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At least 307 records · Page 17

All sources NASA NTRS DOE OSTI

DOE OSTI2018

Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model

Highlights: • Sorafenib decreased blood flow in the vasculature by narrowing the vascular diameter. • Histidine maintained the blood flow by dilating the vascular diameter of the existing vessel. • Histidine was useful for managing the sorafenib related vascular damage. • No positive effect of histidine was seen on the tumor progression or on the novel regenerating vessels. • A fli::GFP transgenic medaka is useful for analyzing the vascular changes under the administration of these chemicals. Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified. We hypothesized that histidine, the largest component among the amino acids contained in DBB, has effects on SFN-induced vascular damage, and evaluated this possibility using a novel medaka fish model.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2019

Polarization of Λ ( Λ ¯ ) Hyperons along the Beam Direction in Au + Au Collisions at s N N = 200 GeV

The Λ ($\bar{Λ}$) hyperon polarization along the beam direction has been measured in Au+Au collisions at $\sqrt{s_{NN}}$=200 GeV, for the first time in heavy-ion collisions. The polarization dependence on the hyperons' emission angle relative to the elliptic flow plane exhibits a second harmonic sine modulation, indicating a quadrupole pattern of the vorticity component along the beam direction, expected due to elliptic flow. The polarization is found to increase in more peripheral collisions, and shows no strong transverse momentum ($p_{T}$) dependence at $p_{T}$ greater than 1 GeV/c. Furthermore, the magnitude of the signal is about 5 times smaller than those predicted by hydrodynamic and multiphase transport models; the observed phase of the emission angle dependence is also opposite to these model predictions. In contrast, the kinematic vorticity calculations in the blast-wave model tuned to reproduce particle spectra, elliptic flow, and the azimuthal dependence of the Gaussian source radii measured with the Hanbury Brown-Twiss intensity interferometry technique reproduce well the modulation phase measured in the data and capture the centrality and transverse momentum dependence of the polarization signal.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

DOE OSTI2015

Large eddy simulation of a turbulent non-reacting spray jet

We performed Large Eddy Simulation (LES) of a turbulent non-reacting n-Heptane spray jet, referred to as Spray H in the Engine Combustion Network (ECN), and executed a data analysis focused on key LES metrics such as fraction of resolved turbulent kinetic energy and similarity index. In the simulation, we used the dynamic structure model for the sub-grid stress, and the Lagrangian-based spray-parcel models coupled with the blob-injection model. The finest mesh-cell size used was characterized by an Adaptive Mesh Refinement (AMR) cell size of 0.0625 mm. To obtain ensemble statistics, we performed 28 numerical realizations of the simulation. Demonstrated by the comparison with experimental data in a previous study [7], this LES has accurately predicted global quantities, such as liquid and vapor penetrations. The analysis in this work shows that 14 realizations of LES are sufficient to provide a reasonable representation of the average flow behavior that is benchmarked against the 28-realization ensemble. With the current mesh, numerical schemes, and sub-grid scale turbulence model, more than 95% of the turbulent kinetic energy is directly resolved in the flow regions of interest. The large-scale flow structures inferred from a statistical analysis reveal a region of disorganized flow around the peripheral region of the spray jet, which appears to be linked to the entrainment process.

Hu, Bing↗

NASA NTRS1990

Exclusive measurements of light fragment production at forward angles in Ne-Pb and Ne-NaF collisions at E/A=400 MeV and 800 MeV

Emission of light fragments at small angles is studied in relativistic heavy ion collisions using the Diogene plastic wall for both symmetrical and non-symmetrical target-projectile systems with 400 MeV per nucleon and 800 MeV per nucleon incident neon nuclei. Efficiency of multiplicity measurements in the small angle range for the selection of central or peripheral collisions is confirmed for asymmetric systems. Differential production cross sections of Z = 1 fragments show evidence for the existence of two emitting sources. The apparent temperature of each source is obtained from comparison with a thermodynamical model.

