Brain

New type of curved acoustic beams to provide manipulations with nanoparticles

image: Normalized sound pressure distributions in XZ planes for different Rexolite® particles: (a) 3λ side cuboid, and a rectangular trapezoidal particle obtained from the 3λ side cuboid and with an interior angle (b) 10°, (c) 15°, (d) 20°, (e) 25° and (f) 30°.

Image: 
Tomsk Polytechnic University

Previously, scientists knew only one type of curved optical rays - Airy beams and their derivatives. They were obtained back in 2007. Due to their physical properties, the beams can be used for manipulating the small particles, which can be applied in microfluidics and cell biology. Obtaining such beams requires advanced equipment. Therefore, researchers from all around the world are looking for new types of curved beams that could be obtained much easier.

"Principles of obtaining new curved beams is an interesting and promising research field for both fundamental and applied areas. In 2018, our team theoretically predicted the existence of a new type of curved hook-like self-accelerating light beam. We named it a photonic hook, which is a curved electromagnetic wave. After that, we wondered if such curved beams could be obtained from an acoustic wave? Our new study positively responded to this challenge. We can obtain this beam incomparably easier than Airy beams," Igor Minin, the head of the project and professor of the TPU Division for Electronic Engineering, says.

To generate an acoustical hook, the researchers used a microparticle made of Rexolite dielectric material with an asymmetric shape. This particle was placed in water during experiments and irradiated with ultrasound. Passing through a particle of this shape, a sound wave was curved in the shape of a hook at the exit from the particle. The experiments were carried out at the Polytechnic University of Valencia (Spain).

"Today, the main application of acoustical hooks is biomedicine, synthesis of new materials, manipulation of nanoparticles using ultrasound with high sub-wave accuracy.

They can be used where other types of curved acoustic beams such as Airy cannot. In the future, we plan to carry out experiments and try to use acoustic hooks directly for particle manipulations, " Igor Minin says.

Credit: 
Tomsk Polytechnic University

Size matters! The neuroanatomy of trigeminal neuralgia´s treatment response

London, UK: A new study published in the journal Cephalalgia, the official journal of the International Headache Society, shows unprecedented data regarding the neuroanatomical influence on the treatment response of patients with trigeminal neuralgia. The study, entitled "Hippocampal and trigeminal nerve volume predict outcome of surgical treatment for trigeminal neuralgia", was conducted by Dr. Tejas Sankar's research group, from the University of Alberta, Canada.

Trigeminal neuralgia (TG) is a facial pain in the lower portion of the face, mostly felt in the cheek next to the nose or in the jaw. According to the 3rd Version of the International Classification of Headache Disorders - ICHD-3, TG is described as follows:

"A disorder characterized by recurrent unilateral brief electric shock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of the trigeminal nerve and triggered by innocuous stimuli. It may develop without apparent cause or be a result of another diagnosed disorder. Additionally, there may be concomitant continuous pain of moderate intensity within the distribution(s) of the affected nerve division(s)."

The two most common forms of TN are non-lesional types, namely, the classic TN, associated with neurovascular compression of the nerve's root entry zone, and idiopathic TN, which occurs in the absence of neurovascular compression. Occasionally, TN may be due to lesions. Microvascular decompression is a neurosurgical procedure adopted as an alternative to patients refractory to pharmacological treatments.

Based on previous data indicating that trigeminal nerve volume and cross-sectional area appear to be consistently reduced on the affected side in patients with TN, Dr. Sankar and his team hypothesized that TN patients who do not respond to surgical treatment could be characterized by distinct neuroanatomical features.

Dr. Sankar's group assessed 37 classic or idiopathic TN patients. Neuroimaging obtained by T2-weighted magnetic resonance imaging (1.5T) was performed within the 12 months previously the microvascular decompression surgery. The trigeminal nerve, and subcortical brain structures involved in the trigeminal sensory relay (thalamus) or as potential contributors to limbic components of chronic pain (hippocampus, amygdala), were analyzed. They compared the ipsilateral and contralateral portions of the side of pain, total nerve volume (ipsilateral + contralateral), and % difference ((ipsilateral -contralateral/ipsilateral)100).

Responders rate (i.e., pain relief/no recurrence/no surgery repeat following 1 year of surgery) was 68 %, in agreement with previous studies. The main findings are listed below:

In all patients, thalamus volume was larger contralateral to the side of pain than ipsilateral;

Non-responders presented larger intracranial volume, trigeminal nerve volume contralateral to the pain side, and larger contralateral hippocampus volume than responders;

Non-responders showed larger total and ipsilateral hippocampus volume than responders as well;

The contralateral trigeminal nerve and hippocampus volume were predictors of treatment response, in which larger volumes of both structures associated with non-responders patients;

Both ipsilateral and contralateral hippocampus were significant contributors of prediction accuracy;

Although the study reports original findings and confirms previous ones, the authors exercise caution interpreting their data and ponder: "The phenomenon of treatment resistance in chronic pain is unlikely to be driven by a single structure, despite our findings. Future network and connectivity examinations between responders and non-responders would complement this work nicely, as the hippocampus - and potentially other limbic structures as well - may represent a node within networks working together to influence pain."

The findings regarding the hippocampus underscore the relevance of this brain area as the emotional integrator of the chronic pain experience, as for headache and facial pain disorders. For example, in migraine, structural brain alterations including higher connectivity in the hippocampus has been recently reported by other researchers.

Credit: 
International Headache Society

World's first public database of mine tailings dams aims to prevent deadly disasters

Environmental organization GRID-Arendal has launched the world's first publicly accessible global database of mine tailings storage facilities. The database, the Global Tailings Portal, was built by Norway-based GRID-Arendal as part of the Investor Mining and Tailings Safety Initiative, which is led by the Church of England Pensions Board and the Swedish National Pension Funds' Council on Ethics, with support from the UN Environment Programme. The initiative is backed by funds with more than US$13 trillion under management.

Until now, there has been no central database detailing the location and quantity of the mining industry's liquid and solid waste, known as tailings. The waste is typically stored in embankments called tailings dams, which have periodically failed with devastating consequences for communities, wildlife and ecosystems.

"This portal could save lives", says Elaine Baker, senior expert at GRID-Arendal and a geosciences professor with the University of Sydney in Australia. "Dams are getting bigger and bigger. Mining companies have found most of the highest-grade ores and are now mining lower-grade ones, which create more waste. With this information, the entire industry can work towards reducing dam failures in the future."

