Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “infection control”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial

HIV-1 therapy with single or dual broadly neutralizing antibodies (bNAbs) has shown viral escape, indicating that at least a triple bNAb therapy may be needed for robust suppression of viremia. We performed a two-part study consisting of a single-center, randomized, double-blind, dose-escalation, placebo-controlled first-in-human trial of the HIV-1 V2-glycan-specific antibody PGDM1400 alone or in combination with the V3-glycan-specific antibody PGT121 in 24 adults without HIV in part 1, as well as a multi-center, open-label trial of the combination of PGDM1400, PGT121 and the CD4-binding-site antibody VRC07-523LS in five viremic adults living with HIV not on antiretroviral therapy (ART) in part 2. The primary endpoints were safety, tolerability and pharmacokinetics for both parts and antiviral activity among viremic adults living with HIV and not on ART for part 2 of the study. The secondary endpoints were changes in CD4 + T cell counts and development of HIV-1 sequence variations associated with PGDM1400, PGT121 and VRC07-523LS resistance in part 2. Intravenously administered PGDM1400 was safe and well-tolerated at doses up to 30 mg kg -1 and when given in combination with PGT121 and VRC07-523LS. A single intravenous infusion of 20 mg kg -1 of each of the three antibodies reduced plasma HIV RNA levels in viremic individuals by a maximum mean of 2.04 log10 copies per ml; however, viral rebound occurred in all participants within a median of 20 days after nadir. Rebound viruses demonstrated partial to complete resistance to PGDM1400 and PGT121 in vitro, whereas susceptibility to VRC07-523LS was preserved. Viral rebound occurred despite mean VRC07-523LS serum concentrations of 93 µg ml -1 . The trial met the pre-specified endpoints. Our data suggest that future bNAb combinations likely need to achieve broad antiviral activity, while also maintaining high serum concentrations, to mediate viral control.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

AeDES: a next-generation monitoring and forecasting system for environmental suitability of Aedes-borne disease transmission

Aedes-borne diseases, such as dengue and chikungunya, are responsible for more than 50 million infections worldwide every year, with an overall increase of 30-fold in the last 50 years, mainly due to city population growth, more frequent travels and ecological changes. In the United States of America, the vast majority of Aedes-borne infections are imported from endemic regions by travelers, who can become new sources of mosquito infection upon their return home if the exposed population is susceptible to the disease, and if suitable environmental conditions for the mosquitoes and the virus are present. Since the susceptibility of the human population can be determined via periodic monitoring campaigns, the environmental suitability for the presence of mosquitoes and viruses becomes one of the most important pieces of information for decision makers in the health sector. We present a next-generation monitoring and forecasting system for Aedes-borne diseases’ environmental suitability (AeDES) of transmission in the conterminous United States and transboundary regions, using calibrated ento-epidemiological models, climate models and temperature observations. After analyzing the seasonal predictive skill of AeDES, we briefly consider the recent Zika epidemic, and the compound effects of the current Central American dengue outbreak happening during the SARS-CoV-2 pandemic, to illustrate how a combination of tailored deterministic and probabilistic forecasts can inform key prevention and control strategies .

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Tomato deploys defence and growth simultaneously to resist bacterial wilt disease

Abstract Plant disease limits crop production, and host genetic resistance is a major means of control. Plant pathogenic Ralstonia causes bacterial wilt disease and is best controlled with resistant varieties. Tomato wilt resistance is multigenic, yet the mechanisms of resistance remain largely unknown. We combined metaRNAseq analysis and functional experiments to identify core Ralstonia ‐responsive genes and the corresponding biological mechanisms in wilt‐resistant and wilt‐susceptible tomatoes. While trade‐offs between growth and defence are common in plants, wilt‐resistant plants activated both defence responses and growth processes. Measurements of innate immunity and growth, including reactive oxygen species production and root system growth, respectively, validated that resistant plants executed defence‐related processes at the same time they increased root growth. In contrast, in wilt‐susceptible plants roots senesced and root surface area declined following Ralstonia inoculation. Wilt‐resistant plants repressed genes predicted to negatively regulate water stress tolerance, while susceptible plants repressed genes predicted to promote water stress tolerance. Our results suggest that wilt‐resistant plants can simultaneously promote growth and defence by investing in resources that act in both processes. Infected susceptible plants activate defences, but fail to grow and so succumb to Ralstonia , likely because they cannot tolerate the water stress induced by vascular wilt.

