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At least 1,675 records · Page 93

Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies

Plus-strand RNA viruses are the largest group of viruses. Many are human pathogens that inflict a socio-economic burden. Interestingly, plus-strand RNA viruses share remarkable similarities in their replication. A hallmark of plus-strand RNA viruses is the remodeling of intracellular membranes to establish replication organelles (so-called “replication factories”), which provide a protected environment for the replicase complex, consisting of the viral genome and proteins necessary for viral RNA synthesis. In the current study, we investigate pan-viral similarities and virus-specific differences in the life cycle of this highly relevant group of viruses. We first measured the kinetics of viral RNA, viral protein, and infectious virus particle production of hepatitis C virus (HCV), dengue virus (DENV), and coxsackievirus B3 (CVB3) in the immuno-compromised Huh7 cell line and thus without perturbations by an intrinsic immune response. Based on these measurements, we developed a detailed mathematical model of the replication of HCV, DENV, and CVB3 and showed that only small virus-specific changes in the model were necessary to describe the in vitro dynamics of the different viruses. Our model correctly predicted virus-specific mechanisms such as host cell translation shut off and different kinetics of replication organelles. Further, our model suggests that the ability to suppress or shut down host cell mRNA translation may be a key factor for in vitro replication efficiency, which may determine acute self-limited or chronic infection. We further analyzed potential broad-spectrum antiviral treatment options in silico and found that targeting viral RNA translation, such as polyprotein cleavage and viral RNA synthesis, may be the most promising drug targets for all plus-strand RNA viruses. Moreover, we found that targeting only the formation of replicase complexes did not stop the in vitro viral replication early in infection, while inhibiting intracellular trafficking processes may even lead to amplified viral growth.

59 BASIC BIOLOGICAL SCIENCES↗

Pathways for Nucleation and Growth in Confined Spaces and at Interfaces

Mineral crystallization is central to myriad natural processes from the formation of snowflakes to stalagmites, but the molecular-scale mechanisms are often far more complex than models reflect. Feedbacks between the hydro-, bio-, and geo-spheres drive complex crystallization processes that challenge our ability to observe and quantify them, motivating an expansion of crystallization theories. Here, in this article, we discuss how the driving forces and timescales of nucleation are influenced by factors ranging from simple geometric confinement to distinct interfacial solution structures involving solvent organization, electrical double layers, and surface charging effects. Taken together, these ubiquitous natural phenomena can preserve metastable intermediates, drive precipitation of undersaturated phases, and modulate crystallization in time and space.

biosphere↗

SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung

Extensive fibrin deposition in the lungs and altered levels of circulating blood coagulation proteins in COVID-19 patients imply local derangement of pathways that limit fibrin formation and/or promote its clearance. We examined transcriptional profiles of bronchoalveolar lavage fluid (BALF) samples to identify molecular mechanisms underlying these coagulopathies. mRNA levels for regulators of the kallikrein–kinin (C1-inhibitor), coagulation (thrombomodulin, endothelial protein C receptor), and fibrinolytic (urokinase and urokinase receptor) pathways were significantly reduced in COVID-19 patients. While transcripts for several coagulation proteins were increased, those encoding tissue factor, the protein that initiates coagulation and whose expression is frequently increased in inflammatory disorders, were not increased in BALF from COVID-19 patients. Our analysis implicates enhanced propagation of coagulation and decreased fibrinolysis as drivers of the coagulopathy in the lungs of COVID-19 patients.

59 BASIC BIOLOGICAL SCIENCES↗

The Strength and Characteristics of VPPA Welded 2219-T87 Aluminum Alloy

A study of the variable polarity plasma arc (VPPA) welding process and those factors that control the structure and properties of VPPA welded aluminum alloy 2219-T87 was conducted. The importance of joint preparation, alignment of parts and welding process variables are already established. Internal weld defects have been eliminated. However, a variation of properties was found to be due to the size variation of interdendritic particles in the fusion zone. These particles contribute to the void formation process, which controls the ultimate tensile strength of the welded alloy. A variation of 150 microns in particle size correlated with a 10 ksi variation of ultimate tensile strength. It was found that all fracture surfaces were of the dimple rupture type, with fracture initiating within the fusion zone.

Jemian, W. A.↗

SAR data compression: Application, requirements, and designs

The feasibility of reducing data volume and data rate is evaluated for the Earth Observing System (EOS) Synthetic Aperture Radar (SAR). All elements of data stream from the sensor downlink data stream to electronic delivery of browse data products are explored. The factors influencing design of a data compression system are analyzed, including the signal data characteristics, the image quality requirements, and the throughput requirements. The conclusion is that little or no reduction can be achieved in the raw signal data using traditional data compression techniques (e.g., vector quantization, adaptive discrete cosine transform) due to the induced phase errors in the output image. However, after image formation, a number of techniques are effective for data compression.

