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At least 613 records · Page 34

Continuous data stream FIFO magnetic bubble domain shift register

There is described a simple first-in, first out (FIFO) magnetic bubble domain shift register which has continuous data storage capability. In a preferred embodiment, two parallel detector branches are associated with a main storage loop. The bubbles in the storage loop are replicated toward each detector branch by passive replicators in the storage loop. Annihilators associated with each of the replicators and each of the detectors are arranged an appropriate distance from the replicators so that selective energization of the annihilators permits certain bits to propagate to one detector and other bits to propagate to the other detector. Connection of the detectors in an appropriate bridge circuit permits full data rate reclamation.

Chen, Thomas T.↗

Development of Grazing Incidence Optics for Neutron Imaging and Scattering

Because of their wave nature, thermal and cold neutrons can be reflected from smooth surfaces at grazing incidence angles, be reflected by multilayer coatings or be refracted at boundaries of different materials. The optical properties of materials are characterized by their refractive indices which are slightly less than unity for most elements and their isotopes in the case of cold and thermal neutrons as well as for x-rays. The motivation for the optics use for neutrons as well as for x-rays is to increase the signal rate and, by virtue of the optic's angular resolution, to improve the signal-to-noise level by reducing the background so the efficiency of the existing neutron sources use can be significantly enhanced. Both refractive and reflective optical techniques developed for x-ray applications can be applied to focus neutron beams. Typically neutron sources have lower brilliance compared to conventional x-ray sources so in order to increase the beam throughput the neutron optics has to be capable of capturing large solid angles. Because of this, the replicated optics techniques developed for x-ray astronomy applications would be a perfect match for neutron applications, so the electroformed nickel optics under development at the Marshall Space Flight Center (MSFC) can be applied to focus neutron beams. In this technique, nickel mirror shells are electroformed onto a figured and superpolished nickel-plated aluminum cylindrical mandrel from which they are later released by differential thermal contraction. Cylindrical mirrors with different diameters, but the same focal length, can be nested together to increase the system throughput. The throughput can be increased further with the use of the multilayer coatings deposited on the reflectivr surface of the mirror shells. While the electroformed nickel replication technique needs to be adopted for neutron focusing, the technology to coat the inside of cylindrical mirrors with neutron multilayers has to be developed. The availability of these technologies would bring new capabilities to neutron instrumentation and, hence, lead to new scientific breakthroughs. We have established a program to adopt the electroformed nickel replication optics technique for neutron applications and to develop the neutron multilayer replication technology.

Gubarev, M. V.↗

Life in the Clouds of Venus? An Experimental Synthetic Biology Approach

The surface of Venus constitutes the most hellish and biologically inhospitable planetary surface in our solar system, boasting a pH of 0, blistering winds that can melt lead, and pressures of 60 atm. However, during the earlier years of the solar system, without the runaway greenhouse effect that has plagued the planet, Venus potentially housed oceans and perhaps even life. There is a possibility that microbes could have retreated into hospitable niches in the atmosphere, as suggested by Carl Sagan as early as 1967 [1]. For example, 50 km above the raging hell of the Venusian surface, exists a relatively temperate environment that might serve as reservoir for life. This astrobiology project seeks to explore life at the extremes and to theorize whether microbial communities could not only survive but also reproduce in the Venusian atmosphere. Specifically, we ask: are aerosols viable microbial environments? But before we can test for life in the clouds, we have to develop a proper reporter to visualize cell growth in situ. For this purpose, we aimed to develop cell-growth dependent reporters to serve as remote biosensors for cell growth. We developed two using the polA promoter, a DNA-replication dependent promoter, and nrd operon promoter, a cell-cycle dependent promoter. Using these cell-growth reporters, the next step is to aerosolize microbes expressing these reporters in a suspension chamber adapted from a Millikan Drop Apparatus to assay reproduction in an aerosolized environment. Better yet is to test the reproduction of microbes in a microgravity regime such as on ISS.Approach: We engineered two cell-cycle dependent genetic reporters. One was the polA promoter which codes for DNA Polymerase I, a gene active in DNA replication [2]. The other was the nrdP. The activation of ribonucleotide reductase reduces ribonucleotides into deoxyribonucleotides and is involved in the bacterial cell cycle [3]. This promoter began activation during the initiation of DNA replication and is cell-cycle dependent [4]. These promoters were fused to a GFP reporter, transformed into E. coli. The constructs were deposited in the iGEM registry as K847210: Escherichia coli DNA-replication dependent polA promoter K847211: Escherichia coli cell-division dependent nrd promoter Results: Our constructs displayed fluorescence when transformed into NEB-5alpha competent cells. While nrdP-E0840 displayed sufficient fluorescence as verified by fluorescent microscopy, the original polAP-E0840 construct (which uses mut3b GFP) exhibited low expression; while fluorescence was visible under the microscope, the signal was too weak for the camera to recognize. The polA promoter was therefore digest-ed with EcoRI and SpeI then ligated into plasmid pNCS containing a RBS, Clover, and a terminator. Clover is a highly engineered green fluorescent protein that exhibits extreme brightness [5] Fluoresence time course data demonsrated that the genes were induced in a cell cycle dependant manner [6]. Our assays via microscopy and the bulk assay shows that our promoters are functional as cell cycle reporters.Conclusions: The application of such tools are widespread and not limited to astrobiology; nrdP could be used to determine doubling times empirically and could possibly extrapolate DNA content from intensity of signals expressed by polAP. However, we are pri-marily interested in its use in astrobiology.