Meline, Valerian↗
NASA NTRS1996

Effect of space flight on cytokine production and other immunologic parameters of rhesus monkeys

During a recent flight of a Russian satellite (Cosmos #2229), initial experiments examining the effects of space flight on immunologic responses of rhesus monkeys were performed to gain insight into the effect of space flight on resistance to infection. Experiments were performed on tissue samples taken from the monkeys before and immediately after flight. Additional samples were obtained approximately 1 month after flight for a postflight restraint study. Two types of experiments were carried out throughout this study. The first experiment determined the ability of leukocytes to produce interleukin-1 and to express interleukin-2 receptors. The second experiment examined the responsiveness of rhesus bone marrow cells to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Human reagents that cross-reacted with monkey tissue were utilized for the bulk of the studies. Results from both studies indicated that there were changes in immunologic function attributable to space flight. Interleukin-1 production and the expression of interleukin-2 receptors was decreased after space flight. Bone marrow cells from flight monkeys showed a significant decrease in their response to GM-CSF compared with the response of bone marrow cells from nonflight control monkeys. These results suggest that the rhesus monkey may be a useful surrogate for humans in future studies that examine the effect of space flight on immune response, particularly when conditions do not readily permit human study.

unmanned↗
NASA NTRS2010

Particular Characterisation of an In-Vitro-DTH Test to Monitor Cellular Immunity - Applications for Patient Care and Space Flight

Goal:i) Characterization of the role of the main immune reactive cell types contributing to the cellular immune response in the in-vitro DTH and ii) Validation of the in-vitro DTH under different clinical and field conditions. Methods:As positive control whole blood was incubated in the in-vitro DTH, supernatants were gathered after 12, 24 and 48h. Readout parameters of this test are cytokines in the assay's supernatant. To determine the role of T-cells, monocytes and natural killer (NK), these cell populations were depleted using magnetic beads prior to in-vitro-DTH incubation. Validation of the test has occurred under clinical (HIV-patients, ICU) and field-conditions (parabolic/space-flights, confinement). Results:T-cell depletion abandoned almost any IL-2 production and reduced IFN-gamma production irrespective of the type of antigen, whereas CD56 depleted cultures tended to lower IL-2 secretion and IFN-gamma and to parallel a IL-10-increase after viral challenge. This IL-10-increase was seen also in CD14-depleted setups. DTH read-out was significantly different under acute stress (parabolic flight) or chronic stress (ISS), respectively. Preliminary data of HIV infected patients demonstrate that this test can display the contemporary immune status during an antiviral therapy. Conclusion:The in-vitro DTH mirrors adaptive and innate immune activation and may serve as tool also for longitudinal follow up of Th1/Th2 weighed immune response under adverse life conditions on earth and in space. It is planned to implement the assay in the on the ISS (MoCISS).

Feurecker, M.↗
DOE OSTI2023

Building a Computational and Experimental Rapid Response Pipeline to Counter the Coronavirus Disease 2019 Outbreak and Emerging Biothreats

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs, especially where protective candidates can be rapidly identified or developed for emerging biothreats and escape variants. Current cutting-edge technologies for this purpose still rely on pathogen-exposed convalescent volunteers and a large screening effort to find a proverbial needle in a haystack. Computational design of protective antibodies based on pre-existing templates skips those requirements and allows for greater control over the breadth and target epitope, while also co-optimizing for potency and developability or other biophysical characteristics. We approached this problem by building and expanding an in vitro experimental rapid antibody production and characterization pipeline to support development of an autonomous, closed loop, active learning software system based on structural simulation and ground truth experimental data to design and evaluate antibody antigen interactions. Starting from early in the pandemic, we targeted SARS-CoV-2, the causative agent of COVID-19, by re-purposing neutralizing antibodies against SARS-CoV-1 that had been identified in the wake of that outbreak in the early 2000’s. We successfully re-targeted three different anti-SARS-CoV-1 antibodies to neutralize SARS-CoV-2 in vitro, where the antibodies were generated externally and tested through conventional binding and neutralization assays internally or with collaborators. As antibodies were identified from the blood of humans infected with SARS-CoV-2, we shifted to collaborate with academic partners to develop improved versions of their human-derived antibodies. This work reached its most important stage in rapid response to the emergence of the Omicron variant of concern (VOC) in late 2021. In a matter of weeks, enabled by on demand innovation to our screening pipeline, we computationally designed and experimentally characterized derivative antibodies of COV2-2130, one of two antibodies from Vanderbilt that form the basis of the AstraZeneca Evusheld prophylactic drug product. This drug product suffers a serious loss of efficacy against Omicron BA.1 and BA.1.1, the first Omicron strains. Due to tight integration of computational design and experimental evaluation, we were able to identify a pair of designs with potent neutralization of the main targets Omicron BA.1 and BA.1.1; but also the earlier Delta variant, and subsequent Omicron strains including BA.2, BA.4, BA.5, and BA.2.75, demonstrating that our multi-target design process can, by its nature, produce robust antibody designs that strictly improve over the parental antibody. These results, recognized by a 2022 Director’s Science and Technology award, have enabled the follow-on GUIDE program, to commence in FY23. While earlier design campaigns were substantially outsourced, we have engineered better and faster processes internally to better compliment, calibrate, and speed computational designs. As part of the follow-on GUIDE program, we will stand up a rapid and high-throughput antibody production and characterization facility staffed with the expertise and capabilities to foster our current collaboration across PLS and ENG as well as other partnerships toward computational design of biologics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Preparing Lamellae from Vitreous Biological Samples using a Dual-Beam Scanning Electron Microscope for Cryo-Electron Tomography