The database allows users to view detailed information on more than 1,700 tailings dams around the world, categorized by location, company, dam type, height, volume, and risk, among other factors.

"Most of this information has never before been publicly available", says Kristina Thygesen, GRID-Arendal's programme leader for geological resources and a member of the team that worked on the portal. When GRID-Arendal began in-depth research on mine tailings dams in 2016, very little data was accessible. In a 2017 report on tailings dams, co-published by GRID and the UN Environment Programme, one of the key recommendations was to establish an accessible public-interest database of tailings storage facilities.

"This database brings a new level of transparency to the mining industry, which will benefit regulators, institutional investors, scientific researchers, local communities, the media, and the industry itself", says Thygesen.

The release of the Global Tailings Portal coincides with the one-year anniversary of the tailings dam collapse in Brumadinho, Brazil, that killed 270 people. After that disaster, a group of institutional investors led by the Church of England Pensions Board asked 726 of the world's largest mining companies to disclose details about their tailings dams. Many of the companies complied, and the information they released has been incorporated into the database.

Credit: 
GRID-Arendal

Scanning system in sperm may control rate of human evolution

image: This is the cover image of the current edition of Cell, which relates to the NYU Langone study.

Image: 
Cell Press

Maturing sperm cells turn on most of their genes, not to follow their genetic instructions like normal, but instead to repair DNA before passing it to the next generation, a new study finds.

Led by NYU Grossman School of Medicine researchers and published online January 23 in Cell, the study focuses on a mystery of biology: human sperm cells activate by far the largest number of genes (90 percent), a pattern also seen in other species like mice, birds, and even fruit flies. Cells in most organs express about 60 percent of their genetic code, or just the subset of genes needed for a cell type to do its particular job.

"It now seems obvious that sperm activate so many more genes as they develop because doing so runs them through a DNA repair process, and protects the integrity of messages about to be inherited," says senior author Itai Yanai, PhD, director of the Institute for Computational Medicine at NYU Langone Health.

"We also found that such repair in sperm is less active in genes that are activated, or transcribed, less often," adds Yanai, also a professor in Department of Biochemistry and Molecular Pharmacology at NYU Grossman School of Medicine. "This supports the theory that evolution is using transcription frequency as a lever, dialing it up to preserve the DNA code in some genes, but turning it down to enable changes elsewhere when it contributes to survival."

An example of genes not activated, not repaired, and free to accumulate changes in sperm were those related to immunity, which must continually evolve if the body is to recognize and attack ever-changing bacterial and viral invaders.

Beyond the Fittest

To conduct the new study, the authors analyzed gene expression patterns during sperm maturation at single-cell resolution. They first collected samples of human testes tissue, biopsied from consented volunteers. Using microfluidics, they then passed all cells in the samples down a tube just large enough for them to flow through in single file.

Within the tube each cell was pushed into its own water droplet, which acted like a mini-test tube in which enzymes opened the cells and then attached cell-specific barcodes to each transcribed snippet of genetic material. The labeled transcripts were then used to create maps of which genes were turned on at each point during sperm maturation. The team then cross-referenced these findings with known DNA variations in human population databases to estimate how often repair occurred in a given gene.

Surprisingly, researchers found that genes activated even a few times during sperm cell development contained 15-20 percent fewer DNA code errors than unexpressed genes, with the difference attributed to transcription-coupled repair (TCR). This process replaces faulty DNA patches just before the instructions they contain are converted into a related genetic material, RNA, during transcription, the first step in gene expression. RNA transcripts are then read to build proteins that make up cell structures and signals.

Cellular processes, including transcription, along with toxins in the environment, continually introduce errors into DNA chains, with TCR weeding out some of the altered code. The difference, the researchers say, is that sperm cells appear to apply TCR to more genes than is normal, but then to halt gene expression by mechanisms unknown before proteins are made.

Moving forward, the research team will seek to confirm whether sperm-derived genetic changes occur more often in genes not expressed during the maturation of sperm.

This may reveal insights into the causes of many genetic diseases linked to changes in the sperm of aging fathers. Male reproductive cells are known to divide and multiply throughout a person's life, with errors introduced each time. The authors say this may provide a rationale for the existence of widespread scanning uniquely in sperm, because egg cells received by each female in the womb do not multiply for the rest of her life.

Furthermore, the team will determine whether cells in the brain, which also express a large percentage of their genes, employ "transcriptional scanning" like sperm cells, and whether the scanning fails with age to increase risk for neurodegenerative diseases. Embryonic stem cells also display the high-transcription, low-mutation signature that could indicate the presence of such scanning during development.

"Survival of the fittest is a foundation of evolutional theory, but what if other mechanisms bias which gene types are more susceptible to change before natural selection can act on them?" asks first author Bo Xia, a PhD candidate in Yanai's lab. "Such a bias in the testes would have a dramatic effect, but only over evolutionary time scales, say millions of years."

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NYU Langone Health / NYU Grossman School of Medicine

For low back pain in older adults, treatment doesn't match guidelines

January 23, 2020 - Many Medicare patients with new episodes of low back pain receive care inconsistent with current guidelines - including high use of opioids and advanced imaging tests, reports a study in the February issue of Medical Care. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Opioids are prescribed to nearly one-third of older adults with "new and persistent" Low Back pain - in most cases without trying guideline-recommended pain medications or physical therapy, according to the new research by Dan Pham Ly, MD, MPP, of Harvard University. He comments, "This study raises concerns about excessive use of low-value and potentially harmful treatments for the common problem of LBP in older adults, with under-use of evidence-based, guideline-recommended treatments."

Many Medicare Patients Don't Receive Evidence-Based Treatments for New LBP

The study used Medicare claims data on more than 162,000 older adults with new LBP from 2011 through 2014. About 70 percent of patients were women; average age was approximately 77. None had received previous opioid treatment. The analysis included information on multiple visits for LBP over the course of a year, providing data on the timing and sequence of care.

Over half of patients (54 percent) made only one healthcare visit for LBP. That's consistent with evidence that many new episodes of LBP are self-limiting. As stated in the current American College of Physicians guidelines, most patients with LBP "improve over time regardless of treatment."

