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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 487 records · Page 27
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Airborne infectious disease isolation units and method of making using prefabricated containers

In one embodiment, a prefabricated container is modified as a medical isolation room by replacing an original door with a clear front door. An intake louver and an adjustable damper are disposed at a lower part of the front end. An exhaust vent is disposed at an upper part of the back wall. An exhaust fan and a HEPA filter are coupled to the exhaust vent. Washable coverings cover interior sides of the container to provide washable, nonslip interior surfaces. The exhaust fan and the adjustable damper at the intake louver are controlled to produce in the medical isolation room a negative air pressure of at least about minus 0.01 inch of water gage (approximately 2.5 pascals) and a displacement ventilation exhaust flow rate through the exhaust vent of at least about 100 cubic feet per minute (cfm) greater than an intake flow rate through the intake louver.

Channell, Michael G.↗
DOE OSTI2025

Animal movement estimation and network-based epidemic modeling: Illustration for the swine industry in Iowa (US)

Animal movement plays a critical role in disease transmission between farms. However, in the United States, the lack of available animal shipment data, sometimes coupled with a lack of detailed information about farm demographics and characteristics, presents great challenges for epidemic modeling and prediction. In this study, we proposed a new method based on the maximum entropy to generate “synthetic” animal movement networks, considering available statistics about the premises operation type, operation size, and the distance between premises. We illustrated our method for the swine movement networks in Iowa and performed network analyses to gain insights into the swine industry. We then applied the generated networks to a network-based epidemic model to identify potential system vulnerabilities in terms of disease transmission. The model was parameterized for African Swine Fever (ASF) as the US swine industry is quite concerned about this disease. Results show that premises with a central role in the network are more vulnerable to disease outbreaks and play an important role in disease spread. Simulations with outbreaks starting from random farms reveal no significant large outbreaks, indicating the system’s relative robustness against arbitrary disease introductions. However, outbreaks originating from high out-degree farms can lead to large epidemic sizes. This underscores the importance for stakeholders and policymakers to continue improving animal movement records and traceability programs in the US and the value of making that data available to epidemiologists and modelers to better understand risk and inform strategies aimed to cost-effectively prevent and control disease transmission. Our approach could be easily adapted to estimate movement networks in other animal production systems and to inform disease spread models for various infectious diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Adaptive Recovery Model: Designing Systems for Testing Tracing and Vaccination to Support COVID-19 Recovery Planning.

This report documents a new approach to designing disease control policies that allocate scarce testing, contact tracing, and vaccination resources to better control community transmission of COVID19 or similar diseases. The Adaptive Recovery Model (ARM) combines a deterministic compartmental disease model with a stochastic network disease propagation model to enable us to simulate COVID-19 community spread through the lens of two complementary modeling motifs. ARM contact networks are derived from cell-phone location data that have been anonymized and interpreted as individual arrivals to specic public locations. Modeling disease spread over these networks allows us to identify locations within communities conducive to rapid disease spread. ARM applies this model- and data-derived abstractions of community transmission to evaluate the effectiveness of disease control measures including targeted social distancing, contact tracing, testing and vaccination. The architecture of ARM provides a unique capacity to help decision makers understand how best to deploy scarce testing, tracing and vaccination resources to minimize disease-spread potential in a community. This document details the novel mathematical formulations underlying ARM, presents a dynamical stability analysis of the deterministic model components, a sensitivity analysis of control parameters and network structure, and summarizes a process for deriving contact networks from cell-phone location data. An example use case steps through applying ARM to evaluate three targeted social distancing policies using Bernalillo County, New Mexico as an exemplar test locale. This step-by-step analysis demonstrates how ARM can be used to measure the relative performance of competing public health policies. Initial scenario tests of ARM shows that ARMs design focus on resource utilization rather than simple incidence prediction can provide decision makers with additional quantitative guidance for managing ongoing public health emergencies and planning future responses.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2022

