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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 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
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 OSTI2016

Development of a PBPK model of thiocyanate in rats with an extrapolation to humans: A computational study to quantify the mechanism of action of thiocyanate kinetics in thyroid

Thyroid homeostasis can be disturbed due to thiocyanate exposure from the diet or tobacco smoke. Thiocyanate inhibits both thyroidal uptake of iodide, via the sodium-iodide symporter (NIS), and thyroid hormone (TH) synthesis in the thyroid, via thyroid peroxidase (TPO), but the mode of action of thiocyanate is poorly quantified in the literature. The characterization of the link between intra-thyroidal thiocyanate concentrations and dose of exposure is crucial for assessing the risk of thyroid perturbations due to thiocyanate exposure. We developed a PBPK model for thiocyanate that describes its kinetics in the whole-body up to daily doses of 0.15 mmol/kg, with a mechanistic description of the thyroidal kinetics including NIS, passive diffusion, and TPO. The model was calibrated in a Bayesian framework using published studies in rats. Goodness-of-fit was satisfactory, especially for intra-thyroidal thiocyanate concentrations. Thiocyanate kinetic processes were quantified in vivo, including the metabolic clearance by TPO. The passive diffusion rate was found to be greater than NIS-mediated uptake rate. The model captured the dose-dependent kinetics of thiocyanate after acute and chronic exposures. Model behavior was evaluated using a Morris screening test. The distribution of thiocyanate into the thyroid was found to be determined primarily by the partition coefficient, followed by NIS and passive diffusion; the impact of the latter two mechanisms appears to increase at very low doses. Extrapolation to humans resulted in good predictions of thiocyanate kinetics during chronic exposure. The developed PBPK model can be used in risk assessment to quantify dose-response effects of thiocyanate on TH. - Highlights: • A PBPK model of thiocyanate (SCN{sup −}) was calibrated in rats in a Bayesian framework. • The intra-thyroidal kinetics of thiocyanate including NIS and TPO was modeled. • Passive diffusion rate for SCN{sup −} seemed to be greater than the NIS-mediated uptake. • The dose-dependent kinetics of SCN{sup −} was captured after an acute and chronic exposure. • The PBPK model of thiocyanate was successfully extrapolated to humans.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

Background: Borna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection. Methods: The acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Results: We identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteins and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT). Conclusions: Upon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites. - Highlights: • We used SILAC-based proteomics to analyze the acetylome of BDV infected OL cells. • We quantified 791Kac sites in 473 proteins. • Bioinformatic analysis revealed altered acetylation of metabolic proteins et al. • BDV manipulates the OL acetylome towards higher energy and transporter levels. • BDV infection is associated with enriched phosphate-associated metabolic processes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

FoxO1 inhibition promotes differentiation of human embryonic stem cells into insulin producing cells

Highlights: • The level of p-FoxO1 protein increases during differentiation of hESCs into IPCs. • FoxO1 knockdown promotes IPC differentiation of hESCs. • FoxO1 overexpression inhibits IPC differentiation of hESCs. • Inhibition of FoxO1 by AS promotes the differentiation of hESCs into IPCs. • AS may promote IPC maturation via modulating subcellular location of FoxO1 and Pdx1. Insulin-producing cells (IPCs) derived from human embryonic stem cells (hESCs) hold great potential for cell transplantation therapy in diabetes. Tremendous progress has been made in inducing differentiation of hESCs into IPCs in vitro, of which definitive endoderm (DE) protocol mimicking foetal pancreatic development has been widely used. However, immaturity of the obtained IPCs limits their further applications in treating diabetes. Forkhead box O1 (FoxO1) is involved in the differentiation and functional maintenance of murine pancreatic β cells, but its role in human β cell differentiation is under elucidation. Here, we showed that although FoxO1 expression level remained consistent, cytoplasmic phosphorylated FoxO1 protein level increased during IPC differentiation of hESCs induced by DE protocol. Lentiviral silencing of FoxO1 in pancreatic progenitors upregulated the levels of pancreatic islet differentiation-related genes and improved glucose-stimulated insulin secretion response in their progeny IPCs, whereas overexpression of FoxO1 showed the opposite effects. Notably, treatment with the FoxO1 inhibitor AS1842856 displayed similar effects with FoxO1 knockdown in pancreatic progenitors. These effects were closely associated with the mutually exclusive nucleocytoplasmic shuttling of FoxO1 and Pdx1 in the AS1842856-treated pancreatic progenitors. Our data demonstrated a promising effect of FoxO1 inhibition by the small molecule on gene expression profile during the differentiation, and in turn, on determining IPC maturation via modulating subcellular location of FoxO1 and Pdx1. Therefore, we identify a novel role of FoxO1 inhibition in promoting IPC differentiation of hESCs, which may provide clues for induction of mature β cells from hESCs and clinical applications in regenerative medicine.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Clock-like mutational processes in human somatic cells