Escherichia↗

The Effects of Spaceflight on Cellular Aging in Saccharomyces cerevisiae

The conditions encountered during spaceflight place unique stresses on physiological processes that oftentimes lead to deleterious effects. Identifying these effects and better understanding their molecular mechanisms will be essential in enabling long-duration space travel by humans. Studies in Saccharomyces cerevisiae suggest an aging model that involves the accumulation of toxic components, such as excess extrachromosomal rDNA and damaged mitochondria. This build-up then limits the replicative lifespan (the number of times a mother cell can form a new daughter cell). Remarkably, each new daughter cell emerges completely renewed from the senescing mother cell through an asymmetric distribution of aging determinants via mechanisms that are intricately linked to the budding process. When exposed to simulated microgravity, S. cerevisiae undergoes an altered budding process characterized by a breakdown in bud scar polarity. Because the budding process is critical to replicative aging, we hypothesize that the replicative lifespan may be affected by microgravity as well. To measure relative replicative aging rates, we will construct a strain of yeast in which daughter cells are inviable. In this strain, the Cre recombinase will be expressed under the control of the daughter cell specific promoter, pSCW11, and LoxP sites will be inserted at both flanks of two essential genes involved in the cell cycle, UBC9 and CDC20, using a CRISPRCas9 system. Thus, UBC9 and CDC20 will be excised from daughter cells, leading to cell-cycle arrest and eventual death. To mimic the low shear conditions encountered in microgravity, this strain will be grown in rotating wall vessels. The number of viable mother cells will be monitored over time, and this rate will be compared to cells growing in standard conditions. Because asymmetric division also occurs in mammalian cells (e.g. in neural stem cells), this study will provide insight into how cellular aging rates may change in mammals and will help empower humans to thrive in space for extended and even indefinite periods of time.

aging↗

Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs

Background: Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. Objectives: In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance. Methods: The co-effects of BA and ETV were conducted in wild-type/NA-resistance mutant HBV cell lines and DHBV-infected duckling models. HBV-DNA/RNAs, HBsAg/HBeAg, host factors (hepatocyte nuclear factors) were explored for possible anti-HBV mechanism. Results and discussion: BA could significantly enhance and reduced HBsAg and HBeAg in hepG2.2.15, a wild-type HBV cell line. Co-treatment of BA and ETV had a more dramatic effect in NA-resistant HBV{sup rtM204V/rtLl80M} transfected hepG2 cells. Our study further revealed that BA mainly inhibited the production of HBV RNAs (3.5, 2.4, 2.1 kb), the templates for viral proteins and HBV-DNA synthesis. BA blocked HBV RNAs transcription possibly by down-regulating transcription and expression of HBV replication dependent hepatocyte nuclear factors (HNF1α and HNF4α). Thus, BA may benefit the anti-HBV therapy via inhibiting HBV viral RNAs. - Highlights: • Baicalin benefits the anti-HBV therapy. • Baicalin enhances ETV antiviral efficacy and overcomes NA-resistant HBV mutation. • The anti-HBV effect of baicalin is achieved by inhibiting HBV RNAs. • Baicalin down-regulates HBV replication-dependent host factors HNF 1α and HNF 4α.

