the glass. This high transparency can reduce the brightness and power demands on displays that could, for example, extend battery life. The glass is antireflective across higher angles, improving viewing angles. The glass also has low haze, less than 0.1%, which results in very clear images and text.

"The glass is superomniphobic, meaning it repels a wide variety of liquids such as orange juice, coffee, water, blood, and milk," explains Sajad Haghanifar, lead author of the paper and doctoral candidate in industrial engineering at Pitt. "The glass is also anti-fogging, as water condensation tends to easily roll off the surface, and the view through the glass remains unobstructed. Finally, the nanostructured glass is durable from abrasion due to its self-healing properties--abrading the surface with a rough sponge damages the coating, but heating it restores it to its original function."

Natural surfaces like lotus leaves, moth eyes and butterfly wings display omniphobic properties that make them self-cleaning, bacterial-resistant and water-repellant--adaptations for survival that evolved over millions of years. Researchers have long sought inspiration from nature to replicate these properties in a synthetic material, and even to improve upon them. While the team could not rely on evolution to achieve these results, they instead utilized machine learning.

"Something significant about the nanostructured glass research, in particular, is that we partnered with SigOpt to use machine learning to reach our final product," says Paul Leu, PhD, associate professor of industrial engineering, whose lab conducted the research. Dr. Leu holds secondary appointments in mechanical engineering and materials science and chemical engineering. "When you create something like this, you don't start with a lot of data, and each trial takes a great deal of time. We used machine learning to suggest variables to change, and it took us fewer tries to create this material as a result."

"Bayesian optimization and active search are the ideal tools to explore the balance between transparency and omniphobicity efficiently, that is, without needing thousands of fabrications, requiring hundreds of days." said Michael McCourt, PhD, research engineer at SigOpt. Bolong Cheng, PhD, fellow research engineer at SigOpt, added, "Machine learning and AI strategies are only relevant when they solve real problems; we are excited to be able to collaborate with the University of Pittsburgh to bring the power of Bayesian active learning to a new application."

"Creating Glasswing-Butterfly Inspired Durable Antifogging Omniphobic Supertransmissive, Superclear Nanostrcutured Glass Through Bayesian Learning and Optimization" was coauthored by Sajad Haghanifar, and Paul Leu, from Pitt's Swanson School of Engineering; Michael McCourt and Bolong Cheng from SigOpt; and Paul Ohodnicki and Jeffrey Wuenschell from the U.S. Department of Energy's National Energy Laboratory.

Researchers at the National Institute of Standards and Technology (NIST) have upgraded their compact atomic gyroscope to enable multitasking measurement capabilities and measure its performance, important steps toward practical applications.

Described in a new paper, the quantum gyroscope design and evaluation processes were led by three women -- a highly unusual situation in physics and a source of pride for project leader Elizabeth Donley at NIST. Postdoctoral researchers Yun-Jhih Chen and Azure Hansen totally rebuilt the apparatus over the past couple of years.

"Not only did we build a simple quantum gyroscope, but this is the first time anyone has demonstrated simultaneous measurement of rotation, rotation angle and acceleration with a single source of atoms," Donley said. "Other gyroscopes, including the classical ones currently used in phones and planes, can measure only one axis of rotation. This is also the first time we're reporting a sensitivity for the acceleration and rotation measurements."

The NIST team previously measured rotation with an earlier version of the quantum gyroscope. The apparatus was upgraded to boost the signal strength and data acquisition speed to enable competitive sensitivity measurements. Researchers also added a pattern recognition algorithm derived from machine learning to automatically extract information from images of the atoms.

The NIST gyroscope is an atom interferometer, taking advantage of the fact that atoms can act as both particles and waves. Rotation and acceleration are deduced from images of interfering matter waves (which show the probability of a particle's position in space) from atoms in two different energy states.

Atom interferometers could be used in navigation and geodesy (the study of the shape of the Earth based on measurements of gravity) because of their sensitivity to acceleration and rotation combined with their long-term stability and accuracy. The development of small, lightweight, low-power atom interferometers is key to moving the instruments out of the laboratory to applications in the field.

