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At least 91 records · Page 5

Novel genetic risk factors influence progression of islet autoimmunity to type 1 diabetes

Type 1 diabetes arises from the autoimmune destruction of insulin-producing beta-cells of the pancreas, resulting in dependence on exogenously administered insulin to maintain glucose homeostasis. In this study, our aim was to identify genetic risk factors that contribute to progression from islet autoimmunity to clinical type 1 diabetes. We analyzed 6.8 million variants derived from whole genome sequencing of 160 islet autoantibody positive subjects, including 87 who had progressed to type 1 diabetes. The Cox proportional-hazard model for survival analysis was used to identify genetic variants associated with progression. We identified one novel region, 20p12.1 (TASP1; genome-wide P < 5 × 10 –8 ) and three regions, 1q21.3 (MRPS21–PRPF3), 2p25.2 (NRIR), 3q22.1 (COL6A6), with suggestive evidence of association (P < 8.5 × 10 –8 ) with progression from islet autoimmunity to type 1 diabetes. Once islet autoimmunity is initiated, functional mapping identified two critical pathways, response to viral infections and interferon signaling, as contributing to disease progression. These results provide evidence that genetic pathways involved in progression from islet autoimmunity differ from those pathways identified once disease has been established. These results support the need for further investigation of genetic risk factors that modulate initiation and progression of subclinical disease to inform efforts in development of novel strategies for prediction and intervention of type 1 diabetes.

59 BASIC BIOLOGICAL SCIENCES↗

Vacuum-assisted carbon molecular sieve membrane reactor for non-oxidative ethane dehydrogenation

Non-oxidative ethane dehydrogenation (EDH) is equilibrium-limited and endothermic. Selective hydrogen removal using a gas-permeable membrane within the EDH reaction zone can overcome the thermodynamic equilibrium, enabling higher ethane conversions. Employing vacuum as the permeation driving force, rather than a sweep gas, enhances the industrial viability of membrane reactors by eliminating additional post-reaction separation units. This study presents a membrane reactor that integrates H 2 -permeable carbon molecular sieve (CMS) hollow fiber membranes embedded in a fixed bed of cobalt in a dealuminated beta zeolite (Co@DeAl-BEA) catalyst, utilizing a vacuum to remove hydrogen efficiently. The CMS membrane exhibits high hydrogen permeance and an excellent H 2 /C 2 H 6 separation factor. The membrane reactor significantly enhanced the ethane conversion under reaction conditions comparable to those reported in the literature. A Langmuir-Hinshelwood kinetic rate expression was developed and incorporated into a one-dimensional steady-state reactor model. The experimentally validated model indicates that increasing the number of hollow fibers improves ethane conversion, although ethane loss to the permeate limits the benefit. The contact area between the catalyst and the membrane limits the reactor performance more than the catalytic throughput. Furthermore, we find that the location of the catalyst packing relative to the hollow fiber membranes influences ethane loss and conversion. Higher reactor pressures and inlet ethane flow rates improve space-time yield at the expense of lower ethane conversion. Increasing reactor temperature or packing length promotes both performance metrics. The EDH membrane reactor demonstrated durability over 200 h of continuous operation, maintaining record-low deactivation rates and high ethylene selectivity. Protocols for catalyst regeneration were developed.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

GLObal Backscatter Experiment (GLOBE) Pacific survey mission

NASA conducted the GLObal Backscatter Experiment (GLOBE) Survey Mission over the near coastal and remote Pacific Ocean during 6 to 30 Nov. 1989 (GLOBE 1) and 13 May to 5 Jun. 1990 (GLOBE 2). These missions studied the optical, physical, and chemical properties of atmospheric aerosols. Particular emphasis was given to the magnitude and spatial variability of aerosol backscatter coefficients at mid-infrared wavelengths, and to the remote middle and upper troposphere, where these aerosol properties are poorly understood. Survey instruments were selected to provide either direct beta measurements at the key wavelengths, empirical links with long term or global scale aerosol climatologies, or aerosol microphysics data required to model any of these quantities. The survey deployment included both long distance 6 to 8 hour transit flights and detailed 4 to 6 hour local flights. Several general features were observed from preliminary Survey data analyses. Validation and intercomparison results have shown good agreement, usually better than a factor of two. Atmospheric aerosols frequently exhibited a three layer vertical structure, with (1) high and fairly uniform backscatter in the shallow cloud capped marine boundary layer; (2) moderate and highly variable backscatter in a deeper overlaying cloud pumped layer; and (3) low, regionally uniform, but seasonally and latitudinally variable backscatter in the middle and upper troposphere. The survey missions represent two isolated snapshots of a small portion of the global aerosol system. Consequently, Survey results can best be understood by synthesizing them with the more comprehensive GLOBE data base, which is being compiled at NASA-Marshall.

