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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 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Advanced Human-System Interface Risk Analysis Based on Redundancy-guided Systems-theoretic Hazard Analysis and Human Reliability Analysis

Human-system interfaces (HSIs) play an important role in enabling operators to communicate with the nuclear power plant (NPP) side. Getting the information required to understand a NPP’s current status or perform necessary actions for responding to a given operational context are representative operator tasks performed using HSIs. To date, HSIs have been mainly evaluated in the context of human reliability analysis (HRA). However, the current HSI evaluation that occurs during HRA may be challengeable on two fronts: (1) reflecting the unique characteristics of HSI systems and (2) considering situations in which HSIs are poorly operated due to software/hardware malfunctions. Accordingly, this study proposes an approach for specifically evaluating HSIs for digital instrumentation and controls (DI&C) systems, using Redundancy-guided Systems-theoretic Hazard Analysis (RESHA) and HRA. RESHA is a method for analyzing DI&C systems with redundancy features. In this study, we investigate how HSIs are evaluated in existing HRA methods, and what challenges exist in the current approaches. To better evaluate HSIs for DI&C systems, this study modifies the existing HSI evaluation process by additionally modeling the HSI back- and front- ends. In this paper, a HSI fault tree for the APR1400 DI&C system is introduced through a piping and instrumentation diagram. It then touches upon what aspects of the suggested method must be further researched.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2020

A review of select human-building interfaces and their relationship to human behavior, energy use and occupant comfort

In recent years, research has emerged to quantitatively and qualitatively understand occupants' interactions with buildings. However, there has been surprisingly little research on building interfaces and how their design, context (e.g., location), and underlying logic impact their usability and occupants’ perceived control, as well as the resulting comfort and energy performance. This means that research is needed to better understand how occupants interact with building interfaces in both commercial and residential applications; both applications are important to address as there are many differences in interface types, level of control and understanding, and even expectations of engagement. Herein, this paper provides a cursory review and discussion of select common building interfaces: windows, window shades/blinds, thermostats, and lighting controls. The goal of this paper is to review literature related to these human-building interfaces to explore interface characteristics, current design and use challenges, and relationships between building interfaces and occupants. Human-building interface interactions are complex, more research is needed to understand design, use, and characteristics. Common themes emerged throughout the literature review to explain occupant interactions (or lack of interactions) with building interfaces, which included thermal and visual comfort, ease and access of control, interface/control placement, poor interface/control design, lack of understanding, and social-behavioral dynamics.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2020

Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2

The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies. Understanding the mode of viral attachment, entry and replication has become a key aspect of such interventions. The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion. The S protein of SARS-CoV-2 binds to human angiotensin converting enzyme 2 (hACE2) for entry. Herein, we describe glycomic and glycoproteomic analysis of hACE2 expressed in HEK293 cells. We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site. To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation. We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation. Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry. Here, the relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Using Temporal Information from Human Mobility Data to Detect Anchor Points

Spatiotemporal mobility data are available in massive quantities, but large quantities of data typically include fewer variables or data fields. Often, the only available fields are User ID, Longitude, Latitude, Timestamp (ULLT). This raises an important question: how much can we infer about human mobility patterns using only these four fields? With ULLT data, we do not know individuals' socioeconomic status information or when they are visiting their anchor points (AP) or locations (such as homes, places of employment, or schools), and it is a modern challenge to use this data to infer these characteristics. When detecting anchor locations with limited input information, verification and validation (VV) are significant challenges. This paper addresses the problem of identifying individuals' anchor locations using only temporal information from spatiotemporal datasets with limited attributes. Our approach does not explicitly use latitude and longitude during analysis. Locationbased information is only employed in the preprocessing stage to identify periods of movement (trips) and stops (dwelling). Beyond this step, all analysis is based on temporal patterns. In theory, if stops and dwell times could be detected through alternative means, our method could function entirely without location-based input. We demonstrate this methodology on the 2017 National Household Travel Survey (NHTS) data, because it includes a carefully designed and collected time use survey with representative sampling and labeled ground truth. The high-quality survey data allows us to test the accuracy of our methods because NHTS contains intended place labels and agent/user characteristics. We have also applied our validated AP identification algorithm on very large-scale GPS based trajectory data for Patterns-of-Life (PoL) assessment and other applications, but due to space limit that could not be presented here.

