Restless legs syndrome gets a real starting point for potential treatments

via The JAMA Network

New research published in the Journal of Physiology presents a breakthrough in the treatment of Restless Legs Syndrome (RLS).

RLS is a common condition of the nervous system that causes an overwhelming irresistible urge to move the legs. Patients complain of unpleasant symptoms such as tingling, burning and painful cramping sensations in the leg. More than 80% of people with RLS experience their legs jerking or twitching uncontrollably, usually at night.

Until now it was thought that RLS is caused by genetic, metabolic and central nervous system mechanisms. For the first time the researchers show that, in fact, it is not only the central nervous system but also the nerve cells targeting the muscles themselves that are responsible.

This new research indicates that the involuntary leg movements in RLS are caused by increased excitability of the nerve cells that supply the muscles in the leg, which results in an increased number of signals being sent between nerve cells.

Targeting the way messages are sent between nerve cells to reduce the number of messages to normal levels may help prevent the symptoms of RLS occurring. This could be achieved by new drugs that block the ion channels that are essential for the communication between nerve cells.

The research conducted by the University of Gottingen in conjunction with the University of Sydney and Vanderbilt University involved measuring the nerve excitability of motor nerve cells of patients suffering with RLS and healthy subjects.

The next step is to investigate the effect of different medications in patients and the effect on RLS.

Dirk Czesnik, corresponding author of the study, commented on the findings:

‘Patients who suffer from Restless legs syndrome complain of painful symptoms in the legs leading to sleep disturbances. The mechanisms for RLS are still not completely understood. We have shown that also the nerve cells supplying muscles in the leg are responsible and hereby additional drug treatments may be ahead targeting these nerve cells.’

Learn more: Breakthrough in treatment of restless legs syndrome

 

 

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Imagine a box you plug into the wall that cleans your toxic air and pays you cash

Small diameter carbon nanotubes grown on a stainless steel surface. (Pint Lab/Vanderbilt University)

Imagine a box you plug into the wall that cleans your toxic air and pays you cash.

That’s essentially what Vanderbilt University researchers produced after discovering the blueprint for turning the carbon dioxide into the most valuable material ever sold – carbon nanotubes with small diameters.

Carbon nanotubes are supermaterials that can be stronger than steel and more conductive than copper. The reason they’re not in every application from batteries to tires is that these amazing properties only show up in the tiniest nanotubes, which are extremely expensive. Not only did the Vanderbilt team show they can make these materials from carbon dioxide sucked from the air, but how to do this in a way that is much cheaper than any other method out there.

These materials, which Assistant Professor of Mechanical Engineering Cary Pint calls “black gold,” could steer the conversation from the negative impact of emissions to how we can use them in future technology.

“One of the most exciting things about what we’ve done is use electrochemistry to pull apart carbon dioxide into elemental constituents of carbon and oxygen and stitch together, with nanometer precision, those carbon atoms into new forms of matter,” Pint said. “That opens the door to being able to generate really valuable products with carbon nanotubes.

“These could revolutionize the world.”

Anna Douglas (Vanderbilt University)

In a report published today in ACS Applied Materials and Interfaces, Pint, interdisciplinary material science Ph.D. student Anna Douglas and their team describe how tiny nanoparticles 10,000 times smaller than a human hair can be produced from coatings on stainless steel surfaces. The key was making them small enough to be valuable.

“The cheapest carbon nanotubes on the market cost around $100-200 per kilogram,” Douglas said. “Our research advance demonstrates a pathway to synthesize carbon nanotubes better in quality than these materials with lower cost and using carbon dioxide captured from the air.”

But making small nanotubes is no small task. The research team showed that a process called Ostwald ripening — where the nanoparticles that grow the carbon nanotubes change in size to larger diameters — is a key contender against producing the infinitely more useful size. The team showed they could partially overcome this by tuning electrochemical parameters to minimize these pesky large nanoparticles.