The NIST team developed a simplified scheme amenable to portable applications using a single, tiny cloud of atoms that falls by only a few millimeters during the measurements. A glass chamber just 1 cubic centimeter in volume contains about 10 million cold rubidium atoms that are trapped and released.

Currently, a full-size optics table is required for the lasers, and a few racks of electronics are needed as well. The laser setup would need to be made more compact and integrated before the gyroscope could be used in the field, Donley said. Other research groups are reducing the size of these laser systems, she added.

The NIST gyroscope's sensitivities for the magnitude and direction of the rotation measurements are 0.033 degrees per second and 0.27 degrees with one second averaging time, respectively. These results are approaching the sensitivity levels achieved by other research groups using much larger atom interferometers, Donley said. Moreover, the NIST gyroscope is unique in that it can measure rotations along two axes and an acceleration along one axis simultaneously with a single source of atoms.

In the NIST gyroscope, when the atoms are first trapped in a cloud and then released to fall under gravity, a laser beam causes them to transition between two energy states. This process involves absorption and emission of light particles, which gives the atoms momentum and causes their matter waves to separate and later recombine to interfere. When the atoms speed up or rotate, their matter waves shift and interfere in predictable ways, visible in images of the expanded cloud.

The atoms are imaged by shining a second, weak laser beam through the cloud. Because atoms in different energy states absorb light of different frequencies, the images show interference bands of atom populations in the two different states. The rotation rate and rotation axis are measured by analyzing the spacing and direction of the interference bands across the atom cloud. Acceleration is measured from changes in the position of the central band. The interferometer is sensitive to acceleration along the direction of the laser beam and sensitive to rotations perpendicular to the beam.

The instrument could be used as a gyrocompass, because the atoms sense rotation in the plane tangential to the surface of Earth. The rotation signals, due to the Earth's rotation, point north, as is useful in navigation.

Astronomers using the NASA/ESA Hubble Space Telescope have observed an unexpected thin disc of material encircling a supermassive black hole at the heart of the spiral galaxy NGC 3147, located 130 million light-years away.

The presence of the black hole disc in such a low-luminosity active galaxy has astronomers surprised. Black holes in certain types of galaxies such as NGC 3147 are considered to be starving as there is insufficient gravitationally captured material to feed them regularly. It is therefore puzzling that there is a thin disc encircling a starving black hole that mimics the much larger discs found in extremely active galaxies.

Of particular interest, this disc of material circling the black hole offers a unique opportunity to test Albert Einstein's theories of relativity. The disc is so deeply embedded in the black hole's intense gravitational field that the light from the gas disc is altered, according to these theories, giving astronomers a unique peek at the dynamic processes close to a black hole.

"We've never seen the effects of both general and special relativity in visible light with this much clarity," said team member Marco Chiaberge of AURA for ESA, STScI and Johns Hopkins Univeristy.

The disc's material was measured by Hubble to be whirling around the black hole at more than 10% of the speed of light. At such extreme velocities, the gas appears to brighten as it travels toward Earth on one side, and dims as it speeds away from our planet on the other. This effect is known as relativistic beaming. Hubble's observations also show that the gas is embedded so deep in a gravitational well that light is struggling to escape, and therefore appears stretched to redder wavelengths. The black hole's mass is around 250 million times that of the Sun.

"This is an intriguing peek at a disc very close to a black hole, so close that the velocities and the intensity of the gravitational pull are affecting how we see the photons of light," explained the study's first author, Stefano Bianchi, of Università degli Studi Roma Tre in Italy.

In order to study the matter swirling deep inside this disc, the researchers used the Hubble Space Telescope Imaging Spectrograph (STIS) instrument. This diagnostic tool divides the light from an object into its many individual wavelengths to determine the object's speed, temperature, and other characteristics at very high precision. STIS was integral to effectively observing the low-luminosity region around the black hole, blocking out the galaxy's brilliant light.