Advanced imaging studies - computed tomography (CT) or magnetic resonance imaging (MRI) scans - were used in about 15 percent of patients overall, and 29 percent of those with two or more LBP visits. In about half of cases, CT or MRI scans were performed within six weeks. That's contrary to an American Academy of Family Physicians statement that most patients don't need advanced imaging studies for initial evaluation of LBP.

Opioids were prescribed to about one-fourth of patients overall, including one-third of those with two or more LBP visits. In contrast, LBP guidelines suggest that other pain relievers - including nonsteroidal anti-inflammatory drugs (NSAIDs), such as naproxen or ibuprofen - should be tried before opioids.

Physical therapy was prescribed to only 11 percent of patients overall and 17 percent of those with two or more visits. Evidence suggests that early use of physical therapy can avoid the use of opioids in patients with LBP.

Most patients treated with opioids had not received a prescription NSAID or physical therapy. Chronic opioid use developed in about one percent of patients overall, and nearly two percent of those with two or more visits.

Low back pain is a common reason for healthcare visits - in a given year, about ten percent of people will develop a new episode of LBP. Studies examining trends in LBP treatment found increasing use of opioids, and decreased use of NSAIDs, up to 2010. The new analysis focused on more recent patterns in evaluation and treatment of LBP in Medicaid patients, including data on repeated visits over one year.

"Many patients who develop new LBP receive guideline non-concordant care such as early advanced imaging and opioids before other modalities like PT and prescription NSAIDs," Dr. Ly writes. At least in the first half of the past decade, one-third of patients making two or more LBP visits received opioids - often without having tried other recommended treatments.

Dr. Ly calls for future studies examining barriers to guideline-recommended treatments for LBP in older adults - particularly physical therapy and NSAIDS. He also points out that pain management can be challenging in older adults, highlighting the need for studies to compare the safety and effectiveness of medication options.

Credit: 
Wolters Kluwer Health

Taking aim at gastric cancer

A novel drug, named "FerriIridium", can simultaneously help diagnose and treat gastric cancer. The initially weakly active precursor (prodrug), based on an iridium-containing compound, is selectively activated only after reaching the interior of a tumor cell. This is possible because of the higher amount of iron present there, report scientists in the journal Angewandte Chemie. Selective activation reduces undesired side effects.

Cells transport substances from their exterior to their interior by folding in small regions of their membrane and then binding them off (endocytosis). This is how FerriIridium enters target cells. The resulting vesicles then fuse with lysosomes. These cell organelles have an acidic environment that contains trivalent iron ions, Fe(III), and enzymes, with which they dismantle cell components that are no longer needed. In gastric cancer cells, the Fe(III) concentration within the lysosomes is significantly elevated.

Scientists working with Yu Chen and Hui Chao at Sun Yat-Sen University, Guangzhou, and Hunan University of Science and Technology, Xiangtan (China) made use of this feature. They equipped FerriIridium with a special functional group (the m-iminocatechol group) that selectively binds to Fe(III). When bound, the functional group is oxidized while the iron ions are reduced to Fe(II). Under the acidic conditions within the lysosomes, the FerriIridium is then split into two components: an iridium complex and a benzoquinone derivative.

This reaction mechanism has a threefold effect. First, Fe(II) ions can catalyze a reaction that produces highly reactive hydroxyl radicals. Second, benzoquinones are highly oxidizing. With certain cellular substances, such as NADPH, they form hydroxyquinones, which react with oxygen to produce radical oxygen species, as well as hydrogen peroxide, which in turn can react with Fe(II) to produce hydroxyl radicals. Benzoquinone compounds can also disrupt cellular respiration. The radicals destroy the lysosomes, releasing their contents. Third, the splitting of FerriIridium drastically increases both the phosphorescence and the toxicity of the iridium complex. The phosphorescence can be used to diagnose the tumor. Most importantly, however, the toxic iridium complex is absorbed by mitochondria, the "cellular power plants". It destroys them from the inside out by collapsing their membrane potential. Together, these effects lead to the death of the gastric cancer cells and shrinking of the tumors, as demonstrated by experiments on cell lines and mice.

Credit: 
Wiley

Quantum experiments explore power of light for communications, computing

image: Researchers in ORNL's Quantum Information Science group summarized their significant contributions to quantum networking and quantum computing in a special issue of Optics & Photonics News.

Image: 
Christopher Tison and Michael Fanto/Air Force Research Laboratory.

A team from the Department of Energy's Oak Ridge National Laboratory has conducted a series of experiments to gain a better understanding of quantum mechanics and pursue advances in quantum networking and quantum computing, which could lead to practical applications in cybersecurity and other areas.

ORNL quantum researchers Joseph Lukens, Pavel Lougovski, Brian Williams, and Nicholas Peters--along with collaborators from Purdue University and the Technological University of Pereira in Colombia--summarized results from several of their recent academic papers in a special issue of the Optical Society's Optics & Photonics News, which showcased some of the most significant results from optics-related research in 2019. Their entry was one of 30 selected for publication from a pool of 91.

Conventional computer "bits" have a value of either 0 or 1, but quantum bits, called "qubits," can exist in a superposition of quantum states labeled 0 and 1. This ability makes quantum systems promising for transmitting, processing, storing, and encrypting vast amounts of information at unprecedented speeds.

To study photons--single particles of light that can act as qubits--the researchers employed light sources called quantum optical frequency combs that contain many precisely defined wavelengths. Because they travel at the speed of light and do not interact with their environment, photons are a natural platform for carrying quantum information over long distances.

Interactions between photons are notoriously difficult to induce and control, but these capabilities are necessary for effective quantum computers and quantum gates, which are quantum circuits that operate on qubits. Nonexistent or unpredictable photonic interactions make two-photon quantum gates much more difficult to develop than standard one-photon gates, but the researchers reached several major milestones in recent studies that addressed these challenges.

For example, they made adjustments to existing telecommunications equipment used in optics research to optimize them for quantum photonics. Their results revealed new ways to use these resources for both traditional and quantum communication.

"Using this equipment to manipulate quantum states is the technological underpinning of all these experiments, but we did not expect to be able to move in the other direction and improve classical communication by working on quantum communication," Lukens said. "These interesting and unanticipated findings have appeared as we delve deeper into this research area."

One such tool, a frequency beam splitter, divides a single beam of light into two frequencies, or colors, of light.

