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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 73 records · Page 4

Validation of pooling strategies of clinical COVID-19 samples for more efficient diagnostic testing

Pooling of COVID-19 clinical samples can offer significant reduction in reagents, time, and labor needed to test large numbers of clinical samples. Especially for testing asymptomatic and return-towork/ school cases, where the prevalence of COVID-19 may be relatively low, large groups of clinical samples can be classified as negative with a single test, with no need to test every sample individually. LANL has performed validation for two different pooling strategies to assess diagnostic assay sensitivity in pooled samples compared to the clinical positive sample alone. (1) Pooling study - Determine diagnostic assay sensitivity in pooled samples with ratios of 1:5, 1:10, 1:20, and 1:30 positive to negative clinical samples. (2) Reloading study - Determine diagnostic assay sensitivity in reloading of multiple clinical samples through a Qiagen column in 5x, 10, and 20x sample volumes (1 positive plus 4, 9, and 19 negative samples).

59 BASIC BIOLOGICAL SCIENCES↗

A Novel use of Direct Simulation Monte-Carlo to Model Dynamics of COVID-19 Pandemic Spread

In this report, we evaluate a novel method for modeling the spread of COVID-19 pandemic. In this new approach we leverage methods and algorithms developed for fully-kinetic plasma physics simulations using Particle-In-Cell (PIC) Direct Simulation Monte-Carlo (DSMC) models. This approach then leverages Sandia-unique simulation capabilities, and High-Performance Computer (HPC) resources and expertise in particle-particle interactions using stochastic processes. Our hypothesis is that this approach would provide a more efficient platform with assumptions based on physical data that would then enable the user to assess the impact of mitigation strategies and forecast different phases of infection. This work addresses key scientific questions related to the assumptions this new approach must make to model the interactions of people using algorithms typically used for modeling particle interactions in physics codes (kinetic plasma, gas dynamics). The model developed uses rational/physical inputs while also providing critical insight; the results could serve as inputs to, or alternatives for, existing models. The model work presented was developed over a four-week time frame, thus far showing promising results and many ways in which this model/approach could be improved. This work is aimed at providing a proof-of-concept for this new pandemic modeling approach, which could have an immediate impact on the COVID-19 pandemic modeling, while laying a basis to model future pandemic scenarios in a manner that is timely and efficient. Additionally, this new approach provides new visualization tools to help epidemiologists comprehend and articulate the spread of this and other pandemics as well as a more general tool to determine key parameters needed in order to better predict pandemic modeling in the future. In the report we describe our model for pandemic modeling, apply this model to COVID-19 data for New York City (NYC), assess model sensitivities to different inputs and parameters and , finally, propagate the model forward under different conditions to assess the effects of mitigation and associated timing. Finally, our approach will help understand the role of asymptomatic cases, and could be extended to elucidate the role of recovered individuals in the second round of the infection, which is currently being ignored.

59 BASIC BIOLOGICAL SCIENCES↗

Reducing COVID-19 Transmission in Homes

Owners and renters all over the world are being encouraged to stay home as much as possible to mitigate the spread of the SARS CoV-2 virus and the COVID-19 disease. It is prudent to take reasonable precautions at home to decrease risks during the pandemic because most COVID-19 transmission happens in the home (see “learn more”). This is particularly true for households with infected or sensitive members. Furthermore, because people infected with COVID-19 can be asymptomatic you may have an infected person in your home for several days before you know it.

60 APPLIED LIFE SCIENCES↗

Daily Forecasting of Regional Epidemics of Coronavirus Disease with Bayesian Uncertainty Quantification, United States

To increase situational awareness and support evidence-based policymaking, we formulated a mathematical model for coronavirus disease transmission within a regional population. This compartmental model accounts for quarantine, self-isolation, social distancing, a nonexponentially distributed incubation period, asymptomatic persons, and mild and severe forms of symptomatic disease. We used Bayesian inference to calibrate region-specific models for consistency with daily reports of confirmed cases in the 15 most populous metropolitan statistical areas in the United States. We also quantified uncertainty in parameter estimates and forecasts. This online learning approach enables early identification of new trends despite considerable variability in case reporting.

