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At least 109 records · Page 6

Dual Spacecraft Observations of Lobe Magnetic Field Perturbations Before, During and after Plasmoid Release

This study examines a unique data set returned by IMP8 and Geotail on January 29, 1995 during a substorm which resulted in the ejection of a plasmoid. The two spacecraft (s/c) were situated in the north lobe of the tail and both observed a traveling compression region (TCR). From single s/c observations only the length of the plasmoid in X and an estimate of its height in Z can be determined. However, we show that dual s/c measurements of TCRs can be used to model all three dimensions of the underlying plasmoid and to estimate of its rate of expansion or contraction. For this event plasmoid dimensions of Delta(X) approximates 18, Delta(Y) approximates 30, and Delta(Z) approximates 10 R(sub e) are inferred from the IMP8 and Geotail lobe magnetic field measurements. The earthward end of the plasmoid was inferred to be near the mean location of the near-earth neutral line, X approximates -26 R(sub e). Its center was underneath IMP 8 at X approximates -34 R(sub e) and its tailward end appeared to be near X approximates -44 R(sub e). Furthermore, a factor of approximately 2 increase in the amplitude of the TCR occurred in the 1.5 min it took to move from IMP 8 to Geotail. Modeled using conservation of the magnetic flux, this increase in lobe compression implies that the underlying plasmoid was expanding at a rate of approximately 140 km/s. Such an expansion is comparable to recently reported V(sub y) speeds in "young" plasmoids in this region of the tail. Finally, the Geotail measurements indicate that a reconfiguration of the lobe magnetic field closely followed the ejection of the plasmoid which moved magnetic flux tubes into the wake behind the plasmoid where they would convect into the near-earth neutral line and reconnect.

Slavin, J. A.↗

T Cell Activation Thresholds are Affected by Gravitational

T cells stimulated in space flight by various mitogenic signals show a dramatic reduction in proliferation and expression of early activation markers. Similar results are also obtained in a ground based model of microgravity, clinorotation, which provides a vector-averaged reduction of the apparent gravity on cells without significant shear force. Here we demonstrate that T cell inhibition is due to an increase in the required threshold for activation. Dose response curves indicate that cells activated during clinorotation require higher stimulation to achieve the same level of activation, as measured by CD69 expression. Interleukin 2 receptor expression, and DNA synthesis. The amount of stimulation necessary for 50% activation is 5 fold in the clinostat relative to static. Correlation of TCR internalization with activation also exhibit a dramatic right shift in clinorotation, demonstrating unequivocally that signal transduction mechanism independent of TCR triggering account for the increased activation threshold. Previous results from space flight experiments are consistent with the dose response curves obtained for clinorotation. Activation thresholds are important aspects of T cell memory, autoimmunity and tolerance Clinorotation is a useful, noninvasive tool for the study of cellular and biochemical event regulating T cell activation threshold and the effects of gravitation forces on these systems.

Adams, Charley↗

MESSENGER Observations of Magnetic Reconnection in Mercury's Magnetosphere

During MESSENGER'S second flyby of Mercury on October 6,2008, very intense reconnection was observed between the planet's magnetic field and a steady southward interplanetary magnetic field (IMF). The dawn magnetopause was threaded by a strong magnetic field normal to its surface, approx.14 nT, that implies a rate of reconnection approx.10 times the typical rate at Earth and a cross-magnetospheric electric potential drop of approx.30 kV. The highest magnetic field observed during this second flyby, approx.160 nT, was found at the core of a large dayside flux transfer event (FTE). This FTE is estimated to contain magnetic flux equal to approx.5% that of Mercury's magnetic tail or approximately one order of magnitude higher fraction of the tail flux than is typically found for FTEs at Earth. Plasmoid and traveling compression region (TCR) signatures were observed throughout MESSENGER'S traversal of Mercury's magnetotail with a repetition rate comparable to the Dungey cycle time of approx.2 min. The TCR signatures changed from south-north, indicating tailward motion, to north-south, indicating sunward motion, at a distance approx.2.6 RM (where RM is Mercury's radius) behind the terminator indicating that the near-Mercury magnetotail neutral line was crossed at that point. Overall, these new MESSENGER observations suggest that magnetic reconnection at the dayside magnetopause is very intense relative to what is found at Earth and other planets, while reconnection in Mercury's tail is similar to that in other planetary magnetospheres, but with a very short Dungey cycle time.