"Imagine you have a beam of light going down an optical fiber that has a particular frequency, say, red," Lukens said. "Then, after going through the frequency beam splitter, the photon will leave as two frequencies, so it will be both red and blue."

The members of this team were the first researchers to successfully design a quantum frequency beam splitter with standard lightwave communications technology. This device takes in red and blue photons simultaneously, then produces energy in either the red or the blue frequency. By using this method to deliberately change the frequencies of photons, the team tricked the stubborn particles into beneficial interactions based on quantum interference, the phenomenon of photons interfering with their own trajectories.

"It turned out that off-the-shelf devices can deliver impressive control at the single-photon level, which people didn't know was possible," Lougovski said.

Additionally, the researchers completed the first demonstration of a frequency tritter, which splits a beam of light into three different frequencies instead of two. Their results indicated that multiple quantum information processing operations can run at the same time without introducing errors or damaging the data.

Another key accomplishment was the team's design and demonstration of a coincidence-basis controlled-NOT gate, which enables one photon to control a frequency shift in another photon. This device completed a universal quantum gate set, meaning any quantum algorithm can be expressed as a sequence within those gates.

"Quantum computing applications require much more impressive control levels than any sort of classical computing," Lougovski said.

The team also encoded quantum information in multiple independent values known as degrees of freedom within a single photon, which allowed them to observe quantum entanglement-like effects without needing two separate particles. Entanglement usually involves two linked particles in which changes made to the state of one particle also apply to the other.

Finally, the researchers have completed quantum simulations of real-world physics problems. In collaboration with scientists at the Air Force Research Laboratory, they are now developing tiny, specialized silicon chips similar to those common in microelectronics in pursuit of even better photonic performance.

"In theory, we can get all these operations onto a single photonic chip, and we see a lot of potential for doing similar quantum experiments on this new platform," Lukens said. "That's the next step to really move this technology forward."

Future quantum computers will allow scientists to simulate incredibly complex scientific problems that would be impossible to study on current systems, even supercomputers. In the meantime, the team's findings could help researchers embed photonic systems into current high-performance computing resources.

"We have a very diverse and talented team," Lougovski said. "The most important thing is we're getting results."

Credit: 
DOE/Oak Ridge National Laboratory

When caregivers need care

WASHINGTON - People who regularly care for or assist a family member or friend with a health problem or disability are more likely to neglect their own health, particularly by not having insurance or putting off necessary health services due to cost, according to a study published by the American Psychological Association.

"Caregivers provide tremendous benefits for their loved ones, yet they may be at risk for lacking access to needed services which puts their health in jeopardy," said Jacob Bentley, PhD, of Seattle Pacific University, co-author of the study. "We found that caregivers were more likely not to have health care coverage or forgo needed medical appointments and services. They were also at an increased risk for experiencing depression in their lifetime as compared with non-caregivers."

The study, published in the journal Rehabilitation Psychology, focused solely on people who provided care to family and friends, not professional caregivers.

More than 43 million adults in the U.S. function as caregivers each year, according to 2015 data from the National Alliance for Caregiving and AARP cited in the study.

"Informal caregiving provides enormous economic value to our society because if we were to replace informal caregiving with formal, paid caregiving services, it could cost the country upwards of $600 billion in wages for home health aides," said Bentley. "Despite the economic benefits for society and valuable assistance provided to care recipients, attention must also be given to caregivers' own financial, physical and emotional challenges."

The study used data from more than 24,000 people who participated in the 2015 Behavioral Risk Factor Surveillance System annual phone survey conducted by the U.S. Centers for Disease Control and Prevention. Most participants were white women under 65 earning between $10,000 and $70,000 per year. Half were employed, half were unemployed or retired.

Participants reported that they had provided regular care or assistance to a family member or friend with a health problem or disability within the 30 days prior to the survey. More than half of the participants provided care for up to eight hours a week, typically doing household tasks such as cleaning, managing money or preparing meals. The vast majority indicated that they did not need support services, such as support groups or individual counseling, suggesting a need for additional research into alternative support services that are prioritized by caregivers, according to Bentley.

Participants were also asked if they had health insurance, if there was a time within the 12 months before the survey that they did not see a doctor because of the cost and if they had ever been diagnosed with a depressive disorder by a health care provider.

"Caregivers had a 26% higher risk of not having health care coverage, compared with non-caregivers, and they were at a significantly higher risk, a 59% additional risk, for not going to the doctor or getting a necessary health service due to cost, " said Bentley.

Further, one-fourth of the caregivers reported that they had been diagnosed with a depressive disorder by a health care provider at some point during their lives, representing a 36% increased risk over non-caregivers, according to the study.

"Also, nearly 30% reported experiencing at least one limitation to daily activities because of physical, mental or emotional problems," said Bentley.

Bentley and his colleagues believe that some of these disparities may be due to financial barriers experienced by caregivers. Previous research has indicated that their duties may interfere with their ability to seek employment outside of the home or advance their careers due to the need for flexible schedules to accommodate their caregiving responsibilities, he said.

"While we expected caregivers to be more at risk in these areas, we were concerned to learn of the extent of these risks and barriers to health care access encountered by caregivers," said Bentley. "Given the scope of difficulties acquiring health care coverage and utilizing needed services in this large national sample, we believe our findings warrant additional research and likely the development of low-cost and accessible services that meet the multifaceted needs of caregivers."

"At a broader level, these findings can serve as evidence for policymakers focused on public health agendas because they have the power to develop policies aimed at reducing financial burdens and heath care service gaps among caregivers who are vital not only to those in our communities who need care, but also to our overall health care economy," he said.

Credit: 
American Psychological Association

Using artificial intelligence to enrich digital maps

A model invented by researchers at MIT and Qatar Computing Research Institute (QCRI) that uses satellite imagery to tag road features in digital maps could help improve GPS navigation.

Showing drivers more details about their routes can often help them navigate in unfamiliar locations. Lane counts, for instance, can enable a GPS system to warn drivers of diverging or merging lanes. Incorporating information about parking spots can help drivers plan ahead, while mapping bicycle lanes can help cyclists negotiate busy city streets. Providing updated information on road conditions can also improve planning for disaster relief.

But creating detailed maps is an expensive, time-consuming process done mostly by big companies, such as Google, which sends vehicles around with cameras strapped to their hoods to capture video and images of an area's roads. Combining that with other data can create accurate, up-to-date maps. Because this process is expensive, however, some parts of the world are ignored.

