Developing “ABCs” for Exploiting New Phenomena in Light-Matter Interactions

A unique class of engineered light-manipulating materials, known as metamaterials or structured materials, makes use of patterns of strongly interacting wavelength or sub-wavelength-sized elements. Because of these intricate internal and surface structures, new properties have emerged, some exhibiting behavior that has resulted in rewriting long-understood “laws” for how light and other electromagnetic (EM) waves interact with materials. These materials have been opening up new options for controlling EM waves in many technological arenas, among them imaging, thermal control, and frequency conversion. Specific applications include night-vision, heat reflection and management in aircraft engines, and temperature regulation of electronics on satellites in the hot-and-cold extremes of space.

Although researchers have been taking steps toward putting these materials to practical use, they remain puzzled about the optimal structure designs for desired matter-light interactions. They have yet to model the materials in ways that enable predictions about how specific structured materials will behave under different conditions, such as increased illumination intensities. To fill in these knowledge gaps, DARPA today announced the Nascent Light-Matter Interactions (NLM) program, which seeks to finally develop theory-anchored models that can expand the state of the art in already-observed phenomena while pointing to never-before-realized and new functionality.

“Recent advances in our understanding of light-matter interactions have revealed nascent concepts that could yield new materials with properties way beyond anything we have now,” said Mike Fiddy, DARPA program manager. “Through NLM we aim to identify building blocks to better understand the physics of 2-D and 3-D structured materials, which can then lead to a systematic design approach for controlling electromagnetic waves through these materials. The end goal is to equip designers with rigorous predictive models and design tools to answer the currently elusive question: ‘If I want a material with X property, how do I build it?’”

For example, can we open new pathways for designing materials that provide more efficiency in up-conversion or down conversion of frequencies, which could benefit military capabilities such as night vision? “At the moment, the state-of-the-art of these complicated structures is you pump them with one frequency and they’ll emit maybe 10 percent at another frequency, but they require lots of power in the process,” he said. “Can we develop design tools to create materials with 80, 90, or 100 percent efficiency in converting infrared light into visible light that require very little or no power?”

As Fiddy sees it, lessons learned in the NLM program also might help engineers design better materials, for example, that automatically block the frequency of a laser if it’s shined directly into the eye. Another example is managing extremely hot temperatures, such as those found in turbine aircraft engines. New engineered materials could help precisely manage temperatures in critical hot parts of the engine, which in turn could lead to more efficiency, thus reducing fuel and maintenance costs.

“Similarly, on satellites, as they orient toward the sun they can get ‘cooked’ and when they are out of the sun they are very cold,” Fiddy said. “Those big temperature extremes have to be controlled somehow in the satellite’s design. But if there were more efficient ways of radiating away the sun’s heat using structured materials, that would be very valuable. A general approach to solving this problem could be beneficial for keeping computer chips cool while at the same time opening up new ways to harvest electromagnetic energy.”

It could take years to realize such possibilities, Fiddy noted, but he hopes the NLM program will deliver new levels of understanding and modeling tools that could hasten that day. As such, he added, this new program should benefit existing programs, such as EXTREME, which focuses on specific uses for engineered materials.

The NLM program will unfold in three phases. The first will challenge performers to develop a model and show that it can predict new phenomena and serve as a design tool. The second phase will push researchers to test the models’ actual utility for identifying new materials useful for specific applications. The goal for Phase 3 is to identify specific challenge problems and tie selected performers and their respective focus and applications to the operational needs of DoD stakeholders.

Source : DARPA

Lost in Translation: Parkinson’s Disease Research Undercut by Study Design

In a review of animal studies of Parkinson’s disease therapies, Yale researchers identified trends that may contribute to the lack of success in human clinical trials. Their finding provides insight to investigators who seek new therapies to slow the progression of the disease.

The study was published Feb. 9 by PLOS ONE.

Many potential therapies for Parkinson’s disease that are successful in animal studies fail in human trials, said the researchers at Yale and Albert Einstein College of Medicine. While flaws in study design and reporting in a variety of diseases have been publicized, the research team decided to examine the impact of other study design issues on the development of new therapies.

The research team reviewed more than 500 animal and human studies of Parkinson’s disease published over the last 40 years. They compared the design of studies for therapies that targeted symptoms with those intended to slow progression of the disease. In addition to previously described design oversights, such as randomization and blinding, they explored whether the study design in animals was aligned with the intended purpose of the therapy in humans.

The researchers found that in studies of therapies to delay the disease, the intervention was given to animals too early — either prior to or soon after disease onset. That stands in stark contrast to how human patients are typically treated.

