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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 541 records · Page 30
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

A first-in-human phase 0 clinical study of RNA interference–based spherical nucleic acids in patients with recurrent glioblastoma

Glioblastoma (GBM) is one of the most difficult cancers to effectively treat, in part because of the lack of precision therapies and limited therapeutic access to intracranial tumor sites due to the presence of the blood-brain and blood-tumor barriers. We have developed a precision medicine approach for GBM treatment that involves the use of brain-penetrant RNA interference–based spherical nucleic acids (SNAs), which consist of gold nanoparticle cores covalently conjugated with radially oriented and densely packed small interfering RNA (siRNA) oligonucleotides. On the basis of previous preclinical evaluation, we conducted toxicology and toxicokinetic studies in nonhuman primates and a single-arm, open-label phase 0 first-in-human trial ( NCT03020017 ) to determine safety, pharmacokinetics, intratumoral accumulation and gene-suppressive activity of systemically administered SNAs carrying siRNA specific for the GBM oncogene Bcl2Like12 (Bcl2L12). Patients with recurrent GBM were treated with intravenous administration of siBcl2L12-SNAs (drug moniker: NU-0129), at a dose corresponding to 1/50th of the no-observed-adverse-event level, followed by tumor resection. Safety assessment revealed no grade 4 or 5 treatment–related toxicities. Inductively coupled plasma mass spectrometry, x-ray fluorescence microscopy, and silver staining of resected GBM tissue demonstrated that intravenously administered SNAs reached patient tumors, with gold enrichment observed in the tumor-associated endothelium, macrophages, and tumor cells. NU-0129 uptake into glioma cells correlated with a reduction in tumor-associated Bcl2L12 protein expression, as indicated by comparison of matched primary tumor and NU-0129–treated recurrent tumor. Our results establish SNA nanoconjugates as a potential brain-penetrant precision medicine approach for the systemic treatment of GBM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

A genome-wide RNA interference screen identifies a role for Wnt/β-catenin signaling during Rift Valley Fever Virus infection

Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses La Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. IMPORTANCE RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. Lastly, these studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Structural Insight into How Bacteria Prevent Interference between Multiple Divergent Type IV Secretion Systems

ABSTRACT Prokaryotes use type IV secretion systems (T4SSs) to translocate substrates (e.g., nucleoprotein, DNA, and protein) and/or elaborate surface structures (i.e., pili or adhesins). Bacterial genomes may encode multiple T4SSs, e.g., there are three functionally divergent T4SSs in some Bartonella species ( vir , vbh , and trw ). In a unique case, most rickettsial species encode a T4SS ( rvh ) enriched with gene duplication. Within single genomes, the evolutionary and functional implications of cross-system interchangeability of analogous T4SS protein components remains poorly understood. To lend insight into cross-system interchangeability, we analyzed the VirB8 family of T4SS channel proteins. Crystal structures of three VirB8 and two TrwG Bartonella proteins revealed highly conserved C-terminal periplasmic domain folds and dimerization interfaces, despite tremendous sequence divergence. This implies remarkable structural constraints for VirB8 components in the assembly of a functional T4SS. VirB8/TrwG heterodimers, determined via bacterial two-hybrid assays and molecular modeling, indicate that differential expression of trw and vir systems is the likely barrier to VirB8-TrwG interchangeability. We also determined the crystal structure of Rickettsia typhi RvhB8-II and modeled its coexpressed divergent paralog RvhB8-I. Remarkably, while RvhB8-I dimerizes and is structurally similar to other VirB8 proteins, the RvhB8-II dimer interface deviates substantially from other VirB8 structures, potentially preventing RvhB8-I/RvhB8-II heterodimerization. For the rvh T4SS, the evolution of divergent VirB8 paralogs implies a functional diversification that is unknown in other T4SSs. Collectively, our data identify two different constraints (spatiotemporal for Bartonella trw and vir T4SSs and structural for rvh T4SSs) that mediate the functionality of multiple divergent T4SSs within a single bacterium. IMPORTANCE Assembly of multiprotein complexes at the right time and at the right cellular location is a fundamentally important task for any organism. In this respect, bacteria that express multiple analogous type IV secretion systems (T4SSs), each composed of around 12 different components, face an overwhelming complexity. Our work here presents the first structural investigation on factors regulating the maintenance of multiple T4SSs within a single bacterium. The structural data imply that the T4SS-expressing bacteria rely on two strategies to prevent cross-system interchangeability: (i) tight temporal regulation of expression or (ii) rapid diversification of the T4SS components. T4SSs are ideal drug targets provided that no analogous counterparts are known from eukaryotes. Drugs targeting the barriers to cross-system interchangeability (i.e., regulators) could dysregulate the structural and functional independence of discrete systems, potentially creating interference that prevents their efficient coordination throughout bacterial infection.

