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At least 865 records · Page 48

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DOE OSTI2019

Comparative Genomics Guides Elucidation of Vitamin B 12 Biosynthesis in Novel Human-Associated Akkermansia Strains

Akkermansia muciniphila is a mucin-degrading bacterium found in the gut of most humans and is considered a “next-generation probiotic.” However, knowledge of the genomic and physiological diversity of human-associated Akkermansia sp. strains is limited. Here, we reconstructed 35 metagenome-assembled genomes and combined them with 40 publicly available genomes for comparative genomic analysis. We identified at least four species-level phylogroups (AmI to AmIV), with distinct functional potentials. Most notably, we identified genes for cobalamin (vitamin B 12 ) biosynthesis within the AmII and AmIII phylogroups. To verify these predictions, 10 Akkermansia strains were isolated from adults and screened for vitamin B 12 biosynthesis genes via PCR. Two AmII strains were positive for the presence of cobalamin biosynthesis genes, while all 9 AmI strains tested were negative. To demonstrate vitamin B 12 biosynthesis, we measured the production of acetate, succinate, and propionate in the presence and absence of vitamin supplementation in representative strains of the AmI and AmII phylogroups, since cobalamin is an essential cofactor in propionate metabolism. Results showed that the AmII strain produced acetate and propionate in the absence of supplementation, which is indicative of vitamin B 12 biosynthesis. In contrast, acetate and succinate were the main fermentation products for the AmI strains when vitamin B 12 was not supplied in the culture medium. Lastly, two bioassays were used to confirm vitamin B 12 production by the AmII phylogroup. This novel physiological trait of human-associated Akkermansia strains may affect how these bacteria interact with the human host and other members of the human gut microbiome.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2015

Preliminary Framework for Human-Automation Collaboration

The Department of Energy’s Advanced Reactor Technologies Program sponsors research, development and deployment activities through its Next Generation Nuclear Plant, Advanced Reactor Concepts, and Advanced Small Modular Reactor (aSMR) Programs to promote safety, technical, economical, and environmental advancements of innovative Generation IV nuclear energy technologies. The Human Automation Collaboration (HAC) Research Project is located under the aSMR Program, which identifies developing advanced instrumentation and controls and human-machine interfaces as one of four key research areas. It is expected that the new nuclear power plant designs will employ technology significantly more advanced than the analog systems in the existing reactor fleet as well as utilizing automation to a greater extent. Moving towards more advanced technology and more automation does not necessary imply more efficient and safer operation of the plant. Instead, a number of concerns about how these technologies will affect human performance and the overall safety of the plant need to be addressed. More specifically, it is important to investigate how the operator and the automation work as a team to ensure effective and safe plant operation, also known as the human-automation collaboration (HAC). The focus of the HAC research is to understand how various characteristics of automation (such as its reliability, processes, and modes) effect an operator’s use and awareness of plant conditions. In other words, the research team investigates how to best design the collaboration between the operators and the automated systems in a manner that has the greatest positive impact on overall plant performance and reliability. This report addresses the Department of Energy milestone M4AT-15IN2302054, Complete Preliminary Framework for Human-Automation Collaboration, by discussing the two phased development of a preliminary HAC framework. The framework developed in the first phase was used as the basis for selecting topics to be investigated in more detail. The results and insights gained from the in-depth studies conducted during the second phase were used to revise the framework. This report describes the basis for the framework developed in phase 1, the changes made to the framework in phase 2, and the basis for the changes. Additional research needs are identified and presented in the last section of the report.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

DOE OSTI2018

The Strategic Value of Human Factors Engineering in Control Room Modernization

Control room modernization is one of the most challenging and complex upgrade projects that a nuclear power plant can undertake. It can have almost as big an impact on operations as, for example, turbine replacement. The challenges of migrating an analog control system to a distributed control system are already well known and a number of nuclear utilities have embarked upon various levels of effort to upgrade some of the systems in the control room. When planning for control room upgrades, plants have to deal with a multitude of engineering, operational, and regulatory impacts. This will inevitably include several human factors considerations, such as workstation ergonomics, viewing angles, lighting, seating, new interaction modalities, new communication requirements, and new concepts of operation. In helping nuclear power utilities to deal with these challenges, the United States Department of Energy researchers located at Idaho National Laboratory (INL) have developed research-based human factors design and evaluation methods to be used in the development of end-state concepts for modernized control rooms and to manage the various phases of the upgrade life cycle. The methodology includes interactive sessions with operators in INL’s Human System Simulation Laboratory, three-dimensional modeling to visualize control board changes and operator-system interaction, and development of human-system prototypes to evaluate various aspects of proposed modifications. This methodology has been applied at a number of U.S. nuclear power plants where modernization projects are underway, including Exelon’s Braidwood and Byron plants, and Arizona Public Service's Palo Verde plant. It was demonstrated that including this methodology in the plant’s engineering process helps to ensure an integrated and cohesive outcome that is consistent with human factors engineering principles and provide substantial improvement in operator performance.