Bowdle, David A.↗

Dust extinction of the stellar continua in starburst galaxies: The ultraviolet and optical extinction law

We analyze the International Ultraviolet Explorer (IUE) UV and the optical spectra of 39 starburst and blue compact galaxies in order to study the average properties of dust extinction in extended regions of galaxies. The optical spectra have been obtained using an aperture which matches that of IUE, so comparable regions within each galaxy are sampled. The data from the 39 galaxies are compared with five models for the geometrical distribution of dust, adopting as extinction laws both the Milky Way and the Large Magellanic Cloud laws. The commonly used uniform dust screen is included among the models. We find that none of the five models is in satisfactory agreement with the data. In order to understand the discrepancy between the data and the models, we have derived an extinction law directly from the data in the UV and optical wavelength range. The resulting curve is characterized by an overall slope which is more gray than the Milky Way extinction law's slope, and by the absence of the 2175 A dust feature. Remarkably, the difference in optical depth between the Balmer emission lines H(sub alpha) and H(sub beta) is about a factor of 2 larger than the difference in the optical depth between the continuum underlying the two Balmer lines. We interpret this discrepancy as a consequence of the fact that the hot ionizing stars are associated with dustier regions than the cold stellar population is. The absence of the 2175 A dust feature can be due either to the effects of the scattering and clumpiness of the dust or to a chemical composition different from that of the Milky Way dust grains. Disentangling the two interpretations is not easy because of the complexity of the spatial distribution of the emitting regions. The extinction law of the UV and optical spectral continua of extended regions can be applied to the spectra of medium- and high-redshift galaxies, where extended regions of a galaxy are, by necessity, sampled.

Calzetti, Daniela↗

Receptor Expression in Rat Skeletal Muscle Cell Cultures

One on the most persistent problems with long-term space flight is atrophy of skeletal muscles. Skeletal muscle is unique as a tissue in the body in that its ability to undergo atrophy or hypertrophy is controlled exclusively by cues from the extracellular environment. The mechanism of communication between muscle cells and their environment is through a group of membrane-bound and soluble receptors, each of which carries out unique, but often interrelated, functions. The primary receptors include acetyl choline receptors, beta-adrenergic receptors, glucocorticoid receptors, insulin receptors, growth hormone (i.e., somatotropin) receptors, insulin-like growth factor receptors, and steroid receptors. This project has been initiated to develop an integrated approach toward muscle atrophy and hypertrophy that takes into account information on the populations of the entire group of receptors (and their respective hormone concentrations), and it is hypothesized that this information can form the basis for a predictive computer model for muscle atrophy and hypertrophy. The conceptual basis for this project is illustrated in the figure below. The individual receptors are shown as membrane-bound, with the exception of the glucocorticoid receptor which is a soluble intracellular receptor. Each of these receptors has an extracellular signalling component (e.g., innervation, glucocorticoids, epinephrine, etc.), and following the interaction of the extracellular component with the receptor itself, an intracellular signal is generated. Each of these intracellular signals is unique in its own way; however, they are often interrelated.

Young, Ronald B.↗

The response of bone to unloading

Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with the expectation that such understanding will lead to effective treatment for disuse osteoporosis.