Slavin. James A.↗

Nanocomposite Strain Gauges Having Small TCRs

Ceramic strain gauges in which the strain-sensitive electrically conductive strips made from nanocomposites of noble metal and indium tin oxide (ITO) are being developed for use in gas turbine engines and other power-generation systems in which gas temperatures can exceed 1,500 F (about 816 C). In general, strain gauges exhibit spurious thermally induced components of response denoted apparent strain. When temperature varies, a strain-gauge material that has a nonzero temperature coefficient of resistance (TCR) exhibits an undesired change in electrical resistance that can be mistaken for the change in resistance caused by a change in strain. It would be desirable to formulate straingauge materials having TCRs as small as possible so as to minimize apparent strain. Most metals exhibit positive TCRs, while most semiconductors, including ITO, exhibit negative TCRs. The present development is based on the idea of using the negative TCR of ITO to counter the positive TCRs of noble metals and of obtaining the benefit of the ability of both ITO and noble metals to endure high temperatures. The noble metal used in this development thus far has been platinum. Combinatorial libraries of many ceramic strain gauges containing nanocomposites of various proportions of ITO and platinum were fabricated by reactive co-sputtering from ITO and platinum targets onto alumina- and zirconia-based substrates mounted at various positions between the targets.

Gregory, Otto↗

Implications for Climate Sensitivity from the Response to Individual Forcings

Climate sensitivity to doubled CO2 is a widely-used metric of the large-scale response to external forcing. Climate models predict a wide range for two commonly used definitions: the transient climate response (TCR: the warming after 70 years of CO2 concentrations that riseat 1 per year), and the equilibrium climate sensitivity (ECS: the equilibrium temperature change following a doubling of CO2 concentrations). Many observational datasets have been used to constrain these values, including temperature trends over the recent past 16, inferences from paleo-climate and process-based constraints from the modern satellite eras. However, as the IPCC recently reported different classes of observational constraints produce somewhat incongruent ranges. Here we show that climate sensitivity estimates derived from recent observations must account for the efficacy of each forcing active during the historical period. When we use single forcing experiments to estimate these efficacies and calculate climate sensitivity from the observed twentieth-century warming, our estimates of both TCR and ECS are revised upward compared to previous studies, improving the consistency with independent constraints.

Sensitivity↗

T-Cell Shenanigans: The Impact of MHC Pathway & Lipid Metabolism Genes on T-Cell Differentiation in the Thymus

Astronaut health and proper immune function are key to the success and sustainability of long term missions in space. While previous studies have observed adaptive immune dysfunction such as diminished WBC counts and cytokine production during spaceflight, the underlying mechanisms behind why immune function worsens are poorly understood. Using transcriptomic data analyzed from mouse thymus tissues available from the GLDS-421 experiment on the Rodent Research-9 mission, we used the GeneLab standardized RNA-Seq pipeline and identified four genes that were largely dysregulated (p<0.05): lipid metabolic genes Hpgd and Pgr and cell cycle regulator genes Cenpe and Kif11. We analyzed how these genes regulate the MHC-TCR interaction, and used this understanding to propose a novel mechanism for alterations to T-cell differentiation. In our experimental methodology, we propose to use 36 transgenic CD4-CD8 mice and 12 wild-type mice from the Jackson Lab to create a microgravity-simulating hindlimb unloading model and test our hypothesis. By silencing the aforementioned genes using custom siRNA based primers, we will use flow cytometry and RNA-Seq to quantify Treg counts in comparison to naive CD4+ cells, Alamar Blue assay for observing the metabolic activity in T-cells, and Enzyme-Linked Immunosorbent Assay (ELISA) to observe the general immune response in terms of T-cell differentiation. We hope this methodology will improve our knowledge of MHC-TCR interaction, contribute to a better understanding of the mechanisms of autoimmune diseases such as lupus, and improve the success rate of newer cancer treatments such as CAR-T cell therapy.

