innovation

Jan 172017
 

Schematic of the BIC laser: a high frequency laser beam (blue) powers the membrane to emit a laser beam at telecommunication frequency (red). Image courtesy of Kanté group at UC San Diego.

Researchers at the University of California San Diego have demonstrated the world’s first laser based on an unconventional wave physics phenomenon called bound states in the continuum. The technology could revolutionize the development of surface lasers, making them more compact and energy-efficient for communications and computing applications.

The new BIC lasers could also be developed as high-power lasers for industrial and defense applications.

“Lasers are ubiquitous in the present day world, from simple everyday laser pointers to complex laser interferometers used to detect gravitational waves. Our current research will impact many areas of laser applications,” said Ashok Kodigala, an electrical engineering Ph.D. student at UC San Diego and first author of the study.

“Because they are unconventional, BIC lasers offer unique and unprecedented properties that haven’t yet been realized with existing laser technologies,” said Boubacar Kanté, electrical engineering professor at the UC San Diego Jacobs School of Engineering who led the research.

For example, BIC lasers can be readily tuned to emit beams of different wavelengths, a useful feature for medical lasers made to precisely target cancer cells without damaging normal tissue. BIC lasers can also be made to emit beams with specially engineered shapes (spiral, donut or bell curve) — called vector beams — which could enable increasingly powerful computers and optical communication systems that can carry up to 10 times more information than existing ones.

“Light sources are key components of optical data communications technology in cell phones, computers and astronomy, for example. In this work, we present a new kind of light source that is more efficient than what’s available today in terms of power consumption and speed,” said Babak Bahari, an electrical engineering Ph.D. student in Kanté’s lab and a co-author of the study.

Bound states in the continuum (BICs) are phenomena that have been predicted to exist since 1929.  BICs are waves that remain perfectly confined, or bound, in an open system. Conventional waves in an open system escape, but BICs defy this norm — they stay localized and do not escape despite having open pathways to do so.

In a previous study, Kanté and his team demonstrated, at microwave frequencies, that BICs could be used to efficiently trap and store light to enable strong light-matter interaction. Now, they’re harnessing BICs to demonstrate new types of lasers. The team published the work Jan. 12 in Nature.

Learn more: New Laser Based on Unusual Physics Phenomenon Could Improve Telecommunications, Computing and More

 

Jan 172017
 

via Electronic Specifier

Immunotherapy has proven to be effective against many serious diseases. But to treat diseases in the brain, the antibodies must first get past the obstacle of the blood-brain barrier. In a new study, a research group at Uppsala University describes their development of a new antibody design that increases brain uptake of antibodies almost 100-fold.

Immunotherapy entails treatment with antibodies; it is the fastest growing field in pharmaceutical development. In recent years, immunotherapy has successfully been used to treat cancer and rheumatoid arthritis, and the results of clinical studies look very promising for several other diseases. Antibodies are unique in that they can be modified to strongly bind to almost any disease-causing protein. In other words, major potential exists for new antibody-based medicines.

The problem with immunotherapy for diseases affecting the brain is that the brain is protected by a very tight layer of cells, called the blood-brain barrier. The blood-brain barrier effectively prevents large molecules, such as antibodies, from passing from the bloodstream into the brain. It has therefore been difficult to use immunotherapy to treat Alzheimer’s and Parkinson’s disease, which affect the brain, as well as cancerous tumours in the brain.

It has been known for a long time that some large proteins are actively transported across the blood-brain barrier. These include a protein called transferrin, whose primary task is to bind to iron in the blood and then transport it to the brain. The research group behind this new study has taken advantage of this process and modified the antibodies they want to transport into the brain using components that bind to the transferrin receptor. Then, like a Trojan horse, the receptor transports antibodies into the brain. The number of modifications to and placement of the antibodies have proven to be important factors for making this process as effective as possible.

“We’ve placed them so that each antibody only binds with one modification at a time, despite being modified in two places. Our design thus doubles the chances of the antibody binding to the transferrin receptor compared with only one modification. We’ve successfully increased the amount of antibodies in the brain almost 100-fold, which is the largest uptake improvement that has ever been shown,” says Greta Hultqvist, researcher at the Department of Public Health and Caring Sciences at Uppsala University.

To try out the new format, researchers have used it on an antibody that binds to a protein involved in the course of Alzheimer’s disease. Without the modification, they could only detect very small quantities of antibody in the brain in a mouse model of Alzheimer’s disease, while they could detect high levels of the modified antibody in the same mice.

“From a long-term perspective, it’s likely that the new format can be used to effectively treat not only Alzheimer’s disease, but also other diseases affecting the brain,” says Dag Sehlin, researcher at the Department of Public Health and Caring Sciences at Uppsala University.

Learn more: New antibody design opens door for brain treatments

 

Jan 172017
 

Trapped Ytterbium ions were used as one of the most advanced laboratory quantum systems for this study. Professor Biercuk’s research laboratories are now located in the Sydney Nanoscience Hub, after six years as a visiting scientist at the National Measurement Institute.

What if you could see the future and stop your IT from breaking?

Sydney physicists have demonstrated it is possible to overcome the most significant hurdle to building reliable quantum technologies, in a major technical achievement. The research is published in Nature Communications.

“We’re developing new capabilities that turn quantum systems from novelties into useful technologies”

Scientists at the University of Sydney have demonstrated the ability to “see” the future of quantum systems, and used that knowledge to preempt their demise, in a major achievement that could help bring the strange and powerful world of quantum technology closer to reality.

The applications of quantum-enabled technologies are compelling and already demonstrating significant impacts – especially in the realm of sensing and metrology.   And the potential to build exceptionally powerful quantum computers using quantum bits, or qubits, is driving investment from the world’s largest companies.

However a significant obstacle to building reliable quantum technologies has been the randomisation of quantum systems by their environments, or decoherence, which effectively destroys the useful quantum character.

The physicists have taken a technical quantum leap in addressing this, using techniques from big data to predict how quantum systems will change and then preventing the system’s breakdown from occurring.

The research is published today in Nature Communications.