The astronomers initially selected this galaxy to validate accepted models about lower-luminosity active galaxies: those with malnourished black holes. These models predict that discs of material should form when ample amounts of gas are trapped by a black hole's strong gravitational pull, subsequently emitting lots of light and producing a brilliant beacon called a quasar.

"The type of disc we see is a scaled-down quasar that we did not expect to exist," Bianchi explained. "It's the same type of disc we see in objects that are 1000 or even 100 000 times more luminous. The predictions of current models for very faint active galaxies clearly failed."

The team hopes to use Hubble to hunt for other very compact discs around low-luminosity black holes in similar active galaxies.

Research conducted at the Irvine Lab at the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology is being utilized in Elicio's AMP-CAR-T Platform

Activation of CAR-T cells with Amphiphiles delivered to the lymph nodes induces massive CAR-T expansion, substantially improved efficacy across cancer types, and durable cures for solid tumors

CAMBRIDGE MA., July 12, 2019 - Elicio Therapeutics, a next generation immuno-oncology company, engineering therapies for cancer killing immune responses, today announced that studies of its Amphiphile platform in combination with CAR-T therapy (AMP-CAR-T) have shown that activation of CAR-T cells in the lymphatic system gives massive CAR-T cell expansion, and significant functional improvements including enhanced CAR-T cell infiltration of solid tumors, increased anti-tumor cytolytic potential, and improved cytokine response. The research, conducted in the labs of Elicio co-founder, Darrell Irvine, at the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, was published on July 12 by the journal Science, in a paper entitled "Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor."1

Through precise targeting and delivery directly to the lymphatic system, Elicio is engineering potent Amphiphile immunotherapies including cell therapy activators, immunomodulators, and vaccines for an array of aggressive cancers. The Amphiphile approach is based on the ground-breaking work of Darrell Irvine, PhD., Professor of Biological Engineering and Materials Sciences and Howard Hughes Investigator at the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. The company is currently utilizing the study findings in its AMP-CAR-T platform to develop therapeutic interventions that activate and amplify CAR-T therapy to combat an array of cancers including solid tumors. In addition to enhancing the magnitude and functionality of co-administered CAR-T cells, the published data further shows that the combination of CAR-T with AMP-CAR-T activators leads to the potent induction of natural immune responses thought to be critical for improving activity in solid tumors, enabling prolonged survival and durable cures where CAR-T alone has no effect. Elicio is developing the AMP-CAR-T platform for combination with CAR-T cell therapies in a variety of settings including those targeting CD19, BCMA, and several solid tumor indications.

"CAR-Ts show great promise but historically they've had issues with durability of response and efficacy beyond hematologic cancers, which we hypothesized could be due to the lack of a means to properly stimulate these cells in vivo," said Darrell Irvine, Elicio co-founder, senior scientific advisor, and a supporting author. "What we saw in this study is that by activating CAR-T cells through their chimeric receptor in the native micro-environment of lymph nodes, it's possible to enhance CAR-T treatment of solid tumors across cancer types."

"We believe that Elicio's AMP-CAR-T platform has the potential to solve many of the major obstacles CAR-T therapy is facing by activating CAR-T cells in the lymph nodes to amplify immune responses which could lead to durable cures for aggressive, liquid and solid tumors," said Julian Adams, Ph.D., board chair, Elicio. "Elicio is developing a pipeline of AMP-CAR-T activators which when administered with CAR-T cells, or other CAR-engineered immune cells, will amplify their function for patients, creating a more powerful and lasting immune response."

A synthetic approach developed by KAUST researchers generates homogeneous and defect-free crystals that could fast-track the commercialization of perovskite solar cells.

"Perovskite solar cells are the fastest developing type of photovoltaic technology, with power-conversion efficiencies rising from 3.8 percent in 2009 to 24.2 percent in 2019 for single-junction devices," says Osman Bakr, who led the study with Omar Mohammed. This rapid increase in performance is associated with inexpensive and simple device fabrication, which makes these solar cells commercially appealing.