Curlander, John C.↗

Jet induced star formation in centrally dominant galaxies?

Using U-I CCD color maps of two centrally dominant cluster galaxies, we find unusual color structures which may be due to star formation which has been induced by their radio sources. These objects, located in the clusters A1795 and A2597, have blue central colors to radii of 20 kpc, spatially extended emission-line structures, and powerful radio sources. They reside at the centers of cooling flows with mass-accretion rates which are estimated to be approximately greater than 300 solar mass/yr. The regions of bluest local color are superposed on or along their radio-source structures. Our observations suggest that the radio sources associated with these objects may be inducing massive star formation in their central 20 kpc. The star formation may be the result of the radio plasma interacting with the warm emission-line gas and dense, x-ray emitting filaments similar to those recently discovered in two other clusters with the ROSAT Observatory. Since radio jets are likely to be transient, this may help to explain the scatter in the correlations between color and mass-accretion rate, although other factors may also contribute. Alternatively, scattered radiation from a hidden active nucleus or recent mergers may be responsible for the color structure. The color and radio properties of these objects are qualitatively similar but smaller in luminosity and spatial extent to those found in high redshift radio galaxies. Our observations of galaxies at z approximately = 0.06-0.1 show that processes similar to 'the alignment effect' found in high redshift radio galaxies occur at more recent epochs.

Mcnamara, Brian R.↗

The Origin and Time Dependence of the Amount and Composition of Non-Constituent Gases Present in Crystal Growth Systems

Presence of different, non-constituent gases may be a critical factor in crystal growth systems. In Physical Vapor Transport processes the cras(es) can be used intentionally (to prevent excessively high, unstable growth conditions), or can evolve unintentionally during the course of the process (which may lead to undesired reduction in the -rowth rate). In melt growth, particularly under low gravity conditions (reduced hydrostatic pressure) the gas present in the system may contribute to formation of voids in the growing crystals and even to a separation of the crystal and the liquid phase [1]. On the other hand, some amount of gas may facilitate 'contactless' crystal growth particularly under reduced gravity conditions [2 - 6]. Different non-constituent gases may be present in growth ampoules, and their amount and composition may change during the crystallization process. Some gases can appear even in empty ampoules sealed originally under high vacuum: they may diffuse in from the outside, and/or desorb from the ampoule walls. Residual gases can also be generated by the source materials: even very high purity commercial elements and compounds may contain trace amounts of impurities, particularly oxides. The oxides may have low volatilities themselves but their reaction with other species, particularly carbon and hydrogen, may produce volatile compounds like water or carbon oxides. The non-constituent gases, either added initially to the system or evolved during the material processing, may diffuse out of the ampoule during the course of the experiment. Gases present outside (e.g. as a protective atmosphere or thermal conductor) may diffuse into the ampoule. In either case the growth conditions and the quality of the crystals may be affected. The problem is of a particular importance in sealed systems where the amount of the gases cannot be directly controlled. Therefore a reasonable knowledge and understanding of the origin, composition, magnitude, and change with time of gases present in sealed ampoules may be important for a meaningful control and interpretation of crystal growth processes. This problem is of a particular importance for processing of electronic materials in space because (i) safety considerations require using sealed systems only, and (ii) high cost of crystal growth experiments in microgravity calls for a throughout, accurate description of the processing conditions necessary for a meaningful, efficient, and conclusive interpretation of the space results. In this paper we present the results of our extensive studies on gases in closed crystal growth systems which include: (a) Degassing properties of fused silica; (b) Generation of inert gases by source materials (CdTe, ZnTe, CdZnTe, ZnSe, PbTe, PbSe, PbSeTe); (c) Diffusive cas losses from silica glass ampoules.

Palosz, Witold↗

Fluorescence Imaging Study of Impinging Underexpanded Jets

An experiment was designed to create a simplified simulation of the flow through a hole in the surface of a hypersonic aerospace vehicle and the subsequent impingement of the flow on internal structures. In addition to planar laser-induced fluorescence (PLIF) flow visualization, pressure measurements were recorded on the surface of an impingement target. The PLIF images themselves provide quantitative spatial information about structure of the impinging jets. The images also help in the interpretation of impingement surface pressure profiles by highlighting the flow structures corresponding to distinctive features of these pressure profiles. The shape of the pressure distribution along the impingement surface was found to be double-peaked in cases with a sufficiently high jet-exit-to-ambient pressure ratio so as to have a Mach disk, as well as in cases where a flow feature called a recirculation bubble formed at the impingement surface. The formation of a recirculation bubble was in turn found to depend very sensitively upon the jet-exit-to-ambient pressure ratio. The pressure measured at the surface was typically less than half the nozzle plenum pressure at low jet pressure ratios and decreased with increasing jet pressure ratios. Angled impingement cases showed that impingement at a 60deg angle resulted in up to a factor of three increase in maximum pressure at the plate compared to normal incidence.