During the course of a lifetime, somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals, and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated, indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This paper provides the first survey of clock-like mutational processes operating in human somatic cells.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Cryo-EM structure of the human neutral amino acid transporter ASCT2

Human ASCT2 belongs to the SLC1 family of secondary transporters and is specific for the transport of small neutral amino acids. ASCT2 is upregulated in cancer cells and serves as the receptor for many retroviruses; hence, it has importance as a potential drug target. Here we used single-particle cryo-EM to determine a structure of the functional and unmodified human ASCT2 at 3.85-Å resolution. ASCT2 forms a homotrimeric complex in which each subunit contains a transport and a scaffold domain. Prominent extracellular extensions on the scaffold domain form the predicted docking site for retroviruses. Relative to structures of other SLC1 members, ASCT2 is in the most extreme inward-oriented state, with the transport domain largely detached from the central scaffold domain on the cytoplasmic side. In conclusion, this domain detachment may be required for substrate binding and release on the intracellular side of the membrane.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Mechanism of error-free DNA synthesis across N1-methyl-deoxyadenosine by human DNA polymerase-$\iota$

N1-methyl-deoxyadenosine (1-MeA) is formed by methylation of deoxyadenosine at the N1 atom. 1-MeA presents a block to replicative DNA polymerases due to its inability to participate in Watson-Crick (W-C) base pairing. Here we determine how human DNA polymerase-ι (Pol$\iota$) promotes error-free replication across 1-MeA. Steady state kinetic analyses indicate that Pol$\iota$ is ~100 fold more efficient in incorporating the correct nucleotide T versus the incorrect nucleotide C opposite 1-MeA. To understand the basis of this selectivity, we determined ternary structures of Polι bound to template 1-MeA and incoming dTTP or dCTP. In both structures, template 1-MeA rotates to the syn conformation but pairs differently with dTTP versus dCTP. Thus, whereas dTTP partakes in stable Hoogsteen base pairing with 1-MeA, dCTP fails to gain a “foothold” and is largely disordered. Together, our kinetic and structural studies show how Polι maintains discrimination between correct and incorrect incoming nucleotide opposite 1-MeA in preserving genome integrity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Crystal structure of the human NK 1 tachykinin receptor

The NK 1 tachykinin G-protein–coupled receptor (GPCR) binds substance P, the first neuropeptide to be discovered in mammals. Through activation of NK 1 R, substance P modulates a wide variety of physiological and disease processes including nociception, inflammation, and depression. Human NK 1 R (hNK 1 R) modulators have shown promise in clinical trials for migraine, depression, and emesis. However, the only currently approved drugs targeting hNK 1 R are inhibitors for chemotherapy-induced nausea and vomiting (CINV). To better understand the molecular basis of ligand recognition and selectivity, we solved the crystal structure of hNK 1 R bound to the inhibitor L760735, a close analog of the drug aprepitant. Our crystal structure reveals the basis for antagonist interaction in the deep and narrow orthosteric pocket of the receptor. We used our structure as a template for computational docking and molecular-dynamics simulations to dissect the energetic importance of binding pocket interactions and model the binding of aprepitant. Furthermore, the structure of hNK 1 R is a valuable tool in the further development of tachykinin receptor modulators for multiple clinical applications.

60 APPLIED LIFE SCIENCES↗
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↗