The performance and stability of solar cells depend on the morphology of the perovskite thin films, which act as light-harvesting layers in the devices. As well as their low cost and easy processing, these materials have exceptional optical and transport properties. Hybrid lead-based perovskites that combine a methylammonium cation with several halides, such as the anionic forms of bromine and iodine, present a narrow and tunable optical bandgap. This bandgap nears the theoretical value required to reach the maximum conversion efficiency for a single-junction solar cell. Therefore, perokskites could become a substitute of choice for silicon-based solar materials.

However, existing perovskite solar cells usually consist of polycrystalline thin films that are highly disordered and defective, which prevents devices from achieving optimal performance.

To address this issue, Bakr and Mohammed have now produced high-aspect-ratio, single-crystal films of methylammonium lead-triiodide perovskites. They achieved this by starting the crystallization between two polymer-coated substrates that would then physically restrict crystal growth to one dimension under heating.

Compared with their polycrystalline counterparts, single-crystal perovskites display substantially lower defect density and much higher charge-carrier diffusion lengths: this is a measure of their ability to maintain light-generated electrons separate from positively charged holes and create electrical current. Therefore, "We reasoned that these single crystals offer a chance for perovskite solar-cell technology to overcome these limitations and get as close as possible to the theoretical efficiency limit," Mohammed says.

The crystals, which exhibited a thickness of 20 micrometers and an area of several square millimeters, provided high-quality solar cells with a maximum power-conversion efficiency of 21.09 percent. These devices set a new performance record for perovskite single-crystal solar cells.

"We were pleasantly surprised by these results," Bakr says. He adds that the researchers initially thought that they would need to grow crystals much thinner than 20 micrometers to achieve this performance, and growing thin crystals is extremely challenging.

The researchers believe that this record efficiency highlights the potential role of single crystals in the development of perovskite-containing devices in parallel with the path taken by their polycrystalline counterparts.

ANN ARBOR--An injection of nanoparticles can prevent the body's immune system from overreacting to trauma, potentially preventing some spinal cord injuries from resulting in paralysis.

The approach was demonstrated in mice at the University of Michigan, with the nanoparticles enhancing healing by reprogramming the aggressive immune cells--call it an "EpiPen" for trauma to the central nervous system, which includes the brain and spinal cord.

"In this work, we demonstrate that instead of overcoming an immune response, we can co-opt the immune response to work for us to promote the therapeutic response," said Lonnie Shea, the Steven A. Goldstein Collegiate Professor of Biomedical Engineering.

Trauma of any kind kicks the body's immune response into gear. In a normal injury, immune cells infiltrate the damaged area and clear debris to initiate the regenerative process.

The central nervous system, however, is usually walled off from the rough-and-tumble of immune activity by the blood-brain barrier. A spinal cord injury breaks that barrier, letting in overzealous immune cells that create too much inflammation for the delicate neural tissues. That leads to the rapid death of neurons, damage to the insulating sheaths around nerve fibers that allow them to send signals, and the formation of a scar that blocks the regeneration of the spinal cord's nerve cells.

All of this contributes to the loss of function below the level of the injury. That spectrum includes everything from paralysis to a loss of sensation for many of the 12,000 new spinal injury patients each year in the United States.

Previous attempts to offset complications from this immune response included injecting steroids like methylprednisolone. That practice has largely been discarded since it comes with side effects that include sepsis, gastrointestinal bleeding and blood clots. The risks outweigh the benefits.

But now, U-M researchers have designed nanoparticles that intercept immune cells on their way to the spinal cord, redirecting them away from the injury. Those that reach the spinal cord have been altered to be more pro-regenerative.

With no drugs attached, the nanoparticles reprogram the immune cells with their physical characteristics: a size similar to cell debris and a negative charge that facilitates binding to immune cells. In theory, their nonpharmaceutical nature avoids unwanted side effects.

With fewer immune cells at the trauma location, there is less inflammation and tissue deterioration. Second, immune cells that do make it to the injury are less inflammatory and more suited to supporting tissues that are trying to grow back together.

"Hopefully, this technology could lead to new therapeutic strategies not only for patients with spinal cord injury but for those with various inflammatory diseases," said Jonghyuck Park, a U-M research fellow working with Shea.