This core technology led Pint and Douglas to co-found SkyNano LLC, a company focused on building upon the science of this process to scale up and commercialize products from these materials.

“What we’ve learned is the science that opens the door to now build some of the most valuable materials in our world, such as diamonds and single-walled carbon nanotubes, from carbon dioxide that we capture from air through our process,” Pint said.

Learn more: “These could revolutionize the world” — Pint cracks code to cheap, small carbon nanotubes

 

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Getting much closer to a revolutionary battery to power renewable energy industry

The prototype battery features high-power output and high-conversion efficiency. Credit: Courtesy of Trung van Nguyen.

Any resident of the Great Plains can attest to the massive scale of wind farms that increasingly dot the countryside. In the Midwest and elsewhere, wind energy accounts for an ever-bigger slice of U.S. energy production: In the past decade, $143 billion was invested into new wind projects, according to the American Wind Energy Association.

However, the boom in wind energy faces a hurdle — how to effectively and cheaply store energy generated by turbines when the wind is blowing, but energy requirements are low.

“We get a lot of wind at night, more than at daytime, but demand for electricity is lower at night, so, they’re dumping it or they lock up turbines —  we’re wasting electricity,” said Trung Van Nguyen, professor of petroleum & chemical engineering at the University of Kansas. “If we could store this excess at night and sell or deliver it during daytime at peak demand, this would allow wind farm owners to make more money and leverage their investment. At the same time, you deploy more wind energy and reduce demand for fossil fuels.”

Since 2010, Nguyen has headed research to develop an advanced hydrogen-bromine flow battery, an advanced industrial-scale battery design — it would be roughly the size of a semi-truck — that engineers have strived to develop since the 1960s. It could work just as well to store electricity from solar farms, to be discharged overnight when there’s no sun.

Funded first by the National Science Foundation and later by the Advanced Research Projects Agency-Energy, Nguyen has worked with researchers from the University of California at Santa Barbara, Vanderbilt University, the University of Texas at Arlington and Case Western Reserve University.  Along the way, Nguyen has overseen breakthrough work on key components of hydrogen-bromine battery design.

For one, there’s the electrode Nguyen developed at KU. A battery’s electrode is where the electrical current enters or leaves the battery when it’s discharged. To be maximally efficient, an electrode needs a lot of surface area. Nguyen’s team has developed a higher-surface-area carbon electrode by growing carbon nanotubes directly on the carbon fibers of a porous electrode.

“Before our work, people used paper-carbon electrodes and had to stack electrodes together to generate high-power output,” he said. “The electrodes had to be a lot thicker and more expensive because you had to use multiples layers — they were bulkier and more resistive. We came up with a simple but novel idea to grow tiny carbon nanotubes directly on top of carbon fibers inside of electrodes — like tiny hairs — and we boosted the surface area by 50-70 times.  We solved the high-surface requirement for hydrogen-bromine battery electrodes.”

A key issue remaining before a hydrogen-bromide battery can be marketed successfully is the development of an effective catalyst to accelerate the reactions on the hydrogen side of the battery and provide higher output while surviving the extreme corrosiveness in the system. Now, with funding from an NSF sub-award through a private company called Proton OnSite, Nguyen is verging on solving this last barrier.

“I think we’re on the verge of a real breakthrough,” he said. “We need a durable catalyst, something that has the same activity as the best catalyst out there, but that can survive this environment. Our previous material didn’t have sufficient surface area to give enough power output. But I’ve been able to continue to work on this rhodium sulfide catalyst. I think we’ve figured out a way to increase surface area. We now have a better way, and we may publish that in three to six months — we have some minor issues to resolve, but I think we’ll have a suitable material for the hydrogen reaction in this system.”

The new results to develop an industrial scale advanced hydrogen-bromine flow battery will be presented at the meeting of the Electrochemical Society in Seattle this May.

Indeed, Nguyen — who has founded several startup companies over his research career — noted the new hydrogen-bromine battery soon could be commercialized, and easily could be scaled to MW (power) MWh (energy) scales, coming in modular container form, about 1MWh in a full-size container. But he cautioned it could only be used in remote, industrial sites — places like wind and solar farms, where the huge batteries likely would be buried underground.