Inman, Jennifer A.↗

DNA Repair Defects and Chromosomal Aberrations

Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of the DNA repair-defective cell lines were smaller than those of normal cells, with the DNA-PK-deficient cells having RBEs near unity. To further investigate the sensitivity differences that were observed in ATM and NBS deficient cells, chromosomal aberrations were analyzed in normal lung fibroblast cells treated with KU-55933 (a specific ATM kinase inhibitor) or Mirin (an Mre11- Rad50-Nbs1 complex inhibitor involved in activation of ATM). We also performed siRNA knockdown of these proteins. Preliminary data indicate that chromosome exchanges increase in cells treated with the specific ATM inhibitor. Possible cytogenetic signatures of acute and low dose-rate gamma irradiation in ATM or nibrin deficient and suppressed cells will be discussed.

Hada, Megumi↗

Linking NASA Environmental Data with a National Public Health Cohort Study and a CDC On-Line System to Enhance Public Health Decision Making

The overall goal of this study is to address issues of environmental health and enhance public health decision making by utilizing NASA remotely-sensed data and products. This study is a collaboration between NASA Marshall Space Flight Center, Universities Space Research Association (USRA), the University of Alabama at Birmingham (UAB) School of Public Health and the Centers for Disease Control and Prevention (CDC) National Center for Public Health Informatics. The objectives of this study are to develop high-quality spatial data sets of environmental variables, link these with public health data from a national cohort study, and deliver the linked data sets and associated analyses to local, state and federal end-user groups. Three daily environmental data sets were developed for the conterminous U.S. on different spatial resolutions for the period 2003-2008: (1) spatial surfaces of estimated fine particulate matter (PM2.5) exposures on a 10-km grid utilizing the US Environmental Protection Agency (EPA) ground observations and NASA s MODerate-resolution Imaging Spectroradiometer (MODIS) data; (2) a 1-km grid of Land Surface Temperature (LST) using MODIS data; and (3) a 12-km grid of daily Solar Insolation (SI) and maximum and minimum air temperature using the North American Land Data Assimilation System (NLDAS) forcing data. These environmental datasets were linked with public health data from the UAB REasons for Geographic and Racial Differences in Stroke (REGARDS) national cohort study to determine whether exposures to these environmental risk factors are related to cognitive decline and other health outcomes. These environmental national datasets will also be made available to public health professionals, researchers and the general public via the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) system, where they can be aggregated to the county, state or regional level as per users need and downloaded in tabular, graphical, and map formats. The linkage of these data provides a useful addition to CDC WONDER, allowing public health researchers and policy makers to better include environmental exposure data in the context of other health data available in this online system. It also substantially expands public access to NASA data, making their use by a wide range of decision makers feasible.

Al-Hamdan, Mohammad↗

The High-Resolution X-Ray Microcalorimeter Spectrometer, SXS, on Astro-H

The science and an overview of the Soft X-ray Spectrometer onboard the STRO-H mission are presented. The SXS consists of X-ray focusing mirrors and a microcalorimeter array and is developed by international collaboration lead by JAXA and NASA with European participation. The detector is a 6 x 6 format microcalorimeter array operated at a cryogenic temperature of 50 mK and covers a 3' x 3' field of view of the X-ray telescope of 5.6 m focal length. We expect an energy resolution better than 7 eV (FWHM, requirement) with a goal of 4 eV. The effective area of the instrument will be 225 square centimeters at 7 keV; by a factor of about two larger than that of the X-ray microcalorimeter on board Suzaku. One of the main scientific objectives of the SXS is to investigate turbulent and/or macroscopic motions of hot gas in clusters of galaxies.