“Much the way the individual components in mobile phones will eventually fail, so too do quantum systems,” said the paper’s senior author Professor Michael J.  Biercuk.

“But in quantum technology the lifetime is generally measured in fractions of a second, rather than years.”

Professor Biercuk, from the University of Sydney’s School of Physics and a chief investigator at the Australian Research Council’s Centre of Excellence for Engineered Quantum Systems, said his group had demonstrated it was possible to suppress decoherence in a preventive manner. The key was to develop a technique to predict how the system would disintegrate.

Professor Biercuk highlighted the challenges of making predictions in a quantum world: “Humans routinely employ predictive techniques in our daily experience; for instance, when we play tennis we predict where the ball will end up based on observations of the airborne ball,” he said.

“This works because the rules that govern how the ball will move, like gravity, are regular and known.  But what if the rules changed randomly while the ball was on its way to you?  In that case it’s next to impossible to predict the future behavior of that ball.

“And yet this situation is exactly what we had to deal with because the disintegration of quantum systems is random. Moreover, in the quantum realm observation erases quantumness, so our team needed to be able to guess how and when the system would randomly break.

“We effectively needed to swing at the randomly moving tennis ball while blindfolded.”

The team turned to machine learning for help in keeping their quantum systems – qubits realised in trapped atoms – from breaking.

What might look like random behavior actually contained enough information for a computer program to guess how the system would change in the future. It could then predict the future without direct observation, which would otherwise erase the system’s useful characteristics.

The predictions were remarkably accurate, allowing the team to use their guesses preemptively to compensate for the anticipated changes.

Doing this in real time allowed the team to prevent the disintegration of the quantum character, extending the useful lifetime of the qubits.

“We know that building real quantum technologies will require major advances in our ability to control and stabilise qubits – to make them useful in applications,” Professor Biercuk said.

Our techniques apply to any qubit, built in any technology, including the special superconducting circuits being used by major corporations.

“We’re excited to be developing new capabilities that turn quantum systems from novelties into useful technologies. The quantum future is looking better all the time,” Professor Biercuk said.

Learn more: Seeing the quantum future… literally

 

Jan 162017
 

Eye and visual cortex nerves via Glaucoma Research Foundation

via Glaucoma Research Foundation

Buck scientists restore long-term vision in blind mice, making a case for addressing the immune system’s role in rejecting transplanted cells

Stem cell therapies hold great promise for restoring function in a variety of degenerative conditions, but one of the logistical hurdles is how to ensure the cells survive in the body long enough to work. Researchers from the Buck Institute report one of the first demonstrations of long-term vision restoration in blind mice by transplanting photoreceptors derived from human stem cells and blocking the immune response that causes transplanted cells to be rejected by the recipient.

Publishing in the Cell Stem Cell, this work highlights immune system rejection as one of the key issues that needs to be addressed to improve efficiency of stem cell regeneration therapies. The findings support a path to improving clinical applications, specifically for restoring vision in humans by allowing photoreceptors derived from human stem cells to integrate and thrive in the eye.

“This turned into a nice story of long-term restoration of vision in completely blind mice,” said Buck faculty and senior author Deepak Lamba, PhD, MBBS. “We show that these mice can now perceive light as far out as 9-months following injection of these cells.”

Photoreceptors are specialized neurons in the retina that convert light into signals that the brain interprets as sight. Loss of these cells is a common endpoint in degenerative eye diseases. Human embryonic stem cells can provide a potential source for photoreceptor replacement, but despite Lamba’s prior work showing that photoreceptors derived from stem cells could function in mice, researchers   hadn’t been able to show long-term sustained vision restoration. A major controversy in field, said Lamba, was whether the transplanted photoreceptors simply die off or were being actively rejected by the immune system – the eye, along with the brain, had long been thought to be “privileged” in that the cells of the immune system didn’t monitor those locations.

Lamba’s group set out to examine in detail the degree to which immune rejection contributes to disappointing outcomes in stem cell therapies for the eye, and to determine if they could find a way around the problem. If rejection was occurring and that could be suppressed, they reasoned, transplanted photoreceptors derived from stem cells might have time to integrate into the visual system and start relaying information to the brain.

The team used a specific mouse strain that is healthy but it is lacking in a specific immune cell receptor, which makes the mouse unable to reject transplanted foreign cells. Called immunodeficient IL2 receptor gamma (IL2r?) null mice, these animals lack the IL2r? receptor that humans also have as part of a functional immune system.

“This mouse strain is great model for this research because they are otherwise healthy and normal, including in their vision, so it allows us to conduct studies focused on cell integration,” said the publication’s lead author, Jie Zhu, PhD, a postdoctoral researcher who started in Lamba’s lab three years ago.

In these mice, the team showed that without the rejection process, there was a 10-fold increase of living human embryonic stem cell-derived donor retinal cells that matured and integrated into the retina.

After seeing significantly improved long-term survival and integration of the transplanted cells, the next step was to see if the cells actually functioned. The team transplanted stem cell-derived photoreceptors into another strain of mouse, called CRX null, which is congenitally blind. The team measured the pupils’ response to light and examined the brains’ visual response centers to show that signals from the eye were going to the appropriate areas of the brain. They found that even nine months to a year after photoreceptor transplantation, eyes were responding to light and transmitting sight messages to the brain.

“That finding gives us a lot of hope for patients, that we can create some sort of advantage for these stem cell therapies so it won’t be just a transient response when these cells are put in, but a sustained vision for a long time,” said Lamba. “Even though the retina is often considered to be ‘immune privileged,’ we have found that we can’t ignore cell rejection when trying to transplant stem cells into the eye.”

Dr. Lamba’s lab is dedicated to the clinical applications of human stem cells, with a special interest in restoring vision that has been compromised by degenerative eye diseases, such as macular degeneration. They are already refining the current work, said Zhu and Lamba. One direction is to use drugs already approved to prevent rejection for organ transplant that target the same IL2? receptor. “Using an antibody against this specific receptor means that the immune system might not need to be suppressed more generally, which can be very toxic,” said Zhu.