GL4HS↗

Platinum nanometal interconnection of copper–carbon nanotube hybrid electrical conductors

This study demonstrates the versatility of Joule heating driven chemical vapor deposition to deposit nanometal interconnections into porous CNT roving with application in the production of high electrical conductivity copper-carbon nanotube (Cu-CNT) hybrids. Modifications of vapor deposition parameters allow for deposited nanometal masses from less than 5% w/w to over 85% w/w and distributions that can be controlled towards either hot-spot site-specificity or overall uniformity. Here, depositions of copper, platinum, nickel, palladium, ruthenium, rhodium, and iridium are demonstrated from acetylacetonate precursors. In particular, platinum acetylacetonate [Pt(acac) 2 ] deposits nanometal seeds that adhere tightly to the CNT roving, producing improvements in resistance and specific conductivity. The properties of the platinum deposition compared to the copper deposition motivate an investigation into its use as an interfacial layer for Cu-CNT hybrids. CNT conductors with ~30% w/w platinum are electroplated with copper, densified, and annealed to produce Cu-CNT hybrid conductors with specific conductivities as high as 5772 S m 2 /kg and TCR (from 300 to 600 K) as low as 3.12 × 10 –3 K –1 , indicating good interconnection of the metal and CNT portions. Room temperature conductivities of 29.8 MS/m are achieved, comparable to metallic conductors. Thus, Pt(acac) 2 seeded Cu-CNT hybrids offer abundant promise in high conductivity applications.

42 ENGINEERING↗

Air oxidation of yttrium hydride as a high temperature moderator for thermal neutron spectrum fission reactors

Yttrium hydride (YH x ) is an attractive moderator material for thermal neutron spectrum fission reactors requiring a small reactor core volume and has been selected as the neutron moderator for the Transformational Challenge Reactor (TCR), an advanced gas-cooled microreactor. Before YH x can be used in this application, it is important to understand the material response to off-normal conditions. In the present study, 550–650 °C isothermal dry air oxidation was performed to simulate a depressurized loss of force circulation (DLOFC) event. The oxidation was performed using thermogravimetric analysis (TGA) on bulk crack-free YHx coupons. Oxidation studies were also performed on Y coupons to elucidate the impact of H on oxidation. Both the chemistry and distribution of processing impurities were found to strongly affect oxidization behavior on a batch-to-batch basis. Regardless of batch, YHx oxidized at a significantly lower rate than Y at all temperatures, and the lower rate was directly correlated with increased hydride content. Metallic Y exhibited complex exponential kinetics, whereas YH x also exhibited complex kinetics but gained considerably less mass. According to literature reports on protonic and native-ion conductivities of Y 2 O 3 and mass spectrometry analysis of gaseous reaction products formed during the oxidation of YH x , a mechanism for the reduced oxidation rate of yttrium hydride is suggested.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Protein 4.1R negatively regulates P815 cells proliferation by inhibiting C-Kit-mediated signal transduction

The proliferation of mast cells (MCs) plays a crucial role in either physiological or pathological progression of human physical. C-Kit-mediated signaling pathway has been confirmed to play a key role in MCs proliferation, and the regulatory mechanisms of C-Kit-mediated MCs proliferation need to be further explored. Our previous study found that protein 4.1R could negatively regulate T cell receptor (TCR) mediated signal pathways in CD4{sup +} T cells. Little is known about the function of 4.1R in C-Kit-mediated proliferation of MCs. In this study, P815-4.1R{sup -/-} cells were constructed by using CRISPR/Cas9 technique. Lack of 4.1R significantly enhanced P815 cells proliferation by accelerating the progression of cell cycle. 4.1R could also significantly alleviate the clinical symptoms of systemic mastocytosis (SM) and improve the overall survival of SM mice. Further study showed that 4.1R could interact directly with C-Kit to inhibit the activation of C-Kit-mediated Ras-Raf-MAPKs and PI3K-AKT signal pathways. Taken together, our findings demonstrate that protein 4.1R, a novel negative regulator, negatively regulates MCs proliferation by inhibiting C-Kit-mediated signal transduction, which maybe provide a potential target to the prevention and treatment of abnormal MCs proliferation-related diseases.

