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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 451 records · Page 25
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

An evaluation of prognostic factors, oncologic outcomes, and management for primary and recurrent squamous cell carcinoma of the vulva

Objective: To evaluate prognostic factors, outcomes, and management patterns of patients treated for squamous cell carcinoma of the vulva. Methods: One hundred sixty-four women were retrospectively identified with primary squamous cell carcinoma of the vulva treated at our institution between 1/1996–12/2018. Descriptive statistics were performed on patient, tumor, and treatment characteristics. The χ 2 tests and t-tests were used to compare categorical variables and continuous variables, respectively. Recurrence free survival (RFS), overall survival (OS), and disease-specific survival (DSS) were analyzed with Kaplan-Meier estimates, the log-rank test, and Cox proportional hazards. Results: Median follow-up was 52.5 months. Five-year RFS was 67.9%, 60.0%, 42.1%, and 20.0% for stage I–IV, respectively. Five-year DSS was 86.2%, 81.6%, 65.0%, and 42.9% for stage I–IV, respectively. On multivariate analysis, positive margins predicted overall RFS (hazard ratio [HR]=3.55; 95% confidence interval [CI]=1.18–10.73; p=0.025), while presence of lichen sclerosus on pathology (HR=2.78; 95% CI=1.30–5.91; p=0.008) predicted local RFS. OS was predicted by nodal involvement (HR=2.51; 95% CI=1.02–6.13; p=0.043) and positive margins (HR=5.19; 95% CI=2.03–13.26; p=0.001). Adjuvant radiotherapy significantly improved RFS (p=0.016) and DSS (p=0.012) in node-positive patients. Median survival after treatment of local, groin, and pelvic/distant recurrence was 52, 8, and 5 months, respectively. Conclusion: For primary treatment, more conservative surgical approaches can be considered with escalation of treatment in patients with concurrent precursor lesions, positive margins, and/or nodal involvement. Further studies are warranted to improve risk stratification in order to optimize treatment paradigms for vulvar cancer patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

First Sagittarius A* Event Horizon Telescope Results. VI. Testing the Black Hole Metric

Astrophysical black holes are expected to be described by the Kerr metric. This is the only stationary, vacuum, axisymmetric metric, without electromagnetic charge, that satisfies Einstein’s equations and does not have pathologies outside of the event horizon. We present new constraints on potential deviations from the Kerr prediction based on 2017 EHT observations of Sagittarius A* (Sgr A*). We calibrate the relationship between the geometrically defined black hole shadow and the observed size of the ring-like images using a library that includes both Kerr and non-Kerr simulations. We use the exquisite prior constraints on the mass-to-distance ratio for Sgr A* to show that the observed image size is within ∼10% of the Kerr predictions. We use these bounds to constrain metrics that are parametrically different from Kerr, as well as the charges of several known spacetimes. To consider alternatives to the presence of an event horizon, we explore the possibility that Sgr A* is a compact object with a surface that either absorbs and thermally reemits incident radiation or partially reflects it. Using the observed image size and the broadband spectrum of Sgr A*, we conclude that a thermal surface can be ruled out and a fully reflective one is unlikely. We compare our results to the broader landscape of gravitational tests. Together with the bounds found for stellar-mass black holes and the M87 black hole, our observations provide further support that the external spacetimes of all black holes are described by the Kerr metric, independent of their mass.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2023

Inhibition of the C1s Protease and the Classical Complement Pathway by 6-(4-Phenylpiperazin-1-yl)Pyridine-3-Carboximidamide and Chemical Analogs

Abstract The classical pathway (CP) is a potent mechanism for initiating complement activity and is a driver of pathology in many complement-mediated diseases. The CP is initiated via activation of complement component C1, which consists of the pattern recognition molecule C1q bound to a tetrameric assembly of proteases C1r and C1s. Enzymatically active C1s provides the catalytic basis for cleavage of the downstream CP components, C4 and C2, and is therefore an attractive target for therapeutic intervention in CP-driven diseases. Although an anti-C1s mAb has been Food and Drug Administration approved, identifying small-molecule C1s inhibitors remains a priority. In this study, we describe 6-(4-phenylpiperazin-1-yl)pyridine-3-carboximidamide (A1) as a selective, competitive inhibitor of C1s. A1 was identified through a virtual screen for small molecules that interact with the C1s substrate recognition site. Subsequent functional studies revealed that A1 dose-dependently inhibits CP activation by heparin-induced immune complexes, CP-driven lysis of Ab-sensitized sheep erythrocytes, CP activation in a pathway-specific ELISA, and cleavage of C2 by C1s. Biochemical experiments demonstrated that A1 binds directly to C1s with a K d of ∼9.8 μM and competitively inhibits its activity with an inhibition constant (K i) of ∼5.8 μM. A 1.8-Å-resolution crystal structure revealed the physical basis for C1s inhibition by A1 and provided information on the structure–activity relationship of the A1 scaffold, which was supported by evaluating a panel of A1 analogs. Taken together, our work identifies A1 as a new class of small-molecule C1s inhibitor and lays the foundation for development of increasingly potent and selective A1 analogs for both research and therapeutic purposes.