Editorial: Nanotechnology for natural products

Humans around the globe have lived through an unprecedented time. The emergence and rapid spread of coronavirus disease 2019 (COVID-19) have resulted in the loss of millions of lives, and this number is still climbing every day and hour. As a consequence, there have been drastic changes over the past two years in how we live, communicate, and work, some of which may have changed forever: remote conferencing has become a new norm for businesses, schools, and academia; work-from-home and hybrid working is now more than just acceptable in many industries; most importantly, COVID-19 has raised global awareness of infectious diseases and pandemic responses to an exceptional level. Certainly, COVID-19 is not the only disease that is causing human suffering at this moment. Other highly contagious and lethal viruses, such as the human immunodeficiency virus (HIV), Ebola, and the recent addition to the list, Monkeypox, pose extraordinary challenges to modern civilizations. On the other hand, non-communicable diseases, such as heart disease, stroke, and cancer, are still claiming the majority of deaths on a global level (World Health Organization, 2020). Before the availability of synthetic drugs, civilizations worldwide relied on natural products extracted from the environment and various organisms for healthcare. Natural products and their derivatives continue to be critical components in the drug library available today. Indeed, almost a quarter of the new drugs approved by the US Food and Drug Administration (FDA) since 1981 are natural products, botanical mixtures, or their derivatives (Newman and Cragg, 2020). Recent developments in analytical characterization, genome mining, and engineering have further increased interest in drug discovery from the pool of natural products (Atanasov et al., 2021). This Research Topic celebrates a collection of studies at the intersection of natural product research and nanotechnological advances. As a successor and extension of the Research Topic in “Nanotechnology in Traditional Medicines and Natural Products” published last year (Zhang et al., 2021), the present collection focused more on recent developments in employing the synthesis and characterization of nanostructures for the delivery of functional natural products. Specifically, the use of carrier nanostructures to conjugate or encapsulate therapeutically active natural products with carrier nanostructures could enable their robust, targeted delivery tailored to either tackle a specific disease or unlock a drug administration pathway. Over the last decade, nanostructures such as liposomes (Pattni et al., 2015) and lipid nanoparticles (Hou et al., 2021) have been developed as versatile platforms for the inclusion and delivery of a wide range of therapeutical compounds; a significant advance in this aspect is the stabilization of mRNA strands for COVID-19 vaccination recently produced by Pfizer/BioNTech and Moderna (Tenchov et al., 2021). Such engineered nanomaterials are now widely used in the development of new drugs, while regulatory forces, such as the US FDA, remain cautious with the evaluation of each product on a case-by-case basis (Wang and Grainger, 2022). In this collection, Zeng et al. provided a timely review of natural products conjugated to and contained within nanomaterials for the ongoing COVID-19 pandemic. Natural products that are potentially useful in the mitigation of this disease, such as chloroquine and curcumin, supported in nanocarrier systems, have been discussed in detail. More broadly, Cheng et al. comprehensively reviewed the use of liposomes as a nanocarrier for natural products. This article provides a summary of natural product compounds and extracts used to form liposomal structures. Readers can further enjoy the practical aspects of these engineered drugs for the treatment of specific diseases as well as insights into future directions in this field.

peptides↗
DOE OSTI2021

Biodiversity and Global Health: Intersection of Health, Security, and the Environment

One of the biggest consequences of large-scale environmental change is the loss of biodiversity. Recent studies predict a loss of 1 million species in the near future. Biodiversity loss and land use change through anthropogenic disturbance are known to affect disease exposure, disease severity, and disease impacts. It is becoming increasingly clear that biodiversity loss will lead to an increase in infectious diseases in certain regions. Changes in biodiversity may contain important signatures for prediction of infectious diseases and outbreaks. Here, we argue that areas of high or rapid biodiversity loss will be critical to monitor under the umbrella of global health security. Global Health Security consists of the actions and activities required to reduce the impact of public health events in populations living in different geographic regions and across international borders. Like infectious diseases, climate change and other causes of environmental changes do not respect international borders and are becoming more widespread in all parts of the world. Here, the relationships among biodiversity, climate and environmental changes, and pathogen prevalence are dynamic, context dependent, and complex. Accounting for this complexity requires the inclusion of the environment sector, presently missing, when evaluating the potential of global health security actions for mitigating disease risks.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Quantitative Resistance Loci to Southern Rust Mapped in a Temperate Maize Diversity Panel

Southern rust is a severe foliar disease of maize (Zea mays) resulting from infection with the obligate biotrophic fungus Puccinia polysora. This disease reduces photosynthetic productivity, which in turn reduces yields, with the greatest yield losses (up to 50%) associated with earlier onset infections. P. polysora urediniospores overwinter only in tropical and subtropical regions but cause outbreaks when environmental conditions favor initial infection. Increased temperatures and humidity during the growing season combined with an increased frequency of moderate winters are likely to increase the frequency of severe southern rust outbreaks in the U.S. Corn Belt. In summer 2020, a severe outbreak of southern rust was observed in eastern Nebraska, United States. We scored a replicated maize association panel planted in Lincoln, NE for disease severity and found that disease incidence and severity showed significant variation among maize genotypes. Genome-wide association studies identified four loci associated with significant quantitative variation in disease severity. These loci were associated with candidate genes with plausible links to quantitative disease resistance. A transcriptome-wide association study identified additional genes associated with disease severity. Together, these results indicate that substantial diversity in resistance to southern rust exists among current temperate-adapted maize germplasm, including several candidate loci that may explain the observed variation in resistance to southern rust. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

Plant Sciences↗
DOE OSTI2022

Phylogenetic conservatism of mycoparasitism and its contribution to pathogen antagonism