Mitsuda, Kazuhisa↗

Global Distribution of Cloud Droplet Number Concentration, Autoconversion Rate, and Aerosol Indirect Effect Under Diabatic Droplet Activation

This study presents a global assessment of the sensitivity of droplet number to diabatic activation (i.e., including effects from entrainment of dry air) and its first-order tendency on indirect forcing and autoconversion. Simulations were carried out with the NASA Global Modeling Initiative (GMI) atmospheric and transport model using climatological metereorological fields derived from the former NASA Data Assimilation Office (DAO), the NASA Finite volume GCM (FVGCM) and the Goddard Institute for Space Studies version II (GISS) GCM. Cloud droplet number concentration (CDNC) is calculated using a physically based prognostic parameterization that explicitly includes entrainment effects on droplet formation. Diabatic activation results in lower CDNC, compared to adiabatic treatment of the process. The largest decrease in CDNC (by up to 75 percent) was found in the tropics and in zones of moderate CCN concentration. This leads to a global mean effective radius increase between 0.2-0.5 micrometers (up to 3.5 micrometers over the tropics), a global mean autoconversion rate increase by a factor of 1.1 to 1.7 (up to a factor of 4 in the tropics), and a 0.2-0.4 W m(exp -2) decrease in indirect forcing. The spatial patterns of entrainment effects on droplet activation tend to reduce biases in effective radius (particularly in the tropics) when compared to satellite retrievals. Considering the diabatic nature of ambient clouds, entrainment effects on CDNC need to be considered in GCM studies of the aerosol indirect effect.

Barahona, Donifan↗

Automated Meta-Aircraft Operations for a More Efficient and Responsive Air Transportation System

A brief overview is given of the on-going NASA Automated Cooperative Trajectories project. Current status and upcoming work is previewed. The motivating factors and innovative aspects of ACT are discussed along with technical challenges and the expected system-level impacts if the project is successful. Preliminary results from the NASA G-III hardware in the loop simulation are included.

flight paths↗

Developing Lanthanide-Nitrate Cluster Chemistry toward Rare Earth Separations

Nitrate-decorated hexamers with a [Ln 6 (μ 6 -O)(μ 3 –OH) 8 ] 8+ core have been reported for nearly every lanthanide ion and are used as precursors for the assembly of functional metal–organic frameworks. Yet, few studies have examined the correlation between the solution and solid-state species, and the formation of mixed-metal clusters. Toward this end, a series of homo- and heterometal lanthanide nitrate hexamers was prepared via pH adjustment of aqueous lanthanide nitrate solutions. Examination of the homometallic europium solutions using Small Angle X-ray Scattering and nESI-MS showed that lower order complexes dominate lanthanide speciation in nitrate media. Yet, powder X-ray diffraction data of the precipitated phase confirmed the formation of [Ln 6 (μ 6 -O)(μ 3 -OH) 8 (NO 3 ) 6 (H 2 O) 12 ]·2(NO 3 )·n(H 2 O), Ln 6 , for Ln = Eu and Tb. For heterometal systems, analysis of the solid-state product by ICP–MS showed the selective incorporation of the heavier rare earths into Ln 6 . Selectivity was quantified by calculating an average separation factor, which is defined as the ratio of recovery factors of both metals. Further examination of the luminescence behavior of mixed metal [Tb 6–x Eu x (μ 6 -O)(μ 3 -OH) 8 (NO 3 ) 6 (H 2 O) 12 ]·2(NO 3 )·n(H 2 O), with x = 1.1–3.6, showed that the relative intensities of the peaks at 489 nm (terbium, 5 D 4 → 7 F 6 ) and 690 nm (europium, 5 D 0 → 7 F 4 ) trend with the percent incorporation of europium and terbium into the cluster.

anions↗

Dislocation half-loop control for optimal V-defect density in GaN-based light emitting diodes

V-defects are morphological defects that typically form on threading dislocations during epitaxial growth of $(0001)$-oriented GaN layers. A V-defect is a hexagonal pyramid-shaped depression with six {$10\bar{1}1$}-oriented sidewalls. These semipolar sidewalls have a lower polarization barrier than the polarization barriers present between the polar c-plane quantum wells and quantum barriers and can laterally inject carriers directly into quantum wells in GaN-based light emitting diodes (LEDs). This is especially important, as the high polarization field in c-plane GaN is a significant factor in the high forward voltage of GaN LEDs. The optimal V-defect density for efficient lateral carrier injection in a GaN LED (∼10 9 cm −2 ) is typically an order of magnitude higher than the threading dislocation density of GaN grown on patterned sapphire substrates (∼10 8 cm −2 ). Pure-edge dislocation loops have been known to exist in GaN, and their formation into large V-defects via low-temperature growth with high Si-doping has recently been studied. Here, in this work, we develop a method for pure-edge threading dislocation half-loop formation and density control via disilane flow, growth temperature, and thickness of the half-loop generation layer. We also develop a method of forming the threading dislocation half-loops into V-defects of comparable size to those originating from substrate threading dislocations.