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2019

Optimal Operator Training Reference Models for Human-in-the-loop Systems

The human operator is an integral part of a stable and safe power system. While there is increasing attention paid to automation improvements, the importance of understanding and training human operators may be understated. This paper discusses a project to enhance operator training programs by evaluating human performance relative to a reference operator model identified using optimal control theory. Along with establishing a simple computer-based operator workstation for future training purpose, this paper describes the optimal control response design methodology for a human-in-the-loop power system experiment. The overall system model is presented. An optimal controller synthesis methodology is applied to the model system and the optimal controller is designed. The performance of the optimal controller is then compared to human subject performance.

24 POWER TRANSMISSION AND DISTRIBUTION↗

DOE OSTI2024

Human Host Cellular Response to HCoV-229E Infection Transcriptomics (ACS-DP1)

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

Human Host Cellular Response to HCoV-229E Infection Proteomics (ACS-JM-DP2)

The purpose of this experiment was to evaluate the human host cellular response to wild-type Human coronavirus strain 229E (HCoV-229E) infection. Sample data was obtained for mock and infected immortalized human lung epithelial cells (A549) (MOI 5) nuclear extracts, immortalized human lung fibroblasts cells (MRC5) (MOI5) nuclear extracts, and primary human airway epithelial (HAE) (MOI 3) cells from lung tissue and processed for proteome analysis. Processed datasets are openly accessible from the download button and contain secondary processed proteomic results files and supporting metadata materials. Experimental proteomics samples were prepared using Limited Proteolysis (LiP) methods for Label-free quantification (LFQ) and global proteomic evaluation. Sample data was acquired using a Q-Exactive HF-X mass spectrometer and was processed and compiled using MaxQuant software (v.1.6.17.0). Processed proteomic data downloads include a sample naming key, processed MaxQuant results/parameters, and protein annotated relative abundance files. See corresponding primary data accessions below and Viral Experiment LiP Analysis source code supporting data transparency and reuse. Experimental transcriptomics samples were collected in parallel and processed for RNA sequencing (RNA-Seq) as summarized under ACS-DP1 (https://data.pnnl.gov/group/nodes/dataset/34069).

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Whole-Genome Sequencing and Bioinformatic Analysis of Environmental, Agricultural, and Human Campylobacter jejuni Isolates From East Tennessee

As a leading cause of bacterial-derived gastroenteritis worldwide, Campylobacter jejuni has a significant impact on human health in both the developed and developing worlds. Despite its prevalence as a human pathogen, the source of these infections remains poorly understood due to the mutation frequency of the organism and past limitations of whole genome analysis. Recent advances in both whole genome sequencing and computational methods have allowed for the high-resolution analysis of intraspecies diversity, leading multiple groups to postulate that these approaches may be used to identify the sources of Campylobacter jejuni infection. To address this hypothesis, our group conducted a regionally and temporally restricted sampling of agricultural and environmental Campylobacter sources and compared isolated C. jejuni genomes to those that caused human infections in the same region during the same time period. Through a network analysis comparing genomes from various sources, we found that human C. jejuni isolates clustered with those isolated from cattle and chickens, indicating these as potential sources of human infection in the region.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Human-Centric Lighting: Foundational Considerations and a Five-Step Design Process

At its best, human-centric lighting considers the visual and non-visual effects of light in support of positive human outcomes. At its worst, it is a marketing phrase used to healthwash lighting products or lighting design solutions. There is no doubt that environmental lighting contributes to human health, but how might one practice human-centric lighting given both the credible potential and the implausible hype? Marketing literature is filled with promises. Technical lighting societies have summarized the science but have not yet offered design guidance. Meanwhile, designers are in the middle, attempting to distinguish credible knowledge from that which is dubious to make design decisions that affect people directly. This article is intended to: (1) empower the reader with fundamental understandings of ways in which light affects health; (2) provide a process for human-centric lighting design that can dovetail with the decision-making process that is already a part of a designer's workflow.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2023