“This energy storage system, because of its corrosiveness, isn’t suitable for residential or commercial systems,” he said. “Bromine is like chlorine gas. Dig a hole, line it with cement or plastic, drop this battery down and cover it up — it should be in an enclosed or sealed system to prevent leakage or emission of bromine gas. This will be suitable only for large-scale remote energy storage like solar farms and wind farms.”

The KU researcher said the rise of renewable energy would depend on technology breakthroughs that make the economics attractive to energy producers and investors, and he hoped his new battery design could play a part.

“The way we use fossil fuel for energy is very inefficient, wasteful and generates greenhouse gasses,” Nguyen said. “For fossil fuels, you make the initial investment, and also you pay for operation every day — pay for coal or for natural gas for rest of the life of the power plant. Once you make the initial investment in renewable, the electricity you make is free.”

Learn more: Research gets closer to producing revolutionary battery to power renewable energy industry

 

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Hijacking human proteins to better deliver anti-cancer drugs

This microscopy photo demonstrates penetration of a fluorescent-labeled siRNA-L2 vs. synthetic nanoparticles into a three-dimensional tumor sample. (Vanderbilt University)

Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Their research gives oncologists a better shot at overcoming the problems of drug resistance, toxicity to patients and a host of other barriers to consistently achieving successful gene therapy for cancer. It is particularly promising for patients with triple-negative breast cancer, an aggressive type that makes up about 15-20 percent of cases.

Craig Duvall, associate professor of biomedical engineering (Steve Green/Vanderbilt)

Craig Duvall, associate professor of biomedical engineering (Steve Green/Vanderbilt)

Craig Duvall, associate professor of biomedical engineering, put the effectiveness of a specialized ribonucleic acid hitchhiking on the human protein albumin up against jetPEI nanoparticles, the mostly widely used synthetic carrier for the task of tumor gene silencing.

His findings, reached with Samantha Sarett, a recent biomedical engineering Ph.D. graduate, are published today (Monday, July 24) in the Proceedings of the National Academy of Sciences.

Albumin is ‘Trojan horse’

Ribonucleic acids can control the behavior of cancer cells, but they require a carrier to get them to the target. Duvall’s team made a simple modification to a small-interfering ribonucleic acid molecule, called siRNA-L2, allowing it to rapidly load into an albumin pocket typically reserved to ferry fatty acids around the body.

They found that the siRNA-L2, using albumin as its carrier, has no apparent dose-limiting toxicity, a significant problem for synthetic nanoparticles. That means a higher dose of the anti-cancer drug can be delivered to the tumor without potentially harming the patient.

“Albumin serves almost like a Trojan Horse where it carries it throughout the blood keeps it in the bloodstream for a longer period of time,” said Duvall.

“We used albumin because it’s the highest-concentrated protein in your blood,” he said. “Our molecule, siRNA-L2, binds into the fatty acid pocket of albumin. If we put siRNA directly into the body without a carrier, it’s cleared out by the kidneys in two minutes. If we load siRNA into synthetic nanoparticles to avoid that, then they’re filtered out by the liver. Albumin circulates in the body for days, making the siRNA-L2 molecules more available for delivery into tumors.”

Because cancer cells show higher metabolic activity, the albumin that’s carrying siRNA-L2 travels to tumors and gets to work quickly. The molecule’s smaller size allows it to penetrate tumors at a higher rate – with 100 percent of tumor cells testing positive for siRNA-L2 as opposed to only 60 percent when the molecule was carried by jetPEI. Once there, Duvall’s molecule silences a gene crucial to the tumor’s growth and survival.

He said he used the synthetic carrier as a comparison because polymer-based jetPEI represents the gold standard available.