A solution is to unleash machine-learning models on satellite images -- which are easier to obtain and updated fairly regularly -- to automatically tag road features. But roads can be occluded by, say, trees and buildings, making it a challenging task. In a paper being presented at the Association for the Advancement of Artificial Intelligence conference, the MIT and QCRI researchers describe "RoadTagger," which uses a combination of neural network architectures to automatically predict the number of lanes and road types (residential or highway) behind obstructions.

In testing RoadTagger on occluded roads from digital maps of 20 U.S. cities, the model counted lane numbers with 77 percent accuracy and inferred road types with 93 percent accuracy. The researchers are also planning to enable RoadTagger to predict other features, such as parking spots and bike lanes.

"Most updated digital maps are from places that big companies care the most about. If you're in places they don't care about much, you're at a disadvantage with respect to the quality of map," says co-author Sam Madden, a professor in the Department of Electrical Engineering and Computer Science (EECS) and a researcher in the Computer Science and Artificial Intelligence Laboratory (CSAIL). "Our goal is to automate the process of generating high-quality digital maps, so they can be available in any country."

The paper's co-authors are CSAIL graduate students Songtao He, Favyen Bastani, and Edward Park; EECS undergraduate student Satvat Jagwani; CSAIL professors Mohammad Alizadeh and Hari Balakrishnan; and QCRI researchers Sanjay Chawla, Sofiane Abbar, and Mohammad Amin Sadeghi.

Combining CNN and GNN

Qatar, where QCRI is based, is "not a priority for the large companies building digital maps," Madden says. Yet, it's constantly building new roads and improving old ones, especially in preparation for hosting the 2022 FIFA World Cup.

"While visiting Qatar, we've had experiences where our Uber driver can't figure out how to get where he's going, because the map is so off," Madden says. "If navigation apps don't have the right information, for things such as lane merging, this could be frustrating or worse."

RoadTagger relies on a novel combination of a convolutional neural network (CNN) -- commonly used for images-processing tasks -- and a graph neural network (GNN). GNNs model relationships between connected nodes in a graph and have become popular for analyzing things like social networks and molecular dynamics. The model is "end-to-end," meaning it's fed only raw data and automatically produces output, without human intervention.

The CNN takes as input raw satellite images of target roads. The GNN breaks the road into roughly 20-meter segments, or "tiles." Each tile is a separate graph node, connected by lines along the road. For each node, the CNN extracts road features and shares that information with its immediate neighbors. Road information propagates along the whole graph, with each node receiving some information about road attributes in every other node. If a certain tile is occluded in an image, RoadTagger uses information from all tiles along the road to predict what's behind the occlusion.

This combined architecture represents a more human-like intuition, the researchers say. Say part of a four-lane road is occluded by trees, so certain tiles show only two lanes. Humans can easily surmise that a couple lanes are hidden behind the trees. Traditional machine-learning models -- say, just a CNN -- extract features only of individual tiles and most likely predict the occluded tile is a two-lane road.

"Humans can use information from adjacent tiles to guess the number of lanes in the occluded tiles, but networks can't do that," He says. "Our approach tries to mimic the natural behavior of humans, where we capture local information from the CNN and global information from the GNN to make better predictions."

Learning weights

To train and test RoadTagger, the researchers used a real-world map dataset, called OpenStreetMap, which lets users edit and curate digital maps around the globe. From that dataset, they collected confirmed road attributes from 688 square kilometers of maps of 20 U.S. cities -- including Boston, Chicago, Washington, and Seattle. Then, they gathered the corresponding satellite images from a Google Maps dataset.

In training, RoadTagger learns weights -- which assign varying degrees of importance to features and node connections -- of the CNN and GNN. The CNN extracts features from pixel patterns of tiles and the GNN propagates the learned features along the graph. From randomly selected subgraphs of the road, the system learns to predict the road features at each tile. In doing so, it automatically learns which image features are useful and how to propagate those features along the graph. For instance, if a target tile has unclear lane markings, but its neighbor tile has four lanes with clear lane markings and shares the same road width, then the target tile is likely to also have four lanes. In this case, the model automatically learns that the road width is a useful image feature, so if two adjacent tiles share the same road width, they're likely to have the same lane count.

Given a road not seen in training from OpenStreetMap, the model breaks the road into tiles and uses its learned weights to make predictions. Tasked with predicting a number of lanes in an occluded tile, the model notes that neighboring tiles have matching pixel patterns and, therefore, a high likelihood to share information. So, if those tiles have four lanes, the occluded tile must also have four.

In another result, RoadTagger accurately predicted lane numbers in a dataset of synthesized, highly challenging road disruptions. As one example, an overpass with two lanes covered a few tiles of a target road with four lanes. The model detected mismatched pixel patterns of the overpass, so it ignored the two lanes over the covered tiles, accurately predicting four lanes were underneath.

The researchers hope to use RoadTagger to help humans rapidly validate and approve continuous modifications to infrastructure in datasets such as OpenStreetMap, where many maps don't contain lane counts or other details. A specific area of interest is Thailand, Bastani says, where roads are constantly changing, but there are few if any updates in the dataset.

"Roads that were once labeled as dirt roads have been paved over so are better to drive on, and some intersections have been completely built over. There are changes every year, but digital maps are out of date," he says. "We want to constantly update such road attributes based on the most recent imagery."

Credit: 
Massachusetts Institute of Technology

Why cells need acidic lysosomes

Just like the body contains lungs, liver, and lymph nodes, so does each of the body's cells contain tiny specialized organs. Perhaps most peculiar among them are lysosomes--bubble-like sacks that act as part recycling bin, part stomach.

Among other things, a lysosome devours cellular debris--and, like a stomach, it needs to be acidic to do its job. In fact, without acidic lysosomes, cells in culture stop dividing and eventually die off.

"We asked a very simple question: Why?" says Kivanç Birsoy, Chapman Perelman Assistant Professor at The Rockefeller University. Experiments in his lab uncovered an equally simple answer: Iron. It turns out that a cell can no longer access this essential nutrient when the pH within its lysosomes rises.

The discovery, recently described in Molecular Cell, has implications for understanding and treating diseases, including cancer.

Cellular multitaskers

The story of lysosomes began in 1955, when Christian de Duve, a cell biologist who would later join Rockefeller, first discovered them. In the years that followed, scientists learned that lysosomes carry out multiple jobs inside cells--from engulfing all sorts of cellular garbage and breaking it down for reuse, to relaying biochemical signal and processing nutrients.