Investigating the impact of environmental factors on West Nile virus human case prediction in Ontario, Canada

West Nile virus is the most common mosquito borne disease in North America and the leading cause of viral encephalitis. West Nile virus is primarily transmitted between birds and mosquitoes while humans are incidental, dead-end hosts. Climate change may increase the risk of human infections as climatic variables have been shown to affect the mosquito life cycle, biting rate, incubation period of the disease in mosquitoes, and bird migration patterns. We develop a zero-inflated Poisson model to investigate how human West Nile virus case counts vary with respect to mosquito abundance and infection rates, bird abundance, and other environmental covariates. We use a Bayesian paradigm to fit our model to data from 2010–2019 in Ontario, Canada. Our results show mosquito infection rate, temperature, precipitation, and crow abundance are positively correlated with human cases while NDVI and robin abundance are negatively correlated with human cases. We find the inclusion of spatial random effects allows for more accurate predictions, particularly in years where cases are higher. Our model is able to accurately predict the magnitude and timing of yearly West Nile virus outbreaks and could be a valuable tool for public health officials to implement prevention strategies to mitigate these outbreaks.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

Immortalization of normal human mammary epithelial cells in two steps by direct targeting of senescence barriers does not require gross genomic alterations

Telomerase reactivation and immortalization are critical for human carcinoma progression. However, little is known about the mechanisms controlling this crucial step, due in part to the paucity of experimentally tractable model systems that can examine human epithelial cell immortalization as it might occur in vivo. We achieved efficient non-clonal immortalization of normal human mammary epithelial cells (HMEC) by directly targeting the 2 main senescence barriers encountered by cultured HMEC. The stress-associated stasis barrier was bypassed using shRNA to p16INK4; replicative senescence due to critically shortened telomeres was bypassed in post-stasis HMEC by c-MYC transduction. Thus, 2 pathologically relevant oncogenic agents are sufficient to immortally transform normal HMEC. The resultant non-clonal immortalized lines exhibited normal karyotypes. Most human carcinomas contain genomically unstable cells, with widespread instability first observed in vivo in pre-malignant stages; in vitro, instability is seen as finite cells with critically shortened telomeres approach replicative senescence. Our results support our hypotheses that: (1) telomere-dysfunction induced genomic instability in pre-malignant finite cells may generate the errors required for telomerase reactivation and immortalization, as well as many additional “passenger” errors carried forward into resulting carcinomas; (2) genomic instability during cancer progression is needed to generate errors that overcome tumor suppressive barriers, but not required per se; bypassing the senescence barriers by direct targeting eliminated a need for genomic errors to generate immortalization. Achieving efficient HMEC immortalization, in the absence of “passenger” genomic errors, should facilitate examination of telomerase regulation during human carcinoma progression, and exploration of agents that could prevent immortalization.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2014

Human Respiratory Coronaviruses Detected In Patients with InfluenzaLike Illness in Arkansas, USA

Acute respiratory viruses often result in significant morbidity and mortality. The potential impact of human respiratory coronavirus (CoV) infections was underestimated until the severe acute respiratory syndrome (SARS-CoV) outbreak in 2003, which showed that new, highly pathogenic coronaviruses could be introduced to humans, highlighting the importance of monitoring the circulating coronaviruses. The use of sensitive molecular methods has contributed to the differential diagnosis of viruses circulating in humans. Our study aim was to investigate the molecular epidemiology of human CoV strains circulating in Arkansas, their genetic variability and their association with reported influenza-like symptoms. We analyzed 200 nasal swab samples, collected by the Arkansas Department of Health in 2010, for influenza diagnosis. All samples were from patients showing acute respiratory symptoms while testing negative for influenza. Samples were pre-screened, using a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) multiprobe for coronavirus, and subjected to confirmatory pancoronavirus and/or strain-specific reverse transcriptase (RT)-PCR followed by sequence analysis. Seventy-nine samples (39.5%) were positive by qRT-PCR and 35 samples (17.5%) were confirmed by conventional RT-PCR. Twenty-three of the confirmed samples (59%) were sequenced. The most frequent strain detected was HCoV-OC43-like followed by NL63-like; only one sample was positive for HCoV-229E and one for HCoV-HKU1. Feline-like CoV strains were detected in three samples, representing possible evidence of interspecies transmission or a new human strain. Seventeen percent of the coronavirus positive samples were also positive for other respiratory viruses, such as Respiratory Syncytial Virus (RSV), Parainfluenza 2 and 3, and Rhinovirus. Thus, HCoV-OC43, NL63, HKU1 and new feline-like strains were circulating in Arkansas in 2010. HCoV was the sole respiratory virus detected in 16% of the patients who showed acute respiratory symptoms with negative diagnoses for influenza virus.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS1993