Immunology↗
DOE OSTI2020

MicroRNAs in laser-induced choroidal neovascularization in mice and rats: their expression and potential therapeutic targets

Choroidal neovascularization characterizes wet age-related macular degeneration. Choroidal neovascularization formation involves a primarily angiogenic process that is combined with both inflammation and proteolysis. A primary cause of choroidal neovascularization pathogenesis is alterations in pro- and anti-angiogenic factors derived from the retinal pigment epithelium, with vascular endothelium growth factor being mainly responsible for both clinical and experimental choroidal neovascularization. MicroRNAs (miRNAs) which are short, non-coding, endogenous RNA molecules have a major role in regulating various pathological processes, including inflammation and angiogenesis. A review of recent studies with the mouse laser-induced choroidal neovascularization model has shown alterations in miRNA expression in choroidal neovascularization tissues and could be potential therapeutic targets for wet age-related macular degeneration. Upregulation of miR-505 (days 1 and 3 post-laser), miR-155 (day 14) occurred in retina; miR-342-5p (days 3 and 7), miR-126-3p (day 14) in choroid; miR-23a, miR-24, miR-27a (day 7) in retina/choroid; miR-505 (days 1 and 3) in retinal pigment epithelium/choroid; downregulation of miR-155 (days 1 and 3), miR-29a, miR-29b, miR-29c (day 5), miR-93 (day 14), miR-126 (day 14) occurred in retinal pigment epithelium/choroid. Therapies using miRNA mimics or inhibitors were found to decrease choroidal neovascularization lesions. Choroidal neovascularization development was reduced by overexpression of miR-155, miR-188-5p, miR-(5,B,7), miR-126-3p, miR-342-5p, miR-93, miR-126, miR-195a-3p, miR24, miR-21, miR-31, miR-150, and miR-184, or suppression of miR-505, miR-126-3p, miR155, and miR-23/27. Further studies are warranted to determine miRNA expression in mouse laser-induced choroidal neovascularization models in order to validate and extend the reported findings. Important experimental variables need to be standardized; these include the strain and age of animals, gender, number and position of laser burns to the eye, laser parameters to induce choroidal neovascularization lesions including wavelength, power, spot size, and duration.

therapeutic targets↗
DOE OSTI2021

Cardinality-Regularized Hawkes-Granger Model

We propose a new sparse Granger-causal learning framework for temporal event data. We focus on a specific class of point processes called the Hawkes process. We begin by pointing out that most of the existing sparse causal learning algorithms for the Hawkes process suffer from a singularity in maximum likelihood estimation. As a result, their sparse solutions can appear only as numerical artifacts. In this paper, we propose a mathematically well-defined sparse causal learning framework based on a cardinality-regularized Hawkes process, which remedies the pathological issues of existing approaches. We leverage the proposed algorithm for the task of instance-wise causal event analysis, where sparsity plays a critical role. We validate the proposed framework with two real use-cases, one from the power grid and the other from the cloud data center management domain.

Ide, Tsuyoshi↗
DOE OSTI2023

Inhibition of the proton-activated chloride channel PAC by PIP 2

Proton-activated chloride (PAC) channel is a ubiquitously expressed pH-sensing ion channel, encoded by PACC1 (TMEM206). PAC regulates endosomal acidification and macropinosome shrinkage by releasing chloride from the organelle lumens. It is also found at the cell surface, where it is activated under pathological conditions related to acidosis and contributes to acid-induced cell death. However, the pharmacology of the PAC channel is poorly understood. Here, we report that phosphatidylinositol (4,5)-bisphosphate (PIP 2 ) potently inhibits PAC channel activity. We solved the cryo-electron microscopy structure of PAC with PIP 2 at pH 4.0 and identified its putative binding site, which, surprisingly, locates on the extracellular side of the transmembrane domain (TMD). While the overall conformation resembles the previously resolved PAC structure in the desensitized state, the TMD undergoes remodeling upon PIP 2 -binding. Structural and electrophysiological analyses suggest that PIP 2 inhibits the PAC channel by stabilizing the channel in a desensitized-like conformation. Our findings identify PIP 2 as a new pharmacological tool for the PAC channel and lay the foundation for future drug discovery targeting this channel.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1964