In spite of their complex functions, however, most functions of lysosomes are dispensable. When they don't function properly, "the cell somehow finds ways to compensate," Birsoy says.

The critical exception, as shown by the lab's recent findings, is converting iron into its nutrient form. "Processing iron seems to be the one thing cells cannot accomplish without lysosomes," he says.

Iron starvation

Ross Weber, a graduate student in Birsoy's lab, made the discovery after he reduced cells' lysosomal acidity enough to stress the cells, but not kill them. In responding to this challenge, the cells activated genes involved in the use of iron, while their iron levels dramatically dropped.

Cells don't cope for long without iron, which is needed to make DNA and other essential molecules. When a rise in pH causes iron depletion, cells stop dividing and eventually die. The scientists think this happens because lysosomes free iron from the molecules that transport it, something they do best at a pH of 4 to 5, the approximate acidity of a tomato.

Because lysosomes are known to be essential for cancer-cell proliferation, the discovery suggests a potentially new way to fight tumors: starving them for iron. In recent years, Birsoy's lab has devised a number of innovative ways to kill cancer cells by blocking their access to essential nutrients; now iron depletion promises to yield yet another weapon in this arsenal of potential drugs.  "In the future, it will be important to determine whether these findings are also relevant in the context of other conditions linked to the loss of acidity, such as lysosomal storage disorders and neurodegenerative diseases," Birsoy says. "We believe there are a lot of exciting possibilities out there."

Credit: 
Rockefeller University

Reducing dangerous swelling in traumatic brain injury

'We believe this may provide the first real treatment for people with traumatic brain injury'

Brain swelling after injury causes severe secondary damage, even death

Traumatic brain injuries affect more than 2.5 million people in in U.S. each year

Could be first line treatment for professional and young athletes

CHICAGO --- After a traumatic brain injury, the most harmful damage is caused by secondary swelling of the brain compressed inside the skull. There is no treatment for this.

In new research, Northwestern Medicine scientists were able to significantly reduce brain swelling and damage after a traumatic brain injury by injecting nanoparticles into the bloodstream within two hours after the injury, they report in a preclinical study.

"The results are vastly better than we predicted," said Dr. Jack Kessler, professor of neurology at Northwestern University Feinberg School of Medicine and senior author on the paper. "We believe this may provide the first real and practical treatment for people who have a significant traumatic brain injury."

The study will be published Jan. 22 in Annals of Neurology.

The nanoparticles are made of an FDA-approved material table and could easily be loaded into a syringe and given immediately after traumatic brain injury in the field by emergency medical technicians or in the emergency room to prevent secondary damage, Kessler noted.

The scientists have begun first steps to obtain FDA approval for a clinical trial.

Traumatic brain injuries affect approximately 2.5 million people in in U.S. each year, according to a 2010 Centers for Disease Control report. However, these numbers don't account for individuals who did not receive medical care, had outpatient care or who received care at a federal facility, such as persons serving in the U.S. military. Soldiers who serve in the U.S. military are at high risk for traumatic brain injury.

After a traumatic brain injury, the body launches an inflammatory reaction that triggers a cascade of immune responses that result in brain swelling.

"A patient can come into the emergency department walking and talking but then their brain swells. They immediately go downhill and can die," Kessler said. "Now, the only thing a surgeon can do is open the skull up to relieve the pressure, but the brain still continues to swell."

How nanoparticles prevent dangerous swelling

The nanoparticles work as a decoy to distract the immune cells from charging into the brain and causing more damage. The particles, named IMPS for immune modifying nanoparticles, are merely empty shells and do not contain any drugs or cargo.

After a traumatic brain injury, a specific population of monocytes -- large white blood cells -- rush to the injury site and attempt to clean up debris from damaged brain cells and secrete inflammatory proteins that stimulate other immune cells. This immune cascade produces swelling and inflammation that inadvertently damages surrounding healthy brain tissue.

But when the scientists inject the nanoparticles into the bloodstream shortly after the injury, these monocytes are tricked into thinking the nanoparticles are invading foreign materials. They engulf the particles and usher them to the spleen for disposal. The distracted monocytes are no longer around to enter the brain and cause problems.

In the study, mice that received the nanoparticles after a traumatic brain injury had greatly reduced swelling and half the damage to brain tissue compared to those who did not receive the nanoparticles. One of the injury models mimicked a closed head traumatic brain injury common in humans. In that model, the animals' motor and visual function improved after the nanoparticle injection.

"We predicted there would be an effect, but the effect turned out to be quite startling. It is remarkable how well the animals do," said lead author Sripadh Sharma, a Feinberg MD-PhD student.

Sharma, who is doing his neurology rotation, sees potential for helping young and professional athletes as well as soldiers. "These particles selectively knock out the damaging cells that begin infiltrating the brain within a couple hours of the injury and reach their peak in three days. We can intervene before the secondary damage begins."

Northwestern scientist Stephen Miller originally co-developed the nanoparticles to introduce food allergens to the immune system to create tolerance in food allergies. The microparticles also were used to treat multiple sclerosis by introducing myelin to the immune system to reduce its reactivity to it.

Nanoparticles for heart attack, colitis and West Nile Encephalitis virus

Then, in a 2014 Science Translational Medicine paper, Miller noted the microparticles prevented death in mice infected with West Nile Encephalitis virus. That led to the work in other models of acute inflammation including heart attack, colitis and peritonitis. Mostly recently, Miller began collaborating with Kessler, whose research focus is brain and spinal cord injury.

Credit: 
Northwestern University

Potential way to halt blinding macular degeneration identified

image: Researcher Brad Gelfand has discovered an unexpected connection between the two main forms of age-related macular degeneration (AMD).

Image: 
Dan Addison | UVA Communications

Researchers have successfully treated age-related macular degeneration (AMD) in mice after finding an unexpected link between the two main forms of the blinding eye disease, the leading cause of vision loss in people 60 and older.

Researcher Brad Gelfand, PhD, of the University of Virginia School of Medicine and the UVA School of Engineering, cautions that his team is far from being able to use the approach in patients with AMD, but he is excited about the potential it holds. "It's not as if this is the final answer to the problem, but it's certainly a big step along the way, hopefully," he said.