NASA Program Fundamental Space Biology↗

Thermal / structural analysis of the HB 650 thermal shield

Fermilab’s PIP-II project’s superconducting linear accelerator will drive the next generation of particle accelerators through a revolution in beam intensity. Key to beam intensification are the high efficiencies of niobium-tin superconducting radiofrequency (SRF) cavities operating at cryogenic temperatures near 5 Kelvin. A multifaceted approach is employed to achieve and maintain the extreme temperature. Vacuum provides the first barrier to thermal convection. Physical thermal intercept zones further isolate the exterior shell vacuum vessel at 300 Kelvin from the supercooled beamline. The first thermal intercept lies just inside the exterior vacuum vessel forming the 40 Kelvin zone. This 40K thermal shield is the focus of this investigation. In preparation for operation, the thermal shield is cooled from 300K to 40K in a slow process over 2-1/2 days. The factors limiting the cooling rate are a high thermal gradient which produces thermal strain and high mechanical stress. D ecreasing the time required to reach operational temperatures is the desired research goal. Physical testing data and finite element method (FEM) computer models from the Single Spoke Resonator – 1 (SSR1) and Linac Coherent Light Source (LCLS-II) cryomodules will be evaluated to determine needed design changes. The thermal shield design for the High Beta 650 MHz (HB650) will be modified and analyzed using FEM computer models to determine maximum cooling rate with a target of 50 thermal cycles of life. Maximum allowable stress will be determined through low cycle fatigue calculations.

43 PARTICLE ACCELERATORS↗

Modularized TGFbeta-Smad Signaling Pathway

The Transforming Growth Factor beta (TGFbeta) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. It can be induced by several factors, including ionizing radiation. It is regulated by Smads in a negative feedback loop through promoting increases in the regulatory Smads in the cell nucleus, and subsequent expression of inhibitory Smad, Smad7 to form a ubiquitin ligase with Smurf targeting active TGF receptors for degradation. In this work, we proposed a mathematical model to study the radiation-induced Smad-regulated TGF signaling pathway. By modularization, we are able to analyze each module (subsystem) and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, along the TGF signaling pathway is discussed by mathematical analysis and numerical simulation.

Li, Yongfeng↗

Determining g A / g V with High-Resolution Spectral Measurements Using a LiInSe 2 Bolometer

Neutrinoless double beta decay (0νββ) processes sample a wide range of intermediate forbidden nuclear transitions, which may be impacted by quenching of the axial vector coupling constant (g A /g V ), the uncertainty of which plays a pivotal role in determining the sensitivity reach of 0νββ experiments. Here we present measurements performed on a high-resolution LiInSe 2 bolometer in a “source = detector” configuration to measure the spectral shape of the fourfold forbidden β decay of 115 In . The value of g A /g V is determined by comparing the spectral shape of theoretical predictions to the experimental β spectrum taking into account various simulated background components as well as a variety of detector effects. We find evidence of quenching of g A /g V at >5 σ with a model-dependent quenching factor of 0.655 ± 0.002 as compared to the free-nucleon value for the interacting shell model. We also measured the 115 In half-life to be [5.18 ± 0.06(stat) $^{+0.005}_{- 0.015}$(sys)] x 10 14 yr within the interacting shell model framework. This Letter demonstrates the power of the bolometeric technique to perform precision nuclear physics single-β decay measurements, which along with improved nuclear modeling can help reduce the uncertainties in the calculation of several decay nuclear matrix elements including those used in 0νββ sensitivity calculations.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

A probabilistic approach to radiative energy loss calculations for optically thick atmospheres - Hydrogen lines and continua

An approximate probabilistic radiative transfer equation and the statistical equilibrium equations are simultaneously solved for a model hydrogen atom consisting of three bound levels and ionization continuum. The transfer equation for L-alpha, L-beta, H-alpha, and the Lyman continuum is explicitly solved assuming complete redistribution. The accuracy of this approach is tested by comparing source functions and radiative loss rates to values obtained with a method that solves the exact transfer equation. Two recent model solar-flare chromospheres are used for this test. It is shown that for the test atmospheres the probabilistic method gives values of the radiative loss rate that are characteristically good to a factor of 2. The advantage of this probabilistic approach is that it retains a description of the dominant physical processes of radiative transfer in the complete redistribution case, yet it achieves a major reduction in computational requirements.