Presented here is a protocol for preparing cryo-lamellae from plunge-frozen grids of Plasmodium falciparum-infected human erythrocytes, which could easily be adapted for other biological samples. The basic principles for preparing samples, milling, and viewing lamellae are common to all instruments and the protocol can be followed as a general guide to on-grid cryo-lamella preparation for cryo-electron microscopy (cryoEM) and cryo-electron tomography (cryoET). Electron microscopy grids supporting the cells are plunge-frozen into liquid nitrogen-cooled liquid ethane using a manual or automated plunge freezer, then screened on a light microscope equipped with a cryo-stage. Frozen grids are transferred into a cryo-scanning electron microscope equipped with a focused ion beam (cryoFIB-SEM). Grids are routinely sputter coated prior to milling, which aids dispersal of charge build-up during milling. Alternatively, an e-beam rotary coater can be used to apply a layer of carbon-platinum to the grids, the exact thickness of which can be more precisely controlled. Once inside the cryoFIB-SEM an additional coating of an organoplatinum compound is applied to the surface of the grid via a gas injection system (GIS). This layer protects the front edge of the lamella as it is milled, the integrity of which is critical for achieving uniformly thin lamellae. Regions of interest are identified via SEM and milling is carried out in a step-wise fashion, reducing the current of the ion beam as the lamella reaches electron transparency, in order to avoid excessive heat generation. A grid with multiple lamellae is then transferred to a transmission electron microscope (TEM) under cryogenic conditions for tilt-series acquisition. A robust and contamination-free workflow for lamella preparation is an essential step for downstream techniques, including cellular cryoEM, cryoET, and sub-tomogram averaging. Development of these techniques, especially for lift-out and milling of high-pressure frozen samples, is of high-priority in the field.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Repetitive diacetyl vapor exposure promotes ubiquitin proteasome stress and precedes bronchiolitis obliterans pathology

Bronchiolitis obliterans (BO) is a devastating lung disease seen commonly after lung transplant but also seen following severe respiratory tract infection or chemical inhalation exposure. Diacetyl (DA; 2,3-butanedione), highly reactive alpha-diketone is known to cause BO when inhaled, however, the mechanisms of how inhalation exposure leads to BO development remains poorly understood. In the current work, we combined two clinically relevant models for studying the pathogenesis of DA-induced BO: (1) an in vivo rat model of repetitive DA vapor exposures with recovery and (2) an in vitro model of primary human airway epithelial cells exposed to pure DA vapors. Rats exposed to 5 consecutive days 200 parts-per-million DA 6 hrs per day had worsening survival, persistent hypoxemia, poor weight gain, and histologic evidence of BO 14 days after DA exposure cessation. At the end of exposure, increased expression of the ubiquitin stress protein, ubiquitin-C, accumulated within DA-exposed rat lung homogenates, localized primarily to the airway epithelium, the primary site of BO development, and did not occur in air-exposed controls. Lung proteasome activity increased concurrently after DA exposure. In primary human airway cultures, global proteomics analysis identified 519 significantly modified proteins in DA-exposed samples relative to controls with the ubiquitin proteasome system, endosomal reticulum transport, and the response to unfolded protein pathways being upregulated while cell-cell adhesion and oxidation-reduction pathways being downregulated in DA-exposed samples. Altogether, repetitive DA vapor exposure resulted in abundant protein damage, accumulation of polyubiquinated proteins, and ubiquitin proteasome stress prior to the development of chemical-induced BO pathology.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2003