“We can also potentially identify other small molecules or recombinant proteins to reduce this interleukin 2 receptor gamma activity in the body – even eye-specific immune responses – that might reduce cell rejection,” said Lamba. “Of course it is not validated yet, but now that we have a target, that is the future of how we can apply this work to humans.”

Learn more: Improving the longevity of functionally integrated stem cells in regenerative vision therapy

 

Jan 162017
 

Cyanobacteria production

Sunscreens and moisturizers derived from biological sources such as cyanobacteria could represent a safer alternative to current, synthetically produced cosmetics, research published in the European Journal of Phycology suggests.

Using organic matter to develop sunscreens could lessen the risk of adverse side effects, such as contact sensitivity and estrogen mimicking, and help prevent potentially harmful chemicals from entering the environment, lead author Peyman Derikvand of the University of Isfahan, Iran, and colleagues from Swansea and London, say.

The use of biological compounds has many potential advantages for the cosmetics industry, one of which is the organism’s ability to self-renew and reproduce, ensuring that supplies are sustainable. This is especially true for photosynthetic organisms that require only light energy, carbon dioxide and basic nutrients.

One group of such organisms, cyanobacteria, could have great potential as a source of cosmetic products for sunscreens and moisturizers because some of its species live in extremely arid habitats and thus produce compounds that give them the ability to cope with both high UV radiation and extreme desiccation.

These compounds include mycosporine-like amino acids (MAAs) and scytonemin, which provide strong screening protection from longwave and shortwave UV radiation respectively. Such natural photoprotectants could be good candidates as alternatives to synthetic UV filters.

In addition, extracellular polymeric substances (EPS) derived from cyanobacteria appear to be much more effective at retaining moisture than EPS from conventional moisture preserving materials, such as urea, glycerin and propylene glycol, currently used in cosmetics.

Cyanobacteria have higher photosynthetic and growth rates than more complex plants, simple nutritional requirements, and the ability to grow under closed cultivation systems that do not compete with agriculture. However, economic and sustainable production of these bio-compounds at the large scales required by the cosmetic industry is a key challenge.

“As we move into an era where we are turning to nature to replace synthetic chemicals, industry is being driven to look to natural product alternatives. Cyanobacteria, tiny photosynthetic microbes, offer new potential. One suite of compounds are synthesised to protect against damaging ultraviolet and intense sunlight. These compounds, as discussed in this review, offer many advantages over current synthetically derived sunscreens,” said author Carole Llewellyn, Associate Professor in Applied Aquatic Bioscience.

“On-going research into the intensive cultivation of photosynthetic microorganisms in photobioreactors is bringing new understanding in terms of design, operation and scale-up, and will steadily improve both the economics and feasibility of industrial production of cyanobacteria,” said Llewellyn.

Technical improvements coupled to market demand should see the increasing application of cyanobacterial metabolites in the cosmetics sector, the authors conclude.

Learn more: Cyanobacteria: the future of sunscreen?

 

Jan 162017
 

Mycobacterium tuberculosis or Mycobacterium bovis. (image: mycobacterium tuberculosis Ziehl-Neelsen stain credit: CDC)

A clever new tuberculosis vaccine has shown promise in trials in mice. If it succeeds, it will be the first new TB vaccine in a century.

With the rise of multidrug resistant tuberculosis, the difficulty of curing the disease, and the large annual death toll, a successful vaccine could be a huge benefit to public health—especially in low- and middle income countries. The research is published January 13th in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.

The vaccine uses “biobeads” as a platform to present the antigens from the tuberculosis bacterium to the immune system. These biobeads are natural polyesters that certain non-tuberculosis bacteria assemble into tiny spheres. Researchers have engineered them to display antigens from tuberculosis bacteria, Mycobacterium tuberculosis or Mycobacterium bovis. (image: mycobacterium tuberculosis Ziehl-Neelsen stain credit: CDC)

In earlier research, these investigators found that mycobacterial antigens displayed on the biobeads could induce cell-mediated immune responses in mice. Those biobeads were assembled by E.coli. “During these experiments the team observed that along with the tuberculosis antigens, E. coli proteins were attached to the surfaces of the crude biobeads,” said principal investigator Axel Heiser, PhD, Senior Scientist, AgResearch Ltd., Palmerston North, New Zealand.

“From these observations, we developed the hypothesis that these proteins could also function as antigens,” said Heiser. “If produced in Mycobacteria instead of E. coli, such biobeads should carry mycobacterial antigens on their surface, including many as yet undiscovered antigens which would have the potential to induce protective immunity.” And that, in addition to antigens from M. tuberculosis and M. bovis that they would deliberately engineer onto the biobeads, would boost immune response to the vaccine, he said.

But unlike E. coli, Mycobacteria lack the enzymes necessary to assemble biobeads, said Heiser. So they developed new cloning strategies that enabled expression of those enzymes in M. smegmatis, a mycobacterium that does not cause tuberculosis. Using M. smegmatis instead of tuberculosis-causing bacteria would avoid the possibility of the vaccine’s causing tuberculosis infection.

Following production of the biobeads, “We killed and broke up the bacteria, and purified the biobeads,” said Heiser. “They are completely natural, and have been shown to be biodegradable.”

“We then used these mycobacterial biobeads to vaccinate mice and tested the mice for immune responses,” said Heiser. “We saw evidence of cell-mediated immunity with the potential to be protective against TB. Future studies will include a vaccination followed by challenge with TB to show protection, and also the development of more efficient production and purification methods for the vaccine.”

Thus, said Heiser, mycobacterial biobeads would provide a new platform for combining a large antigenic repertoire, comparable to that of live vaccines, with high safety through the use of non-infectious material in the vaccine, including absence of any genetic material. Heiser also said that production would be cost-efficient.

In 2015, 10.4 million people contracted tuberculosis, and 1.8 million died, worldwide, according to the World Health Organization. Nearly half a million of the new cases were multidrug-resistant. 95 percent of the deaths occur in middle- and low-income countries. TB is a leading killer of people with HIV. The only existing vaccine was first used in 1921, and has a variety of shortcomings, including that it can cause the disease in immunocompromised people.