Canfield, R. C.↗

The variability of the double-peaked Balmer lines in the active nucleus of NGC 1097

We present spectroscopic observations of the nucleus of the Seyfert/low-ionization nuclear emission-line region galaxy NGC 1097 spanning the period 1991-1994. The goal was to monitor anticipated variations of the broad, double-peaked Balmer lines which appeared abruptly in 1991. We find that the broad Balmer lines have varied significantly over the monitoring period, both in their integrated fluxes and in their profile shapes. The integrated H-alpha flux has decreased by a factor of 2, the (H-alpha)/(H-beta) ratio has increased, and the originally asymmetric H-alpha profile has become symmetric. The decline of the H-alpha flux and the change in the (H-alpha)/(H-beta) ratio can be interpreted as consequences of either increased obscuration along the line of sight, or a decline in the ionizing continuum, but neither of these scenarios can account for the change in profile shapes. A model attributing the line emission to a precessing elliptical ring around a 10(exp 6) solar mass nuclear black hole can reproduce the observed profile variations. In this scenario, the line-emitting ring is the result of the tidal disruption of a star by the black hole. Alternative scenarios associating the broad-line emission with a collimated bipolar outflow also remain viable, but binary black holes and inhomogeneous accretion disks are disfavored by the observed pattern of variability.

Storchi-Bergmann, Thaisa↗

Wind variability in the Large Magellanic Cloud B(e) supergiant HD 34664

We present optical linear spectropolarimetry of the B(e) supergiant HD 34664. The polarization and position angle display significant spectral features which correspond to the H-alpha and H-beta emission lines. We use the line polarizations to separate the interstellar foreground polarization from the intrinsic polarization of HD 34664. The intrinsic polarization is consistent with electron scattering in a circumstellar disk seen at high inclination and provides further and independent evidence for the two-component wind model of the B(e) supergiants. We compare the polarization and spectrum of HD 34664 to observations published in the literature. In our data the continuum polarization is by a factor of two larger and the H-alpha line-to-continuum ratio is by a factor of at least four increased over previous observations. Since both the polarization and the line intensity are measures of the electron density in the stellar wind, we suggest that the observed variations can be attributed to a rise in the stellar mass-loss rate.

Schulte-Ladbeck, R. E.↗

CUPID: The Next-Generation Neutrinoless Double Beta Decay Experiment

We report CUPID is a next-generation tonne-scale bolometric neutrinoless double beta decay experiment that will probe the Majorana nature of neutrinos and discover lepton number violation in case of observation of this singular process. CUPID will be built on experience, expertise and lessons learned in CUORE and will be installed in the current CUORE infra-structure in the Gran Sasso underground laboratory. The CUPID detector technology, successfully tested in the CUPID-Mo experiment, is based on scintillating bolometers of Li 2 MoO 4 enriched in the isotope of interest 100 Mo. In order to achieve its ambitious science goals, the CUPID collaboration aims to reduce the backgrounds in the region of interest by a factor 100 with respect to CUORE. This performance will be achieved by introducing the high efficient α/β discrimination demonstrated by the CUPID-0 and CUPID-Mo experiments, and using a high transition energy double beta decay nucleus such as 100 Mo to minimize the impact of the gamma background. CUPID will consist of about 1500 hybrid heat-light detectors for a total isotope mass of 250 kg. The CUPID scientific reach is supported by a detailed and safe background model based on CUORE, CUPID-Mo and CUPID-0 results. The required performances have already been demonstrated and will be presented.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

UV stellar occultation measurements of nighttime equatorial ozone

The ultraviolet spectrometer-telescope on Copernicus was used for stellar occultation measurements of atmospheric ozone. Two sets of observations of the target star Beta-Cen were carried out on 26 July 1975 and 13-14 June 1976 at wavelengths from 2550 A to 3100 A. After unfolding of the data, ozone density profiles near the equator within 3 hours of local midnight were obtained at altitudes from 47 to 114 km. A secondary maximum at 97 km has been observed in both sets of data. The ozone density between 47 and 75 km is a factor of 2 to 3 times as large as current models predict. At the lower boundary, about half the ozone destruction should be caused by NOx and ClOx. Above 55 km, virtually all loss is due to HOx. These results suggest an overestimate of HOx and ClOx loss processes or a serious underestimate of the Ox production rate.

