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At least 649 records · Page 36
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Inflammatory Bowel Disease Gene Discovery Final Report CRADA No. TC-1335-96

The ultimate goal of this project is to identify the human gene( s) responsible for the disorder known as IBD. As a first step towards this goal, the Parties agreed to carry out experiments to c011fim1 and refine linkage of IBD to the chromosomal region( s) of interest identified by gene/Networks, Inc. If results confirmed association of these region(s) with the disease, the Parties planned to complete a physical map of the genetically defined region(s). The work was planned in two phases. The desired products resulting from Phase I were BAC clone(s) containing the genetic marker(s) identified by gene\Networks, Inc. as potentially linked to IBD, plasmid subclones of those BAC(s), and new genetic markers developed from these plasmid subclones. The newly developed markers would be genotyped by gene/Networks, Inc. to ascertain evidence for linkage or non-linkage of IBD to this region. If non-linkage was indicated, the project would move to investigation of other candidate chromosomal regions. Where linkage was indicated, the project would move to Phase II, in which a physical map of the candidate region(s) would be developed. The products of this phase would be contig(s) of BAC clones in the region exhibiting linkage to IBD, as well as plasmid subclones of the BACs and further genetic marker development. There would also be continued genotyping with new polymorphic markers during this phase. It was anticipated that clones identified and developed during these two phases would provide the physical resources for eventual disease gene discovery.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Conditioning multi-model ensembles for disease forecasting

In this study we investigate how an ensemble of disease models can be conditioned to observational data, in a bid to improve its predictive skill. We use the ensemble of influenza forecasting models gathered by the US Centers for Disease Control and Prevention (CDC) as the exemplar. This ensemble is used every year to forecast the annual influenza outbreak in the United States. The models constituting this ensemble draw on very different modeling assumptions and approximations and are a diverse collection of methods to approximate epidemiological dynamics. Currently, each models' predictions are accorded the same importance, or weight, when compiling the ensemble's forecast. We consider this equally-weighted ensemble as the baseline case which has to be improved upon. In this study, we explore whether an ensemble forecast can be improved by "conditioning" the ensemble to whatever observational data is available from the ongoing outbreak. "Conditioning" can imply according the ensemble's members different weights which evolve over time, or simply perform the forecast using the top k (equally-weighted) models. In the latter case, the composition of the "top-k-see of models evolves over time. This is called "model averaging" in statistics. We explore four methods to perform model-averaging, three of which are new. We find that the CDC ensemble responds best to the "top-k-models" approach to model-averaging. All the new MA methods perform better than the baseline equally-weighted ensemble. The four model-averaging methods treat the models as black-boxes and simply use their forecasts as inputs i.e., one does not need access to the models at all, but rather only their forecasts. The model-averaging approaches reviewed in this report thus form a general framework for model-averaging any model ensemble.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Water Cycle-Driven Infectious Diseases as Multiscale, Reliable, Continuously Updating Water Cycle Sensors

We propose a novel synthesis of observational and simulated data (climatological and biological) to enhance understanding of the real-world interplay between climate (here, the water cycle) and the epidemiology of water cycle-driven infectious disease. Aligning with Focal Area 2, predictive modeling using AI techniques, we will develop systems of hierarchical models to discover latent features of the water cycle. Our approach will leverage state-of-the-art in Artificial Intelligence (AI) to measure the degree to which climate change-driven shifts in water cycle can be predicted by supplementing sparse and irregular climate data with water cycle-driven infectious disease resources.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Disease Precognition [Slides]

How can we reduce the health and economic impacts future epidemics and pandemics? Global Real-Time Disease Forecasting is not just for weather anymore! Disease precognition technology is discussed.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Plant Disease Detection Technology Assessment