Learn more: CLEVERLY DESIGNED TUBERCULOSIS VACCINE SHOWS PROMISE IN MICE

 

Jan 162017
 

via Angewandte Chemie

Fresh, clean water coming directly from the tap is a true luxury. In developing countries, people often have no choice but to use a contaminated river for drinking water. Water filters can help by quickly converting polluted surface or ground water into safe drinking water. In the journal Angewandte Chemie, researchers have now introduced a novel multifunctional composite material that removes inorganic, organic, radioactive, and microbial impurities from water.

Usually, water purification involves a series of filters, each designed to remove a single type of impurity. In contrast, this new filter material is an all-rounder. Scientists from the Universities of Ulm (Germany) and Zaragoza (Spain) have now seized upon a relatively new approach for designing materials, which allows molecular components to be assembled into multifunctional composites called SILP materials (supported ionic liquid phases). An ionic liquid is a salt that is melted at room temperature, making it liquid without being dissolved in a solvent. When such an ionic liquid is adsorbed onto a solid substrate it forms a solid composite material with properties that can be selectively tuned through chemical modification.

The researchers led by Scott G. Mitchell and Carsten Streb have now produced the first SILPs based on polyoxometallates (POM). POMs are molecular transition metal-oxygen clusters in which the metal atoms are bridged by oxygen atoms to form a three-dimensional network. For the new filter materials, they selected polyoxotungstate anions. These anions have a binding site which can trap heavy metal ions. The counterions they selected are voluminous tetraalkylammonium cations known for their antimicrobial effect. The resulting ionic liquids are hydrophobic, immiscible with water, and form stable thin layers on surfaces. By using a porous silicon dioxide support, the researchers obtained dry, free-flowing powders that are easy to transport and handle.

In laboratory experiments, the anions of the new composites reliably removed lead, nickel, copper, chromium, and cobalt ions. Radioactive uranium in the form of UO22+ was trapped directly by the silicon dioxide support. Similarly, the water-soluble blue trityl dye commonly used in the textile industry was also removed as a result of the lipophilic character of the ionic liquid. The antimicrobial cations effectively halt the growth of E. coli. bacteria.

The researchers hope that their new “POM-SILP” filter materials will form the basis for the development of contaminant-specific chemically designed filter systems that can be used for the reliable purification of water in remote areas and developing nations, as well as after natural disasters and chemical accidents.

Learn more: Composite Material for Water Purification: Removal of multiple contaminants from water by supported ionic liquid phases

 

Jan 152017
 

A fluorescent stained image of a tumor marking bacterial nanocarriers in pink, cancer cell nuclei in blue, and human mitochondria (another indicator of tumor cells) in green.

New approach produces 20 percent survival rate in rat model where few typically live

Biomedical engineers at Duke University have recruited an unlikely ally in the fight against the deadliest form of brain cancer—a strain of salmonella that usually causes food poisoning.

Clinicians sorely need new treatment approaches for glioblastoma, the most aggressive form of brain cancer. The blood-brain barrier—a protective sheath separating brain tissue from its blood vessels—makes it difficult to attack the disease with drugs. It’s also difficult to completely remove through surgery, as even tiny remnants inevitably spawn new tumors. Even with the best care currently available, median survival time is a dire 15 months, and only 10 percent of patients survive five years once diagnosed.

The Duke team decided to pursue an aggressive treatment option to match its opponent, turning to the bacterium Salmonella typhimurium. With a few genetic tweaks, the engineers turned the bacterium into a cancer-seeking missile that produces self-destruct orders deep within tumors. Tests in rat models with extreme cases of the disease showed a remarkable 20 percent survival rate over 100 days—roughly equivalent to 10 human years—with the tumors going into complete remission.

The results appeared online on December 21, 2016, in the journal Molecular Therapy – Oncolytics.

“Since glioblastoma is so aggressive and difficult to treat, any change in the median survival rate is a big deal,” said Johnathan Lyon, a PhD student working with Ravi Bellamkonda, Vinik Dean of Duke’s Pratt School of Engineering, whose laboratory is currently transitioning to Duke from Georgia Tech, where much of the work was completed. “And since few survive a glioblastoma diagnosis indefinitely, a 20 percent effective cure rate is phenomenal and very encouraging.”

Previous studies have shown, quite accidentally, that the presence of bacteria can cause the immune system to recognize and begin attacking tumors. However, follow-up clinical trials with genetically detoxified strains of S. typhimurium have since proven ineffective by themselves.

To use these common intestinal bacteria as tumor-seeking missiles, Lyon and Bellamkonda, working with lead co-author Nalini Mehta, selected a detoxified strain of S. typhimurium that was also deficient in a crucial enzyme called purine, forcing the bacteria to seek supplies elsewhere.

Tumors just so happen to be an excellent source of purine, causing the bacteria to flock to them in droves.

Ravi Bellamkonda, Vinik Dean of the Pratt School of Engineering at Duke University

Then, the Duke engineers made a series of genetic tweaks so that the bacteria would produce two compounds called Azurin and p53 that instruct cells to commit suicide—but only in the presence of low levels of oxygen. And since cancerous cells are multiplying so energetically, the environment around and within tumors has unusually low oxygen.

“A major challenge in treating gliomas is that the tumor is dispersed with no clear edge, making them difficult to completely surgically remove. So designing bacteria to actively move and seek out these distributed tumors, and express their anti-tumor proteins only in hypoxic, purine rich tumor regions is exciting,” said Ravi Bellamkonda, Vinik Dean of Duke’s Pratt School of Engineering and corresponding author of the paper. “And because their natural toxicity has been deactivated, they don’t cause an immunological response. At the doses we used in the experiments, they were naturally cleared once they’d killed the tumors, effectively destroying their own food source.”

The researchers tested the modified bacteria by injecting them directly into the rats’ brains. While this may sound like an extreme delivery option, the first course of action usually performed with glioblastoma is to surgically remove the primary tumor, if possible, leaving the opportunity to directly deliver therapeutics.