Gillespie, Joseph J.↗
DOE OSTI2012

Charge-magnetic interference resonant scattering studies of ferromagnetic crystals and thin films

The element- and site-specificity of X-ray resonant magnetic scattering (XRMS) makes it an ideal tool for furthering our understanding of complex magnetic systems. In the hard X-rays, XRMS is readily applied to most antiferromagnets where the relatively weak resonant magnetic scattering (10 -2 –10 -6 I c ) is separated in reciprocal space from the stronger, Bragg charge scattered intensity, I c . In ferro(ferri)magnetic materials, however, such separation does not occur and measurements of resonant magnetic scattering in the presence of strong charge scattering are quite challenging. We discuss the use of charge-magnetic interference resonant scattering for studies of ferromagnetic (FM) crystals and layered films. We review the challenges and opportunities afforded by this approach, particularly when using circularly polarized X-rays. Here we illustrate current capabilities at the Advanced Photon Source with studies aimed at probing site-specific magnetism in ferromagnetic crystals, and interfacial magnetism in films.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Oak Ridge Spoofing and Interference Test Battery (OAKBAT) - GPS

This dataset contains the RF data recordings for the GPS L1C/A only OAKBAT scenarios. The files are binary data in the format described in the paper: Albright, A., Powers, S. Bonior, J., and Combs, F., 'A Tool for Furthering GNSS Security Research: The Oak Ridge Spoofing and Interference Test Battery (OAKBAT),' in Proceedings of ION GNSS+ 2020, 2020. The metadata, equipment documentation and configuration files, collection procedures and more materials that allow the independent reproduction of the OAKBAT data are https://github.com/oakbat/. Additionally, this site includes a complete listing of all the RF data files, not just this series, available as part of OAKBAT.

42 ENGINEERING↗
DOE OSTI2020

Oak Ridge Spoofing and Interference Test Battery (OAKBAT) - Galileo

This dataset contains the RF data recordings for the Galileo E1 only OAKBAT scenarios. The files are binary data in the format described in the paper: Albright, A., Powers, S. Bonior, J., and Combs, F., 'A Tool for Furthering GNSS Security Research: The Oak Ridge Spoofing and Interference Test Battery (OAKBAT),' in Proceedings of ION GNSS+ 2020, 2020. The metadata, equipment documentation and configuration files, collection procedures and more materials that allow the independent reproduction of the OAKBAT data are https://github.com/oakbat/. Additionally, this site includes a complete listing of all the RF data files, not just this series, available as part of OAKBAT.

42 ENGINEERING↗
DOE OSTI2020

Oak Ridge Spoofing and Interference Test Battery (OAKBAT) - Pure Tones

This dataset contains the pure 1.57542 GHz (L1) pure tone recordings provided to allow characterization of the recording equipment used to digitize the OAKBAT scenarios. The equipment includes the cable, two LNAs, and the software-defined radio. The files are binary data in the format described in the paper: Albright, A., Powers, S. Bonior, J., and Combs, F., A Tool for Furthering GNSS Security Research: The Oak Ridge Spoofing and Interference Test Battery (OAKBAT), in Proceedings of ION GNSS+ 2020, 2020. The metadata, equipment documentation and configuration files, collection procedures and more materials that allow the independent reproduction of the OAKBAT data are https://github.com/oakbat/. Additionally, this site includes a complete listing of all the RF data files, not just this series, available as part of OAKBAT.

42 ENGINEERING↗
DOE OSTI2011

Soft holographic interference lithography microlens for enhanced organic light emitting diode light extraction