60 APPLIED LIFE SCIENCES↗

Virtual Log-Structured Storage for High-Performance Streaming

Over the past decade, given the higher number of data sources (e.g., Cloud applications, Internet of things) and critical business demands, Big Data transitioned from batch-oriented to real-time analytics. Stream storage systems, such as Apache Kafka, are well known for their increasing role in real-time Big Data analytics. For scalable stream data ingestion and processing, they logically split a data stream topic into multiple partitions. Stream storage systems keep multiple data stream copies to protect against data loss while implementing a stream partition as a replicated log. This architectural choice enables simplified development while trading cluster size with performance and the number of streams optimally managed. This paper introduces a shared virtual log-structured storage approach for improving the cluster throughput when multiple producers and consumers write and consume in parallel data streams. Stream partitions are associated with shared replicated virtual logs transparently to the user, effectively separating the implementation of stream partitioning (and data ordering) from data replication (and durability). We implement the virtual log technique in the KerA stream storage system. When comparing with Apache Kafka, KerA improves the cluster ingestion throughput by up to 4x when multiple producers write over hundreds of data streams.

consistent stream ordering↗

Toward General Software Level Silent Data Corruption Detection for Parallel Applications

Silent data corruption (SDC) poses a great challenge for high-performance computing (HPC) applications as we move to extreme-scale systems. Mechanisms have been proposed that are able to detect SDC in HPC applications by using the peculiarities of the data (more specifically, its “smoothness” in time and space) to make predictions. However, these data-analytic solutions are still far from fully protecting applications to a level comparable with more expensive solutions such as full replication. In this work, we propose partial replication to overcome this limitation. More specifically, we have observed that not all processes of an MPI application experience the same level of data variability at exactly the same time. Thus, we can smartly choose and replicate only those processes for which the lightweight data-analytic detectors would perform poorly. In addition, we propose a new evaluation method based on the probability that a corruption will pass unnoticed by a particular detector (instead of just reporting overall single-bit precision and recall). Here in our experiments, we use four applications dealing with different explosions. Finally, our results indicate that our new approach can protect the MPI applications analyzed with 7–70% less overhead (depending on the application) than that of full duplication with similar detection recall.

97 MATHEMATICS AND COMPUTING↗

CoREC: Scalable and Resilient In-memory Data Staging for In-situ Workflows

The dramatic increase in the scale of current and planned high-end HPC systems is leading new challenges, such as the growing costs of data movement and IO, and the reduced mean time between failures (MTBF) of system components. In-situ workflows, i.e., executing the entire application workflows on the HPC system, have emerged as an attractive approach to address data-related challenges by moving computations closer to the data, and staging-based frameworks have been effectively used to support in-situ workflows at scale. However, the resilience of these staging-based solutions has not been addressed, and they remain susceptible to expensive data failures. Furthermore, naive use of data resilience techniques such as n-way replication and erasure codes can impact latency and/or result in significant storage overheads. In this article, we present CoREC, a scalable and resilient in-memory data staging runtime for large-scale in-situ workflows. CoREC uses a novel hybrid approach that combines dynamic replication with erasure coding based on data access patterns. It also leverages multiple levels of replications and erasure coding to support diverse data resiliency requirements. Furthermore, the article presents optimizations for load balancing and conflict-avoiding encoding, and a low overhead, lazy data recovery scheme. We have implemented the CoREC runtime and have deployed with the DataSpaces staging service on leadership class computing machines and present an experimental evaluation in the article. Here, the experiments demonstrate that CoREC can tolerate in-memory data failures while maintaining low latency and sustaining high overall storage efficiency at large scales.

97 MATHEMATICS AND COMPUTING↗

A Structural Perspective on the Alphavirus Life Cycle

Alphaviruses are mosquito-borne, enveloped viruses with a positive-sense, single-stranded RNA genome. Alphaviruses enter host cells via receptor-mediated endocytosis, using various cellular surface receptors such as matrix remodeling-associated protein 8 (MXRA8), low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3), and very low-density lipoprotein receptor (VLDLR), which facilitate binding to the viral glycoproteins. Following entry, viral proteins are expressed and nonstructural proteins assemble into replication complexes in host cells, driving RNA synthesis and genome replication. Viral assembly occurs at the plasma membrane, where nascent virions bud from the host cell in a process driven by capsid and spike proteins. Recent combinatorial structural studies have provided detailed molecular insights into various steps of the alphavirus life cycle. These structural insights into the alphavirus life cycle enhance our understanding of viral replication and assembly, with significant implications for antiviral strategies and the development of alphavirus-based vaccine vectors.