The treatment worked in 20 percent of the rats, causing complete tumor regression and extending their lives by 100 days, which translates to roughly 10 human years.

In the 80 percent that did not survive, however, the treatment didn’t change the length of time the rats survived. After testing for common signs of resistance to the anti-tumor compounds and finding none, the researchers concluded the ineffectiveness was likely due to inconsistencies in the bacteria’s penetration, or to the aggressive tumor growth outpacing the bacteria. But every rat showed initial signs of improvement after treatment.

“It might just be a case of needing to monitor the treatment’s progression and provide more doses at crucial points in the cancer’s development,” said Lyon. “However, this was our first attempt at designing such a therapy, and there is some nuance to the specific model we used, thus more experiments are needed to know for sure.”

The researchers now plan to program their bacteria to produce different drugs that cause stronger reactions in the tumors. These will be more difficult to implement, however, as other drugs are not as specific to tumor cells as those used in this study, making potential side effects more of a concern.

Learn more: Tumor-Seeking Salmonella Treats Brain Tumors

 

Jan 152017
 

This is an illustration of the seven cecal character states included in this study: (A) Appendix-like cecum of a common wombat (Vombatus ursinus); (B) Spiral-shaped cecum of a common brushtail possum (Trichosurus vulpecula); (C) Elongated, tapering cecum of a rabbit (Oryctolagus cuniculus); (D) Cylindrical cecum of a North American beaver (Castor canadensis); (E) Paired ceca (or colonic appendages) of a rock hyrax (Procavia habessinica); (F) Rounded cecum of an orangutan (Pongo pygmaeus); (G) Absent cecum in a bush-tailed phascogale (Phascogale tapoatafa). The cecum and appendix are oriented toward the top of each drawing, with the appendix (if present) demarcated from the cecum by a line. A cecal appendix is most frequently found in association with spiral (B) and tapering (C) and cecal shapes. Images redrawn from Stevens and Hume (1995) and Hume (1999).
CREDIT
Brent Adrian, Senior Research Associate, Midwestern University

The human appendix, a narrow pouch that projects off the cecum in the digestive system, has a notorious reputation for its tendency to become inflamed (appendicitis), often resulting in surgical removal. Although it is widely viewed as a vestigial organ with little known function, recent research suggests that the appendix may serve an important purpose. In particular, it may serve as a reservoir for beneficial gut bacteria. Several other mammal species also have an appendix, and studying how it evolved and functions in these species may shed light on this mysterious organ in humans.

Heather F. Smith, Ph.D., Associate Professor, Midwestern University Arizona College of Osteopathic Medicine, is currently studying the evolution of the appendix across mammals. Dr. Smith’s international research team gathered data on the presence or absence of the appendix and other gastrointestinal and environmental traits for 533 mammal species. They mapped the data onto a phylogeny (genetic tree) to track how the appendix has evolved through mammalian evolution, and to try to determine why some species have an appendix while others don’t.

They discovered that the appendix has evolved independently in several mammal lineages, over 30 separate times, and almost never disappears from a lineage once it has appeared. This suggests that the appendix likely serves an adaptive purpose. Looking at ecological factors, such as diet, climate, how social a species is, and where it lives, they were able to reject several previously proposed hypotheses that have attempted to link the appendix to dietary or environmental factors. Instead, they found that species with an appendix have higher average concentrations of lymphoid (immune) tissue in the cecum. This finding suggests that the appendix may play an important role as a secondary immune organ. Lymphatic tissue can also stimulate growth of some types of beneficial gut bacteria, providing further evidence that the appendix may serve as a “safe house” for helpful gut bacteria.

They also found that animals with certain shaped ceca (tapering or spiral-shaped) were more likely to have an appendix than animals with a round or cylindrical cecum. Therefore, they concluded that the appendix isn’t evolving independently, but as part of a larger “cecoappendicular complex” including both the appendix and cecum.

Learn more: New Midwestern University research suggests appendix may have important function

 

Jan 152017
 

Multiplexed image analysis with HySP is faster and less expensive than other methods. Image courtesy of Francesco Cutrale.

A computer algorithm for analyzing time-lapse biological images could make it easier for scientists and clinicians to find and track multiple molecules in living organisms. The technique is faster, less expensive and more accurate than current methods — and it even works with cell phone images.

A new image analysis technique makes finding important biological molecules — including tell-tale signs of disease — and learning how they interact in living organisms much faster and far less expensive. Called Hyper-Spectral Phasor analysis, or HySP, it could even be useful for diagnosing and monitoring diseases using cell phone images.

Researchers use fluorescent imaging to locate proteins and other molecules in cells and tissues. It works by tagging the molecules with dyes that glow under certain kinds of light — the same principle behind so-called “black light” images.

Fluorescent imaging can help scientists understand which molecules are produced in large amounts in cancer or other diseases, information that may be useful in diagnosis or in identifying possible targets for therapeutic drugs.

Looking at just one or two molecules in cell or tissue samples is fairly straightforward. Unfortunately, it doesn’t provide a clear picture of how those molecules are behaving in the real world. For that, scientists need to expand their view.

“Biological research is moving toward complex systems that extend across multiple dimensions, the interaction of multiple elements over time,” said postdoctoral fellow Francesco Cutrale. He developed HySP with Scott Fraser

, Elizabeth Garrett Chair in Convergent Bioscience and Provost Professor of Biological Science. The work was done at USC’s Translational Imaging Center, a joint venture of USC Dornsife and USC Viterbi School of Engineering.

“By looking at multiple targets, or watching targets move over time, we can get a much better view of what’s actually happening within complex living systems,” Cutrale said.

Currently, researchers must look at different labels separately, then apply complicated techniques to layer them together and figure out how they relate to one another, a time-consuming and expensive process, Cutrale said. HySP can look at many different molecules in one pass.

“Imagine looking at 18 targets,” Cutrale said. “We can do that all at once, rather than having to perform 18 separate experiments and try to combine them later.”