Tested on human tissue

To make sure their results were translatable to human therapy, the team – in collaboration with Vanderbilt University Medical Center cancer biologist Dana Brantley-Sieders — tested siRNA-L2 in human breast tumor tissue removed from the donor. The Vanderbilt molecule remained more effective, with siRNA-L2 more than three times as present in the tumor than siRNA delivered with synthetic nanoparticles.

Brantley-Sieders said their research has the potential of overcoming the biggest barriers to clinical application of gene-silencing ribonucleic acids.

“What fascinates and excites me most about this approach, in addition to improved tumor penetration, is lack of toxicity at a relatively high dose,” she said. “We could potentially use our siRNA delivery system to target several genes simultaneously or sequentially. Most cancers are driven by multiple abnormal genes, so targeting one often leads to activation of others as the tumor adapts.”

Learn more: Molecular hitchhiker on human protein signals tumors to self-destruct

 

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Ultrathin energy harvesting device so thin it can be embedded in clothing

Transmission electron microscope image showing the ultrathin layers of black phosphorus used in the energy harvesting device An angstrom (Å) is about the width of a single atom and is one tenth of a nanometer (nm). (Nanomaterials and Energy Devices Laboratory / Vanderbilt)

Imagine slipping into a jacket, shirt or skirt that powers your cell phone, fitness tracker and other personal electronic devices as you walk, wave and even when you are sitting down.

A new, ultrathin energy harvesting system developed at Vanderbilt University’s Nanomaterials and Energy Devices Laboratory has the potential to do just that. Based on battery technology and made from layers of black phosphorus that are only a few atoms thick, the new device generates small amounts of electricity when it is bent or pressed even at the extremely low frequencies characteristic of human motion.

“In the future, I expect that we will all become charging depots for our personal devices by pulling energy directly from our motions and the environment,” said Assistant Professor of Mechanical Engineering Cary Pint, who directed the research.

The new energy harvesting system is described in a paper titled “Ultralow Frequency Electrochemical Mechanical Strain Energy Harvester using 2D Black Phosphorus Nanosheets” published Jul. 21 online by the journal ACS Energy Letters.

“This is timely and exciting research given the growth of wearable devices such as exoskeletons and smart clothing, which could potentially benefit from Dr. Pint’s advances in materials and energy harvesting,” observed Karl Zelik, assistant professor of mechanical and biomedical engineering at Vanderbilt, an expert on the biomechanics of locomotion who did not participate in the device’s development.

Graduate student Kathleen Moyer holds up the guts of the ultrathin energy harvesting device in a glove box. It is so thin it can be embedded in fabric. (John Russell / Vanderbilt)

Currently, there is a tremendous amount of research aimed at discovering effective ways to tap ambient energy sources. These include mechanical devices designed to extract energy from vibrations and deformations; thermal devices aimed at pulling energy from temperature variations; radiant energy devices that capture energy from light, radio waves and other forms of radiation; and, electrochemical devices that tap biochemical reactions.

“Compared to the other approaches designed to harvest energy from human motion, our method has two fundamental advantages,” said Pint. “The materials are atomically thin and small enough to be impregnated into textiles without affecting the fabric’s look or feel and it can extract energy from movements that are slower than 10 Hertz—10 cycles per second—over the whole low-frequency window of movements corresponding to human motion.”

“When you look at Usain Bolt, you see the fastest man on Earth. When I look at him, I see a machine working at 5 Hertz,”Doctoral students Nitin Muralidharan and Mengya Lico-led the effort to make and test the devices. “When you look at Usain Bolt, you see the fastest man on Earth. When I look at him, I see a machine working at 5 Hertz,” said Muralidharan.

Extracting usable energy from such low frequency motion has proven to be extremely challenging. For example, a number of research groups are developing energy harvesters based on piezoelectric materials that convert mechanical strain into electricity. However, these materials often work best at frequencies of more than 100 Hertz. This means that they don’t work for more than a tiny fraction of any human movement so they achieve limited efficiencies of less than 5-10 percent even under optimal conditions.