NASA Discipline Number 04-10↗

DOE OSTI2015

Targeting Human Central Nervous System Protein Kinases: An Isoform Selective p38αMAPK Inhibitor That Attenuates Disease Progression in Alzheimer’s Disease Mouse Models

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, pursuit of the neurotherapeutic hypothesis requires kinase isoform selective inhibitors with appropriate neuropharmacology features. Synaptic dysfunction disorders offer a potential for enhanced pharmacological efficacy due to stress-induced activation of p38αMAPK in both neurons and glia, the interacting cellular components of the synaptic pathophysiological axis to be modulated. We report a novel isoform selective p38αMAPK inhibitor, MW01-18-150SRM (= MW150), that is efficacious in suppression of hippocampal-dependent associative and spatial memory deficits in two distinct synaptic dysfunction mouse models. A synthetic scheme for biocompatible product and positive outcomes from pharmacological screens are presented. The high-resolution crystallographic structure of the p38αMAPK:MW150 complex documents active site binding, reveals a potential low energy conformation of the bound inhibitor, and suggests a structural explanation for MW150’s exquisite target selectivity. As far as we are aware, MW150 is without precedent as an isoform selective p38MAPK inhibitor or as a kinase inhibitor capable of modulating in vivo stress related behavior

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2016

Neutron-rich rare-isotope production from projectile fission of heavy nuclei near 20 MeV/nucleon beam energy

We investigate the possibilities of producing neutron-rich nuclides in projectile fission of heavy beams in the energy range of 20 MeV/nucleon expected from low-energy facilities. We report our efforts to theoretically describe the reaction mechanism of projectile fission following a multinucleon transfer collision at this energy range. Our calculations are mainly based on a two-step approach: The dynamical stage of the collision is described with either the phenomenological deep-inelastic transfer model (DIT) or with the microscopic constrained molecular dynamics model (CoMD). The de-excitation or fission of the hot heavy projectile fragments is performed with the statistical multifragmentation model (SMM). We compared our model calculations with our previous experimental projectile-fission data of 238 U (20 MeV/nucleon) + 208 Pb and 197 Au (20 MeV/nucleon) + 197 Au and found an overall reasonable agreement. Furthermore, our study suggests that projectile fission following peripheral heavy-ion collisions at this energy range offers an effective route to access very neutron-rich rare isotopes toward and beyond the astrophysical r-process path.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

DOE OSTI2022

Evidence of Mass Ordering of Charm and Bottom Quark Energy Loss in Au+Au Collisions at RHIC

Abstract Partons traversing the strongly interacting medium produced in heavy-ion collisions are expected to lose energy depending on their color charge and mass. We measure the nuclear modification factors for charm- and bottom-decay electrons, defined as the ratio of yields, divided by the number of binary nucleon–nucleon collisions, in $$\sqrt{s_{\textrm{NN}}}=200$$ s NN = 200 GeV Au+Au collisions to p + p collisions ( $$R_{\textrm{AA}}$$ R AA ), or in central to peripheral Au+Au collisions ( $$R_{\textrm{CP}}$$ R CP ). We find the bottom-decay electron $$R_{\textrm{AA}}$$ R AA and $$R_{\textrm{CP}}$$ R CP to be significantly higher than those of charm-decay electrons. Model calculations including mass-dependent parton energy loss in a strongly coupled medium are consistent with the measured data. These observations provide evidence of mass ordering of charm and bottom quark energy loss when traversing through the strongly coupled medium created in heavy-ion collisions.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

NASA NTRS1999

Hyperspectral Remote Sensing and Ecological Modeling Research and Education at Mid America Remote Sensing Center (MARC): Field and Laboratory Enhancement

The purpose of this project was to establish a new hyperspectral remote sensing laboratory at the Mid-America Remote sensing Center (MARC), dedicated to in situ and laboratory measurements of environmental samples and to the manipulation, analysis, and storage of remotely sensed data for environmental monitoring and research in ecological modeling using hyperspectral remote sensing at MARC, one of three research facilities of the Center of Reservoir Research at Murray State University (MSU), a Kentucky Commonwealth Center of Excellence. The equipment purchased, a FieldSpec FR portable spectroradiometer and peripherals, and ENVI hyperspectral data processing software, allowed MARC to provide hands-on experience, education, and training for the students of the Department of Geosciences in quantitative remote sensing using hyperspectral data, Geographic Information System (GIS), digital image processing (DIP), computer, geological and geophysical mapping; to provide field support to the researchers and students collecting in situ and laboratory measurements of environmental data; to create a spectral library of the cover types and to establish a World Wide Web server to provide the spectral library to other academic, state and Federal institutions. Much of the research will soon be published in scientific journals. A World Wide Web page has been created at the web site of MARC. Results of this project are grouped in two categories, education and research accomplishments. The Principal Investigator (PI) modified remote sensing and DIP courses to introduce students to ii situ field spectra and laboratory remote sensing studies for environmental monitoring in the region by using the new equipment in the courses. The PI collected in situ measurements using the spectroradiometer for the ER-2 mission to Puerto Rico project for the Moderate Resolution Imaging Spectrometer (MODIS) Airborne Simulator (MAS). Currently MARC is mapping water quality in Kentucky Lake and vegetation in the Land-Between-the Lakes (LBL) using Landsat-TM data. A Landsat-TM scene of the same day was obtained to relate ground measurements to the satellite data. A spectral library has been created for overstory species in LBL. Some of the methods, such as NPDF and IDFD techniques for spectral unmixing and reduction of effects of shadows in classifications- comparison of hyperspectral classification techniques, and spectral nonlinear and linear unmixing techniques, are being tested using the laboratory.