'Equal Parts Excitement and Disbelief'

The new discovery links the "dry" and "wet" forms of macular degeneration in a surprising way. Gelfand has focused primarily on the more common, and currently untreatable, dry form. But after making a discovery about dry AMD, he went on to determine that the finding held true for wet AMD as well. "It was almost chance - we were like, 'Why don't we just go ahead and look for wet?' When we first saw the results, I was very surprised," he said. "Initially, it was equal parts excitement and disbelief."

Gelfand, of UVA's Center for Advanced Vision Science, found that the absence of a particular enzyme could drive both forms of AMD. The enzyme, called Dicer, is lost with age, and that loss leads to an overgrowth of blood vessels in the retina and other damage, he and his team determined.

The discovery was so unexpected he wanted to confirm. "We weren't really satisfied with just one system," he said. "We actually got a different model that had originated from a totally different lab, in Japan, and found the same exact thing. Then we went back to some of our old models where we had gotten rid of Dicer and found the same exact thing."

An Enzyme to Stop Macular Degeneration

Gelfand was able to restore the enzyme in mice by adapting a form of gene therapy already used to treat other eye diseases in people. His work suggests that a similar approach could treat both forms of AMD, but much more testing will need to be done to determine a potential treatment's safety and effectiveness. If successful, though, it would be the first treatment for dry age-related macular degeneration and could significantly improve treatment for wet AMD.

"As it stands, patients with [wet] AMD have to undergo frequent injections into their eye, which can be painful and comes with some risks. They have to come to the eye doctor once a month or every other month. A lot of these people can't drive. So it's a huge burden," he said. "The idea behind using gene therapy like the one we propose is that one treatment would last for a very long time. It's a sustained therapy. So we can improve their vision and reduce the number of doctor's visits they have to make."

Developing a Dicer-based treatment will likely take several years if all goes well. For now, though, Gelfand's discovery has shed important light on the poorly understood relationship between the two forms of AMD. "It certainly solidifies the idea that wet and dry AMD share a lot of mechanisms," he said. "It's something that researchers today are still trying to grapple with - why might one person have wet AMD and one person have dry. Sometimes it's the case that the same person has wet in one eye and the other eye has dry. Sometimes the same eye has both. This adds another important piece of evidence that the underlying mechanisms of these two processes are really tightly linked."

AMD Findings Published

The researchers have described their findings in an article in the scientific journal Proceedings of the National Academy of Sciences (PNAS). The research team consisted of Charles B. Wright, Hironori Uehara, Younghee Kim, Tetsuhiro Yasuma, Reo Yasuma, Shuichiro Hirahara, Ryan D. Makin, Ivana Apicella, Felipe Pereira, Yosuke Nagasaka, Siddharth Narendran, Shinichi Fukuda, Romulo Albuquerque, Benjamin J. Fowler, Ana Bastos-Carvalho, Philippe Georgel, Izuho Hatada, Bo Chang, Nagaraj Kerur, Balamurali K. Ambati, Jayakrishna Ambati and Gelfand.

Credit: 
University of Virginia Health System

Americans perceive likelihood of nuclear weapons risk as 50/50 tossup

It has been 30 years since the end of the Cold War, yet, on average, Americans still perceive that the odds of a nuclear weapon detonating on U.S. soil is as likely as a coin toss, according to new research from Stevens Institute of Technology.

"That's exceptionally high," said Kristyn Karl, a political scientist at Stevens who co-led the work with psychologist Ashley Lytle. "People don't generally believe that highly rare events are slightly less likely than a 50/50 tossup."

The finding, reported in the January 2020 issue of International Journal of Communication, represents the end of a decades long gap in the research literature on Americans' perceptions on nuclear weapons threat. It also provides an initial look at how younger generations, namely Millennials and Gen Z (18-37 years old), think about the topic and what influences their behavior in an era of evolving nuclear threat.

Using their combined expertise in political science and psychology, Karl and Lytle fielded two nationally diverse online surveys totaling more than 3,500 Americans to measure individual characteristics and attitudes, such as perceptions of nuclear risk, apathy toward nuclear topics, media use, and interest in following current events.

They also analyzed how these characteristics and attitudes such as perceptions of nuclear risk influence behaviors, including the likelihood of seeking information and initiating conversations about nuclear topics, as well as preparing emergency kits in the event that the worst were to happen.

The ultimate goal of the work, which is part of the larger Reinventing Civil Defense project supported by the Carnegie Corporation of New York, is to learn more about how to best develop new communication tools to increase awareness among Americans about topics related to nuclear weapons, particularly what to do in the event of a nuclear detonation.

"The overarching narrative from the Reinventing Civil Defense project is that younger Americans just don't hear anything about nuclear weapons risk," said Karl. "Unlike older Americans, Millennials and Gen Z didn't grow up during the Cold War, so what they know about nuclear risk is what's in the media, and what's in the media isn't necessarily reflective of the true state of affairs."

And media use matters.

Karl and Lytle find that consuming media has a striking effect on how younger and older adults think about topics related to nuclear weapons, especially as it relates to apathy. Specifically, as younger generations report using more media, they are increasingly likely to report being apathetic about nuclear topics.

But this pattern is different for older adults, as there is no association between their media use and their willingness to think about nuclear threats or how to survive them. In terms of behavior, apathy about nuclear topics is associated with a decrease in seeking information on the issue.

Interestingly, as Americans age, the lower they estimate the likelihood of a nuclear detonation in their lifetime. "Among lots of possibilities, they may be thinking if it didn't happen during the Cold War, it won't happen now; or perhaps I have fewer years to live, so it probably won't happen in my lifetime," said Lytle. However, older adults and those who tend to more closely follow the news tend to seek more information about nuclear topics.

Broadly, perceptions of nuclear weapons risk prove powerful as they lead Americans and take various actions to prepare in the event of a nuclear attack. On average, city dwellers estimate the risk as 5-7% higher than their rural or suburban peers whereas women estimate nuclear risk as 3-5% higher than men. Since men report significantly higher levels of media use and more closely following current events, this research presents several opportunities for targeting messages based on these varying perceptions.

One pattern is clear: as perception of nuclear weapons risk increases, so too does Americans' intent to take action and that's true across multiple measures, whether it putting forward effort to think and plan for it, seeking information about it, communicating with others on the topic, or taking steps to prepare for an attack.