In addition, the algorithm effectively filters through interference to discern the true signal, even if that signal is extremely weak — very much like finding the proverbial needle in a haystack. Recent technology from NASA’s Jet Propulsion Laboratory can also do this, but the equipment and process are both extremely expensive and time-consuming.

“HySP uses much less computing time, and we don’t need the expensive imaging instrumentation,” said Fraser, who holds joint appointments at USC Viterbi and Keck School of Medicine of USC.

In research published Jan. 9 online by the scientific journal Nature Methods, Cutrale and Fraser, along with researchers from Keck School of Medicine, Caltech and the University of Cambridge in the United Kingdom, have used zebra fish to test and develop HySP. In this common laboratory model, the system works extremely well. But what about in people?

“In experimental models, we can use genetic manipulation to label molecules, but we can’t do that with people,” said Fraser. “In people, we have to use the intrinsic signals of those molecules.”

Those inherent signals, the natural fluorescence from biomolecules, normally gets in the way of imaging, Fraser said. However, using this new computer algorithm that can effectively find weak signals in a cluttered background, the team can pinpoint their targets in the body.

Portrait Right 

Different fluorescent light wavelengths reveal features of a zebra fish embryo. Photo courtesy of Francesco Cutrale.

The scientists hope to test the process in the next couple of years with the help of soldiers whose lungs have been damaged by chemicals and irritants they may have encountered in combat. The researchers will extend a light-emitting probe down into the soldiers’ lungs while the probe records images of the fluorescence in the surrounding tissues. They will then use HySP to create what amounts to a fluorescent map and compare it with that of healthy lung tissue to see if they can discern the damage. If so, they hope to further develop the technology so it may one day help these soldiers and other lung patients receive more targeted treatment.

It might also be possible one day for clinicians to use HySP to analyze cell phone pictures of skin lesions to determine if they are at risk of being cancerous, according to Fraser and Cutrale.

“We could determine if the lesions have changed color or shape over time,” Cutrale said. Clinicians could then examine the patient further to be certain of a diagnosis and respond appropriately.

Cutrale and Fraser see the technology as a giant leap forward for both research and medicine.

“Both scientists at the bench and scientists at the clinic will be able to perform their work faster and with greater confidence in the results,” Cutrale said. “Better, faster, cheaper. That’s the payoff here.”

Learn more: New technology enables 5-dimensional imaging in live animals and humans

 

 

Jan 152017
 

Scott (right) and Zach Vader inside their Amherst, New York, factory. Credit: Douglas Levere.

A father and son team in the START-UP NY program have invented a liquid metal printing machine that could represent a significant transformation in manufacturing. A breakthrough idea five years ago by former University at Buffalo student Zack Vader, then 19, has created a machine that prints three-dimensional objects using liquid metal.

Vader Systems is innovating and building the machines in a factory in the CrossPoint Business Park in Getzville. Zack’s father Scott, a mechanical engineer, is the CEO. Zack is the chief technology officer. His mother, Pat Roche, is controller.

The machine is so novel it represents a quantum leap in the ability to print three-dimensional objects in metal. Other metal printers exist, but most use a process of laying down powered metal and melting it with a laser or electron beam. In that process, some particles of the powder do not get melted, creating weakened spots.

Manufacturers are very interested in the Vader machine, with one automotive parts maker expressing an interest in eventually buying at least 50 of them. A printer with multiple nozzles could cost more than $1 million.

UB engineering faculty and students work closely with the company

UB has been a source of intellectual assistance, grants and personnel for the startup as it transforms from a brilliant idea into an industry.

The Vaders were working on their invention in the basement of their home in Amherst when Scott decided to reach out to UB for help. “We were working alone in our basement and tackling some pretty deep technical problems,” he said.

“We knocked at the door of the university and they welcomed us in,” he said. “They set up an impressive first meeting with faculty experts within UB, and they said, ‘What are you trying to do? What are your problems and how can we help?’”

The Vaders now have three faculty advisors, are part of the START-UP NY tax-free entrepreneurial program and have won grants from UB’s Center for Industrial Effectiveness (UB TCIE), UB’s Center for Advanced Biomedical and Bioengineering Technology (UB CAT) grant and a National Grid grant through UB.

In addition, and perhaps most importantly, Scott Vader said, access to university students for internships has helped the company grow. Vader Systems already has hired three mechanical engineering graduates.

“This is what makes really good young engineers, to go from the theory and being able to mix in an internship with a local industry,” he said. “They realize that the lab they took is something a company really needs.”

Inspiration spawned by disappointment

Zack Vader, now 24, started focusing on metal printing when his plans to hire a company to 3-D print parts for a microturbine generator were stymied. No company could print the parts he needed, so he decided to make his own metal printer. His breakthrough came when he thought to expose molten metal in a confined chamber with an orifice to a pulsed magnetic field. The transient field induces a pressure with the metal that ejects a droplet. That was the key to making droplets of liquid metal eject from a nozzle.

Professor Edward P. Furlani, PhD, in UB’s Chemical and Biological Engineering and Electrical Engineering departments, said that Vader’s process mimics drop-on-demand inkjet printing and is based on the principles of magnetohydrodynamics, i.e. the manipulation of conductive fluids using a magnetic field. In Vader’s device, an electrically-pulsed magnetic field permeates liquid metal in an ejection chamber and creates circulating electrical currents that interact with the magnetic field to produce a pressure that squeezes a droplet out of the ejector nozzle.

“It’s a transformative technology,” Furlani said. “It’s very exciting interdisciplinary engineering. I think its application base will continue to broaden and expand for the foreseeable future.”

Ciprian N. Ionita, PhD, a research assistant professor in the Biomedical Engineering Department — a joint effort of the School of Engineering and Applied Sciences and the Jacobs School of Medicine and Biomedical Sciences at UB — foresees the Vader Systems printer ultimately printing out custom stents and other surgical devices right in the hospital.

“This is a game changer,” he said. The metal powder used in the current metal printing processes is a contaminant that is difficult to clean up and can be toxic inside the body.