Cetin, Haluk↗

DOE OSTI2013

High-Efficacy Modeling of Human Perceptual Similarity Opinions

The computer code relates to human nature studies and more specifically to a novel graphical user interface (GUI) that facilitates high-efficacy collection of perceptual similarity opinions of a user in an effective and intuitive manner. The GUI presents a base image for rating its similarity to seven peripheral images that are displayed simultaneously following a circular layout. The user is asked to report the base image's pairwise similarity to each peripheral image on a fixed scale while preserving the relative ranking among all peripheral images. The collected data are then used to predict the user's subjective opinions regarding the perceptual similarity of images.

Xu, Songhua↗

DOE OSTI2016

Mice housed on coal dust-contaminated sand: A model to evaluate the impacts of coal mining on health

Coal dust is the most important air pollutant in coal mining in regards to producing deleterious health effects. It permeates the surrounding environment threatening public health. The aim of this study was to evaluate the toxic effects associated with exposure to sand contaminated with coal dust particles below 38 μm in diameter, obtained from a mineral sample collected in the largest coal mine in South America, La Loma, Cesar, Colombia. Sterilized sand was spiked with coal dust to obtain concentrations ranging from zero to 4% coal dust. To model natural exposure, mice were housed for eight weeks in boxes containing this mixture as bedding after which, they were euthanized and blood and tissue samples were collected. Real time PCR analysis revealed an increase in Cyp1A1 mRNA for living on sand with coal dust concentrations greater than 2% compared to mice living on sand without coal dust. Unexpectedly, for mice on coal dust-polluted sand, Sod1, Scd1 and Nqo1 hepatic mRNA were downregulated. The Comet assay in peripheral blood cells and the micronucleus test in blood smears, showed a significant potential genotoxic effect only at the highest coal dust concentration. Histopathological analysis revealed vascular congestion and peribronchial inflammation in the lungs. A dose–response relationship for the presence of hepatic steatosis, vacuolization and nuclei enlargements was observed in the exposed animals. The data suggest living on a soil polluted with coal dust induces molecular, cellular and histopathological changes in mice. Accordingly, the proposed model can be used to identify deleterious effects of exposure to coal dust deposited in soils that may pose health risks for surrounding wildlife populations. - Highlights: • Mice were exposed to coal dust-contaminated sand. • mRNA Markers for PAH exposure, lipid metabolism and oxidative stress increased. • ALT activity in plasma increased at the highest exposure to coal dust. • Liver tissues of exposed mice showed steatosis and inflammation. • Coal dust exposure produced changes in several blood components.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2019

Measurement of prompt D 0 , D + , D *+ , and DS+$ {\mathrm{D}}_{\mathrm{S}}^{+} $ production in p–Pb collisions at sNN$ \sqrt{{\mathrm{s}}_{\mathrm{NN}}} $ = 5.02 TeV