McBride, Liz [ORNL] (ORCID:0000000286925869)↗
DOE OSTI2023

Human-in-the-Loop Motion Control of a Two-DOF Hydraulic Backhoe Powered by the Hybrid Hydraulic Electric Architecture (HHEA)

Abstract The Hybrid Hydraulic-Electric Architecture (HHEA) combines the respective power density and control advantages of hydraulic and electric actuation to save energy for off-road vehicles. It uses a set of selectable common pressure rails to transmit the majority of power and electric actuation to modulate that power. As it is critical that off-road vehicles can perform tasks dexterously and exactly as commanded by the operator, the switchings between discrete pressure rails pose a potential challenge for smooth and precise motion. A control strategy consisting of a backstepping nominal control and least norm transition control has previously been developed to address this issue. It has been tested on 1 degree of freedom (DOF) testbeds where known trajectories were able to be tracked precisely. This paper presents the implementation of the HHEA motion control strategy on a 2-DOF backhoe operated by a human operator via a 2-DOF joystick. Unlike previous studies, the duty cycle is unknown beforehand and the decision to change pressure rails is taken in real-time. The efficacy of the motion control strategy has been validated experimentally. Several strategies to improve the user interface: control in workspace coordinates, pressure feedback, and velocity field-based task specification, have also been implemented and demonstrated to make operating the multiple DOF, HHEA actuated machine more intuitive to novice operators.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2021

The Human Proteoform Project: Defining the human proteome

Proteins are the primary effectors of function in biology, and thus, complete knowledge of their structure and properties is fundamental to deciphering function in basic and translational research. The chemical diversity of proteins is expressed in their many proteoforms, which result from combinations of genetic polymorphisms, RNA splice variants, and posttranslational modifications. This knowledge is foundational for the biological complexes and networks that control biology yet remains largely unknown. We propose here an ambitious initiative to define the human proteome, that is, to generate a definitive reference set of the proteoforms produced from the genome. Several examples of the power and importance of proteoform-level knowledge in disease-based research are presented along with a call for improved technologies in a two-pronged strategy to the Human Proteoform Project.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Purification, Crystallization, and Preliminary Crystallographic Studies of Human As(III) S-Adenosylmethionine Methyltransferase (hAS3MT)

Exposure to environmental arsenic is associated with serious of health issues such as cancer, diabetes and developmental delays in infants and children. In human liver, As(III) S-adenosylmethionine methyl transferase (hAS3MT) (EC 2.1.1.137) was proposed to be an detoxification process by methylation of inorganic arsenite into pentavalent methyl MAs(V) and dimethyl arsenite DMAs(V). More recently the first product was shown to be highly toxic and potentially carcinogenic trivalent methylarsenite (MAs(III)). Our studies are designed to elucidate the mechanism of AS3MT and its contribution to arsenic-related diseases. Here, in this paper, we report the first crystallization and preliminary X-ray diffraction analysis of the human AS3MT enzyme. The crystals belong to the monoclinic P12 1 1 space group with unit cell parameters of a = 135.03 Å, b = 260.44 Å, c = 279.03 Å, α = 90.00°, β = 93.36°, γ = 90.00°.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Cognitive Aging as a Human Factor: Effects of Age on Human Performance

Nuclear power plant (NPP) control room operators must make ongoing computations and decisions that maximize production and ensure safety, which places a high cognitive burden on the operators. How cognitions such as attention, visuospatial ability, and working memory interact with socio-technical systems to achieve optimal operations is well studied. However, there is an absence of research that examines how cognitive functioning within the NPP control room environment is moderated by developmental aging processes. This is of critical importance because different types of cognitive actions are known to develop and peak at different times across the adult life span, and it is becoming increasingly clear that there is no age at which all cognitive faculties operate at maximum capacity. Thus, given that NPPs are experiencing an aging workforce, it is vital to identify how mission critical cognitions change with age. This paper reviews implications of aging on reactor operators in the current and new fleet. We highlight lessons that can be learned from state-of-the-art human factors research that considers aging, lessons from the large cognitive aging literature, and lessons from aging workers in other industries that use sophisticated socio-technical systems, such as aviation. We also consider the important subject of aging effects versus expertise and present preliminary data that support the premise that age of operator is linked to effective and efficient operations but that this relationship may be moderated by level of operations expertise. In conclusion, we apply these lessons to future considerations for aging research in current nuclear operations and with the advent of advanced modernized control rooms.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2021