Crystallographic defects↗

Simulations of axion minihalos

The axion, motivated as a solution to the strong CP problem, is also a viable dark matter candidate. The axion field takes random values in causally disconnected regions if the symmetry breaking that establishes the particle occurs after inflation, leading to white-noise density fluctuations at low wave numbers and forming dense minihalos with sub-planetary masses subsequently. There have been two recent proposals that appear capable of testing this scenario, namely using pulsar timing arrays and studying cosmological microlensing caustics. Motivated by these proposals, we use N-body simulations to study the formation of substructures from white-noise density fluctuations. The density profiles of our relaxed axion minihalos can be described by the Navarro–Frenk–White profile, and the minihalos’ concentration number agrees well with a simple, physically-motivated model. We develop a semi-analytic formula to fit the mass function from our simulation, which agrees broadly at different redshifts and only differs at factor of two level from classic halo mass functions. This analytic mass function allows us to consider uncertainties in the post-inflation axion scenario, as well as extrapolate our high-redshift simulations results to the present. Our work estimates the present-day abundance of axion substructures, as is necessary for predicting their effect on cosmological microlensing caustics and pulsar timing. Our calculations suggest that if pulsar timing and microlensing probes can reach recent sensitivity forecasts, they may be sensitive to the post-inflation axion dark matter scenario, even when accounting for uncertainties pertaining to axion strings. For pulsar timing, the most significant caveat is whether axion minihalos are disrupted by stars, which our estimates show is mildly important at the most relevant masses. In conclusion, as our gravitational simulations are scale invariant, the results can be extended to models where the dark matter is comprised of other axion-like particles and even clusters of primordial black holes.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

The ALMaQUEST Survey. VII. Star Formation Scaling Relations of Green Valley Galaxies

We utilize the ALMA-MaNGA QUEnch and STar formation (ALMaQUEST) survey to investigate the kpc-scale scaling relations, presented as the resolved star-forming MS (rSFMS: Σ SFR versus Σ * ), the resolved Schmidt–Kennicutt relation (rSK: Σ SFR versus ${{\rm{\Sigma }}}_{{{\rm{H}}}_{2}}$), and the resolved molecular gas MS (rMGMS: ${{\rm{\Sigma }}}_{{{\rm{H}}}_{2}}$ versus Σ * ), for 11,478 star-forming and 1414 retired spaxels (oversampled by a factor of ~20) located in 22 GV and 12 MS galaxies. For a given galaxy type (MS or GV), the retired spaxels are found to be offset from the sequences formed by the star-forming spaxels on the rSFMS, rSK, and rMGMS planes, toward lower absolute values of sSFR, SFE, and ${f}_{{{\rm{H}}}_{2}}$ by ~1.1, 0.6, and 0.5 dex. The scaling relations for GV galaxies are found to be distinct from that of the MS galaxies, even if the analyses are restricted to the star-forming spaxels only. It is found that, for star-forming spaxels, sSFR, SFE, and ${f}_{{{\rm{H}}}_{2}}$ in GV galaxies are reduced by ~0.36, 0.14, and 0.21 dex, respectively, compared to those in MS galaxies. Therefore, the suppressed sSFR/SFE/f gas in GV galaxies is associated with not only an increased proportion of retired regions in GV galaxies but also a depletion of these quantities in star-forming regions. Finally, the reduction of SFE and ${f}_{{{\rm{H}}}_{2}}$ in GV galaxies relative to MS galaxies is seen in both bulge and disk regions (albeit with larger uncertainties), suggesting that, statistically, quenching in the GV population may persist from the inner to the outer regions.

79 ASTRONOMY AND ASTROPHYSICS↗

On the seasonal sea ice cover of the Sea of Okhotsk

Satellite microwave imagery has allowed determination of sea ice conditions in the Sea of Okhotsk over years 1973-1976. Comparisons of the general features of the cycle of sea ice distribution with basic oceanographic factors shows that ice forms first in cold, shallow, low-salinity waters and then seems to drift in a direction approximating the Okhotsk-Kuril current system. The heaviest ice cover occurred in 1973, followed by a much weaker ice cover in 1974. Only the 1972-73 growth season experienced close to monotonic advance. A much greater weakening of the ice cover through polynya formation occurred during the 1976 decay season than in any of the other three years. Two fairly common ice macrostructures in the Sea of Okhotsk were identified as a rectangular structure and a wedge structure; these are strongly correlated with the bathymetry of the region and with the known current system.

Parkinson, C. L.↗