Virginia Commonwealth University

Three-dimensional carbon goes metallic.

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A theoretical, three-dimensional (3D) form of carbon that is metallic under ambient temperature and pressure has been discovered by an international research team.

The findings, which may significantly advance carbon science, are published online this week in the Early Edition of the Proceedings of the National Academy of Sciences.

3-dimensional carbon goes metallic

Carbon science is a field of intense research. Not only does carbon form the chemical basis of life, but it has rich chemistry and physics, making it a target of interest to material scientists. From graphite to diamond to Buckminster fullerenes, nanotubes and graphene, carbon can display in a range of structures.

But the search for a stable three-dimensional form of carbon that is metallic under , including temperature and pressure, has remained an ongoing challenge for scientists in the field.

Researchers from Peking University, Virginia Commonwealth University and Shanghai Institute of Technical Physics employed state-of-the-art theoretical methods to show that it is possible to manipulate carbon to form a three-dimensional metallic phase with interlocking hexagons.

“The interlocking of hexagons provides two unique features – hexagonal arrangement introduces metallic character, and the interlocking form with tetrahedral bonding guarantees stability,” said co-lead investigator Puru Jena, Ph.D., distinguished professor of physics in the VCU College of Humanities and Sciences.

The right combination of these properties could one day be applied to a variety of technologies.

“Unlike high-pressure techniques that require three terapascals of pressure to make carbon metallic, the studied structures are stable at ambient conditions and may be synthesized using benzene or polyacenes molecules,” said co-lead investigator Qian Wang, Ph.D., who holds a professor position at Peking University and an adjunct faculty position at VCU.

“The new metallic  structures may have important applications in lightweight metals for space applications, catalysis and in devices showing negative differential resistance or superconductivity,” Wang said.

According to Jena, the team is still early in its discovery process, but hope that these findings may move the work from theory to the experimental phase.

The study is titled, “Three-dimensional Metallic Carbon: Stable Phases with Interlocking Hexagons.”

Brain Researchers Discover How Retinal Neurons Claim the Best Connections

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Discovery may shed light on brain disease, development of regenerative therapies

Real estate agents emphasize location, location, and – once more for good measure – location. It’s the same in a developing brain, where billions of neurons vie for premium property to make connections. Neurons that stake out early claims often land the best value, even if they don’t develop the property until later.

Scientists at the Virginia Tech Carilion Research Institute and the University of Louisville have discovered that during neurodevelopment, neurons from the brain’s cerebral cortex extend axons to the edge of the part of the brain dedicated to processing visual signals – but then stop. Instead of immediately making connections, the cortical neurons wait for two weeks while neurons from the retina connect to the brain.

Now, in a study to be published in the Nov. 14 issue of the journal Cell Reports, the scientists have discovered how. The retinal neurons stop their cortical cousins from grabbing prime real estate by controlling the abundance of a protein called aggrecan.

Understanding how aggrecan controls the formation of brain circuits could help scientists understand how to repair the injured brain or spinal cord after injury or disease.

“Usually when neuroscientists talk about repairing injured brains, they’re thinking about putting neurons, axons, and synapses back in the right place,” said Michael Fox, an associate professor at the Virginia Tech Carilion Research Institute and lead author of the study. “It may be that the most important synapses – the ones that drive excitation – need to get there first. By stalling out the other neurons, they can get the best spots. This study shows that when we think about repairing damaged neural networks, we need to consider more than just where connections need to be made. We also need to think about the timing of reinnervation.”

The researchers genetically removed the retinal neurons, which allowed the cortical axons to move into the brain earlier than they normally would.

“We were interested in what environmental molecular cues allow the retinal neurons to control the growth of cortical neurons,” said Fox, who is also an associate professor of biological sciences in Virginia Tech’s College of Science. “After years of screening potential mechanisms, we found aggrecan.”

Aggrecan is a protein that has been well studied in cartilage, bones, and the spinal cord, where it is abundant after injuries. According to Fox, aggrecan may be able to isolate damaged areas of the spinal cord to stop inflammation and prevent further destruction. The downside, however, is that aggrecan inhibits axonal growth, which prevents further repair from taking place.

“Axons see this environment and either stop growing or turn around and grow in the opposite direction,” said Fox.

Although it is less studied in the developing brain, aggrecan appears in abundance there. In the new study, the researchers found that retinal neurons control aggrecan in a region that receives ascending signals from retinal cells as well as descending signals from the cerebral cortex.

Once the retinal neurons have made connections, they cause the release of enzymes that break down the aggrecan, allowing cortical neurons to move in.

Fox said it is interesting that the retinal axons can grow in this region of the developing brain, despite the high levels of aggrecan. He suspects that it may be because retinal neurons express a receptor – integrin – that cortical axons do not express.