Room temperature crystallography of human acetylcholinesterase bound to a substrate analogue 4K-TMA: Towards a neutron structure

Acetylcholinesterase (AChE) catalyzes hydrolysis of acetylcholine thereby terminating cholinergic nerve impulses for efficient neurotransmission. Human AChE (hAChE) is a target of nerve agent and pesticide organophosphorus compounds that covalently attach to the catalytic Ser203 residue. Reactivation of inhibited hAChE can be achieved with nucleophilic antidotes, such as oximes. Understanding structural and electrostatic (i.e. protonation states) determinants of the catalytic and reactivation processes is crucial to improve design of oxime reactivators. Here we report X-ray structures of hAChE conjugated with a reversible covalent inhibitor 4K-TMA (4K-TMA:hAChE) at 2.8 Å resolution and of 4K-TMA:hAChE conjugate with oxime reactivator methoxime, MMB4 (4K-TMA:hAChE:MMB4) at 2.6 Å resolution, both at physiologically relevant room temperature, as well as cryo-crystallographic structure of 4K-TMA:hAChE at 2.4 Å resolution. 4K-TMA acts as a substrate analogue reacting with the hydroxyl of Ser203 and generating a reversible tetrahedral hemiketal intermediate that closely resembles the first tetrahedral intermediate state during hAChE-catalyzed acetylcholine hydrolysis. Structural comparisons of room temperature with cryo-crystallographic structures of 4K-TMA:hAChE and published mAChE complexes with 4K-TMA, as well as the effect of MMB4 binding to the peripheral anionic site (PAS) of the 4K-TMA:hAChE complex, revealed only discrete, minor differences. The active center geometry of AChE, already highly evolved for the efficient catalysis, was thus indicative of only minor conformational adjustments to accommodate the tetrahedral intermediate in the hydrolysis of the neurotransmitter acetylcholine (ACh). To map protonation states in the hAChE active site gorge we collected 3.5 Å neutron diffraction data paving the way for obtaining higher resolution datasets that will be needed to determine locations of individual hydrogen atoms.

4K-TMA↗
DOE OSTI2023

Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates

The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

From Mouse to Human: Cellular Morphometric Subtype Learned From Mouse Mammary Tumors Provides Prognostic Value in Human Breast Cancer

Mouse models of cancer provide a powerful tool for investigating all aspects of cancer biology. In this study, we used our recently developed machine learning approach to identify the cellular morphometric biomarkers (CMB) from digital images of hematoxylin and eosin (H&E) micrographs of orthotopic Trp53-null mammary tumors (n = 154) and to discover the corresponding cellular morphometric subtypes (CMS). Of the two CMS identified, CMS-2 was significantly associated with shorter survival (p = 0.0084). We then evaluated the learned CMB and corresponding CMS model in MMTV-Erbb2 transgenic mouse mammary tumors (n = 53) in which CMS-2 was significantly correlated with the presence of metastasis (p = 0.004). We next evaluated the mouse CMB and CMS model on The Cancer Genome Atlas breast cancer (TCGA-BRCA) cohort (n = 1017). Kaplan–Meier analysis showed significantly shorter overall survival (OS) of CMS-2 patients compared to CMS-1 patients (p = 0.024) and added significant prognostic value in multi-variable analysis of clinical and molecular factors, namely, age, pathological stage, and PAM50 molecular subtype. Thus, application of CMS to digital images of routine workflow H&E preparations can provide unbiased biological stratification to inform patient care.

60 APPLIED LIFE SCIENCES↗