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At least 703 records · Page 39
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults

Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). Diet is one method of intervention, and yet little is known about the association between diet and antimicrobial resistance. To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24 ® ] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. These data suggest diet may be a potential method for reducing the burden of AMR.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics

We report structural analysis of HIV protease variant PR S17 which was rationally selected by machine learning to represent wide classes of highly drug-resistant variants. Crystal structures were solved of PR S17 in the inhibitor-free form and in complex with antiviral inhibitor, darunavir. Despite its 17 mutations, PR S17 has only one mutation (V82S) in the inhibitor/substrate binding cavity, yet exhibits high resistance to all clinical inhibitors. PR S17 has none of the major mutations (I47V, I50V, I54ML, L76V and I84V) associated with darunavir resistance, but has 10,000-fold weaker binding affinity relative to the wild type PR. Comparable binding affinity of 8000-fold weaker than PR is seen for drug resistant mutant PR20, which bears 3 mutations associated with major resistance to darunavir (I47V, I54L and I84V). Inhibitor-free PR S17 shows an open flap conformation with a curled tip correlating with G48V flap mutation. NMR studies on inactive PR S17 D25N unambiguously confirm that the flaps adopt mainly an open conformation in solution very similar to that in the inhibitor-free crystal structure. In PR S17 , the hinge loop cluster of mutations, E35D, M36I and S37D, contributes to the altered flap dynamics by a mechanism similar to that of PR20. An additional K20R mutation anchors an altered conformation of the hinge loop. Flap mutations M46L and G48V in PR S17 /DRV complex alter the Phe53 conformation by steric hindrance between the side chains. Unlike the L10F mutation in PR20, L10I in PR S17 does not break the inter-subunit ion pair or diminish the dimer stability, consistent with a very low dimer dissociation constant comparable to that of wild type PR. Distal mutations A71V, L90M and I93L propagate alterations to the catalytic site of PR S17 . PRS17 exhibits a molecular mechanism whereby mutations act synergistically to alter the flap dynamics resulting in significantly weaker binding yet maintaining active site contacts with darunavir.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Physiological and Molecular-Genetic Characterization of Basal Resistance in Sorghum (Final Report)

This is the final technical report for project #: DE-SC0014116, "Physiological and Molecular-Genetic Characterization of Basal Resistance in Sorghum". In this project we identified variation in the basal defense response of sorghum among different sorghum lines. We evaluated the relationship between levels of basal defense response and levels of disease resistance in the field. There were five major goals of this project: 1) Develop robust assays to measure the MAMP response and disease resistance in sorghum; 2) Screen a set of diverse sorghum germplasm for variation in the MAMP response and disease resistance; 3) Identify genes differentially regulated during the MAMP response in high and low responding sorghum genotypes; 4) Assess the effect of MTI on disease progression in sorghum; 5) Identify loci associated with variation in disease resistance and the MAMP response.

09 BIOMASS FUELS↗
DOE OSTI2023

Introgressions of novel diseases resistance genes from Miscanthus into energycane

Sugarcane (Saccharum) is among the world’s leading bioenergy crops. However, modern sugarcane cultivars are derived from a relatively small set of founder genotypes, which has contributed to cultivar susceptibility to diseases. Miscanthus is a close relative of sugarcane that is genetically diverse and a potential source of genes for improving sugarcane. We found that Miscanthus is a source of resistance to four major diseases of sugarcane and we crossed these disease-resistance genes into a predominantly sugarcane genetic background (BC1 generation). Additionally, we found that Miscanthus could also confer genes for chilling-tolerant photosynthesis to sugarcane, which would be highly advantageous for production of energycane in subtropical environments, like the southern coastal plain of the US. Using advanced modeling techniques, we found that standard marker-assisted selection could be effective for breeding resistance conferred by a small number of genes each with large effect (i.e. vertical resistance), but to breed for many genes each of small effect (i.e. horizontal resistance), genomic selection would be the better strategy. Lastly, we learned that Miscanthus can be induced to flower sooner by giving the plants short days (long nights) but that the ideal day length for a given accession depends on its adaptation to its latitude of origin, with tropical accessions requiring shorter days to flower than accessions from high latitudes. This information will facilitate plant breeders’ ability to make crosses between Miscanthus and sugarcane, and enable greater use of Miscanthus as a genetic resource to improve sugarcane.

