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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 1,369 records · Page 76
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study

Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Evaluation of Novel Design Strategies for Developing Zinc Finger Nucleases Tools for Treating Human Diseases

Zinc finger nucleases (ZFNs) are associated with cell death and apoptosis by binding at countless undesired locations. This cytotoxicity is associated with the binding ability of engineered zinc finger domains to bind dissimilar DNA sequences with high affinity. In general, binding preferences of transcription factors are associated with significant degenerated diversity and complexity which convolutes the design and engineering of precise DNA binding domains. Evolutionary success of natural zinc finger proteins, however, evinces that nature created specific evolutionary traits and strategies, such as modularity and rank-specific recognition to cope with binding complexity that are critical for creating clinical viable tools to precisely modify the human genome. Our findings indicate preservation of general modularity and significant alteration of the rank-specific binding preferences of the three-finger binding domain of transcription factor SP1 when exchanging amino acids in the 2nd finger.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Applications of immunoPET: Using 124 I-anti-PSCA A11 minibody for imaging disease progression and response to therapy in mouse xenograft models of prostate cancer

Here, prostate stem cell antigen (PSCA) is highly expressed in local prostate cancers and prostate cancer bone metastases and its expression correlates with androgen receptor activation and a poor prognosis. Here in this study, we investigate the potential clinical applications of immunoPET with the anti-PSCA A11 minibody, an antibody fragment optimized for use as an imaging agent. We compare A11 minibody immunoPET to 18 F-Fluoride PET bone scans for detecting prostate cancer bone tumors and evaluate the ability of the A11 minibody to image tumor response to androgen deprivation. Osteoblastic, PSCA expressing, LAPC-9 intratibial xenografts were imaged with serial 124 I-anti-PSCA A11 minibody immunoPET and 18 F-Fluoride bone scans. Mice bearing LAPC-9 subcutaneous xenografts were treated with either vehicle or MDV-3100 and imaged with A11 minibody immunoPET/CT scans pre- and post-treatment. Ex vivo flow cytometry measured the change in PSCA expression in response to androgen deprivation. A11 minibody demonstrated improved sensitivity and specificity over 18 F-Fluoride bone scans for detecting LAPC-9 intratibial xenografts at all time points. Finally, LAPC-9 subcutaneous xenografts showed downregulation of PSCA when treated with MDV-3100 which A11 minibody immunoPET was able to detect in vivo .

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

Pharmacologic or genetic interference with atrogene signaling protects against glucocorticoid-induced musculoskeletal and cardiac disease

Despite their beneficial actions as immunosuppressants, glucocorticoids (GC) have devastating effects on the musculoskeletal and cardiac systems, as long-term treated patients exhibit high incidence of falls, bone fractures, and cardiovascular events. Herein, we show that GC upregulate simultaneously in bone, skeletal muscle, and the heart the expression of E3 ubiquitin ligases (atrogenes), known to stimulate the proteasomal degradation of proteins. Activation of vitamin D receptor (VDR) signaling with the VDR ligands calcitriol or eldecalcitol prevented GC-induced atrogene upregulation in vivo and ex vivo in bone/muscle organ cultures and preserved tissue structure/mass and function of the 3 tissues in vivo. Direct pharmacologic inhibition of the proteasome with carfilzomib also conferred musculoskeletal protection. Genetic loss of the atrogene MuRF1-mediated protein ubiquitination in ΔRING mice afforded temporary or sustained protection from GC excess in bone or skeletal and heart muscle. We concluded that the atrogene pathway downstream of MuRF1 underlies GC action in bone, muscle, and the heart, and it can be pharmacologically or genetically targeted to confer protection against the damaging actions of GC simultaneously in the 3 tissues.

Research & Experimental Medicine↗
DOE OSTI2024

Human limits in machine learning: prediction of potato yield and disease using soil microbiome data

Abstract Background The preservation of soil health is a critical challenge in the 21st century due to its significant impact on agriculture, human health, and biodiversity. We provide one of the first comprehensive investigations into the predictive potential of machine learning models for understanding the connections between soil and biological phenotypes. We investigate an integrative framework performing accurate machine learning-based prediction of plant performance from biological, chemical, and physical properties of the soil via two models: random forest and Bayesian neural network. Results Prediction improves when we add environmental features, such as soil properties and microbial density, along with microbiome data. Different preprocessing strategies show that human decisions significantly impact predictive performance. We show that the naive total sum scaling normalization that is commonly used in microbiome research is one of the optimal strategies to maximize predictive power. Also, we find that accurately defined labels are more important than normalization, taxonomic level, or model characteristics. ML performance is limited when humans can’t classify samples accurately. Lastly, we provide domain scientists via a full model selection decision tree to identify the human choices that optimize model prediction power. Conclusions Our study highlights the importance of incorporating diverse environmental features and careful data preprocessing in enhancing the predictive power of machine learning models for soil and biological phenotype connections. This approach can significantly contribute to advancing agricultural practices and soil health management.