59 BASIC BIOLOGICAL SCIENCES↗

A Coupled Mathematical Model of the Intracellular Replication of Dengue Virus and the Host Cell Immune Response to Infection

Dengue virus (DV) is a positive-strand RNA virus of the Flavivirus genus. It is one of the most prevalent mosquito-borne viruses, infecting globally 390 million individuals per year. The clinical spectrum of DV infection ranges from an asymptomatic course to severe complications such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), the latter because of severe plasma leakage. Given that the outcome of infection is likely determined by the kinetics of viral replication and the antiviral host cell immune response (HIR) it is of importance to understand the interaction between these two parameters. In this study, we use mathematical modeling to characterize and understand the complex interplay between intracellular DV replication and the host cells' defense mechanisms. We first measured viral RNA, viral protein, and virus particle production in Huh7 cells, which exhibit a notoriously weak intrinsic antiviral response. Based on these measurements, we developed a detailed intracellular DV replication model. We then measured replication in IFN competent A549 cells and used this data to couple the replication model with a model describing IFN activation and production of IFN stimulated genes (ISGs), as well as their interplay with DV replication. By comparing the cell line specific DV replication, we found that host factors involved in replication complex formation and virus particle production are crucial for replication efficiency. Regarding possible modes of action of the HIR, our model fits suggest that the HIR mainly affects DV RNA translation initiation, cytosolic DV RNA degradation, and naïve cell infection. We further analyzed the potential of direct acting antiviral drugs targeting different processes of the DV lifecycle in silico and found that targeting RNA synthesis and virus assembly and release are the most promising anti-DV drug targets.

59 BASIC BIOLOGICAL SCIENCES↗

Comparative Virulence and Genomic Analysis of Streptococcus suis Isolates

Streptococcus suis is a zoonotic bacterial swine pathogen causing substantial economic and health burdens to the pork industry. Mechanisms used by S. suis to colonize and cause disease remain unknown and vaccines and/or intervention strategies currently do not exist. Studies addressing virulence mechanisms used by S. suis have been complicated because different isolates can cause a spectrum of disease outcomes ranging from lethal systemic disease to asymptomatic carriage. The objectives of this study were to evaluate the virulence capacity of nine United States S. suis isolates following intranasal challenge in swine and then perform comparative genomic analyses to identify genomic attributes associated with swine-virulent phenotypes. No correlation was found between the capacity to cause disease in swine and the functional characteristics of genome size, serotype, sequence type (ST), or in vitro virulence-associated phenotypes. A search for orthologs found in highly virulent isolates and not found in non-virulent isolates revealed numerous predicted protein coding sequences specific to each category. While none of these predicted protein coding sequences have been previously characterized as potential virulence factors, this analysis does provide a reliable one-to-one assignment of specific genes of interest that could prove useful in future allelic replacement and/or functional genomic studies. Collectively, this report provides a framework for future allelic replacement and/or functional genomic studies investigating genetic characteristics underlying the spectrum of disease outcomes caused by S. suis isolates.

59 BASIC BIOLOGICAL SCIENCES↗

SARS-CoV-2 Omicron (B.1.1.529) Infection of Wild White-Tailed Deer in New York City

There is mounting evidence of SARS-CoV-2 spillover from humans into many domestic, companion, and wild animal species. Research indicates that humans have infected white-tailed deer, and that deer-to-deer transmission has occurred, indicating that deer could be a wildlife reservoir and a source of novel SARS-CoV-2 variants. We examined the hypothesis that the Omicron variant is actively and asymptomatically infecting the free-ranging deer of New York City. Between December 2021 and February 2022, 155 deer on Staten Island, New York, were anesthetized and examined for gross abnormalities and illnesses. Paired nasopharyngeal swabs and blood samples were collected and analyzed for the presence of SARS-CoV-2 RNA and antibodies. Of 135 serum samples, 19 (14.1%) indicated SARS-CoV-2 exposure, and 11 reacted most strongly to the wild-type B.1 lineage. Of the 71 swabs, 8 were positive for SARS-CoV-2 RNA (4 Omicron and 4 Delta). Two of the animals had active infections and robust neutralizing antibodies, revealing evidence of reinfection or early seroconversion in deer. Variants of concern continue to circulate among and may reinfect US deer populations, and establish enzootic transmission cycles in the wild: this warrants a coordinated One Health response, to proactively surveil, identify, and curtail variants of concern before they can spill back into humans.