Conference on Nutrition in Space and Related Waste Problems

As part of a continuing process man constantly seeks new habitats. In the late 1950's, he ventured into a vast and challenging new habitat, extraterrestrial space. Extending the realm of human life has always been a challenge to man, and inherent to all successful extensions of man into new domains is his ability to provide the essentials for life itself, his nutrition and controlled use of metabolic products. The provision of these essential requirements has always been a challenge and a motivating force in maintaining and extending human life on Earth. This challenge has now been extended beyond the Earth. As illustrated in this volume, many men and women of vision who continually devote their energies to feeding man on Earth have accepted the additional challenge of nutrition in space. They have already made inroads into the new problem of nutrition and waste handling in space and have already collected much physiological, psychological, toxicological, and pathological data related to space nutrition, feeding and elimination. They have elucidated man-machine interactions and the effects of these interactions on alimentation and elimination requirements in space. Thus light has been shed on specific research and development programs needed to establish requirements for nutrition and handling of metabolic wastes during manned space missions of 20 days' to 3 years' duration. These initial accomplishments have entailed the considerable efforts of many people and the knowledge and experience in nutrition and feeding gained by the Space Science Board of the National Academy of Sciences. This volume clearly represents the ability of scientists, engineers, and administrators to attack a problem as it arises; it clearly demonstrates the capability of the scientific and engineering communities to combine efforts, mobilize quickly, and devote their talents to a national need

Space environment↗
NASA NTRS1966

Progress in Development of Methods in Bone Densitometry

The effects of weightlessness and decreased activity on the astronaut's musculoskeletal system during prolonged space flight, missions are of concern to NASA. This problem was anticipated from the knowledge that human subjects lose significant quantities of calcium from the skeleton during periods of bedrest, immobilization, and water immersion. An accurate method of measurement of the changes in mineral content of the skeleton is required not only in the space program but also in the biological, medical, and dental fields for mineral metabolism studies and for studying various pathological conditions of the skeleton and teeth. This method is a difficult one requiring the coordinated efforts of physiologists, biophysicists, radiologists, and clinicians. The densitometry methods reported in this conference which have been used or are being developed include X-ray, beta excited X-rays, radioisotopes, sonic vibration, and neutron activation analysis Studies in the Gemini, Biosatellite, and Apollo flights use the X-ray bone densitometry method which requires making X-rays before and after the flights. An in-flight method of bone densitometry would be valuable, and use of radioisotope sources has been suggested. Many advances in bone densitometry have been made in the last five years, and the urgency of the requirement makes this working conference timely and valuable. In such a rapidly developing field with investigators working independently in a variety of scientific disciplines, a working conference is of great value in exchanging information and ideas, critically evaluating approaches and methods, and pointing out new research pathways.

DENSITOMETER↗
NASA NTRS1965

Rheology of synovial fluid and its role in joint lubrication

A review of studies by Barnett, Davies, MacConaill, Charnley, Ogston, Sundblad, and others indicates that there exists a tendency to explain the lubricating mechanism existing in synovial joints by either the lubricating properties of synovial fluid or the lubricating properties of the articular surfaces. The proponents of the respective hypothesis attempted to apply either the theory of hydrodynamic lubrication or the theory of boundary lubrication. Neither of these theories, however, can represent the lubrication mechanism in joints; both theories are too crude for this purpose. The nearest approach to reality appears to be represented by more recent elastohydrodynamic theories. It is the aim of this paper to show that both the synovial fluid and the articular cartilage play an important role in the joint lubrication, and that thixotropy of synovial fluid is the key parameter in the lubricating performance of the synovial fluid itself, and of the cartilage whose pores it fills. It will be suggested also that any pathological changes in either the synovial fluid or the articular cartilage, lead to a breakdown of joint lubrication.

LUBRICATION↗
NASA NTRS1968

Color-televised medical microscopy

Color television microscopy used at laboratory range magnifications, reproduces a slide image with sufficient fidelity for medical laboratory and instructional use. The system is used for instant pathological reporting between operating room and remotely located pathologist viewing a biopsy through this medium.

Heath, M. A.↗
NASA NTRS1969

Carbon offers advantages as implant material in human body

Because of such characteristics as high strength and long-term biocompatability, aerospace carbonaceous materials may be used as surgical implants to correct pathological conditions in the body resulting from disease or injury. Examples of possible medical uses include bone replacement, implantation splints and circulatory bypass implants.

Benson, J.↗