Stress-Induced Subclinical Reactivation of Varicella Zoster Virus in Astronauts

After primary infection, varicella-zoster virus (VZV) becomes latent in ganglia. VZV reactivation occurs primarily in elderly individuals, organ transplant recipients, and patients with cancer and AIDS, correlating with a specific decline in cell-mediated immunity to VZV. VZV can also reactivate after surgical stress. To determine whether VZV can also reactivate after acute non-surgical stress, we examined total DNA extracted from 312 saliva samples of eight astronauts before, during and after space flight for VZV DNA by PCR: 112 samples were obtained 234 to 265 days before flight, 84 samples on days 2 through 13 of space flight, and 116 samples on days 1 through 15 after flight. Before space flight only one of the 112 saliva samples from a single astronaut was positive for VZV DNA. In contrast, during and after space flight, 61 of 200 (30%) saliva samples were positive in all 8 astronauts. No VZV DNA was detected in any of 88 saliva samples from 10 healthy control subjects. These data indicate that VZV can reactivate subclinically in healthy individuals after acute stress.

Mehta, Satish K.↗
DOE OSTI2023

A scoping review of zoonotic parasites and pathogens associated with abattoirs in Eastern Africa and recommendations for abattoirs as disease surveillance sites

Abattoirs are facilities where livestock are slaughtered and are an important aspect in the food production chain. There are several types of abattoirs, which differ in infrastructure and facilities, sanitation and PPE practices, and adherence to regulations. In each abattoir facility, worker exposure to animals and animal products increases their risk of infection from zoonotic pathogens. Backyard abattoirs and slaughter slabs have the highest risk of pathogen transmission because of substandard hygiene practices and minimal infrastructure. These abattoir conditions can often contribute to environmental contamination and may play a significant role in disease outbreaks within communities. To assess further the risk of disease, we conducted a scoping review of parasites and pathogens among livestock and human workers in abattoirs across 13 Eastern African countries, which are hotspots for zoonoses. Our search results (n = 104 articles) showed the presence of bacteria, viruses, fungi, and macroparasites (nematodes, cestodes, etc.) in cattle, goats, sheep, pigs, camels, and poultry. Most articles reported results from cattle, and the most frequent pathogen detected was Mycobacterium bovis, which causes bovine tuberculosis. Some articles included worker survey and questionnaires that suggested how the use of PPE along with proper worker training and safe animal handling practices could reduce disease risk. Based on these findings, we discuss ways to improve abattoir biosafety and increase biosurveillance for disease control and mitigation. Abattoirs are a ‘catch all’ for pathogens, and by surveying animals at abattoirs, health officials can determine which diseases are prevalent in different regions and which pathogens are most likely transmitted from wildlife to livestock. We suggest a regional approach to biosurveillance, which will improve testing and data gathering for enhanced disease risk mapping and forecasting. Next generation sequencing will be key in identifying a wide range of pathogens, rather than a targeted approach.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Glacier ice archives nearly 15,000-year-old microbes and phages