Previous research has shown success for nanoparticles mitigating trauma caused by the West Nile virus and multiple sclerosis, for example.

"The immune system underlies autoimmune disease, cancer, trauma, regeneration--nearly every major disease," Shea said. "Tools that can target immune cells and reprogram them to a desired response have numerous opportunities for treating or managing disease."

The German Act on the Reform of the Market for Medicinal Products (AMNOG) was introduced in 2011 to regulate the early benefit assessment of new drugs. More than half of the drugs that have entered the market in Germany since then have emerged from these assessments without any proven added benefit. In a publication in the British Medical Journal using the first 216 assessments, researchers from the Institute for Quality and Efficiency in Health Care (IQWiG) examine the reasons for this sobering result and develop suggestions for improvements in drug development.

Beate Wieseler, Head of IQWiG's Drug Assessment Department and first author of the article notes: "There are three reasons for the conclusion 'added benefit not proven'. Often simply no studies are available comparing the new drug with the standard treatment for the disease. In other cases studies are available, but the control treatment is unsuitable, for example, because it is not approved for the patients investigated. In this situation, there is no information that could support the decision by patients and physicians for one of the available treatment alternatives. In a smaller number of cases, suitable studies comparing new drugs and standard treatment are available, but do not show any clear advantages or disadvantages.

Close knowledge gaps

One reason for these information deficits could be the accelerated drug approval procedures, which leave less and less time to collect meaningful data for the use of drugs. The hope that the information deficits could be remedied by so-called post-marketing studies has so far not been fulfilled. Such studies are rarely conducted and published - and if they are, they rarely confirm the added benefit of the new drugs. Identifying knowledge gaps after approval and closing them with meaningful data is therefore a very important task for the future.

Furthermore, the authors call for the mandatory requirement to provide meaningful comparisons between new drugs and standard treatment as early as the date of market access. New approaches to drug development that are more strongly orientated towards gaps in treatment options or the goals of healthcare systems could also contribute to better patient care.

The idea of genetically modifying a patient's own immune cells and deploying them against infections and tumors has been around since the 1980s. But to this day modified T cells are still not as effective as natural T cells and have been only been of limited clinical value. Using the new CRISPR-Cas9 gene editing tool, a team at the Technical University of Munich (TUM) has now engineered T cells that are very similar to physiological immune cells.

There are two forms of T cell therapy: either a recipient receives cells from a donor, or the recipient's own T cells are removed, genetically reprogrammed in a laboratory and unleashed against an infection or tumor in the body. While the first method has proven to be successful in clinical models, reprogramming T cells is still beset with problems.

Modifying T cell receptors

The team led by Professor Dirk Busch, Director of the Institute for Medical Microbiology, Immunology and Hygiene at the TUM, has generated modified T cells for the first time that are very similar to their natural counterparts and could solve some of those problems. To do so, they utilized the new CRISPR-Cas9 gene scissors, which can be used to snip out and replace targeted segments of the genome.

Both the conventional methods and the new method target the key homing instrument of T cells, known as the T cell receptor. The receptor, residing on the cell's surface, recognizes specific antigens associated with pathogens or tumor cells, which the T cell is then able to attack. Each receptor is made up of two molecular chains that are linked together. The genetic information for the chains can be genetically modified to produce new receptors that are able to recognize any desired antigen. In this way, it is possible to reprogram T cells.

Targeted exchange using the CRISPR-Cas9 gene scissors

The problem with conventional methods is that the genetic information for the new receptors is randomly inserted into the genome. This means that T cells are produced with both new and old receptors or with receptors having one old and one new chain. As a result, the cells do not function as effectively as physiological T cells and are also controlled differently. Moreover, there is a danger that the mixed chains could trigger dangerous side effects (Graft-versus-Host Disease, GvHD).

"Using the CRISPR method, we've been able to completely replace the natural receptors with new ones, because we're able to insert them into the very same location in the genome. In addition, we've replaced the information for both chains so that there are no longer any mixed receptors," explains Kilian Schober, who is a lead author of the new study along with his colleague Thomas Müller.