Very uniform 2 {micro}m-pitch square microlens arrays ({micro}LAs), embossed on the blank glass side of an indium-tin-oxide (ITO)-coated 1.1 mm-thick glass, are used to enhance light extraction from organic light-emitting diodes (OLEDs) by {approx}100%, significantly higher than enhancements reported previously. The array design and size relative to the OLED pixel size appear to be responsible for this enhancement. The arrays are fabricated by very economical soft lithography imprinting of a polydimethylsiloxane (PDMS) mold (itself obtained from a Ni master stamp that is generated from holographic interference lithography of a photoresist) on a UV-curable polyurethane drop placed on the glass. Green and blue OLEDs are then fabricated on the ITO to complete the device. When the {mu}LA is {approx}15 x 15 mm{sup 2}, i.e., much larger than the {approx}3 x 3 mm{sup 2} OLED pixel, the electroluminescence (EL) in the forward direction is enhanced by {approx}100%. Similarly, a 19 x 25 mm{sup 2} {mu}LA enhances the EL extracted from a 3 x 3 array of 2 x 2 mm{sup 2} OLED pixels by 96%. Simulations that include the effects of absorption in the organic and ITO layers are in accordance with the experimental results and indicate that a thinner 0.7 mm thick glass would yield a {approx}140% enhancement.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2017

Interference effects in laser-induced plasma emission from surface-bound metal micro-particles

Here, the light-matter interaction of an optical beam and metal micro-particulates at the vicinity of an optical substrate surface is critical to the many fields of applied optics. Examples of impacted fields are laser-induced damage in high power laser systems, sub-wavelength laser machining of transmissive materials, and laser-target interaction in directed energy applications. We present a full-wave-based model that predicts the laser-induced plasma pressure exerted on a substrate surface as a result of light absorption in surface-bound micron-scale metal particles. The model predictions agree with experimental observation of laser-induced shallow pits, formed by plasma emission and etching from surface-bound metal micro-particulates. It provides an explanation for the prototypical side lobes observed along the pit profile, as well as for the dependence of the pit shape on the incident laser and particle parameters. Furthermore, the model highlights the significance of the interference of the incident light in the open cavity geometry formed between the micro-particle and the substrate in the resulting pit shape.

42 ENGINEERING↗
DOE OSTI2023

Suppression of coherent interference to electric-field-induced second-harmonic (E-FISH) signals for the measurement of electric field in mesoscale confined geometries

We present spatially enhanced electric-field-induced second-harmonic (SEEFISH) generation with a chirped femtosecond beam for measurements of electric field in mesoscale confined geometries subject to destructive spurious second-harmonic generation (SHG). Spurious SHG is shown to interfere with the measured E-FISH signal coherently, and thus simple background subtraction is not sufficient for single-beam E-FISH approaches, especially in a confined system with a large surface-to-volume ratio. The results show that a chirped femtosecond beam is effective in preventing higher-order mixing and white light generation in windows near the beam focal point which further contaminates the SEEFISH signal. The successful measurements of electric field of a nanosecond dielectric barrier discharge in a test cell demonstrated that spurious SHG detected with a congruent traditional E-FISH approach can be eliminated using the SEEFISH approach.

Vorenkamp, Madeline↗
DOE OSTI2026

Redefining precision interferometry and spectroscopy with high-performance optical interference coatings

High-performance optical interference coatings have transformed precision interferometry and spectroscopy by enabling unparalleled control over light–matter interactions. This review explores recent innovations in ion-beam sputtered amorphous dielectric, as well as substrate-transferred crystalline coatings, and their impact on systems at the forefront of precision metrology. These state-of-the-art coating techniques generate multilayers with ultralow optical losses, yielding mirrors with exceptional reflectivity. Refinements in their noise performance push the ultimate limits of sensitivity, resolution, and stability in demanding laser-based metrology applications. These technologies underpin the most advanced timekeeping and spatial measurement tools, enabling high-finesse reference cavities for the world’s most precise optical atomic clocks and low-noise reflective test masses for km-baseline gravitational-wave detectors. Emerging hybrid designs combining these techniques expand access to the mid-infrared spectral region, enabling the first ultralow-optical-loss coatings in the 3000–5000 nm wavelength range for enhanced spectroscopy and trace-gas detection. We highlight how these technologies redefine coating performance metrics and set new benchmarks in quantum science, fundamental physics, and precision optical sensing.