Piloting Vertical Flight Aircraft: A Conference on Flying Qualities and Human Factors

This document contains papers from a specialists' meeting entitled "Piloting Vertical Flight Aircraft. A Conference on Flying Qualities and Human Factors." The conference was co-sponsored by the American Helicopter Society--San Francisco Bay Chapter, and the NASA Ames Research Center. It was held January 20-22, 1993 at the Sheraton Hotel Fisherman's Wharf, San Francisco, California. Vertical flight aircraft, including helicopters and a variety of Vertical Takeoff and Landing (VTOL) concepts, place unique requirements on human perception, control, and performance for the conduct of their design missions. The intent of this conference was to examine, for these vehicles, advances in: (1) design of flight control systems for ADS-33C standards; (2) assessment of human factors influences of cockpit displays and operational procedures; (3) development of VTOL design and operational criteria; and (4) development of theoretical methods or models for predicting pilot-vehicle performance and mission suitability. Recognizing that human capabilities and limitations form an integral aspect of the operations for these classes of vehicles, a secondary goal of the conference was to provide an initial venue for enhanced interaction between human factors and handling qualities specialists.

Helicopter↗

NASA NTRS2002

Gene conversion is strongly induced in human cells by double-strand breaks and is modulated by the expression of BCL-x(L)

Homology-directed repair (HDR) of DNA double-strand breaks (DSBs) contributes to the maintenance of genomic stability in rodent cells, and it has been assumed that HDR is of similar importance in DSB repair in human cells. However, some outcomes of homologous recombination can be deleterious, suggesting that factors exist to regulate HDR. We demonstrated previously that overexpression of BCL-2 or BCL-x(L) enhanced the frequency of X-ray-induced TK1 mutations, including loss of heterozygosity events presumed to arise by mitotic recombination. The present study was designed to test whether HDR is a prominent DSB repair pathway in human cells and to determine whether ectopic expression of BCL-x(L) affects HDR. Using TK6-neo cells, we find that a single DSB in an integrated HDR reporter stimulates gene conversion 40-50-fold, demonstrating efficient DSB repair by gene conversion in human cells. Significantly, DSB-induced gene conversion events are 3-4-fold more frequent in TK6 cells that stably overexpress the antiapoptotic protein BCL-X(L). Thus, HDR plays an important role in maintaining genomic integrity in human cells, and ectopic expression of BCL-x(L) enhances HDR of DSBs. This is the first study to highlight a function for BCL-x(L) in modulating DSB repair in human cells.

NASA Discipline Radiation Health↗

NASA NTRS2003

Critical issues in connection with human missions to Mars: protection of and from the Martian environment

Human missions to Mars are planned to happen within this century. Activities associated therewith will interact with the environment of Mars in two reciprocal ways: (i) the mission needs to be protected from the natural environmental elements that can be harmful to human health, the equipment or to their operations; (ii) the specific natural environment of Mars should be protected so that it retains its value for scientific and other purposes. The following environmental elements need to be considered in order to protect humans and the equipment on the planetary surface: (i) cosmic ionizing radiation, (ii) solar particle events; (iii) solar ultraviolet radiation; (iv) reduced gravity; (v) thin atmosphere; (vi) extremes in temperatures and their fluctuations; and (vii) surface dust. In order to protect the planetary environment, the requirements for planetary protection as adopted by COSPAR for lander missions need to be revised in view of human presence on the planet. Landers carrying equipment for exobiological investigations require special consideration to reduce contamination by terrestrial microorganisms and organic matter to the greatest feasible extent. Records of human activities on the planet's surface should be maintained in sufficient detail that future scientific experimenters can determine whether environmental modifications have resulted from explorations. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Extraterrestrial Environment↗

NASA NTRS1992

Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude mice. Neoplastic transformation was achieved by irradiating cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level.