09 BIOMASS FUELS↗
DOE OSTI2023

Dynamic subcanopy leaf traits drive resistance of net primary production across a disturbance severity gradient

Across the globe, the forest carbon sink is increasingly vulnerable to an expanding array of low- to moderate-severity disturbances. However, some forest ecosystems exhibit functional resistance (i.e., the capacity of ecosystems to continue functioning as usual) following disturbances such as extreme weather events and insect or fungal pathogen outbreaks. Unlike severe disturbances (e.g., stand-replacing wildfires), moderate severity disturbances do not always result in near-term declines in forest production because of the potential for compensatory growth, including enhanced subcanopy production. Community-wide shifts in subcanopy plant functional traits, prompted by disturbance-driven environmental change, may play a key mechanistic role in resisting declines in net primary production (NPP) up to thresholds of canopy loss. However, the temporal dynamics of these shifts, as well as the upper limits of disturbance for which subcanopy production can compensate, remain poorly characterized. In this study, we leverage a 4-year dataset from an experimental forest disturbance in northern Michigan to assess subcanopy community trait shifts as well as their utility in predicting ecosystem NPP resistance across a wide range of implemented disturbance severities. Through mechanical girdling of stems, we achieved a gradient of severity from 0% (i.e., control) to 45, 65, and 85% targeted gross canopy defoliation, replicated across four landscape ecosystems broadly representative of the Upper Great Lakes ecoregion. We found that three of four examined subcanopy community weighted mean (CWM) traits including leaf photosynthetic rate (p = 0.04), stomatal conductance (p = 0.07), and the red edge normalized difference vegetation index (p < 0.0001) shifted rapidly following disturbance but before widespread changes in subcanopy light environment triggered by canopy tree mortality. Surprisingly, stimulated subcanopy production fully compensated for upper canopy losses across our gradient of experimental severities, achieving complete resistance (i.e., no significant interannual differences from control) of whole ecosystem NPP even in the 85% disturbance treatment. Additionally, we identified a probable mechanistic switch from nutrient-driven to light-driven trait shifts as disturbance progressed. Our findings suggest that remotely sensed traits such as the red edge normalized difference vegetation index (reNDVI) could be particularly sensitive and robust predictors of production response to disturbance, even across compositionally diverse forests. The potential of leaf spectral indices to predict post-disturbance functional resistance is promising given the capabilities of airborne to satellite remote sensing. We conclude that dynamic functional trait shifts following disturbance can be used to predict production response across a wide range of disturbance severities.

resistance↗
DOE OSTI2022

Proteomic Signatures of Antimicrobial Resistance in Yersinia pestis and Francisella tularensis

Antimicrobial resistance (AMR) is a well-recognized, widespread, and growing issue of concern. With increasing incidence of AMR, the ability to respond quickly to infection with or exposure to an AMR pathogen is critical. Approaches that could accurately and more quickly identify whether a pathogen is AMR also are needed to more rapidly respond to existing and emerging biological threats. We examined proteins associated with paired AMR and antimicrobial susceptible (AMS) strains of Yersinia pestis and Francisella tularensis, causative agents of the diseases plague and tularemia, respectively, to identify whether potential existed to use proteins as signatures of AMR. We found that protein expression was significantly impacted by AMR status. Antimicrobial resistance-conferring proteins were expressed even in the absence of antibiotics in growth media, and the abundance of 10–20% of cellular proteins beyond those that directly confer AMR also were significantly changed in both Y. pestis and F. tularensis. Most strikingly, the abundance of proteins involved in specific metabolic pathways and biological functions was altered in all AMR strains examined, independent of species, resistance mechanism, and affected cellular antimicrobial target. We have identified features that distinguish between AMR and AMS strains, including a subset of features shared across species with different resistance mechanisms, which suggest shared biological signatures of resistance. These features could form the basis of novel approaches to identify AMR phenotypes in unknown strains.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Transcriptome Analysis of Drought-Resistant and Drought-Sensitive Sorghum ( Sorghum bicolor ) Genotypes in Response to PEG-Induced Drought Stress