Near-natural properties

Thomas Müller explains the advantages of the modified T cells: "They're much more similar to physiological T cells, yet they can be changed flexibly. They're controlled like physiological cells and have the same structure, but are capable of being genetically modified." The scientists have demonstrated in a cell culture model that T cells modified in this way behave nearly exactly like their natural counterparts.

"Another advantage is that the new method allows multiple T cells to be modified simultaneously so that they're able to recognize different targets and can be used in combination. This is especially interesting for cancer therapy, because tumors are highly heterogeneous," Dirk Busch adds. In the future, the team plans to investigate the new cells and their properties in preclinical mouse models, an important step in preparing for clinical trials with humans.

The acidification of the oceans is recorded in the crystals of the coral skeleton. This is a new tool for studying past environmental changes and combating climate change. Such is the main conclusion of a study led by the Spanish scientist Ismael Coronado Vila, from the Institute of Paleobiology in Warsaw (Poland).

Coral skeletons are composed of (micrometric) crystals of aragonite, a variety of calcium carbonate. Their function within their skeletons is highly varied: it is the support that allows them to grow, provides protection against predators and sometimes helps them to ascend from the ocean floor in order to benefit from the light, as some corals live with symbiotic algae in their interior, which provides them with nutrients.

A study published in the journal Nature Communications shows, for the first time, the relationship between physiological changes caused in corals living in the acidified ocean and changes in the organization of their skeleton on an atomic or crystallographic scale.

"Our research has shown that the reef-forming coral, Stylophora pistillata, records subtle changes in its skeleton at different seawater pHs," says Ismael Coronado Vila, a scientist at the Institute of Paleobiology of the Polish Academy of Sciences in Warsaw (Poland), who is leading the work together with Jarosław Stolarski.

Thus, coral skeletons formed under ocean acidification conditions (low pH) undergo systematic changes in the arrangement of skeletal crystals and physiological alterations of the coral. "For example, in acidic conditions there is a greater incorporation of organic matrix into the skeleton," adds the expert.

To complete this study, these scientists incubated coral colonies in aquariums for 14 months at the Inter-University Institute of Marine Sciences in Eilat (Israel) and these were subsequently studied in Spanish laboratories at the Complutense University of Madrid and the Spanish National Research Council, among others.

"The acidic conditions of the experiments simulated everything from the current pH in the Red Sea, where Stylophora lives, to the worst scenarios predicted for the end of the 21st century in our oceans," continues Coronado Vila.

Tracing the history of acidification in the seas

The accumulation of corals on the seabed is what forms the reefs and these, although they take up a mere 0.2% of the earth's surface, constitute one of the planet's hot spots of diversity, as are tropical rainforests. Many other species of organisms depend on them.

The coral studied, Stylophora pistillata, is one of the best-studied corals in the world and its ancestry spans the past for as long as millions of years. "Which makes it a good candidate for exploring these processes in the fossil record, for example, since the Cenozoic (66 million years ago)," argues the scientist.

These results cannot be extrapolated to all corals in the world as it is known that not all of them respond in the same way to climate change. For the researcher, "it is a first approximation to how these processes affect corals of this type: tropical reef corals."

However, knowing where and when episodes of ocean acidification occurred in the geological past and how they affected floras and marine faunas (particularly reefs), and therefore terrestrial ones as well, will help to predict the effects the process that our oceans are undergoing will have in the near future.

"Global warming is already affecting and damaging our reefs and not only harms our biosphere, but also our economy; 25% of marine fish depend on them and the losses that are occurring may be irreparable," warns Coronado Vila.

For the better part of a century, life expectancy in industrialized countries like the United States steadily improved. But during the past three decades, and particularly since 2010, the trend has slowed or, in some places, reversed for non-Hispanic white populations in the U.S. It's been especially stark for 25- to 44-year-olds and for women, as well as in rural communities.

Those are the key findings of research from University of Pennsylvania demographers Irma Elo and Samuel Preston and colleagues, which they published in the journal Population and Development Review.