60 APPLIED LIFE SCIENCES↗

CT584 Is Not a Protective Vaccine Antigen against Respiratory Chlamydial Challenge in Mice

Background: Chlamydia trachomatis is the most prevalent bacterial sexually transmitted pathogen in humans worldwide. Since chlamydial infection is largely asymptomatic with the potential for serious complications, a preventative vaccine is likely the most viable long-term answer to this public health threat. Cell-free protein synthesis (CFPS) utilizes the cellular protein manufacturing machinery decoupled from the requirement for maintaining cellular viability, offering the potential for flexible, rapid, and decentralized production of recombinant protein vaccine antigens. Methods: Here, we use CFPS to produce the full-length putative chlamydial type three secretion system (T3SS) needle-tip protein, CT584, for evaluation as a vaccine antigen in mouse models. High-speed atomic force microscopy (HS-AFM) (RIBM, Tsukuba, Japan) imaging and computer simulations confirm that CFPS-produced CT584 retains a native-like structure prior to immunization. Female mice were primed with CT584 adjuvanted with CpG-1826 intranasally (i.n.) or CpG-1826 + Montanide ISA 720 intramuscularly (i.m.), followed four weeks later by an i.m. boost before respiratory challenge with 10 4 inclusion forming units (IFU) of Chlamydia muridarum. Results: Immunization with CT584 generated robust antibody responses but weak cell-mediated immunity and failed to protect against i.n. challenge as demonstrated by body weight loss, increased lung weights, and the presence of high numbers of IFUs in the lungs. Conclusion: While CT584 was not a protective vaccine candidate, the speed and flexibility with which CFPS can be used to produce other potential chlamydial antigens make it an attractive technique for antigen production.

60 APPLIED LIFE SCIENCES↗

Untoward effects of a sympathomimetic amine

Presentation and discussion of a clinical report describing asymptomatic multifocal ventricular premature contractions in a professional pilot. He had been taking heavy doses of a systemic decongestant agent, pseudoephedrine, prescribed by a physician. He was taken off the medication, and over the next few days the PVCs became less frequent, then disappeared. It is pointed out that physician's instructions to pilots must be given with the realization that some airmen may follow the instructions too zealously in an attempt to remain on flying status.

Billings, C. E.↗

Coronary heart disease index based on longitudinal electrocardiography

A coronary heart disease index was developed from longitudinal ECG (LCG) tracings to serve as a cardiac health measure in studies of working and, essentially, asymptomatic populations, such as pilots and executives. For a given subject, the index consisted of a composite score based on the presence of LCG aberrations and weighted values previously assigned to them. The index was validated by correlating it with the known presence or absence of CHD as determined by a complete physical examination, including treadmill, resting ECG, and risk factor information. The validating sample consisted of 111 subjects drawn by a stratified-random procedure from 5000 available case histories. The CHD index was found to be significantly more valid as a sole indicator of CHD than the LCG without the use of the index. The index consistently produced higher validity coefficients in identifying CHD than did treadmill testing, resting ECG, or risk factor analysis.

Townsend, J. C.↗

Fluid control mechanisms in weightlessness

Experiments performed on Space Shuttle flights have emphasized study of the earliest effects of the cephalad fluid shift resulting from microgravity. Analysis of one subject's urine collected during flight showed that a sharp increase in antidiuretic hormone occurred within 2 h of launch, followed by an increase in cortisol excretion. Although this subject had symptoms of the space adaptation syndrome (SAS), inflight data from Spacelab missions suggested that these transient changes were not caused by SAS. Unpaired t-tests and Mann-Whitney tests showed that before and after flight, plasma thyroxine and urine osmolality were significantly higher in Shuttle crewmembers who exhibited more severe symptoms of SAS than in asymptomatic crewmembers.