“Our harvester is calculated to operate at over 25 percent efficiency in an ideal device configuration, and most importantly harvest energy through the whole duration of even slow human motions, such as sitting or standing,” Pint said.

The Vanderbilt lab’s ultrathin energy harvester is based on the group’s research on advanced battery systems. Over the past 3 years, the team has explored the fundamental response of battery materials to bending and stretching. They were the first to demonstrate experimentally that the operating voltage changes when battery materials are placed under stress. Under tension, the voltage rises and under compression, it drops.

Graduate students Mengya Li and Nitin Muralidharan adjust the energy harvesting device on the arm of undergraduate Thomas Metke while Professor Cary Pint looks on. (John Russell / Vanderbilt)

The team collaborated with Greg Walker, associate professor of mechanical engineering, who used computer models to validate these observations for lithium battery materials. Results of the study were published Jun. 27 in the journal ACS Nano in an article titled “The MechanoChemistry of Lithium Battery Electrodes.”

These observations led Pint’s team to reconstruct the battery with both positive and negative electrodes made from the same material. Although this prevents the device from storing energy, it allows it to fully exploit the voltage changes caused by bending and twisting and so produce significant amounts of electrical current in response to human motions.

The lab’s initial studies were published in 2016. They were further inspired by a parallel breakthrough by a group at Massachusetts Institute of Technology who produced a postage-stamp-sized device out of silicon and lithium that harvested energy via the effect Pint and his team were investigating.

In response, the Vanderbilt researchers decided to go as thin as possible by using black phosphorus nanosheets: A material has become the latest darling of the 2D materials research community because of its attractive electrical, optical and electrochemical properties.

Graph showing the operating ranges of different types of energy harvesting devices. The red stars denote piezoelectric devices that use crystals which produce electricity when deformed. The blue circle represents another solid-state device called an ionic diode that generates electricity when compressed. The orange triangles depict triboelectric nanogenerators that produce electricity by sliding friction. The purple circles show the performance of the ultrathin strain harvester developed at Vanderbilt. (Nanomaterials and Energy Devices Laboratory / Vanderbilt)

Because the basic building blocks of the harvester are about 1/5000th the thickness of a human hair, the engineers can make their devices as thin or as thick as needed for specific applications. They have found that bending their prototype devices produces as much as 40 microwatts per square foot and can sustain current generation over the full duration of movements as slow as 0.01 Hertz, one cycle every 100 seconds.

The researchers acknowledge that one of the challenges they face is the relatively low voltage that their device produces. It’s in the millivolt range. However, they are applying their fundamental insights of the process to step up the voltage. They are also exploring the design of electrical components, like LCD displays, that operate at lower than normal voltages.

“One of the peer reviewers for our paper raised the question of safety,” Pint said. “That isn’t a problem here. Batteries usually catch on fire when the positive and negative electrodes are shorted, which ignites the electrolyte. Because our harvester has two identical electrodes, shorting it will do nothing more than inhibit the device from harvesting energy. It is true that our prototype will catch on fire if you put it under a blowtorch but we can eliminate even this concern by using a solid-state electrolyte.”

Engineering undergraduate Thomas Metke demonstrates the ultrathin energy harvesting device. The device is taped across his elbow. The electrical current that it generates when he pumps his arm is displayed on the computer monitor. (John Russell / Vanderbilt)

One of the more futuristic applications of this technology might be electrified clothing. It could power clothes impregnated with liquid crystal displays that allow wearers to change colors and patterns with a swipe on their smartphone. “We are already measuring performance within the ballpark for the power requirement for a medium-sized low-power LCD display when scaling the performance to thickness and areas of the clothes we wear.” Pint said.

Pint also believes there are potential applications for their device beyond power systems. “When incorporated into clothing, our device can translate human motion into an electrical signal with high sensitivity that could provide a historical record of our movements. Or clothes that track our motions in three dimensions could be integrated with virtual reality technology. There are many directions that this could go.”

Learn more: Ultrathin device harvests electricity from human motion

 

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