The Vader printer also will be valuable making custom knee and hip replacements, he said.

Cheaper, faster, better

The third UB professor advising the Vaders, Chi Zhou, an assistant professor in the Industrial Systems Engineering Department and a 3-D printing expert, said another advantage of the Vader system is that it is “much, much cheaper” than using powered metal.

“I can see at this stage that it can complement traditional metal printing, but later, maybe 10 years later, it can dominate the metal printing market because it can print better quality, cheaper and faster,” Zhou said.

Zhou has helped write original open-source software to control the printer. “If they want to add functionality, we can. We have the source code,” he said.

One of the most fascinating qualities of a 3-D printer is that a complex part is just as cheap to make as a simple part.

“Complexity does not add cost,” Zack Vader said, which is the opposite of traditional manufacturing. That makes the machines very attractive to companies making many complex parts.

Steel printing on the horizon

On a Vader machine, a strand of aluminum is fed into a heat element that melts it at 750 degrees Celsius (1,382 degrees Fahrenheit). The liquefied metal is then passed to a ceramic tube that forms an ejection chamber and has a submillimeter orifice. A magnetic coil surrounds the tube and receives a short-lived electrical pulse to create a pressure within the tube that ejects a droplet of liquid metal through the orifice. The ejected drop is projected downward onto a heated platform that maneuvers to create solid 3-D shapes based on layer-by-layer deposition and the coalescence of the droplets.

Zack Vader said plans are to modify the device, adding nozzles to make it faster. Eventually the machines will be able to melt and print steel at 1,400 C (2,552 F).

As the machine evolves, the Vaders plan to expand their operation into an assembly line manufacturing facility. Applications for the device run the gamut. Scott Vader said the automotive industry may be interested in making parts that are now solid metal into hollow and honey-combed structures. The hollow parts would be lighter, stronger and much cheaper.

And as for the tiny generator that Zack Vader was hoping to print, it may emerge again someday, now that the technology to make it is advancing.

“That’s just been put on the shelf for a while,” he said.

Learn more: Vader Systems may have created a quantum leap in manufacturing

 

Jan 142017
 

via RAND Corporation

Personal technology such as fitness trackers and smartphones that record users’ daily activities are likely to be used increasingly in criminal investigations, raising questions about individuals’ rights that the legal system is not yet fully prepared to address, according to a new RAND Corporation study.

Information such as location, travel patterns and even physiological details such as heart rate and activity levels could be retrieved from devices as a part of criminal investigations. Such technology offers new tools to law enforcement, but raises unique issues regarding important constitutional rights such as self-incrimination, according to the report.

Courtrooms also are poised to change because of technology, with teleconferencing, digital records and even virtual reality entering the scene — all intended to speed up proceedings and reduce the cost to the justice system. These technologies raise issues of fairness for defendants and may change the notion of whether a trial by videoconference is equal to proceedings where everyone appears in person, according to the report.

“When changes are gradual, the law and the criminal justice systems have time to react and adapt naturally as conflicts appear,” said Brian Jackson, lead author of the study and a physical scientist at RAND, a nonprofit research organization. “But new technologies are developing rapidly and are likely to create conflicts before the legal system is fully prepared to deal with them.”

Both the courts and law enforcement agencies need to make greater efforts to identify the conflicts ahead, as well educate the criminal justice workforce about how to both properly use and address concerns regarding the emerging tools, according to the report.

These efforts should focus on trying to identify and arbitrate disputes about technology before they reach a critical point. One example of such a conflict was when investigators probing the mass shooting that took place in San Bernardino in 2015 wanted to unlock a smartphone belonging to one of the shooters. Those efforts were delayed while investigators unsuccessfully tried to convince the phone’s manufacturer to aid their efforts.

Researchers say working through the issues surrounding new technologies outside the pressure of a public safety crisis is needed to better balance the value of using technologies in investigations versus the potential infringements on privacy and individual rights.

As a part of a multi-year project to look at the challenges that technology poses for the criminal justice system, researchers from RAND and RTI International assembled a group of practitioners, legal scholars and advocates to examine issues involving technology and individual rights.

The group of 13 experts identified more than three dozen needs, each related to a specific problem or challenge posed to the protection of individual rights by new technology.

The area they flagged as requiring the most attention is assuring the quality and integrity of data used by the criminal justice system across a wide range of uses, according to the report. This includes both the quality of information gathered about crimes and placed into a digital record, as well as how that data is analyzed such as in risk assessment tools used by both police and the courts.

For example, significant effort has been devoted to the creation of risk assessment models that predict the likelihood that a person will fail to appear at their trial or commit crimes in the future.

When used in courts, these models may allow an individual to be released with a lower bail or no bail if they are assessed to be a low risk — creating cost savings for both the public and the defendant, according to the report. To the extent the tools increase consistency between judges, the models could increase fairness. But if the predictive models unknowingly incorporate bias, then the tools could create systematic bias in the process.

The report also recommends better technical training and education for workers across the criminal justice system about how to properly use digital tools. And having that capability broadly available is key for the system to do its job well. While a database of evidence may be available to both the prosecution and defense, if an overworked public defender does not have a skilled data analyst as a part of his or her team, then digital tools may tip the scales of justice in one direction, experts warn.

“Digital tools hold the promise to speed proceedings and increase fairness, but both sides should have the skills and resources necessary to use them,” Jackson said. “For example, hundreds of hours of surveillance recordings may hold important evidence, but will both parties have the skills and resources to comb through and analyze all the data?”

The report notes that personal technology devices already have become important tools in criminal investigations. In at least one case, a fitness tracker was used in court to disprove a women’s allegation that she was sexually assaulted in her home — the fitness tracker showed she had been awake and walking the entire night.

As medical devices such as cardiac pacemakers become more advanced to include features such as Wi-Fi, it opens the possibility that life-sustaining technology also could be used to collect evidence against a user, according to the report.

Learn more: Rise of Technology in Criminal Proceedings Poses Risk to Protecting Individuals’ Rights

 

Jan 142017
 

Haibo Huang, an assistant professor at the Virginia Polytechnic Institute and State University, squeezes bio-oil out of PETROSS sugarcane to process into biodiesel.