Background Glacier ice archives information, including microbiology, that helps reveal paleoclimate histories and predict future climate change. Though glacier-ice microbes are studied using culture or amplicon approaches, more challenging metagenomic approaches, which provide access to functional, genome-resolved information and viruses, are under-utilized, partly due to low biomass and potential contamination. Results We expand existing clean sampling procedures using controlled artificial ice-core experiments and adapted previously established low-biomass metagenomic approaches to study glacier-ice viruses. Controlled sampling experiments drastically reduced mock contaminants including bacteria, viruses, and free DNA to background levels. Amplicon sequencing from eight depths of two Tibetan Plateau ice cores revealed common glacier-ice lineages including Janthinobacterium, Polaromonas, Herminiimonas, Flavobacterium, Sphingomonas, and Methylobacterium as the dominant genera, while microbial communities were significantly different between two ice cores, associating with different climate conditions during deposition. Separately, ~355- and ~14,400-year-old ice were subject to viral enrichment and low-input quantitative sequencing, yielding genomic sequences for 33 vOTUs. These were virtually all unique to this study, representing 28 novel genera and not a single species shared with 225 environmentally diverse viromes. Further, 42.4% of the vOTUs were identifiable temperate, which is significantly higher than that in gut, soil, and marine viromes, and indicates that temperate phages are possibly favored in glacier-ice environments before being frozen. In silico host predictions linked 18 vOTUs to co-occurring abundant bacteria (Methylobacterium, Sphingomonas, and Janthinobacterium), indicating that these phages infected ice-abundant bacterial groups before being archived. Functional genome annotation revealed four virus-encoded auxiliary metabolic genes, particularly two motility genes suggest viruses potentially facilitate nutrient acquisition for their hosts. Finally, given their possible importance to methane cycling in ice, we focused on Methylobacterium viruses by contextualizing our ice-observed viruses against 123 viromes and prophages extracted from 131 Methylobacterium genomes, revealing that the archived viruses might originate from soil or plants. Conclusions Together, these efforts further microbial and viral sampling procedures for glacier ice and provide a first window into viral communities and functions in ancient glacier environments. Such methods and datasets can potentially enable researchers to contextualize new discoveries and begin to incorporate glacier-ice microbes and their viruses relative to past and present climate change in geographically diverse regions globally.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

cGAS-like receptors sense RNA and control 3'2'-cGAMP signalling in Drosophila

Cyclic GMP–AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger cG[2'–5']pA[3'–5']p (2'3'-cGAMP) and controls activation of innate immunity in mammalian cells. Animal genomes typically encode multiple proteins with predicted homology to cGAS, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors that are capable of recognizing divergent molecular patterns and catalysing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signalling core shared with cGAS and a diversified primary ligand-binding surface modified with notable insertions and deletions. We demonstrate that surface remodelling of cGLRs enables altered ligand specificity and used a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. We show that RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3'–5']pA[2'–5']p (3'2'-cGAMP). A crystal structure of Drosophila stimulator of interferon genes (dSTING) in complex with 3'2'-cGAMP explains selective isomer recognition, and 3'2'-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Perceptions of Seasonal Influenza Vaccine Among U.S. Army Civilians and Dependents in the Kaiserslautern Military Community: A Mixed-Methods Survey

ABSTRACT Introduction Influenza is a globally occurring viral respiratory infection that can lead to hospitalizations and death. An influenza outbreak can interfere with combat readiness in a military setting, as the infection can incapacitate soldiers. Vaccination remains the most effective tool to prevent and mitigate seasonal influenza. Although influenza vaccinations for U.S. Army soldiers can be monitored through military health systems, those systems cannot capture DoD civilians and Army dependents who may not use military health services. This study aims to gauge flu vaccine uptake and perceptions in U.S. Army civilians and dependents. Materials and Methods An online survey was e-mailed to civilian and dependent enrollees of Landstuhl Regional Medical Center. The survey contained 24 questions pertaining to demographics, vaccine history, history of the flu, and beliefs toward vaccines. Chi-square tests, t-tests, and logistic regressions were performed to investigate the association between demographic, behavior, and belief factors with vaccine uptake. Free-text answers were coded and categorized by themes. Results Over 70% of respondents were vaccinated for the flu. There were differences between vaccinated and unvaccinated respondents regarding their perceptions of barriers to vaccination, benefits of the flu vaccine, severity of flu symptoms, and personal risk of getting ill with the flu. After controlling for confounders, flu vaccination in the previous season and healthcare worker status were associated with increased vaccine uptake, while perceived barriers to influenza vaccination were associated with decreased vaccine uptake. Conclusions Flu vaccine uptake may be increased by increasing access to vaccination, promoting vaccination and addressing concerns at the provider level, and engaging positively framed public messaging. Increasing flu vaccine uptake is of particular importance as the flu season approaches during the COVID-19 (Coronavirus disease 2019) pandemic.