Visual inspections by US Customs and Border Protection agriculture specialists have identified approximately 20,000 regulated, quarantined pests each year in agricultural products entering the United States. Most of these pests identified in the Agriculture Quarantine and Inspection (AQI) program are insects. Many pathogens are difficult to detect in agricultural products, particularly in early stages of infection. New technologies can help to detect plant pathogens and the diseases that they cause. This technology assessment was performed for the US Department of Homeland Security Science and Technology Directorate (DHS S&T) through the Food, Agriculture, and Veterinary Defense (FAV-D) program to identify emerging technologies that could address this hard problem. These emerging technologies differ in their diagnostic sensitivities and specificities, as well as in their measurement time and training requirements. New instruments that detect volatile organic compounds characteristic of plant disease or pathogens could provide a less invasive inspection method. Dogs, which can successfully detect many concealed agricultural products, have also been trained to detect some plant pests and pathogens. Simple immunological tests offer sensitive and specific detection of many pathogens at the point of use. Advanced imaging methods that use AI to sort fruits and vegetables and recognize anomalies at high speeds could be used in cooperation with exporters to improve food quality and reduce pests. Advances in nucleic acid–based detection methods that have become gold standards for confirmatory diagnostics are now making those methods available for faster, point-of-use detection. These new methods should be developed in the context of AQI operational requirements, which apply risk-based sampling protocols to protect agriculture and facilitate commerce and passenger transit.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Surveilling Influenza Incidence With Centers for Disease Control and Prevention Web Traffic Data: Demonstration Using a Novel Dataset

Influenza epidemics result in a public health and economic burden worldwide. Traditional surveillance techniques, which rely on doctor visits, provide data with a delay of 1 to 2 weeks. A means of obtaining real-time data and forecasting future outbreaks is desirable to provide more timely responses to influenza epidemics. This study aimed to present the first implementation of a novel dataset by demonstrating its ability to supplement traditional disease surveillance at multiple spatial resolutions. We used internet traffic data from the Centers for Disease Control and Prevention (CDC) website to determine the potential usability of this data source. Additionally, we tested the traffic generated by 10 influenza-related pages in 8 states and 9 census divisions within the United States and compared it against clinical surveillance data.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Novel Mutant Alleles Reveal a Role of the Extra-Large G Protein in Rice Grain Filling, Panicle Architecture, Plant Growth, and Disease Resistance

Plant growth and grain filling are the key agronomical traits for grain weight and yield of rice. The continuous improvement in rice yield is required for a future sustainable global economy and food security. The heterotrimeric G protein complex containing a canonical α subunit (RGA1) couples extracellular signals perceived by receptors to modulate cell function including plant development and grain weight. We hypothesized that, besides RGA1, three atypical, extra-large GTP-binding protein (XLG) subunits also regulate panicle architecture, plant growth, development, grain weight, and disease resistance. Here, we identified a role of XLGs in agronomic traits and stress tolerance by genetically ablating all three rice XLGs individually and in combination using the CRISPR/Cas9 genome editing in rice. For this study, eight (three single, two double, and three triple) null mutants were selected. Three XLG proteins combinatorically regulate seed filling, because loss confers a decrease in grain weight from 14% with loss of one XLG and loss of three to 32% decrease in grain weight. Null mutations in XLG2 and XLG4 increase grain size. The mutants showed significantly reduced panicle length and number per plant including lesser number of grains per panicle compared to the controls. Loss-of-function of all individual XLGs contributed to 9% more aerial biomass compared to wild type (WT). The double mutant showed improved salinity tolerance. Moreover, loss of the XLG gene family confers hypersensitivity to pathogens. Our findings suggest that the non-canonical XLGs play important roles in regulating rice plant growth, grain filling, panicle phenotype, stress tolerance, and disease resistance. Genetic manipulation of XLG s has the potential to improve agronomic properties in rice.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Inactivation of highly transmissible livestock and avian viruses including influenza A and Newcastle disease virus for molecular diagnostics

There is a critical need for an inactivation method that completely inactivates pathogens at the time of sample collection while maintaining the nucleic acid quality required for diagnostic PCR testing. This inactivation method is required to alleviate concerns about transmission potential, minimize shipping complications and cost, and enable testing in lower containment laboratories, thereby enhancing disease diagnostics through improved turn-around time. This study evaluated a panel of 10 surrogate viruses that represent highly pathogenic animal diseases. These results showed that a commercial PrimeStore® molecular transport media (PSMTM) completely inactivated all viruses tested by >99.99%, as determined by infectivity and serial passage assays. However, the detection of viral nucleic acid by qRT-PCR was comparable in PSMTM and control-treated conditions. These results were consistent when viruses were evaluated in the presence of biological material such as sera and cloacal swabs to mimic diagnostic sample conditions for non-avian and avian viruses, respectively. The results of this study may be utilized by diagnostic testing laboratories for highly pathogenic agents affecting animal and human populations. These results may be used to revise guidance for select agent diagnostic testing and the shipment of infectious substances.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Long-Term Effects of Very Low Dose Particle Radiation on Gene Expression in the Heart: Degenerative Disease Risks