Today many biofuel refineries operate for only seven months each year, turning freshly harvested crops into ethanol and biodiesel. When supplies run out, biorefineries shut down for the other five months. However, according to recent research, dual-purpose biofuel crops could produce both ethanol and biodiesel for nine months of the year—increasing profits by as much as 30%.

“Currently, sugarcane and sweet sorghum produce sugar that may be converted to ethanol,” said co-lead author Stephen Long, Gutgsell Endowed Professor of Plant Biology and Crop Sciences at the Carl R. Woese Institute for Genomic Biology at the University of Illinois. “Our goal is to alter the plants’ metabolism so that it converts this sugar in the stem to oil—raising the levels in current cultivars from 0.05% oil, not enough to convert to biodiesel, to the theoretical maximum of 20% oil. With 20% oil, the plant’s sugar stores used for ethanol production would be replaced with more valuable and energy dense oil used to produce biodiesel or jet fuel.”

A paper published in Industrial Biotechnology simulated the profitability of Plants Engineered to Replace Oil in Sugarcane and Sweet Sorghum (PETROSS) with 0%, 5%, 10%, and 20% oil. They found that growing sorghum in addition to sugarcane could keep biorefineries running for an additional two months, increasing production and revenue by 20-30%.

Today, PETROSS sugarcane produces 13% oil by dry weight, 8% of which is the kind of oil used to make biodiesel. At 20% oil, sugarcane would produce 13 times more oil—and six times more profit—per acre than soybeans.

A biorefinery plant processing PETROSS sugarcane with 20% oil would have a 24% international rate of return—a metric used to measure the profitability of potential investments—which increases to 29% when PETROSS sorghum with 20% oil is processed for an additional two months during the sugarcane offseason.

“When a sugarcane plant has to shut down, the company is still paying for capital utilization; they have spent millions of dollars on equipment that isn’t used for five months,” said co-lead author Vijay Singh, Director of the Integrated Bioprocessing Research Laboratory at Illinois. “We propose bringing in another crop, sweet sorghum, to put that equipment to use and decrease capital utilization costs.”

By decreasing capital utilization costs, the cost to produce ethanol and biodiesel drops by several cents per liter. Processing lipid-sorghum during the lipid-cane off-season increased annual biofuel production by 20 to 30%, thereby increasing total revenue without any additional investment in equipment.

The simulations in this paper accounted for the equipment required to retrofit ethanol plants to produce biodiesel. In the U.S., about 90 percent of ethanol plants are already retrofitted to produce biodiesel. According to Singh, in places like Brazil where they produce a large amount of sugarcane, it makes sense to retrofit ethanol plants. “Our study shows that it is cost effective to do it.”

Learn more: Dual-purpose biofuel crops could extend production, increase profits

 

Jan 142017
 

via Autonomous Motion department

A draft report submitted to the European Parliament’s legal affairs committee has recommended that robots be equipped with a “kill switch” in order to manage the potential dangers in the evolving field of self-learning autonomous robotics.

The broad-ranging report, recently approved by the legal affairs committee, contains a variety of proposals designed to address possible legal and ethical issues that could arise through the development of autonomous artificial intelligences. These include the establishment of a European Agency for robotics and AI, plus a call for discussing the implementation of a universal basic income as a strategy to address the possible mass unemployment that could result from robotics replacing large portions of the workforce.

In a supreme case of life imitating art, the report opens by referencing Mary Shelley’s Frankenstein and later suggests Issac Asimov’s Three Laws of Robotics as a general principle that designers and producers of robotics should abide by.

Issues of identifying legal liability in regards to the potential harmful actions of robots are prominently discussed in the report. As robots develop cognitive abilities that give them the ability to learn from experience and make independent decisions, the question of legal responsibility becomes an urgent one to address. The report asks how a robot could be held responsible for its actions, and at what point that responsibility falls on either the manufacturer, owner or user.

Interestingly, a proportionate scale of responsibility is proposed that takes into account the capacity of a robot’s self-learning abilities. The report states,

“the greater a robot’s learning capability or autonomy is, the lower other parties’ responsibility should be, and the longer a robot’s ‘education’ has lasted, the greater the responsibility of its ‘teacher’ should be.”

Learn more: EU to debate robot legal rights, mandatory “kill switches”

 

Jan 132017
 

via University of Manchester

Scientists at The University of Manchester have produced the most tightly knotted physical structure ever known – a scientific achievement which has the potential to create a new generation of advanced materials.

The University of Manchester researchers, led by Professor David Leigh in Manchester’s School of Chemistry, have developed a way of braiding multiple molecular strands enabling tighter and more complex knots to be made than has previously been possible.

The breakthrough knot has eight crossings in a 192-atom closed loop – which is about 20 nanometres long (ie 20 millionths of a millimeter).

Being able to make different types of molecular knots means that scientists should be able to probe how knotting affects strength and elasticity of materials which will enable them to weave polymer strands to generate new types of materials.

Professor Leigh said: “Tying knots is a similar process to weaving so the techniques being developed to tie knots in molecules should also be applicable to the weaving of molecular strands.

“For example, bullet-proof vests and body armour are made of kevlar, a plastic that consists of rigid molecular rods aligned in a parallel structure – however, interweaving polymer strands have the potential to create much tougher, lighter and more flexible materials in the same way that weaving threads does in our everyday world.

“Some polymers, such as spider silk, can be twice as strong as steel so braiding polymer strands may lead to new generations of light, super-strong and flexible materials for fabrication and construction.”

Professor Leigh said he and his team were delighted to have achieved this scientific landmark.

He explained the process behind their success: “We ‘tied’ the molecular knot using a technique called ‘self-assembly’, in which molecular strands are woven around metal ions, forming crossing points in the right places just like in knitting – and the ends of the strands were then fused together by a chemical catalyst to close the loop and form the complete knot.

“The eight-crossings molecular knot is the most complex regular woven molecule yet made by scientists.”