60 APPLIED LIFE SCIENCES↗

CTPS and IMPDH form cytoophidia in developmental thymocytes

The cytoophidium, a filamentous structure formed by metabolic enzymes, has emerged as a novel regulatory machinery for certain proteins. The rate-limiting enzymes of de novo CTP and GTP synthesis, cytidine triphosphate synthase (CTPS) and inosine monophosphate dehydrogenase (IMPDH), are the most characterized cytoophidium-forming enzymes in mammalian models. Although the assembly of CTPS cytoophidia has been demonstrated in various organisms including multiple human cancers, a systemic survey for the presence of CTPS cytoophidia in mammalian tissues in normal physiological conditions has not yet been reported. Herein, we examine major organs of adult mouse and observe that CTPS cytoophidia are displayed by a specific thymocyte population ranging between DN3 to early DP stages. Most of these cytoophidium-presenting cells have both CTPS and IMPDH cytoophidia and undergo rapid cell proliferation. In addition, we show that cytoophidium formation is associated with active glycolytic metabolism as the cytoophidium-presenting cells exhibit higher levels of c-Myc, phospho-Akt and PFK. Inhibition of glycolysis with 2DG, however, disrupts most of cytoophidium structures and impairs cell proliferation. Our findings not only indicate that the regulation of CTPS and IMPDH cytoophidia are correlated with the metabolic switch triggered by pre-TCR signaling, but also suggest physiological roles of the cytoophidium in thymocyte development.

60 APPLIED LIFE SCIENCES↗

Metal–Carbodithioate-Based 3D Semiconducting Metal–Organic Framework: Porous Optoelectronic Material for Energy Conversion

Solar energy conversion requires the working compositions to generate photoinduced charges with high potential and the ability to deliver charges to the catalytic sites and/or external electrode. These two properties are typically at odds with each other and call for new molecular materials with sufficient conjugation to improve charge conductivity but not as much conjugation as to overly compromise the optical band gap. In this work, we developed a semiconducting metal-organic framework (MOF) prepared explicitly through metal-carbodithioate"(-CS 2 ) n M" linkage chemistry, entailing augmented metal-linker electronic communication. The stronger ligand field and higher covalent character of metal-carbodithioate linkages-when combined with spirofluorene-derived organic struts and nickel-(II) ion-based nodes-provided a stable, semiconducting 3D-porous MOF, Spiro-CS 2 Ni. This MOF lacks long-range ordering and is defined by a flexible structure with non-aggregated building units, as suggested by reverse Monte Carlo simulations of the pair distribution function obtained from total scattering experiments. The solvent-removed "closed pore"material recorded a Brunauer-Emmett-Teller area of similar to 400m 2 /g, where the "open pore" form possesses90 wt % solvent-accessible porosity. Electrochemical measurements suggest that Spiro-CS 2 Ni possesses a band gap of 1.57 eV(sigma = 10 -7 S/cm at -1.3 V bias potential),which can be further improved by manipulating the d-electron configuration through an axial coordination (ligand/substrate), the latter of which indicates usefulness as an electrocatalyst and/or a photoelectrocatalyst(upon substrate binding). Transient-absorption spectroscopy reveals a long-lived photo-generated charge-transfer state (τ CR = 6.5 mu s) capable of chemical transformation under a biased voltage. Spiro-CS 2 Ni can endure a compelling range of pH(1-12 for weeks) and hours of electrochemical and photoelectrochemical conditions in the presence of water and organic acids. We believe this work provides crucial design principles for low-density, porous,light-energy-conversion materials.

36 MATERIALS SCIENCE↗

Structural basis for oligoclonal T cell recognition of a shared p53 cancer neoantigen

Adoptive cell therapy (ACT) with tumor-specific T cells can mediate cancer regression. The main target of tumor-specific T cells are neoantigens arising from mutations in self-proteins. Although the majority of cancer neoantigens are unique to each patient, and therefore not broadly useful for ACT, some are shared. We studied oligoclonal T-cell receptors (TCRs) that recognize a shared neoepitope arising from a driver mutation in the p53 oncogene (p53R175H) presented by HLA-A2. Here we report structures of wild-type and mutant p53–HLA-A2 ligands, as well as structures of three tumor-specific TCRs bound to p53R175H–HLA-A2. These structures reveal how a driver mutation in p53 rendered a self-peptide visible to T cells. The TCRs employ structurally distinct strategies that are highly focused on the mutation to discriminate between mutant and wild-type p53. The TCR–p53R175H–HLA-A2 complexes provide a framework for designing TCRs to improve potency for ACT without sacrificing specificity.