Compared to low doses of gamma irradiation (γ-IR), high-charge-and-energy (HZE) particle IR may have different biological response thresholds in cardiac tissue at lower doses, and these effects may be IR type and dose dependent. Three- to four-month-old female CB6F1/Hsd mice were exposed once to one of four different doses of the following types of radiation: γ-IR 137Cs (40-160 cGy, 0.662 MeV), 14Si-IR (4-32 cGy, 260 MeV/n), or 22Ti-IR (3-26 cGy, 1 GeV/n). At 16 months post-exposure, animals were sacrificed and hearts were harvested and archived as part of the NASA Space Radiation Tissue Sharing Forum. These heart tissue samples were used in our study for RNA isolation and microarray hybridization. Functional annotation of twofold up/down differentially expressed genes (DEGs) and bioinformatics analyses revealed the following: (i) there were no clear lower IR thresholds for HZE- or γ-IR; (ii) there were 12 common DEGs across all 3 IR types; (iii) these 12 overlapping genes predicted various degrees of cardiovascular, pulmonary, and metabolic diseases, cancer, and aging; and (iv) these 12 genes revealed an exclusive non-linear DEG pattern in 14Si- and 22Ti-IR-exposed hearts, whereas two-thirds of γ-IR-exposed hearts revealed a linear pattern of DEGs. Thus, our study may provide experimental evidence of excess relative risk (ERR) quantification of low/very low doses of full-body space-type IR-associated degenerative disease development.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2024

Comparison of Routes of Administration, Frequency, and Duration of Favipiravir Treatment in Mouse and Guinea Pig Models of Ebola Virus Disease

Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013–2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Towards prevention and prediction of infectious diseases with virus sterilization using ultraviolet light and low-temperature plasma and bio-sensing devices for health and hygiene care

Inspired by the ideas of many authors, we provide insight on state-of-the-art potential technologies for the prevention and prediction of infectious diseases before they spread. This review also surveys virus sterilization with ultraviolet light and low temperature plasma technologies. Researchers in the various fields of medicine, materials, electronics, and plasma sciences have addressed increasingly challenging demands and the discussion encompasses the major challenges in societies that are faced with the threat of infectious diseases. In addition, technologies that use nanomaterials are evaluated for infection prevention and hygiene purposes. Advances in biomedical diagnostics for health care in terms of complementary metal-oxide-semiconductor transistors-based devices and telemetry for health monitoring are also reviewed.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A Structural Basis for Inhibition of the Complement Initiator Protease C1r by Lyme Disease Spirochetes

Abstract Complement evasion is a hallmark of extracellular microbial pathogens such as Borrelia burgdorferi, the causative agent of Lyme disease. Lyme disease spirochetes express nearly a dozen outer surface lipoproteins that bind complement components and interfere with their native activities. Among these, BBK32 is unique in its selective inhibition of the classical pathway. BBK32 blocks activation of this pathway by selectively binding and inhibiting the C1r serine protease of the first component of complement, C1. To understand the structural basis for BBK32-mediated C1r inhibition, we performed crystallography and size-exclusion chromatography–coupled small angle X-ray scattering experiments, which revealed a molecular model of BBK32-C in complex with activated human C1r. Structure-guided site-directed mutagenesis was combined with surface plasmon resonance binding experiments and assays of complement function to validate the predicted molecular interface. Analysis of the structures shows that BBK32 inhibits activated forms of C1r by occluding substrate interaction subsites (i.e., S1 and S1’) and reveals a surprising role for C1r B loop–interacting residues for full inhibitory activity of BBK32. The studies reported in this article provide for the first time (to our knowledge) a structural basis for classical pathway–specific inhibition by a human pathogen.

Garrigues, Ryan J. (ORCID:0000000259233250)↗
DOE OSTI2016

Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia

The most common cause of early onset primary dystonia, a neuromuscular disease, is a glutamate deletion (ΔE) at position 302/303 of TorsinA, a AAA+ ATPase that resides in the endoplasmic reticulum. While the function of TorsinA remains elusive, the ΔE mutation is known to diminish binding of two TorsinA ATPase activators: lamina-associated protein 1 (LAP1) and its paralog, luminal domain like LAP1 (LULL1). Using a nanobody as a crystallization chaperone, we obtained a 1.4 Å crystal structure of human TorsinA in complex with LULL1. This nanobody likewise stabilized the weakened TorsinAΔE-LULL1 interaction, which enabled us to solve its structure at 1.4 Å also. A comparison of these structures shows, in atomic detail, the subtle differences in activator interactions that separate the healthy from the diseased state. This information may provide a structural platform for drug development, as a small molecule that rescues TorsinAΔE could serve as a cure for primary dystonia.