Burns, MSC, Veronica M.↗
DOE OSTI2023

The increasing threat of Rift Valley fever virus globalization: strategic guidance for protection and preparation

Rift Valley fever virus (RVFV) (Bunyavirales: Phlebovirus) is a prominent vector-borne zoonotic disease threat to global agriculture and public health. Risks of introduction into nonendemic regions are tied to changing climate regimes and other dynamic environmental factors that are becoming more prevalent, as well as virus evolutionary factors and human/animal movement. Endemic to the African continent, RVFV has caused large epizootics at the decadal scale since the early 20th century but has spread to the Arabian Peninsula and shows increasing patterns of interepizootic transmission on the annual scale. This virus can be transmitted by mosquitoes as well as through direct contact with infected tissues and can cause sporadic to widespread morbidity and mortality in domestic ungulate livestock as well as humans. High viremias in infected livestock moved for legal and illegal trade as well as in infected mosquitoes or human travelers can spread this virus worldwide. With increasing global commerce, it is likely RVFV will be introduced to new areas with suitable hosts, mosquito vector species, and environments. However, the strong mosquito component of RVFV epidemiology combined with advancements in vaccines, diagnostics, and virus evolutionary factors create opportunities for strategies to leverage models of connectivity among potential source and emerging regions to target surveillance and mitigation activities to reduce the risk of RVFV introduction, or contain the virus should it be introduced, into new regions.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2018

Gene Expression of Pathogens in Simulated Microgravity

Extended exposure to radiation and microgravity in space has been linked to astronauts developing chronic diseases upon returning to Earth. The Gram-negative pathogen Serratia marcescens has been shown to potentially cause significant infections in humans and in insect models on Earth. Our recent findings also showed that S. marcescens shows an increase in virulence after a short period of growth in the spaceflight environment, which raises initiatives to find the correlation between space environment and the increased virulence. Because we know that the health of astronauts is immunocompromised in space, it is possible that the combination of increased bacterial virulence and the weakened immune system will cause astronauts to be more susceptible to chronic diseases in extended spaceflight. With 75% of human disease genes being conserved in the fruit fly Drosophila melanogaster, these insects act as an ideal model organism to study the human immune system. The high accessibility, low cost, high rate of reproductivity, and short lifespans of D. melanogaster facilitate efficient, high-quality research that seeks to understand altered virulence of this opportunistic pathogen. In this ground-based study, we will use a rotating wall vessel apparatus to simulate microgravity and determine how pathogenicity changes by evaluating differences in gene expression for S. marcescens between bacteria grown in simulated microgravity conditions and controls. We will compare the results of our findings to gene expression patterns in actual spaceflight samples of S. marcescens grown on the ISS (International Space Station) during a recent validation mission, to see if there are common mechanisms across our simulated microgravity and actual spaceflight microgravity samples that both show increased virulence in the fruit fly. With extended space travel in the foreseeable future, understanding how human physiology will be affected by these different factors will help mitigate risks and deaths.

spaceflight analogue↗
DOE OSTI2024

Efficacy of commercial recombinant HVT vaccines against a North American clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus in chickens

The outbreak of clade 2.3.4.4b H5 highly pathogenic avian influenza (HPAI) in North America that started in 2021 has increased interest in applying vaccination as a strategy to help control and prevent the disease in poultry. Two commercially available vaccines based on the recombinant herpes virus of turkeys (rHVT) vector were tested against a recent North American clade 2.3.4.4b H5 HPAI virus isolate: A/turkey/Indiana/22-003707-003/2022 H5N1 in specific pathogen free white leghorn (WL) chickens and commercial broiler chickens. One rHVT-H5 vaccine encodes a hemagglutinin (HA) gene designed by the computationally optimized broadly reactive antigen method (COBRA-HVT vaccine). The other encodes an HA gene of a clade 2.2 virus (2.2-HVT vaccine). There was 100% survival of both chicken types COBRA-HVT vaccinated groups and in the 2.2-HVT vaccinated groups there was 94.8% and 90% survival of the WL and broilers respectively. Compared to the 2.2-HVT vaccinated groups, WL in the COBRA-HVT vaccinated group shed significantly lower mean viral titers by the cloacal route and broilers shed significantly lower titers by the oropharyngeal route than broilers. Virus titers detected in oral and cloacal swabs were otherwise similar among both vaccine groups and chicken types. To assess antibody-based tests to identify birds that have been infected after vaccination (DIVA-VI), sera collected after the challenge were tested with enzyme-linked lectin assay-neuraminidase inhibition (ELLA-NI) for N1 neuraminidase antibody detection and by commercial ELISA for detection of antibodies to the NP protein. As early as 7 days post challenge (DPC) 100% of the chickens were positive by ELLA-NI. ELISA was less sensitive with a maximum of 75% positive at 10DPC in broilers vaccinated with 2.2-HVT. Both vaccines provided protection from challenge to both types of chickens and ELLA-NI was sensitive at identifying antibodies to the challenge virus therefore should be evaluated further for DIVA-VI.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Precursor Analysis Report: Blackmatter Ransomware Attack on New Cooperative 2021