Additional study shortcomings included a preference for young male animal subjects, a singular time point to assess the outcome, use of measures not validated in clinical settings, and dependence on non-progressive models of Parkinson’s disease. These were all factors that impaired the generalizability of results from relatively narrowly defined animal systems to a more complex system, such as humans, the researchers report.

“These data suggest that study designs in animals, particularly mice, are perpetuated based on accepted norms despite little evidence for translation to humans,” said first author Caroline Zeiss, professor of comparative medicine at Yale.

“Reproducibility and translation are related but distinct issues — our study focuses predominantly on factors affecting translation. Unless study designs in animals change to reflect the human disease more accurately, proposed measures to improve reproducibility are unlikely to have a significant impact on translation of new therapies to the clinic,” Zeiss noted.

Other authors are Heather G. Allore and Amanda P. Beck.

The research was supported in part by the NLM Research Participation Program and the NIH/NIA (Yale Alzheimer’s Disease Research Center, Data Management and Statistics Core).

Test Created in Brazil Can Diagnose 416 Viruses from Tropical Regions

Researchers from the University of São Paulo (USP) at Ribeirão Preto in Brazil have developed a platform that analyzes clinical samples from patients to diagnose infection by 416 viruses found in the world’s tropical regions.

According to its creators, the tool can be used by reference laboratories such as Adolfo Lutz Institute, Oswaldo Cruz Foundation (Fiocruz) and Evandro Chagas Institute in Brazil to assist epidemiological surveillance by detecting pathogens with the potential to cause epidemics in humans.

Results of the research project, which was coordinated by Victor Hugo Aquino, a professor at the University of São Paulo’s Ribeirão Preto Pharmaceutical School (FCFRP-USP), and supported by FAPESP, have been published in PLoS Neglected Tropical Diseases.

“The number of patients with suspected dengue, Zika or chikungunya infection will increase when summer arrives,” said Aquino, lead author of the article. “Conventional methods are frequently unable to confirm diagnosis of these diseases, so we don’t know which viruses are circulating.”

In his view, if a tool like this had been available when Zika began circulating in Brazil, it might have been possible to restrict its spread to the initial outbreak location. “We took a long time to realize an epidemic was under way because no one was thinking of Zika at the time,” he said.

In addition to the pathogens that are already having a significant impact on public health in Brazil, such as those mentioned above, the platform detects others that as yet have been identified only sporadically but could become epidemics.

Examples include Mayaro, an alphavirus related to chikungunya that is transmitted by wild mosquitoes such as Haemagogus janthinomys, and Oropouche, which to date has caused epidemics confined to riverine communities in the Amazon region and is transmitted mainly by midges of the species Culicoides paraensis.

“There are several other viruses that haven’t yet caused problems in humans but may do so one day,” Aquino said. “They’re evolving all the time, and with the degradation of natural environments infectious agents once confined to natural niches could spread farther afield.”

Although the platform is designed above all to detect pathogens transmitted by arthropods such as mosquitoes and ticks, it can also diagnose infectious agents transmitted by small mammals, like hantavirus.

Aquino explained that the selection encompasses all viruses occurring in tropical regions with DNA sequences deposited in GenBank, a public database maintained by the National Center for Biotechnology Information (NCBI), which is part of the United States National Library of Medicine (NLM).

How it works

The platform consists of a DNA microarray slide with eight identical sub-arrays containing viral probes replicated at least three times to complete the array with 15,000 probes. Each probe contains the sequences for 60 nucleotides that are complementary to the genomes of the viruses to be detected.

According to Aquino, the sequences were mounted on the basis of information from GenBank using bioinformatics.

“If a blood sample contains one of the 416 viruses included on the microchip, the pathogen’s genome will bind with one of the probes to produce a marker that can be detected by a scanner,” Aquino said.

The device that reads the results is the same as that used in microarray assays for the analysis of gene expression, a method not yet in common use by clinical laboratories.

“Initially, the test will not be for the entire population because of high cost,” Aquino said. “It will be used on patients with suspected dengue, Zika or other febrile diseases whose diagnosis isn’t confirmed by conventional methods.”

He reckoned it would be possible to test samples from eight patients for about US$2,000 at present. “The platform is still under development and the reagents are all customized, but we’re working on ways to cut the cost,” he said.

The methodology was validated using 20 viruses available at FCFRP-USP’s Virology Laboratory. The validation tests did not point to cross-hybridization, which produces a positive result for more than one infectious agent and hinders correct identification of single viruses.

Nevertheless, the method proved effective to diagnose cases of co-infection, such as when the same patient has been infected by both Zika and dengue.

Some of the results described in the recent article in PLoS Neglected Diseases were produced during Mohd Jaseem Khan’s PhD research, which was supported by FAPESP.