The measurement of the production of prompt D 0 , D + , D *+, and $D_S^+$ mesons in proton–lead (p–Pb) collisions at the centre-of-mass energy per nucleon pair of \mathrm{\sqrt{s_{NN}}}$ = 5.02 TeV, with an integrated luminosity of 292 ± 11 μb -1 , are reported. Differential production cross sections are measured at mid-rapidity (-96 < y cms < 0.04) as a function of transverse momentum (p T ) in the intervals 0 < p T < 36 GeV/c for D 0 , 1 < p T < 36 GeV/c for D + and D *+ , and 2 < p T < 24 GeV/c for D + mesons. For each species, the nuclear modification factor R pPb is calculated as a function of p T using a proton-proton (pp) reference measured at the same collision energy. The results are compatible with unity in the whole p T range. The average of the non-strange D mesons R pPb is compared with theoretical model predictions that include initial-state effects and parton transport model predictions. The p T dependence of the D 0 , D + , and D *+ nuclear modification factors is also reported in the interval 1 < p T < 36 GeV/c as a function of the collision centrality, and the central-to-peripheral ratios are computed from the D-meson yields measured in different centrality classes. The results are further compared with charged-particle measurements and a similar trend is observed in all the centrality classes. The ratios of the p T -differential cross sections of D 0 , D + , D *+ , and $D_S^+$ mesons are also reported. The $D_S^+$ and D + yields are compared as a function of the charged-particle multiplicity for several p T intervals. No modification in the relative abundances of the four species is observed with respect to pp collisions within the statistical and systematic uncertainties.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

NASA NTRS2002

Insulin secretion and sensitivity in space flight: diabetogenic effects

Nearly three decades of space flight research have suggested that there are subclinical diabetogenic changes that occur in microgravity. Alterations in insulin secretion, insulin sensitivity, glucose tolerance, and metabolism of protein and amino acids support the hypothesis that insulin plays an essential role in the maintenance of muscle mass in extended-duration space flight. Experiments in flight and after flight and ground-based bedrest studies have associated microgravity and its experimental paradigms with manifestations similar to those of diabetes, physical inactivity, and aging. We propose that these manifestations are characterized best by an etiology that falls into the clinical category of "other" causes of diabetes, including, but not restricted to, genetic beta-cell defects, insulin action defects, diseases of the endocrine pancreas, endocrinopathies, drug or chemically induced diabetes, infections, immune-mediated metabolic alteration, and a host of genetic related diseases. We present data showing alterations in tumor necrosis factor-alpha production, insulin secretion, and amino acid metabolism in pancreatic islets of Langerhans cultured in a ground-based cell culture bioreactor that mimics some of the effects of microgravity. Taken together, space flight research, ground-based studies, and bioreactor studies of pancreatic islets of Langerhans support the hypothesis that the pancreas is unable to overcome peripheral insulin resistance and amino acid dysregulation during space flight. We propose that measures of insulin secretion and insulin action will be necessary to design effective countermeasures against muscle loss, and we advance the "disposition index" as an essential model to be used in the clinical management of space flight-induced muscle loss.

Review↗

DOE OSTI2019

Mode Purity of Electron Cyclotron Waves after Their Passage through the Peripheral Plasma in the Large Helical Device

Plasma heating and current drive with Electron Cyclotron Waves (ECWs) require precise control over the polarization state of ECWs to ensure that the entire input power is deposited where intended. However, due to the magnetic shear in the peripheral plasma, the polarization state can change. This effect is particularly pronounced in the Large Helical Device (LHD), where the magnetic field is sheared strongly. Here, we present a new code PARADE (PAraxial RAy DEscription) that can simulate the evolution of the polarization state along the beam propagation without resorting to full-wave modeling. We apply PARADE to the LHD plasma and simulate the evolution of the beam transverse structure, including the local amplitudes of the two electromagnetic eigenmodes. Here, the results surpass those yielded by the code LHDGauss used in the past. Based on these new results, we discuss how to improve the mode purity of ECWs by controlling the initial polarization state. A remarkable improvement is predicted numerically.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2024

Relativistic diffusion model for hadron production in p -Pb collisions at energies available at the CERN Large Hadron Collider

We investigate charged-hadron production in relativistic heavy-ion collisions of asymmetric systems within a nonequilibrium-statistical framework. Calculated centrality-dependent pseudorapidity distributions for p-Pb collisions at s NN = 5.02 and 8.16 TeV are compared with data from the Large Hadron Collider. Our approach combines a relativistic diffusion model with formulations based on quantum chromodynamics while utilizing numerical solutions of a Fokker-Planck equation to account for the shift and broadening of the fragmentation sources for particle-production with respect to the stopping (net-baryon) rapidity distributions. To represent the centrality dependence of charged-hadron production in asymmetric systems over a broad region of pseudorapidities, the consideration and precise modeling of the fragmentation sources, along with the central gluon-gluon source, is found to be essential. Specifically, this results in an inversion of the particle-production amplitude from backward to forward dominance when transitioning from central to peripheral collisions, in agreement with recent ATLAS and ALICE p-Pb data at s NN = 5.02 T e V . Published by the American Physical Society 2024