"The trends vary by region," says Elo, a professor of sociology and part of Penn's Population Studies Center (PSC). "Large central metropolitan areas have done extremely well, particularly compared to the non-metropolitan areas that have done poorly. To varying degrees, that pattern is evident across the country."

In the past 10 or so years, the mortality trajectory of non-Hispanic whites in the U.S. has worsened, diverging from progress seen for Hispanic and non-Hispanic black populations. This prompted Elo and colleagues to take a closer look at what was happening with this population and why. They also broadened their focus to include adults as young as 25 and as old as 64.

To draw their conclusions, they analyzed age, sex, race/ethnicity, and cause-of-death data compiled by the National Center for Vital Health Statistics, then estimated death rates by age, year, and geographic region. Finally, they distilled the data into four locality categories: large central metropolitan areas, large metro suburbs, small/medium metros, and non-metros.

"The biggest contrast we saw was between large metropolitan areas and their suburbs and non-metropolitan areas, which have moved in different directions," says Preston, a Penn professor of sociology and member of the PSC. "Between 1990 and 2016, non-metropolitan areas had rising mortality, which is extremely unusual in the context of life expectancy that has gotten better nearly every year for nearly every group for more than a century."

Women in general and younger adults also didn't fare well, the former perhaps because of educational disparities, the latter largely due to drug overdoses. Though the opioid epidemic initially seemed gravest in Appalachia and other non-metropolitan areas, it has since proven much more widespread.

It's one plausible cause for the bleak mortality trends for non-Hispanic whites as a whole. Elo and Preston also point to increases in mortality from mental and nervous-system disorders and respiratory disease, likely a lingering result of the smoking epidemic.

"Compared to other countries in 1990, the U.S. started out doing very poorly, and we are now in a much worse situation," says Preston. "But there are two pieces of good news: The decline in HIV/AIDS mortality has been important in all central metros, but particularly in the mid-Atlantic, south Atlantic, and some of the Pacific region. And there have been declines in cardiovascular diseases pretty much everywhere."

Plus, he adds, deaths from screenable cancers like prostate, breast, cervical, and colon cancer are down in all areas, too.

Other in-progress research from this team looks at non-Hispanic black populations and the U.S. population as a whole. But Elo says the work this paper highlights is an important step toward grasping and potentially reversing the negative trend. "There's a lot to be done to try to understand what's driving these patterns and, most importantly, what could be done to change them," she says. "I don't think anyone has the crystal ball yet for how to do it."

SAN FRANCISCO (July 11, 2019) - Africa has new purple-clad warriors more than 200 feet beneath the ocean's surface. Deep-diving scientists from the California Academy of Sciences' Hope for Reefs initiative and the University of Sydney spotted dazzling fairy wrasses--previously unknown to science--in the dimly lit mesophotic coral reefs of eastern Zanzibar, off the coast of Tanzania. The multicolored wrasses sport deep purple scales so pigmented, they even retain their color (which is typically lost) when preserved for research. The scientists name this "twilight zone" reef-dweller Cirrhilabrus wakanda (common name "Vibranium Fairy Wrasse") in honor of the mythical nation of Wakanda from the Marvel Entertainment comics and movie Black Panther. The new fish is described today in ZooKeys.

"When we thought about the secretive and isolated nature of these unexplored African reefs, we knew we had to name this new species after Wakanda," says Yi-Kai Tea, lead author and ichthyology PhD student from the University of Sydney. "We've known about other related fairy wrasses from the Indian Ocean, but always thought there was a missing species along the continent's eastern edge. When I saw this amazing purple fish, I knew instantly we were dealing with the missing piece of the puzzle."

Underwater Wakanda

The Academy scientists say Cirrhilabrus wakanda's remote home in mesophotic coral reefs--below recreational diving limits--probably contributed to their long-hidden status in the shadows of the Indian Ocean. Hope for Reefs' scientific divers are highly trained for the dangerous process of researching in these deep, little-known mesophotic reefs, located 200 to 500 feet beneath the ocean's surface. Accessing them requires technical equipment and physically intense training well beyond that of shallow-water diving. The team's special diving gear (known as closed-circuit rebreathers) includes multiple tanks with custom gas blends and electronic monitoring equipment that allow the divers to explore deep reefs for mere minutes before a lengthy, hours-long ascent to the surface.