Cole, Garrett D. [University of Arizona, Tucson, A↗
DOE OSTI2021

Zika virus dynamics: Effects of inoculum dose, the innate immune response and viral interference

Experimental Zika virus infection in non-human primates results in acute viral load dynamics that can be well-described by mathematical models. The inoculum dose that would be received in a natural infection setting is likely lower than the experimental infections and how this difference affects the viral dynamics and immune response is unclear. Here we study a dataset of experimental infection of non-human primates with a range of doses of Zika virus. We develop new models of infection incorporating both an innate immune response and viral interference with that response. We find that such a model explains the data better than models with no interaction between virus and the immune response. We also find that larger inoculum doses lead to faster dynamics of infection, but approximately the same total amount of viral production.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2011

Comments on Bechtel's "Radio Frequency Interference Test Procedure for Instrument and Control Systems"

A copy of the Radio Frequency Interference Test Procedure and sketches for the interconnections was provided to me by Mazhar Haq for review. The intent is to determine whether adverse interactions will be observed at the Russell City Energy Center (RCEC) site due to coupled RF fields from the KFAX / KTRB AM broadcast antenna array. Construction of the RCEC has been impacted by the generation of RF currents in closed loops when large cranes are used for moving materials, appropriate measures have been employed to eliminate safety issues affecting the workers. The impact of the larger RF fields on the sensors and control actuators is yet a concern. The Test Procedure describes the use of a temporary, 100 foot tall assembly of raceway, conduit, wiring and sensors that will be supported by a crane in the area of heat recovery system located closest to the antenna array. Sensors and actuators will be operated to observe whether the normal daytime operation of the broadcast transmitters results in functional impairment.

42 ENGINEERING↗
DOE OSTI2014

KONGMING: Performance Prediction in the Cloud via Multidimensional Interference Surrogates

As more and more applications are deployed in the cloud, it is important for both the user and the operator of the cloud that the resources of the cloud are utilized efficiently. Virtualization and workload consolidation techniques are pervasively applied in the cloud to increase resource utilization while providing isolated execution environments for different users. While virtualization hides the architectural details of the underlying hardware, it can also increase the variability in application execution times due to heterogeneity in available hardware, and interference from other applications sharing the same hardware resources. This reduces both the productivity of cloud platforms and limits the degree to which software colocation can be used to increase its efficiency.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2010

Numerical Electromagnetics Simulations of the Leakage Through the Pump-out Holes in the DISC Electromagnetic Interference Shield

In order to prevent electromagnetic interference (EMI) from affecting the DISC diagnostic, an EMI shield was added. Figure 1 is a cross section from a CAD model of DISC and shows the EMI shield in situ. The shield is orange and at the top of the figure. Figure 2 is a drawing of just the EMI shield. The slit in the center of the EMI shield is covered by a metal mesh, which is not shown in this drawing. The small holes toward the base of the conical portion of the EMI shield are the pump-out holes, and the electromagnetic leakage through these holes is the subject of this report1. An alternate design for the EMI shield is considered in order to determine how to increase the EMI effectiveness of the pump-out holes in the shield without compromising the flow rate through the shield. Both the original and alternate designs are simulated and compared.

42 ENGINEERING↗
DOE OSTI2016

Investigation of Aerodynamic Interference between Twin Deck Bridges

Construction of a twin bridge can be a cost effective and minimally disruptive way to increase capacity when an existing bridge is not near the end of its service life. With ever growing vehicular traffic, when demand approaches the capacity of many existing roads and bridges. Remodeling a structure with an insufficient number of lanes can be a good solution in case of smaller and less busy bridges. Closing down or reducing traffic on crossings of greater importance for the construction period, however, can result in major delays and revenue loss for commerce and transportation as well as increasing the traffic load on alternate route bridges. Multiple-deck bridges may be the answer to this issue. A parallel deck can be built next to the existing one, without reducing the flow. Additionally, a new bridge can be designed as a twin or multi-deck structure. Several such structures have been built throughout the United States, among them: - The New NY Bridge Project - the Tappan Zee Hudson River Crossing, - SR-182 Columbia River Bridge, - The Thaddeus Kosciusko Bridge (I-87), - The Allegheny River Bridge, Pennsylvania, which carries I76, - Fred Hartman Bridge, TX, see Figure 1.2. With a growing number of double deck bridges, additional, more detailed, studies on the interaction of such bridge pairs in windy conditions appears appropriate. Aerodynamic interference effects should be examined to assure the aerodynamic stability of both bridges. There are many studies on aerodynamic response of single deck bridges, but the literature on double-deck structures is not extensive. The experimental results from wind tunnels are still limited in number, as a parametric study is required, they can be very time consuming. Literature review shows that some investigation of the effects of gap-width and angle of wind incidence has been done. Most of the CFD computational studies that have been done were limited to 2D simulations. Therefore, it is desirable to investigate twin decks of various cross-sections, gap-to-width ratios, wind speed and direction using three-dimensional CFD simulations. After verification with wind tunnel test results, this type of analysis could become a powerful tool for future designs as well as for monitoring of existing bridges.

42 ENGINEERING↗