60 APPLIED LIFE SCIENCES↗

Hydrophobic interactions dominate the recognition of a KRAS G12V neoantigen

Specificity remains a major challenge to current therapeutic strategies for cancer. Mutation associated neoantigens (MANAs) are products of genetic alterations, making them highly specific therapeutic targets. MANAs are HLA-presented (pHLA) peptides derived from intracellular mutant proteins that are otherwise inaccessible to antibody-based therapeutics. Here, we describe the cryo-EM structure of an antibody-MANA pHLA complex. Specifically, we determine a TCR mimic (TCRm) antibody bound to its MANA target, the KRAS G12V peptide presented by HLA-A*03:01. Hydrophobic residues appear to account for the specificity of the mutant G12V residue. We also determine the structure of the wild-type G12 peptide bound to HLA-A*03:01, using X-ray crystallography. Based on these structures, we perform screens to validate the key residues required for peptide specificity. These experiments led us to a model for discrimination between the mutant and the wild-type peptides presented on HLA-A*03:01 based exclusively on hydrophobic interactions.

36 MATERIALS SCIENCE↗

GRB2 dimerization mediated by SH2 domain-swapping is critical for T cell signaling and cytokine production

GRB2 is an adaptor protein required for facilitating cytoplasmic signaling complexes from a wide array of binding partners. GRB2 has been reported to exist in either a monomeric or dimeric state in crystal and solution. GRB2 dimers are formed by the exchange of protein segments between domains, otherwise known as “domain-swapping”. Swapping has been described between SH2 and C-terminal SH3 domains in the full-length structure of GRB2 (SH2/C–SH3 domain-swapped dimer), as well as between α-helixes in isolated GRB2 SH2 domains (SH2/SH2 domain-swapped dimer). Interestingly, SH2/SH2 domain-swapping has not been observed within the full-length protein, nor have the functional influences of this novel oligomeric conformation been explored. We herein generated a model of full-length GRB2 dimer with an SH2/SH2 domain-swapped conformation supported by in-line SEC–MALS–SAXS analyses. This conformation is consistent with the previously reported truncated GRB2 SH2/SH2 domain-swapped dimer but different from the previously reported, full-length SH2/C-terminal SH3 (C–SH3) domain-swapped dimer. Our model is also validated by several novel full-length GRB2 mutants that favor either a monomeric or a dimeric state through mutations within the SH2 domain that abrogate or promote SH2/SH2 domain-swapping. GRB2 knockdown and re-expression of selected monomeric and dimeric mutants in a T cell lymphoma cell line led to notable defects in clustering of the adaptor protein LAT and IL-2 release in response to TCR stimulation. These results mirrored similarly-impaired IL-2 release in GRB2-deficient cells. These studies show that a novel dimeric GRB2 conformation with domain-swapping between SH2 domains and monomer/dimer transitions are critical for GRB2 to facilitate early signaling complexes in human T cells.

59 BASIC BIOLOGICAL SCIENCES↗

Multiphysics Analyses of the Bottom Components of the 3D Printed Transformational Challenge Reactor

This research presents multi-physics analyses on the bottom components of the Transformational Challenge Reactor (TCR) facility. These components include the bottom axial reflector and the steel exit cone. The bottom axial reflector is made of pure silicon carbide elements hosting helium cooling channels These elements are 3D printed and therefore can host any arbitrary shape of the helium cooling channels. The design of the bottom reflector considers the neutronics and thermo-fluid dynamics performances as well as the manufacturing process optimization. More precisely, the best design of the bottom reflector reduces neutron leakage by avoiding straight cylindrical helium channels that facilitate neutron leakage, minimizes the helium flow pressure drop, and reduces the number of 3D printed silicon carbide pieces. The exit cone steel structure collects the hot helium from the bottom fuel assemblies and channels the cold helium to the top of the fuel assemblies. The steel simultaneous contact with hot and cold helium flows sets a large thermal gradient. Different designs of the exit cone are proposed to reduce the steel equivalent stress from the helium thermal load. The multi-physics analyses have been performed using Ansys Fluent, Ansys Mechanical, STAR-CCM+, and Serpent computer programs.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Comparative analysis of the sensitivity of nanometallic thin film thermometers