Drought is a major limiting factor of crop yields. In response to drought, plants reprogram their gene expression, which ultimately regulates a multitude of biochemical and physiological processes. The timing of this reprogramming and the nature of the drought-regulated genes in different genotypes are thought to confer differential tolerance to drought stress. Sorghum is a highly drought-tolerant crop and has been increasingly used as a model cereal to identify genes that confer tolerance. Also, there is considerable natural variation in resistance to drought in different sorghum genotypes. Here, we evaluated drought resistance in four genotypes to polyethylene glycol (PEG)-induced drought stress at the seedling stage and performed transcriptome analysis in seedlings of sorghum genotypes that are either drought-resistant or drought-sensitive to identify drought-regulated changes in gene expression that are unique to drought-resistant genotypes of sorghum. Our analysis revealed that about 180 genes are differentially regulated in response to drought stress only in drought-resistant genotypes and most of these (over 70%) are up-regulated in response to drought. Among these, about 70 genes are novel with no known function and the remaining are transcription factors, signaling and stress-related proteins implicated in drought tolerance in other crops. This study revealed a set of drought-regulated genes, including many genes encoding uncharacterized proteins that are associated with drought tolerance at the seedling stage.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

Corrosion-resistant high-entropy alloys: A review

Corrosion destroys more than three percent of the world’s gross domestic product. Therefore, the design of highly corrosion-resistant materials is urgently needed. By breaking the classical alloy-design philosophy, high-entropy alloys (HEAs) possess unique microstructures, which are solid solutions with random arrangements of multiple elements. The particular locally-disordered chemical environment is expected to lead to unique corrosion-resistant properties. In this review, the studies of the corrosion-resistant HEAs during the last decade are summarized. The corrosion-resistant properties of HEAs in various aqueous environments and the corrosion behavior of HEA coatings are presented. The effects of environments, alloying elements, and processing methods on the corrosion resistance are analyzed in detail. Finally, the possible directions of future work regarding the corrosion behavior of HEAs are suggested.

36 MATERIALS SCIENCE↗
DOE OSTI2020

A Rapid and High Throughput MIC Determination Method to Screen Uranium Resistant Microorganisms

The assessment of minimum inhibitory concentration (MIC) is a conventional technique used for the screening of microbial resistance against antibiotics, biocides, and contaminants such as heavy metals. However, as part of our ongoing work, we have observed biases associated with using traditional liquid MIC method to screen microbial heavy metal resistance, including both bacterial and fungal strains. Specifically, the addition of uranium into synthetic media causes immediate precipitation prior to the initiation of microbial growth, thus hampering the optical density measurements, and the obtained MIC values are thus flawed and inaccurate. To address this discrepancy, we report the optimization and development of a serial-dilution-based MIC method conducted on solid growth media supplemented with uranium, which is more accurate, relative to the testing of MICs performed in liquid cultures. Notably, we report on the efficacy of this method to screen not only bacteria that are resistant to uranium but also demonstrate the successful application to yeast and fungal isolates, for their ability to resist uranium, is more accurate and sensitive relative to the liquid method. We believe that this newly developed method to screen heavy metal resistance, such as uranium, is far superior to the existing liquid MIC method and propose replacing the liquid assay with the solid plate MIC reported herein.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Noncured Graphene Thermal Interface Materials for High-Power Electronics: Minimizing the Thermal Contact Resistance

We report on experimental investigation of thermal contact resistance, RC, of the noncuring graphene thermal interface materials with the surfaces characterized by different degree of roughness, Sq. It is found that the thermal contact resistance depends on the graphene loading, ξ, non-monotonically, achieving its minimum at the loading fraction of ξ ~15 wt%. Decreasing the surface roughness by Sq~1 μm results in approximately the factor of ×2 decrease in the thermal contact resistance for this graphene loading. The obtained dependences of the thermal conductivity, KTIM, thermal contact resistance, RC, and the total thermal resistance of the thermal interface material layer on ξ and Sq can be utilized for optimization of the loading fraction of graphene for specific materials and roughness of the connecting surfaces. Our results are important for the thermal management of high-power-density electronics implemented with diamond and other wide-band-gap semiconductors.

36 MATERIALS SCIENCE↗
NASA NTRS1996

Development of an in-vitro circulatory system with known resistance and capacitance

An in-vitro (hydrodynamic) model of the circulatory system was developed. The model consisted of a pump, compliant tubing, and valves for resistance. The model is used to simulate aortic pressure and flow. These parameters were measured using a Konigsburg Pressure transducer and a Triton ART2 flow probe. In addition, venous pressure and flow were measured on the downstream side of the resistance. The system has a known compliance and resistance. Steady and pulsatile flow tests were conducted to determine the resistance of the model. A static compliance test was used to determine the compliance of the system. The aortic pressure and flow obtained from the hydrodynamic model will be used to test the accuracy of parameter estimation models such as the 2-element and 4-element Windkessel models and the 3-element Westkessel model. Verifying analytical models used in determining total peripheral resistance (TPR) and systemic arterial compliance (SAC) is important because it provides insight into hemodynamic parameters that indicate baroreceptor responsiveness to situations such as changes in gravitational acceleration.