"Preparation for these deep dives is very intense and our dive gear often weighs more than us," says Dr. Luiz Rocha, Academy Curator of Fishes and co-leader of the Hope for Reefs initiative. "When we reach these reefs and find unknown species as spectacular as this fairy wrasse, it feels like our hard work is paying off."

Using a microscope, the team examined the specimens' scales, fin rays, and body structures. DNA and morphological analyses revealed the new fairy wrasse to be different from the other seven species in the western Indian Ocean as well as other relatives in the Pacific. The new species' common name is inspired by the fictional metal vibranium, a rare, and, according to Rocha, "totally awesome" substance found in the Black Panther nation of Wakanda. The Vibranium Fairy Wrasse's purple chain-link scale pattern reminded the scientists of Black Panther's super-strong suit and the fabric motifs worn by Wakandans in the hit film.

Precious life in deep reefs

In a recent landmark paper, the Academy team found that twilight zone reefs are unique ecosystems bursting with life and are just as vulnerable to human threats as their shallow counterparts. Their findings upended the long-standing assumption that species might avoid human-related stressors on those deeper reefs. The Hope for Reefs team will continue to visit and study twilight zone sites around the world to shed light on these often-overlooked ecosystems.

In addition to this new fish from Zanzibar, Rocha and his colleagues recently published descriptions of mesophotic fish from Rapa Nui [Easter Island] and Micronesia. Luzonichthys kiomeamea is an orange, white, and sunny yellow dwarf anthias endemic to Rapa Nui, and the basslet Liopropoma incandescens (another new species published today in Zookeys) inhabits Pohnpei's deep reefs--a neon orange and yellow specimen collected from a rocky slope 426 feet beneath the ocean's surface.

"It's a time of global crisis for coral reefs, and exploring little-known habitats and the life they support is now more important than ever," says Rocha. "Because they are out of sight, these deeper reefs are often left out of marine reserves, so we hope our discoveries inspire their protection."

Since light-emitting diodes only produce monochrome light, manufacturers use various additive colour-mixing processes to produce white light.

Since the first development of white OLEDs in the 1990s, numerous efforts have been made to achieve a balanced white spectrum and high luminous efficacy at a practical luminance level. However, the external quantum efficiency (EQE) for white OLEDs without additional outcoupling techniques can only reach 20 to 40 percent today. About 20 percent of the generated light particles (photons) remain trapped in the glass layer of the device. The reason for this is the total internal reflection of the particles at the interface between glass and air.

Further photons are waveguided in the organic layers, while others get ultimately lost at the interface to the top metal electrode.

Numerous approaches have been investigated to extract the trapped photons from OLEDs. An international research team led by Dr. Simone Lenk and Prof. Sebastian Reineke from the TU Dresden has now presented a new method for freeing the light particles in the renowned journal Nature Communications.

The physicists introduce a facile, scalable and especially lithography-free method for the generation of controllable nanostructures with directional randomness and dimensional order, significantly boosting the efficiency of white OLEDs. The nanostructures are produced by reactive ion etching. This has the advantage that the topography of the nanostructures can be specifically controlled by adjusting the process parameters.

In order to understand the results obtained, the scientists have developed an optical model that can be used to explain the increased efficiency of OLEDs. By integrating these nanostructures into white OLEDs, an external quantum efficiency of up to 76.3% can be achieved.

For Dr. Simone Lenk, the new method opens up numerous new avenues: "We had been looking for a way to specifically manipulate nanostructures for a long time already. With reactive ion etching, we have found a cost-effective process that can be used for large surfaces and is also suitable for industrial use. The advantage lies in the fact that the periodicity and height of the nanostructures can be completely adjusted via the process parameters and that thus an optimal outcoupling structure for white OLEDs could be found. These quasi-periodic nanostructures are not only suitable as outcoupling structures for OLEDs, but also have the potential for further applications in optics, biology and mechanics".