Demircioglu, F. Esra (ORCID:0000000238662742)↗
NASA NTRS1972

Potentiality for obtaining poria disease signatures in the Oregon Cascades from orbital altitudes

A prime photographic signature indicator of an important forest disease was identified in valuable Douglas-fir stands of the Pacific Northwest. The disease signature was verified by a multidisciplinary team of scientists to be the direct result of the Poria weirii root-rot syndrome in the Douglas-fir and hemlock stands of the high Cascades in Oregon. It is readily discernible on small-scale suborbital photography and has good potential for detection from earth-orbiting satellites or remote sensing platforms.

Wear, J. F.↗
NASA NTRS1969

Psychosocial factors in coronary heart disease

The relationship between job satisfaction and coronary heart disease is explored for blue and white collar groups, different personalities and physiological risk factors. Differences found among administrators, engineers and scientists with regard to variables associated with heart disease are in terms of physiology, personality, reported job stress, and smoking.

French, J. R. P., Jr.↗
NASA NTRS1974

Studies on disease transmission in spacecraft environments

The effects of the Skylab gas mixtures on general health and immunocompetence of mice and ferrets subjected to the Skylab space cabin environment (SCE) were initially studied in a stainless steel low pressure facility which was maintained at gas ratios of 30% nitrogen and 70% oxygen under 5 psia, and which consisted of two subchambers, that permitted mutual isolation of experimental groups and/or selective removal of animals without return of the entire cabin to ambient pressure was developed. The studies demonstrated that ferrets immunized with Brucella Strain 19 prior to being housed in SCE had decreased synthesis of IgG compared to their respective controls. The possibility of latent infections being responsible for stress-induced upper respiratory diseases of astronauts required that the role of neutralizing antibody as a function of antibody affinity/avidity be investigated. The model consisted of Aleutian disease virus (ADV) which infects ferrets and mink resulting in nonneutralized immune complexes. These studies demonstrated that early antibody to ADV had lower affinity/avidity than late antibody with respect to chronicity. These studies culminated in a description of antibody affinity, first isolation of ADV and its cultivation in vitro.

Kenyon, A. J.↗
NASA NTRS1975

Investigations of remote sensing techniques for early detection of Dutch elm disease

Several forms of aerial photography were pursued in quest of a technique which could provide early detection of Dutch elm disease. The two most promising techniques tested were multispectral photography with object enhancement and biband ratioing coupled with scanning microdensitometry. For practical purposes the multispectral system has the advantage of providing a readily interpretable image in a relatively short time. Laboratory studies indicated that less emphasis should be placed on the use of a red filter or the near infrared beyond 750 mm for early detection of stress within a single plant species. Color infrared film would be optimal when used for a long term detection of loss of plant vigor which results in a physical change in a plant canopy, but should find minimal practicality for early detection of specific sources of plant stress such as Dutch elm disease. Considerable discretion should be used when interpreting imagery on copy film because of loss of resolution and color definition.

Hammerschlag, R. S.↗
NASA NTRS1978

Evaluation of thallium-201 scanning for detection of latent coronary artery disease

The use of thallium imaging as a noninvasive method to accurately screen shuttle passengers for latent coronary artery disease was investigated. All radionuclide procedures were performed using an Anger type camera with a high resolution collimator. A minimum of 200,000 counts were collected for each image using a 20% window centered on the 69-83 keV X-rays. For the images obtained following injection with the patient at rest, the testing was begun 10 minutes after injection. Injections of TT during exercise were made at a point near the termination of the treadmill procedure as determined by either the appearance of ST segment changes on the electrocardiogram consistant with subendocardial ischemia, the appearance of angina-like chest pain in the patient or fatigue in the patient which required cessation of the test. The severity of heart disease was based on the medical history, physical exam, exercise electrocardiograms, chest X-rays and the coronary arteriogram.

Johnson, P. C.↗