NASA Discipline Cardiopulmonary↗
DOE OSTI2011

Characterization and monitoring of subsurface processes using parallel computing and electrical resistivity imaging

This newsletter discusses recent advancement in subsurface resistivity characterization and monitoring capabilities. The BC Cribs field desiccation treatability test resistivity monitoring data is use an example to demonstrate near-real time 3D subsurface imaging capabilities. Electrical resistivity tomography (ERT) is a method of imaging the electrical resistivity distribution of the subsurface. An ERT data collection system consists of an array of electrodes, deployed on the ground surface or within boreholes, that are connected to a control unit which can access each electrode independently (Figure 1). A single measurement is collected by injecting current across a pair of current injection electrodes (source and sink), and measuring the resulting potential generated across a pair of potential measurement electrodes (positive and negative). An ERT data set is generated by collecting many such measurements using strategically selected current and potential electrode pairs. This data set is then processed using an inversion algorithm, which reconstructs an estimate (or image) of the electrical conductivity (i.e. the inverse of resistivity) distribution that gave rise to the measured data.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2010

Enhancing Advanced Candu Proliferation Resistance Fuel with Minor Actinides

The advanced nuclear system will significantly advance the science and technology of nuclear energy systems and to enhance the spent fuel proliferation resistance. Minor actinides (MA) are viewed more as a resource to be recycled, and transmuted to less hazardous and possibly more useful forms, rather than simply disposed of as a waste stream in an expensive repository facility. MAs can play a much larger part in the design of advanced systems and fuel cycles, not only as additional sources of useful energy, but also as direct contributors to the reactivity control of the systems into which they are incorporated. In this work, an Advanced CANDU Reactor (ACR) fuel unit lattice cell model with 43 UO 2 fuel rods will be used to investigate the effectiveness of a Minor Actinide Reduction Approach (MARA) for enhancing proliferation resistance and improving the fuel cycle performance. The main MARA objective is to increase the 238 Pu / Pu isotope ratio by using the transuranic nuclides ( 237 Np and 241 Am) in the high burnup fuel and thereby increase the proliferation resistance even for a very low fuel burnup. As a result, MARA is a very effective approach to enhance the proliferation resistance for the on power refueling ACR system nuclear fuel. The MA transmutation characteristics at different MA loadings were compared and their impact on neutronics criticality assessed. The concept of MARA, significantly increases the 238Pu/Pu ratio for proliferation resistance, as well as serves as a burnable absorber to hold-down the initial excess reactivity. It is believed that MARA can play an important role in atoms for peace and the intermediate term of nuclear energy reconnaissance.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2018

FBXW 7 deletion contributes to lung tumor development and confers resistance to gefitinib therapy

Gefitinib, an epidermal growth factor receptor–tyrosine kinase inhibitor ( EGFR ‐ TKI ), is an effective treatment for non‐small‐cell lung cancer ( NSCLC ) with EGFR activating mutations, but inevitably, the clinical efficacy is impeded by the emergence of acquired resistance. The tumor suppressor gene FBXW 7 modulates chemosensitivity in various human cancers. However, its role in EGFR ‐ TKI therapy in NSCLC has not been well studied. Here, we demonstrate that the mice with deficient Fbxw7 have greater susceptibility to urethane‐induced lung tumor development. Through analysis of The Cancer Genome Atlas data, we show that deletion of FBXW 7 occurs in 30.9% of lung adenocarcinomas and 63.5% of lung squamous cell carcinomas, which significantly leads to decrease in FBXW 7 mRNA expression. The reduction in FBXW 7 mRNA level is associated with poor overall survival in lung cancer patients. FBXW 7 knockdown dramatically promotes epithelial–mesenchymal transition, migration, and invasion in NSCLC cells. Moreover, with silenced FBXW 7, EGFR ‐ TKI ‐sensitive cells become resistant to gefitinib, which is reversed by the mammalian target of rapamycin inhibitor, rapamycin. Furthermore, xenograft mouse model studies show that FBXW 7 knockdown enhances tumorigenesis and resistance to gefitinib. Combination of gefitinib with rapamycin treatment suppresses tumor formation of gefitinib‐resistant (GR) FBXW 7‐knockdown cells. In conclusion, our findings suggest that loss of FBXW 7 promotes NSCLC progression as well as gefitinib resistance and combination of gefitinib and rapamycin may provide an effective therapy for GR NSCLC.