Leach, Carolyn S.↗

Studies of the horizontal vestibulo-ocular reflex on STS 7 and 8

Unpaced voluntary horizontal head oscillation was used to study the Vestibulo-Ocular Reflex (VOR) on Shuttle flights STS 7 and 8. Ten subjects performed head oscillations at 0.33 Hz + or - 30 deg amplitude under the followng conditions: VVOR (visual VOR), eyes open and fixed on a stationary target; VOR-EC, with eyes closed and fixed on the same target in imagination; and VOR-S (VOR suppression), with eyes open and fixed on a head-synchronized target. Effects of weightlessness, flight phase, and Space Motion Sickness (SMS) on head oscillation characteristics were examined. A significant increase in head oscillation frequency was noted inflight in subjects free from SMS. In subjects susceptible to SMS, frequency was reduced during their Symptomatic period. The data also suggest that the amplitude and peak velocity of head oscillation were reduced early inflight. No significant changes were noted in reflex gain or phase in any of the test conditions; however, there was a suggestion of an increase in VVOR and VOR-ES gain early inflight in asymptomatic subjects. A significant difference in VOR-S was found between SMS susceptible and non-susceptible subjects. There is no evidence that any changes in VOR characteristics contributed to SMS.

Thornton, William E.↗

Monitoring cognitive function and need with the automated neuropsychological assessment metrics in Decompression Sickness (DCS) research

Hypobaric decompression sickness (DCS) research presents the medical monitor with the difficult task of assessing the onset and progression of DCS largely on the basis of subjective symptoms. Even with the introduction of precordial Doppler ultrasound techniques for the detection of venous gas emboli (VGE), correct prediction of DCS can be made only about 65 percent of the time according to data from the Armstrong Laboratory's (AL's) hypobaric DCS database. An AL research protocol concerned with exercise and its effects on denitrogenation efficiency includes implementation of a performance assessment test battery to evaluate cognitive functioning during a 4-h simulated 30,000 ft (9144 m) exposure. Information gained from such a test battery may assist the medical monitor in identifying early signs of DCS and subtle neurologic dysfunction related to cases of asymptomatic, but advanced, DCS. This presentation concerns the selection and integration of a test battery and the timely graphic display of subject test results for the principal investigator and medical monitor. A subset of the Automated Neuropsychological Assessment Metrics (ANAM) developed through the Office of Military Performance Assessment Technology (OMPAT) was selected. The ANAM software provides a library of simple tests designed for precise measurement of processing efficiency in a variety of cognitive domains. For our application and time constraints, two tests requiring high levels of cognitive processing and memory were chosen along with one test requiring fine psychomotor performance. Accuracy, speed, and processing throughout variables as well as RMS error were collected. An automated mood survey provided 'state' information on six scales including anger, happiness, fear, depression, activity, and fatigue. An integrated and interactive LOTUS 1-2-3 macro was developed to import and display past and present task performance and mood-change information.

Nesthus, Thomas E.↗

Maintaining the Body's Immune System: Incidence of Latent Virus Shedding During Space Flight

Your body protects you from illness with its own security system - the immune system. This system keeps illness at bay not only by mounting a defense against foreign organisms, but also by controlling the population of bacteria and viruses that normally live in your body. But there's no need to panic: certain microbes can actually exist in your body without causing illness. Some bacteria are even beneficial - like the E. coli in the large intestine that are an important source of vitamin K. While viruses are not exactly considered beneficial, they can also inhabit the human body without causing immediate harm or infection. A good example is the herpes simplex virus type 1 (HSV1), more commonly known as cold sores or fever blisters. This virus infects 70 to 80 percent of all adults but remains latent much of the time. While latent, the virus within cells remains dormant. Activation of the dormant virus causes it to make copies of itself (known as replication) constantly detectable in body fluids such as urine or saliva in a process called shedding. When a person becomes sick or stressed, however, this weakened condition allows the virus to reactivate and multiply. These elevated levels may be enough to produce symptoms, but shedding can also occur without symptoms. This ability to shed without showing signs of infection, or asymptomatic shedding, is of great interest, as it increases the chances of infecting others. The stresses associated with space flight - adapting to microgravity, isolation from family and friends, living and working in a confined space, sleep deprivation, and busy schedules, to name but a few - may weaken astronauts' immune systems, leaving them at greater risk of viral reactivation. Members of the STS-107 crew will participate in this experiment, Incidence of Latent Viral Shedding in Space Flight, to help scientists understand how reactivation works in space, and at what level replication reaches before symptoms begin to show. This study also promises more insight into the behavior of the larger virus family, herpesvirus, which will help us understand how to prevent infection in populations on Earth and reactivation in those already infected.