Aghdam, Rosa↗
DOE OSTI2015

Analysis of the interaction between host factor Sam68 and viral elements during foot-and-mouth disease virus infections

Background: The nuclear protein Src-associated protein of 68 kDa in mitosis (Sam68) is known to bind RNA and be involved in cellular processes triggered in response to environmental stresses, including virus infection. Interestingly, Sam68 is a multi-functional protein implicated in the life cycle of retroviruses and picornaviruses and is also considered a marker of virus-induced stress granules (SGs). Recently, we demonstrated the partial redistribution of Sam68 to the cytoplasm in FMDV infected cells, its interaction with viral protease 3C pro , and found a significant reduction in viral titers as consequence of Sam68-specific siRNA knockdowns. Despite of that, details of how it benefits FMDV remains to be elucidated. Methods: Sam68 cytoplasmic localization was examined by immunofluorescent microscopy, counterstaining with antibodies against Sam68, a viral capsid protein and markers of SGs. The relevance of RAAA motifs in the IRES was investigated using electromobility shift assays with Sam68 protein and parental and mutant FMDV RNAs. In addition, full genome WT and mutant or G-luc replicon RNAs were tested following transfection in mammalian cells. The impact of Sam68 depletion to virus protein and RNA synthesis was investigated in a cell-free system. Lastly, through co-immunoprecipitation, structural modeling, and subcellular fractionation, viral protein interactions with Sam68 were explored. Results: FMDV-induced cytoplasmic redistribution of Sam68 resulted in it temporarily co-localizing with SG marker: TIA-1. Mutations that disrupted FMDV IRES RAAA motifs, with putative affinity to Sam68 in domain 3 and 4 cause a reduction on the formation of ribonucleoprotein complexes with this protein and resulted in non-viable progeny viruses and replication-impaired replicons. Furthermore, depletion of Sam68 in cell-free extracts greatly diminished FMDV RNA replication, which was restored by addition of recombinant Sam68. The results here demonstrated that Sam68 specifically co-precipitates with both FMDV 3D pol and 3C pro consistent with early observations of FMDV 3C pro -induced cleavage of Sam68. Conclusion: We have found that Sam68 is a specific binding partner for FMDV non-structural proteins 3C pro and 3D pol and showed that mutations at RAAA motifs in IRES domains 3 and 4 cause a decrease in Sam68 affinity to these RNA elements and rendered the mutant RNA non-viable. Interestingly, in FMDV infected cells re-localized Sam68 was transiently detected along with SG markers in the cytoplasm. These results support the importance of Sam68 as a host factor co-opted by FMDV during infection and demonstrate that Sam68 interact with both, FMDV RNA motifs in the IRES and viral non-structural proteins 3C pro and 3D pol .

3C protease↗
DOE OSTI2019

Concurrent measurement of microbiome and allergens in the air of bedrooms of allergy disease patients in the Chicago area

The particulate and biological components of indoor air have a substantial impact on human health, especially immune respiratory conditions such as asthma. To better explore the relationship between allergens, the microbial community, and the indoor living environment, we sampled the bedrooms of 65 homes in the Chicago area using 23the patient-friendly Inspirotec electrokinetic air sampling device, which collects airborne particles for characterization of both allergens and microbial DNA. The sampling device captured sufficient microbial material to enable 16S rRNA amplicon sequencing data to be generated for every sample in the study. Neither the presence of HEPA filters nor the height at which the air sampling device was placed had any influence on the microbial community profile. A core microbiota of 31 OTUs was present in more than three quarters of the samples, comprising around 45% of the relative sequence counts in each bedroom. The most abundant single organisms were Staphylococcus, with other core taxa both human and outdoor-associated. Bacterial alpha diversity was significantly increased in bedrooms that reported having open windows, those with flowering plants in the vicinity, and those in homes occupied by dogs. Porphyromonas, Moraxella, Sutterella, and Clostridium, along with family Neisseraceae, were significantly enriched in homes with dogs; interestingly, cats did not show a significant impact on microbial diversity or relative abundance. While dog allergen load was significantly correlated with bacterial alpha diversity, the taxa that significantly correlated with allergen burden did not exclusively overlap with those enriched in homes with dogs. Alternaria allergen load was positively correlated with bacterial alpha diversity, while Aspergillus allergen load was negatively correlated. The Alternaria allergen load was also significantly correlated with open windows. Microbial communities were significantly differentiated between rural, suburban, and urban homes and houses that were physically closer to each other maintained significantly more similar microbiota. We have demonstrated that it is possible to determine significant associations between allergen burden and the microbiota in air from the same sample and that these associations relate to the characteristics of the home and neighborhoods.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Multi-dimensional resilience: A quantitative exploration of disease outcomes and economic, political, and social resilience to the COVID-19 pandemic in six countries

The COVID-19 pandemic has highlighted a need for better understanding of countries’ vulnerability and resilience to not only pandemics but also disasters, climate change, and other systemic shocks. A comprehensive characterization of vulnerability can inform efforts to improve infrastructure and guide disaster response in the future. In this paper, we propose a data-driven framework for studying countries’ vulnerability and resilience to incident disasters across multiple dimensions of society. To illustrate this methodology, we leverage the rich data landscape surrounding the COVID-19 pandemic to characterize observed resilience for several countries (USA, Brazil, India, Sweden, New Zealand, and Israel) as measured by pandemic impacts across a variety of social, economic, and political domains. We also assess how observed responses and outcomes (i.e., resilience) of the COVID-19 pandemic are associated with pre-pandemic characteristics or vulnerabilities, including (1) prior risk for adverse pandemic outcomes due to population density and age and (2) the systems in place prior to the pandemic that may impact the ability to respond to the crisis, including health infrastructure and economic capacity. Our work demonstrates the importance of viewing vulnerability and resilience in a multi-dimensional way, where a country’s resources and outcomes related to vulnerability and resilience can differ dramatically across economic, political, and social domains. This work also highlights key gaps in our current understanding about vulnerability and resilience and a need for data-driven, context-specific assessments of disaster vulnerability in the future.

59 BASIC BIOLOGICAL SCIENCES↗