NASA Discipline Number 04-10↗

NASA NTRS2000

Food and nutrition in space: application to human health

The National Aeronautics and Space Administration begins the new millennium with the hope of expanding human space exploration beyond Earth's orbit. These extended-duration missions (3-5 years) require an in-depth assessment of the critical risks (referred to as "show stoppers") to humans when exposed to the remote environment and reduced gravity conditions for such long periods of time. Food, and the nutrition it provides, is paramount to crew health. For short-duration spaceflight (30 days), the nutrient requirements pertaining to physiological adaptations are likely to be satisfied without significant impact on crew performance or health. However, prolonged exposure to reduced gravity, or microgravity, and isolation may alter human nutrient requirements as well as increase the psychosocial role of food/meals in daily activities. An outline of critical questions and related research needs in the area of food and nutrition has been drafted (1) at NASA JSC with the help of the National Space Biomedical Research Institute (http://www.nsbri.org). The research areas outlined in this plan will directly impact the success of extended-duration human space missions. Findings from this research will have direct applications to human health issues faced here on Earth.

NASA Discipline Regulatory Physiology↗

NASA NTRS2000

Measuring the spectrum of mutation induced by nitrogen ions and protons in the human-hamster hybrid cell line A(L)C

Astronauts can be exposed to charged particles, including protons, alpha particles and heavier ions, during space flights. Therefore, studying the biological effectiveness of these sparsely and densely ionizing radiations is important to understanding the potential health effects for astronauts. We evaluated the mutagenic effectiveness of sparsely ionizing 55 MeV protons and densely ionizing 32 MeV/nucleon nitrogen ions using cells of two human-hamster cell lines, A(L) and A(L)C. We have previously characterized a spectrum of mutations, including megabase deletions, in human chromosome 11, the sole human chromosome in the human-hamster hybrid cell lines A(L)C and A(L). CD59(-) mutants have lost expression of a human cell surface antigen encoded by the CD59 gene located at 11p13. Deletion of genes located on the tip of the short arm of 11 (11p15.5) is lethal to the A(L) hybrid, so that CD59 mutants that lose the entire chromosome 11 die and escape detection. In contrast, deletion of the 11p15.5 region is not lethal in the hybrid A(L)C, allowing for the detection of chromosome loss or other chromosomal mutations involving 11p15.5. The 55 MeV protons and 32 MeV/nucleon nitrogen ions were each about 10 times more mutagenic per unit dose at the CD59 locus in A(L)C cells than in A(L) cells. In the case of nitrogen ions, the mutations observed in A(L)C cells were predominantly due to chromosome loss events or 11p deletions, often containing a breakpoint in the pericentromeric region. The increase in the CD59(-) mutant fraction for A(L)C cells exposed to protons was associated with either translocation of portions of 11q onto a hamster chromosome, or discontinuous or "skipping" mutations. We demonstrate here that A(L)C cells are a powerful tool that will aid in the understanding of the mutagenic effects of different types of ionizing radiation.

Non-NASA Center↗

NASA NTRS1999

Localization of the human 64kD autoantigen D1 to myofibrils in a subset of extraocular muscle fibers

PURPOSE. To evaluate the tissue-specific expression pattern of the 64kD human autoantigen D1, a tropomodulin-related protein that may be involved in thyroid-associated ophthalmopathy. METHODS. Recombinant 64kD human autoantigen D1 was generated in a bacterial expression system and used to immunize rabbits. Specific antibodies were affinity-purified and used for Western blots on normal and hyperthyroid rat and rabbit tissue, and immunofluorescence localization on cryosections of rat tissue. RESULTS. Anti-64kD human autoantigen D1 antibodies recognize specifically a approximately 70kD polypeptide in western blots of extraocular muscle, sternothyroid muscle, and smooth muscle. Immunofluorescence staining demonstrates that the 64kD human autoantigen D1 localizes to myofibrils in slow fibers from rat extraocular and sternothyroid muscle. The level of this protein is not altered in extraocular muscles from hyperthyroid rabbits. CONCLUSIONS. The 64kD human autoantigen D1 is expressed in slow fibers of extraocular and sternothyroid muscles as a component of myofibrils, and is not upregulated in conditions of hyperthyroidism.

Proteins/genetics/immunology/metabolism↗