Karl and Lytle explain that many people are fatalistic: if a nuclear weapon were to go off in New York City, then we would all be dead, 'so why should I put any effort forward in thinking about it?'

Karl explains that the size of the weapon, the location, and even the weather, are important. In cities, for example, many nuclear weapons detonations would be funneled upward by tall buildings and modeling suggests that many people could survive. The most important thing people could do is get inside a building and stay there for three days.

"Our gut reaction is that everybody would die. But not everybody," said Lytle. "We are trying to figure out how to educate people that this is not always true so that people feel like they have some sort of agency in a situation like this. Many people could survive the initial blast and then their subsequent behavior would determine what happens from there."

While Lytle and Karl emphasize that they don't wish to make claims about the actual degree of nuclear weapons risk, they maintain that perceptions of this risk are crucially important. Even if we assume the risk is low in the real world, it could be life-saving for Americans to know just a small amount about what you should do.

Credit: 
Stevens Institute of Technology

New method to enable the production of cheaper, longer-lasting vaccines

A new method to produce vaccines that have a longer shelf-life, are cheaper and can be stored without the need for cooling is being presented in the open access journal BMC Biotechnology.

Vaccines currently need to be refrigerated during transport and storage and have a short shelf-life, in some cases as little as a few months. This can be a problem in low-income countries and remote areas with no electricity. Some vaccines also rely on additional pharmacological or immunological substances, called adjuvants, to boost their desired immune response, which may have unwanted side-effects, such as allergies.

Luis Vaca, at Universidad Nacional Autonoma de Mexico, the corresponding author said: "The vaccines that are currently available require constant cold storage, meaning they rely on a temperature-controlled supply chain, which constitutes over 80% of their cost. We have developed a novel technology to produce vaccines which require no refrigeration and have a shelf life of many years. These vaccines could be transported to regions of the world without electricity and refrigeration."

Vaca and a team of researchers adapted a strategy used by insect viruses that allows them to survive outside of their host for extended periods of time. A key component of this strategy is a protein known as polyhedrin that forms crystals around the virus, protecting it from the environment. Previous research by the authors showed that a short sequence of the first 110 amino acids that make up polyhedrin (PH(1-110)) maintains the ability of the full length protein to form crystals, even when other proteins, including viruses, are attached to it.

Combining part of porcine circovirus, which can cause disease in pigs, with PH(1-110) has been shown to prompt the production of antibodies in vaccinated pigs. However, the exact characteristics of the particles that form after combining PH(1-110) and a virus, including thermostability (the ability to withstand heat), have not been investigated, and neither has the strength of a possible immune response.

To investigate these characteristics and the possible usefulness of PH(1-110) as a vaccine carrier, the authors combined PH(1-110) with the green fluorescent protein (GFP), which normally generates a weak immune response. Once PH(1-110) had formed polyhedrin crystals around the protein, the authors injected mice with the PH(1-110)GFP crystals to evaluate the immune response.

They found that mice injected with PH(1-110)GFP produced anti-GFP antibodies and showed a strong immune response, similar to one observed in mice injected with GFP and an adjuvant. As GFP on its own does not create a strong immune response, an adjuvant would normally be needed. Anti-GFP antibodies remained in the blood of vaccinated mice after 24 weeks, indicating the production of a lasting immune response.

The authors also found that PH(1-110)GFP particles stored as dry powder at room temperature still generated antibodies when they were used to vaccinate mice after up to twelve months of storage. The results suggest that PH(1-110) could enable the production of thermostable vaccines that generate a sufficient immune response without the need for an adjuvant, or refrigeration.

Luis Vaca said: "As PH(1-110) could be paired with any protein, our technology opens up the possibility of reducing the cost of conservation and distribution of vaccines by about 80% - the cost of the temperature-controlled supply chain. Pharmaceutical companies could maintain their profits, but the consumer would pay less, reducing the cost of vaccination in low-income countries significantly."

Credit: 
BMC (BioMed Central)

Cultural difference play crucial role in when people would sacrifice one to save group

Cultural differences play a pivotal role in how people in different parts of the world perceive when it is acceptable to sacrifice one person to save a larger group, new research has shown.

An innovative new research, led by Edmond Awad from the University of Exeter's Business School, looked at how people on different continents reacted to a new version of the famous ethical thought experiment, known as the "trolley dilemma".

It found that those in more traditional communities, such as those in Asia, were less inclined to support sacrificing someone to save more lives.

The results could have serious implications for the development of Artificial Intelligence, such as driverless cars, and the future of ethical programming.

The study is published in Proceedings of the National Academy of Sciences.

Dr Edmond Awad, from Exeter's Business School said: "Sacrificial dilemmas provide a useful tool to study and understand how the public want driverless cars to distribute unavoidable risk on the road."

The 'Trolley Dilemma' is an ethical thought experiment where there is a runaway trolley moving down railway tracks. In its path, there are five people tied up and unable to move and the trolley is heading straight for them.

People are told that they are standing some distance off in the train yard, next to a lever. If they pull this lever, the trolley will switch to a different set of tracks - but will kill one person who is standing on the side track.

The people have the option to either do nothing, and allow the trolley to kill the five people on the main track, or pull the lever, diverting the trolley onto the side track where it will kill one person.

The results showed that, overridingly, people in Europe, Australia and the Americas were more willing than those in eastern countries to switch the track, or to sacrifice the man, to save more lives

In Eastern countries such as China, Japan and Korea, there were far lower rates of people likely to support this 'morally questionable' view.

In traditional communities, where people may stay in close, small communities where it is hard to form new relationships, they don't want to alienate their current connections by suggesting they would sacrifice someone, expert suggest.

In western countries, where it is easier to move on and find new social groups if someone disagrees with you, people may find it easier to voice, or think, such thoughts.

The study asked 70,000 people across 42 countries the ethical dilemma - one of the largest studies of its type.

Overall, 81 per cent were willing to switch the carriage to a separate train track to kill one person instead of five, and half would throw a man off a footbridge on to the tracks to spare five.

Dr Awad said these results could offer a pivotal new impetus in the development of ethical programming, for AI including driverless cars.

He said that, policymakers would have to take into consideration how local ethics differed across the world, when regulating future programming.

Dr Award added: It's hard to see from now whether these cross-country differences are big enough to require different rules for machines in different countries, but the results suggest that it's worth further investigation.

Credit: 
University of Exeter