Thin film platinum resistive thermometers are conventionally applied for resistance thermometry techniques due to their stability and proven measurement accuracy. Depending upon the required thermometer thickness and temperature measurement, however, performance benefits can be realized through the application of alternative nanometallic thin films. Herein, a comparative experimental analysis is provided on the performance of nanometallic thin film thermometers most relevant to microelectronics and thermal sensing applications: Al, Au, Cu, and Pt. Sensitivity is assessed through the temperature coefficient of resistance, measured over a range of 10–300 K for thicknesses nominally spanning 25–200 nm. In this work, the interplay of electron scattering sources, which give rise to the temperature-dependent TCR properties for each metal, are analyzed in the framework of a Mayadas–Shatzkes based model. Despite the prevalence of evaporated Pt thin film thermometers, Au and Cu films fabricated in a similar manner may provide enhanced sensitivity depending upon thickness. These results may serve as a guide as the movement toward smaller measurement platforms necessitates the use of smaller, thinner metallic resistance thermometers.

36 MATERIALS SCIENCE↗

Biophysical and Structural Features of αβT ‐Cell Receptor Mechanosensing: A Paradigmatic Shift in Understanding T‐Cell Activation

ABSTRACT αβT cells protect vertebrates against many diseases, optimizing surveillance using mechanical force to distinguish between pathophysiologic cellular alterations and normal self‐constituents. The multi‐subunit αβT‐cell receptor (TCR) operates outside of thermal equilibrium, harvesting energy via physical forces generated by T‐cell motility and actin‐myosin machinery. When a peptide‐bound major histocompatibility complex molecule (pMHC) on an antigen presenting cell is ligated, the αβTCR on the T cell leverages force to form a catch bond, prolonging bond lifetime, and enhancing antigen discrimination. Under load, the αβTCR undergoes reversible structural transitions involving partial unfolding of its clonotypic immunoglobulin‐like (Ig) domains and coupled rearrangements of associated CD3 subunits and structural elements. We postulate that transitions provide critical energy to initiate the signaling cascade via induction of αβTCR quaternary structural rearrangements, associated membrane perturbations, exposure of CD3 ITAMs to phosphorylation by non‐receptor tyrosine kinases, and phase separation of signaling molecules. Understanding force‐mediated signaling by the αβTCR clarifies long‐standing questions regarding αβTCR antigen recognition, specificity and affinity, providing a basis for continued investigation. Future directions include examining atomistic mechanisms of αβTCR signal initiation, performance quality, tissue compliance adaptability, and T‐cell memory fate. The mechanotransduction paradigm will foster improved rational design of T‐cell based vaccines, CAR‐Ts, and adoptive therapies.

Immunology↗

Development and Characterization of 3D-Printed Cementitious Sytems for Innovative Nuclear Systems

The Transformational Challenge Reactor (TCR) is being developed to demonstrate a revolutionary approach to deploying new nuclear power systems by building and operating an additively manufactured microreactor. This initiative provides a unique opportunity to investigate the possibility of taking advantage of the recent development of the 3D-printed concrete system using the Sky Big Area Additive Manufacturing (SkyBAAM) printer at the Manufacturing Demonstration Facility (MDF) at Oak Ridge National Laboratory. Two pathways have been pursued in parallel since the end of the second quarter of FY19: 1. Development of methods to characterize the performance of additive manufacturing concrete using traditional Portland-cement based solution, and 2. Investigation of the opportunity to develop innovation of printable materials with higher irradiation-resistance performance using nontraditional concrete solutions in favor of carbonated cementitious materials (CCMs). This report describes the results achieved to date for both pathways. The main results are listed below: 1. A test protocol has been established to characterize the fracture properties of 3D-printed concrete; this protocol will be used to assess the performance of printed traditional and nontraditional cementitious materials, with a focus on performance of the interfaces inherent to the additive manufacturing process. 2. A state-of-the-art review of the mechanisms, fabrication method, and performance of CCMs was conducted. CCMs appear to be a viable, highly innovative, more performant alternative to Portland-based cementitious solution for the erection of biological shield pending some materials development.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