Riegler, G. R.↗

First Measurements of Ambient PM2.5 in Kinshasa, Democratic Republic of Congo and Brazzaville, Republic of Congo Using Field-calibrated Low-cost Sensors

Estimates of air pollution mortality in sub-Saharan Africa are limited by a lack of surface observations of fine particulate matter (PM2.5). Despite being large metropolises, Kinshasa, Democratic Republic of the Congo (DRC), population 14.3 million, and Brazzaville, Republic of the Congo (ROC), population 2.4 million, have no reference air pollution monitors at the time of writing. Recently, a few reference monitors have been deployed in other parts of sub-Saharan Africa, including Kampala, Uganda. A low-cost PurpleAir PM2.5 monitor was collocated next to the Kampala US Embassy BAM-1020 (Met One Beta Attenuation Monitor) starting in August 2019. Raw PurpleAir data are strongly correlated with the BAM (r(exp 2) = 0.88), but have a mean absolute error of approximately 14 μg/cu.m. Two calibration models, multiple linear regression and a random forest approach, decrease mean absolute error (MAE) from 14.3 μg/cu.m to 3.4 µg/cu.m or less and improve the the r(exp 2) from 0.88 to 0.96. Given )the similarity in climate and emissions in Kampala, we apply the collocated field correction factors to four PurpleAir sensors in Kinshasa, DRC and one in neighboring Brazzaville, ROC deployed beginning April 2018. Annual average PM2.5 for 2019 in Kinshasa is estimated at 43.5 µg/cu.m, more than 4 times higher than WHO Interim Target 1 of 10 µg/cu.m. Surface PM2.5 and aerosol optical depth were each about 40% lower during the 2020 COVID19 lockdown period compared to the same time period in 2019, which cannot be explained by changes in meteorology or wildfire emissions alone. Our results highlight the need for clean air solutions implementation in the Congo.

Celeste McFarlane↗

The discovery of 'Sco X-1 type' behaviour from the X-ray burster 4U 1735 - 44

A series of Copernicus, Ariel V and optical observations of the X-ray burst source 4U 1735 - 44 (= MXB 1735 - 44) revealed properties very similar to those of the 'Sco X-1 like' sources. During one run, the non-burst X-ray flux varied by a factor of 2 on a time-scale of hours and this was associated with a general hardening of the spectrum. The source was relatively constant throughout the remaining observations. An Ariel V spectrum obtained during a quiescent interval deviated from a simple thermal model in that it showed both a high energy deficiency and a low energy excess. Near simultaneous spectroscopy of the optical counterpart confirmed the general features reported by McClintock et al. Spectra taken on successive nights revealed the H-beta emission to be variable.

White, N. E.↗

Vibrational force alters mRNA expression in osteoblasts

Serum-deprived mouse osteoblastic (MC3T3E1) cells were subjected to a vibrational force modeled by NASA to simulate a space shuttle launch (7.83 G rms). The mRNA levels for eight genes were investigated to determine the effect of vibrational force on mRNA expression. The mRNA levels of two growth-related protooncogenes, c-fos and c-myc, were up-regulated significantly within 30 min after vibration, whereas those of osteocalcin as well as transforming growth factor-beta1 were decreased significantly within 3 h after vibration. No changes were detected in the levels of beta-actin, histone H4, or cytoplasmic phospholipase A2 after vibration. No basal levels of cyclooxygenase-2 expression were detected. In addition, the extracellular concentrations of prostaglandin E2 (PGE2), a potent autocrine/paracrine growth factor in bone, were not significantly altered after vibration most likely due to the serum deprivation state of the osteoblasts. In comparison with the gravitational launch profile, vibrational-induced changes in gene expression were greater both in magnitude and number of genes activated. Taken together, these data suggest that the changes in mRNA expression are due to a direct mechanical effect of the vibrational force on the osteoblast cells and not to changes in the local PGE2 concentrations. The finding that launch forces induce gene expression is of utmost importance since many of the biological experiments do not dampen vibrational loads on experimental samples. This lack of dampening of vibrational forces may partially explain why 1-G onboard controls sometimes do not reflect 1-G ground controls. These data may also suggest that scientists use extra ground controls that are exposed to launch forces, have these forces dampened on launched samples, or use facilities such as Biorack that provide an onboard 1-G centrufuge in order to control for space shuttle launch forces.

NASA Discipline Cell Biology↗

Modeling beta-adrenergic control of cardiac myocyte contractility in silico

The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.

Non-NASA Center↗