Pierson, Duane↗

T wave alternans threshold late after repair of tetralogy of Fallot

INTRODUCTION: Sustained microvolt-level T wave alternans (TWA) is a marker of increased risk for malignant ventricular arrhythmia. There is a significant risk of arrhythmia and sudden death after repair of congenital heart disease. The aim of this study was to determine the prevalence and characteristics of TWA after repair of tetralogy of Fallot (TOF). METHODS AND RESULTS: TWA was evaluated during bicycle exercise in 49 subjects who had consecutively undergone transatrial-transpulmonary repair. Median values for age, age at repair, and follow-up duration were 14.9 years (11.5-20.8), 1.6 years (0.2-4.9), and 11.6 years (9.4-17.2), respectively. All patients were in New York Heart Association functional class I and were asymptomatic. Median QRS duration was 120 msec (80-150). Sustained TWA was detected in 7 (23%) of 31 subjects with adequate tests. In these 7 subjects, median onset heart rate (HR) was 120 (98-155). Median HR threshold as a percentage of predicted maximum HR (220 - age) was 58% (48-77). Sustained TWA prevalence was not significantly different compared with normal subjects (7/31 vs 9/83; P = 0.1). Onset HR in the TOF group was significantly lower [mean (SD) of 122 (20) vs 139 (12), P < 0.05]. In the TOF group with sustained TWA, the TWA occurred in 4 of 7 at <60% predicted maximum HR versus 1 of 9 normal subjects (P < 0.05); 3 of 7 had onset HR <120 versus 0 of 9 normal subjects (P < 0.03). There was no significant difference in age, gender, transannular patch use, restrictive right ventricular physiology, QRS duration, QTc, QT/QRS dispersion, or nonsustained ventricular tachycardia in subjects with or those without sustained TWA. CONCLUSION: The onset HR for sustained TWA is significantly lower after repair of TOF. Further study is required to determine whether this represents an increased risk for arrhythmia in this patient group.

Non-NASA Center↗

Seedborne fungal contamination: consequences in space-grown wheat

Plants grown in microgravity are subject to many environmental stresses that may promote microbial growth and result in disease symptoms. Wheat (cv. Super Dwarf) recovered from an 8-day mission aboard a NASA (National Aeronautics and Space Administration) space shuttle showed disease symptoms, including girdling of leaf sheaths and chlorosis and necrosis of leaf and root tissues. A Neotyphodium species was isolated from the seed and leaf sheaths of symptomatic wheat used in the spaceflight mission. Certain isozymes of a peroxidase unique to extracts from the microgravity-grown plants were observed in extracts from earth-grown Neotyphodium-infected plants but were not present in noninfected wheat. The endophytic fungus was eliminated from the wheat seed by prolonged heat treatment at 50 degrees C followed by washes with water at 50 degrees C. Plants from wheat seed infected with the Neotyphodium endophyte were symptomless when grown under greenhouse conditions, whereas symptoms appeared after only 4 days of growth in closed containers. Disease spread from an infected plant to noninfected plants in closed containers. Dispersion via spores was found on asymptomatic plants at distances of 7 to 18 cm from infected plants. The size and shape of the conidia, mycelia, and phialide-bearing structures and the ability to grow rapidly on carbohydrates, especially xylose, resembled the characteristics of N. chilense, which is pathogenic on orchard grass, Doctylis glomerati. The Neotyphodium wheat isolate caused disease symptoms on other cereals (wheat cv. Malcolm, orchard grass, barley, and maize) grown in closed containers.

NASA Discipline Plant Biology↗

An episode of ventricular tachycardia during long-duration spaceflight

An episode of nonsustained ventricular tachycardia was recorded from a crew member during the second month aboard the MIR space station. Although asymptomatic, this cardiac event increases the concern that serious cardiac dysrhythmias may be a limiting factor during long-duration spaceflight.

NASA Center JSC↗