Schulz, Philipp (ORCID:0009000266642148)↗

DOE OSTI2015

Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch{sup ICN-TG}). Following exposure of adult Notch{sup ICN-TG} mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch{sup ICN-TG} offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch{sup ICN-TG} offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch-induced thymoma was different in offspring exposed to TCDD developmentally. • Developmental AHR activation attenuates later-life Notch1-dependent impacts on T cell differentiation.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2013

A Novel Graphical User Interface for High-Efficacy Modeling of Human Perceptual Similarity Opinions

We present a novel graphical user interface (GUI) that facilitates high-efficacy collection of perceptual similarity opinions of a user in an effective and intuitive manner. The GUI is based on a hybrid mechanism that combines ranking and rating. Namely, it presents a base image for rating its similarity to seven peripheral images that are displayed simultaneously following a circular layout. The user is asked to report the base image s pairwise similarity to each peripheral image on a fixed scale while preserving the relative ranking among all peripheral images. The collected data are then used to predict the user s subjective opinions regarding the perceptual similarity of images. We tested this new approach against two methods commonly used in perceptual similarity studies: (1) a ranking method that presents triplets of images for selecting the image pair with the highest internal similarity and (2) a rating method that presents pairs of images for rating their relative similarity on a fixed scale. We aimed to determine which data collection method was the most time efficient and effective for predicting a user s perceptual opinions regarding the similarity of mammographic masses. Our study was conducted with eight individuals. By using the proposed GUI, we were able to derive individual user profiles that were 41.4% to 46.9% more accurate than those derived with the other two data collection GUIs. The accuracy improvement was statistically significant.

Kress, James M↗

DOE OSTI2019

Phase field modeling of chemomechanical fracture of intercalation electrodes: Role of charging rate and dimensionality

We investigate the fracture of Li-ion battery cathodic particles using a thermodynamically consistent phase-field approach that can describe arbitrarily complex crack paths and captures the full coupling between Li-ion diffusion, stress, and fracture. Building on earlier studies that introduced the concept of electrochemical shock, we use this approach to quantify the relationships between stable or unstable crack propagation, flaw size, and C-rate for 2D disks and 3D spherical particles. We find that over an intermediate range of flaw sizes, the critical flaw size for the onset of crack propagation depends on charging rate as an approximate power-law that we derive analytically. This scaling law is quantified in 2D by exhaustive simulations and is also supported by 3D simulations. In addition, our results reveal a significant difference between 2D and 3D geometries. In 2D, cracks propagate deep inside the particle in a rectilinear manner while in 3D they propagate peripherally on the surface and bifurcate into daughter cracks, thereby limiting inward penetration and giving rise to complex crack geometries.

36 MATERIALS SCIENCE↗

NASA NTRS2002

Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity

Inflammatory adherence to, and locomotion through the interstitium is an important component of the immune response. Conditions such as microgravity and modeled microgravity (MMG) severely inhibit lymphocyte locomotion in vitro through gelled type I collagen. We used the NASA rotating wall vessel bioreactor or slow-turning lateral vessel as a prototype for MMG in ground-based experiments. Previous experiments from our laboratory revealed that when lymphocytes (human peripheral blood mononuclear cells [PBMCs]) were first activated with phytohemaglutinin followed by exposure to MMG, locomotory capacity was not affected. In the present study, MMG inhibits lymphocyte locomotion in a manner similar to that observed in microgravity. Phorbol myristate acetate (PMA) treatment of PBMCs restored lost locomotory capacity by a maximum of 87%. Augmentation of cellular calcium flux with ionomycin had no restorative effect. Treatment of lymphocytes with mitomycin C prior to exposure to MMG, followed by PMA, restored locomotion to the same extent as when nonmitomycin C-treated lymphocytes were exposed to MMG (80-87%), suggesting that deoxyribonucleic acid replication is not essential for the restoration of locomotion. Thus, direct activation of protein kinase C (PKC) with PMA was effective in restoring locomotion in MMG comparable to the normal levels seen in Ig cultures. Therefore, in MMG, lymphocyte calcium signaling pathways were functional, with defects occurring at either the level of PKC or upstream of PKC.

NASA Discipline Cell Biology↗