The study, “A molecular mechanism regulating the timing of corticogeniculate innervation,” is by Fox, Jianmin Su, a research assistant professor, and Carl Levy, an undergraduate from Suffolk, Va., all with the Virginia Tech Carilion Research Institute; graduate student Justin Brooks and undergraduate Jessica Wang from Virginia Commonwealth University; and Tania Seabrook, a postdoctoral associate, and William Guido, a professor and the chair of the Department of Anatomical Sciences and Neurobiology, both with the University of Louisville School of Medicine.

New tools automatically match patients with clinical trials.

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The majority of Americans—72%—say they would take part in a clinical trial recommended by their doctor, according to a survey released last month by the Alexandria, Virginia-based science advocacy group Research!America. Despite that enthusiasm, though, there’s a shortage of enrollment. According to US government estimates, only about 3% of patients with advanced cancer enroll in phase 1 trials. Part of the problem, experts believe, comes down to a lack of awareness: the general public doesn’t know about investigational trials, and few physicians discuss the option with their patients.

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New tools unveiled this year that automatically prescreen patients for trials based on their electronic medical records and email matches to doctors could help solve the problem. “We’ve needed these kinds of tools for a long time,” says Eric Topol, a cardiologist and director of the Scripps Translational Science Institute in La Jolla, California. “Physicians are really busy, and there are so many clinical trials that no human could track them all.”

The US federal registry, ClinicalTrials.gov, currently lists more than 145,000 trials in all 50 states, as well as 184 foreign countries. Wading through those listings is a daunting task for individuals interested in signing up for a study, assuming that they know of the resource to begin with. Ultimately, problems with patient recruitment delay clinical trials by 4.6 months, on average, according to the Center for Information and Study on Clinical Trial Research Participation, a nonprofit organization in Boston. That holdup means it takes longer for treatments to reach the market.

To increase enrollment, some patient-advocacy groups have started playing matchmaker. A year ago, the Michael J. Fox Foundation for Parkinson’s Research launched the Fox Trial Finder, a web portal designed to help pair people with Parkinson’s with clinical studies (see Nat. Med. 18, 837,2012). The Alzheimer’s Association’s TrialMatch, meanwhile, has been up and running since 2010. Anyone can register online or by phone and see if he or she—or a patient or loved one—is a good fit for any of the 153 trials in 621 locations. To date, there have been 11,166 referrals, says Heather Snyder, the Chicago-based association’s director of medical and scientific operations.

In addition to the Fox Trial Finder and TrialMatch, for-profit companies have unveiled web portals to link people with studies. New York’s EmergingMed helps connect individuals with cancer trials, and in late May, Michigan-based CureLauncher unveiled a clinical-trial-matching service for a range of disorders. But tools such as these rely on the gumption of patients and doctors to wade through web listings. A new wave is emerging of automated tools that do away with the need for patients or physicians to manually enter information.

On alerts

Earlier this year, the Virginia Commonwealth University’s Massey Cancer Center in Richmond unveiled two new tools that work with its Clinical Trials Eligibility Database, which stores information about patients and clinical trials at the center. Since February, its MD Alert Notification System has automatically prescreened the list of scheduled patients each morning and emailed physicians when it finds that one of those individuals is eligible for one or more of 75 open trials at the center.

“If the patient is interested, one click by the physician refers them to the research nurse associated with that trial,” says Lynne Penberthy, director of the Massey Cancer Center’s informatics core who oversees the tracking and matching tools. Another new computer application there, the Automated Matching Tool, has been available since January. It screens all patients in the system on a scheduled basis, not just those coming in for a visit.

An algorithm known as Trial Prospector offers even greater automation for clinical trial enrollment. In a pilot study presented at last month’s American Society of Clinical Oncology meeting in Chicago, the program reached into the medical records of 60 people with gastrointestinal cancer who had scheduled appointments at the University Hospitals Seidman Cancer Center of the Case Comprehensive Cancer Center in Cleveland, Ohio. It pulled out 15 pieces of information—including age, diagnosis and blood count—that it compared to eligibility criteria of the 300-plus trials in Cases’s database. It then emailed doctors lists of any matches, and it also shows the studies for which the patient didn’t qualify and explains why; for example, some factors, such as low red blood cell count, might be easily fixed with a transfusion. The algorithm was 100% accurate, and 11% of the patients ended up enrolling in a trial suggested to the doctor by the algorithm.

“In theory this could be readily adapted anywhere, but we’ve still got a long way to go,” says Neal Meropol, associate director for clinical research at the Case Comprehensive Cancer Center. His team plans to refine Trial Prospector over the next 6 to 12 months, expand it to other cancers, and test it in a community-practice setting, where physicians aren’t highly specialized and may not have as much knowledge of open trials.

Penberthy similarly sees automated trial matching tools as a way to reach a more diverse set of participants. “We’re hoping that this is going help increase the equity,” she says. “It may help to increase minority patients enrolled in clinical trials,” an underrepresented population.

Topol, who isn’t involved with the programs, says that although automated matching programs are in their infancy, “eventually they could build something that’s extraordinary.”

Source: Nature