Abstract Closely related species are expected to have similar functional traits due to shared ancestry and phylogenetic inertia. However, few tests of this hypothesis are available for plant‐associated fungal symbionts. Fungal leaf endophytes occur in all land plants and can protect their host plant from disease by a variety of mechanisms, including by parasitizing pathogens (e.g., mycoparasitism). Here, we tested whether phylogenetic relatedness among species of Cladosporium , a widespread genus that includes mycoparasitic species, predicts the effect of this endophyte on the severity of leaf rust disease. First, we used congruence among different marker sequences (i.e., genealogical concordance phylogenetic species recognition criterion) to delimit species of Cladosporium . Next, in a controlled experiment, we quantified both mycoparasitism and disease modification for the selected Cladosporium species. We identified 17 species of Cladosporium ; all the species reduced rust disease severity in our experiment. Cladosporium phylogeny was a significant predictor of mycoparasitism. However, we did not observe a phylogenetic effect on disease severity overall, indicating that other mechanism/s operating independently of shared ancestry also contributed to endophyte effects on disease severity. Indeed, a second experiment showed that Cladosporium endophyte exudates (no live organism) from divergent species groups equally reduced disease severity. Our results reveal that multiple mechanisms contribute to the protective effects of an endophyte against a plant pathogen, but not all traits underlying these mechanisms are phylogenetically conserved.

Barge, Edward G.↗
DOE OSTI2022

Improving Traditional Registrational Trial End Points: Development and Application of a Desirability of Outcome Ranking End Point for Complicated Urinary Tract Infection Clinical Trials

Abstract Background Traditional end points used in registrational randomized, controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials that incorporates benefits and risks of novel treatment strategies and provides a global assessment of patient experience. Methods Through a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience, we developed a DOOR end point for infectious disease syndromes and demonstrated how this could be applied to 3 registrational drug trials (ZEUS, APEKS-cUTI, and DORI-05) for complicated urinary tract infections (cUTIs). ZEUS compared fosfomycin to piperacillin/tazobactam, APEKS-cUTI compared cefiderocol to imipenem, and DORI-05 compared doripenem to levofloxacin. Using DOOR, we estimated the probability of a more desirable outcome with each investigational antibacterial drug. Results In each RCT, the DOOR distribution was similar and the probability that a patient in the investigational arm would have a more desirable outcome than a patient in the control arm had a 95% confidence interval containing 50%, indicating no significant difference between treatment arms. DOOR facilitated improved understanding of potential trade-offs between clinical efficacy and safety. Partial credit and subgroup analyses also highlight unique attributes of DOOR. Conclusions DOOR can effectively be used in registrational cUTI trials. The DOOR end point presented here can be adapted for other infectious disease syndromes and prospectively incorporated into future clinical trials.

Immunology↗
DOE OSTI2022

Mapping the Spatial Distribution of Fibrillar Polymorphs in Human Brain Tissue

Alzheimer’s disease (AD) is a neurodegenerative disorder defined by the progressive formation and spread of fibrillar aggregates of Aβ peptide and tau protein. Polymorphic forms of these aggregates may contribute to disease in varying ways since different neuropathologies appear to be associated with different sets of fibrillar structures and follow distinct pathological trajectories that elicit characteristic clinical phenotypes. The molecular mechanisms underlying the spread of these aggregates in disease may include nucleation, replication, and migration all of which could vary with polymorphic form, stage of disease, and region of brain. Given the linkage between mechanisms of progression and distribution of polymorphs, mapping the distribution of fibrillar structures in situ has the potential to discriminate between mechanisms of progression. However, the means of carrying out this mapping are limited. Optical microscopy lacks the resolution to discriminate between polymorphs in situ, and higher resolution tools such as ssNMR and cryoEM require the isolation of fibrils from tissue, destroying relevant spatial information. Here, we demonstrate the use of scanning x-ray microdiffraction (XMD) to map the locations of fibrillar polymorphs of Aβ peptides and tau protein in histological thin sections of human brain tissue. Coordinated examination of serial sections by immunohistochemistry was used to aid in the interpretation of scattering patterns and to put the observations in a broader anatomical context. Scattering from lesions in tissue shown to be rich in Aβ fibrils by immunohistochemistry exhibited scattering patterns with a prototypical 4.7 Å cross-β peak, and overall intensity distribution that compared well with that predicted from high resolution structures. Scattering from lesions in tissue with extensive tau pathology also exhibited a 4.7 Å cross-β peak but with intensity distributions that were distinct from those seen in Aβ-rich regions. In summary, these observations demonstrate that XMD is a rich source of information on the distribution of fibrillar polymorphs in diseased human brain tissue. When used in coordination with neuropathological examination it has the potential to provide novel insights into the molecular mechanisms underlying disease.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Aptamer Applications in Neuroscience

Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, prion disease, or brain tumors. The diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theragnostic applications to meet these needs. This review covers pioneering studies in applying aptamers, which shows promise for future diagnostics and treatments of neurological disorders that pose increasingly dire worldwide health challenges.

60 APPLIED LIFE SCIENCES↗