Oncology↗
DOE OSTI2018

High‐Efficiency Thin‐Film Superlattice Thermoelectric Cooler Modules Enabled by Low Resistivity Contacts

Abstract V‐telluride superlattice thin films have shown promising performance for on‐chip cooling devices. Recent experimental studies have indicated that device performance is limited by the metal/semiconductor electrical contacts. One challenge in realizing a low resistivity contact is the absence of fundamental knowledge of the physical and chemical properties of interfaces between metal and V‐telluride materials. This study presents a combination of experimental and theoretical efforts to understand, design, and harness low resistivity contacts to V‐tellurides. Ab initio calculations are used to explore the effects of interfacial structure and chemical compositions on the electrical contacts, and an ab initio based macroscopic model is employed to predict the fundamental limit of contact resistivity as a function of both carrier concentration and temperature. Under the guidance of theoretical studies, an experimental approach is developed to fabricate low resistivity metal contacts to V‐telluride thin film superlattices, achieving a 100‐fold reduction compared to previous work. Interfacial characterization and analysis using both scanning transmission electron microscopy and energy‐dispersive X‐ray spectroscopy show unusual interfacial morphology and the potential for further improvement in contact resistivity. Finally, the improved contacts are harnessed to realize an improved high‐performance thermoelectric cooling module.

He, Yuping↗
DOE OSTI2019

Effects of Transition Layer on Bending Resistance in Copper-Clad Aluminum Composite Casting

The performance of the transition layer in a Cu/Al composite casting directly affects the quality of subsequent plastic deformation processing; however, there are no universal or standardized measurement indices for the performance of the transition layer. In this study, Cu/Al composite castings were prepared using the pouring aluminum method, and the resulting solidification microstructures on the bending resistance were investigated. The results of this study lay a theoretical foundation for the development of the plastic processing technologies of these composite castings. A thinner transition layer in the Cu/Al composite casting led to improved bending resistance. In addition, for a fixed total thickness of the transition layer, the bending resistance was mainly controlled by the γ/β interface and β + eutectic (α + β) microstructure, and the thickness of the γ phase had a negligible effect on the bending resistance. The γ/β interface cracked first when the transition layer bore the tensile and shear stress during the bending process, which resulted in the transition layer easily separating from the copper. The bending resistance of the transition layer can be feasibly judged by measuring the bending angle of the specimen tip, which can be easily performed when the specimen bends toward the aluminum direction, suggesting that our proposed method has considerable practical significance.

36 MATERIALS SCIENCE↗
DOE OSTI2012

On the multiscale origins of fracture resistance in human bone and its biological degradation

Akin to other mineralized tissues, human cortical bone can resist deformation and fracture due to the nature of its hierarchical structure, which spans the molecular to macroscopic length-scales. Deformation at the smallest scales, mainly through the composite action of the mineral and collagen, contributes to bone?s strength or intrinsic fracture resistance, while crack-tip shielding mechanisms active on the microstructural scale contribute to the extrinsic fracture resistance once cracking begins. The efficiency with which these structural features can resist fracture at both small and large length-scales becomes severely degraded with such factors as aging, irradiation and disease. Indeed aging and irradiation can cause changes to the cross-link profile at fibrillar length-scales as well as changes at the three orders of magnitude larger scale of the osteonal structures, both of which combine to inhibit the bone&#x27;s overall resistance to the initiation and growth of cracks.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Modeling the electrical resistivity of deformation processed metal-metal composites

Deformation processed metal–metal (matrix–reinforcement) composites (DMMCs) are high-strength, high-conductivity in situ composites produced by severe plastic deformation. The electrical resistivity of DMMCs is rarely investigated mechanistically and tends to be slightly higher than the rule-of-mixtures prediction. In this paper, we analyze several possible physical mechanisms (i.e. phonons, interfaces, mutual solution, grain boundaries, dislocations) responsible for the electrical resistivity of DMMC systems and how these mechanisms could be affected by processing conditions (i.e. temperature, deformation processing). As an innovation, we identified and assembled the major scattering mechanisms for specific DMMC systems and modeled their electrical resistivity in combination. From this analysis, it appears that filament coarsening rather than dislocation annihilation is primarily responsible for the resistivity drop observed in these materials after annealing and that grain boundary scattering contributes to the resistivity at least at the same magnitude as does interface scattering.

36 MATERIALS SCIENCE↗