The BlackMatter Ransomware Attack on New Cooperative 2021 Precursor Analysis Report leverages publicly available information about the New Cooperative cyber attack and catalogs anomalous observables for each technique employed in the attack. This analysis is based upon the methodology of the Cybersecurity for the Operational Technology Environment (CyOTE) program. The BlackMatter ransomware was first identified in July 2021 and is reported to have infected more than 50 corporations around the world. , The Iowa-based grain cooperative, New Cooperative, was impacted by the BlackMatter ransomware on or before 18 September 2021. The adversary likely resided on New Cooperative’s networks for 15 days prior to encrypting its network and demanding New Cooperative pay $5.9 million in ransom by 25 September to unlock systems and prevent 1 terabyte (TB) of sensitive data from being publicly released. It is not clear if New Cooperative paid the ransom. The full impact of the ransomware attack is not known; however, according to New Cooperative’s general manager, the attack caused the company’s automated processes to revert back to processes used in the 1970s. , As of 6 October, only 50 percent of New Cooperative’s operations were utilizing automated processes. The company took eight weeks to rebuild the entire network and information technology (IT) systems from the ground up, which puts the date of fully recovery around 13 November. Researchers and analysts identified 20 unique techniques utilized during the attack with a total of 404 observables using MITRE ATT&CK® for Industrial Control Systems. The CyOTE program assesses observables accompanying techniques used prior to the triggering event to identify opportunities to detect malicious activity. If observables accompanying the attack techniques are perceived and investigated prior to the triggering event, earlier comprehension of malicious activity can take place. Seventeen of the identified techniques used during the New Cooperative cyber attack were precursors to the triggering event. Analysis identified 360 observables associated with these precursor techniques, 284 of which were assessed to have an increased likelihood of being perceived in the 15 days preceding the triggering event. The response and comprehension time could have been reduced if the observables had been identified earlier. The information gathered in this report contributes to a library of observables tied to a repository of artifacts, data sources, and technique detection references for practitioners and developers to support the comprehension of indicators of attack. Asset owners and operators can use these products if they experience similar observables or to prepare for comparable scenarios.

45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEF↗
NASA NTRS2007

Surveillance and Control of Malaria Transmission in Thailand using Remotely Sensed Meteorological and Environmental Parameters

These slides address the use of remote sensing in a public health application. Specifically, this discussion focuses on the of remote sensing to detect larval habitats to predict current and future endemicity and identify key factors that sustain or promote transmission of malaria in a targeted geographic area (Thailand). In the Malaria Modeling and Surveillance Project, which is part of the NASA Applied Sciences Public Health Applications Program, we have been developing techniques to enhance public health's decision capability for malaria risk assessments and controls. The main objectives are: 1) identification of the potential breeding sites for major vector species; 2) implementation of a risk algorithm to predict the occurrence of malaria and its transmission intensity; 3) implementation of a dynamic transmission model to identify the key factors that sustain or intensify malaria transmission. The potential benefits are: 1) increased warning time for public health organizations to respond to malaria outbreaks; 2) optimized utilization of pesticide and chemoprophylaxis; 3) reduced likelihood of pesticide and drug resistance; and 4) reduced damage to environment. !> Environmental parameters important to malaria transmission include temperature, relative humidity, precipitation, and vegetation conditions. The NASA Earth science data sets that have been used for malaria surveillance and risk assessment include AVHRR Pathfinder, TRMM, MODIS, NSIPP, and SIESIP. Textural-contextual classifications are used to identify small larval habitats. Neural network methods are used to model malaria cases as a function of the remotely sensed parameters. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records. Discrete event simulations are used for modeling the detailed interactions among the vector life cycle, sporogonic cycle and human infection cycle, under the explicit influences of selected extrinsic and intrinsic factors. The output of the model includes the individual infection status and the quantities normally observed in field studies, such as mosquito biting rates, sporozoite infection rates, gametocyte prevalence and incidence. Results are in good agreement with mosquito vector and human malaria data acquired by Coleman et al. over 4.5 years in Kong Mong Tha, a remote village in western Thailand. Application of our models is not restricted to the Greater Mekong Subregion. Our models have been applied to malaria in Indonesia, Korea, and other regions in the world with similar success.

Kiang, Richard K.↗