RNA virus↗

Development of a reverse genetics system for Sosuga virus allows rapid screening of antiviral compounds

Sosuga virus (SOSV) is a recently discovered zoonotic paramyxovirus isolated from a single human case in 2012; it has been ecologically and epidemiologically associated with transmission by the Egyptian rousette bat (Rousettus aegyptiacus). Bats have long been recognized as sources of novel zoonotic pathogens, including highly lethal paramyxoviruses like Nipah virus (NiV) and Hendra virus (HeV). The ability of SOSV to cause severe human disease supports the need for studies on SOSV pathogenesis to better understand the potential impact of this virus and to identify effective treatments. Here we describe a reverse genetics system for SOSV comprising a minigenome-based assay and a replication-competent infectious recombinant reporter SOSV that expresses the fluorescent protein ZsGreen1 in infected cells. First, we used the minigenome assay to rapidly screen for compounds inhibiting SOSV replication at biosafety level 2 (BSL-2). The antiviral activity of candidate compounds was then tested against authentic viral replication using the reporter SOSV at BSL-3. We identified several compounds with anti-SOSV activity, several of which also inhibit NiV and HeV. Alongside its utility in screening for potential SOSV therapeutics, the reverse genetics system described here is a powerful tool for analyzing mechanisms of SOSV pathogenesis, which will facilitate our understanding of how to combat the potential public health threats posed by emerging bat-borne paramyxoviruses.

59 BASIC BIOLOGICAL SCIENCES↗

Test–retest reliability for a social discounting of personal information task

Increasing cybercrime rates means identifying potential victims is critically important. Social discounting tasks show that individuals share less personally identifying information as social distance increases. However, the test–retest reliability and uniqueness of this measure is unclear. The current study assessed social discounting for personally identifying information (SDPII), delay discounting, risk taking, and personality at two measurement waves 30 days apart for 64 undergraduate students. Test–retest reliability was statistically significant for the SDPII and all other measures, replicating previous studies. SDPII rates were not significantly correlated with other measures during both measurement waves, showing discriminant validity. SDPII rates were lower than those reported in a previous study but were still well described by a hyperbolic discounting function, suggesting replicability across studies. Furthermore, the high test–retest reliability, uniqueness, and replicability of the SDPII suggests that it may quantitatively identify cybercrime victimization. Future research should test which measure or combination of measures can accurately predict scam and cybercrime victimization to inform data-based interventions.

99 GENERAL AND MISCELLANEOUS↗

Computational models of direct and indirect X‐ray breast imaging detectors for in silico trials

Abstract Background To facilitate in silico studies that investigate digital mammography (DM) and breast tomosynthesis (DBT), models replicating the variety in imaging performance of the DM and DBT systems, observed across manufacturers are needed. Purpose The main purpose of this work is to develop generic physics models for direct and indirect detector technology used in commercially available systems, with the goal of making them available open source to manufacturers to further tweak and develop the exact in silico replicas of their systems. Methods We recently reported on an in silico version of the SIEMENS Mammomat Inspiration DM/DBT system using an open‐source GPU‐accelerated Monte Carlo x‐ray imaging simulation code (MC‐GPU). We build on the previous version of the MC‐GPU codes to mimic the imaging performances of two other Food and Drug Administration (FDA)‐approved DM/DBT systems, such as Hologic Selenia Dimensions (HSD) and the General Electric Senographe Pristina (GSP) systems. In this work, we developed a hybrid technique to model the optical spread and signal crosstalk observed in the GSP and HSD systems. MC simulations are used to track each x‐ray photon till its first interaction within the x‐ray detector. On the other hand, the signal spread in the x‐ray detectors is modeled using previously developed analytical equations. This approach allows us to preserve the modeling accuracy offered by MC methods in the patient body, while speeding up secondary carrier transport (either electron–hole pairs or optical photons) using analytical equations in the detector. The analytical optical spread model for the indirect detector includes the depth‐dependent spread and collection of optical photons and relies on a pre‐computed set of point response functions that describe the optical spread as a function of depth. To understand the capabilities of the computational x‐ray detector models, we compared image quality metrics like modulation transfer function (MTF), normalized noise power spectrum (NNPS), and detective quantum efficiency (DQE), simulated with our models against measured data. Please note that the purpose of these comparisons with measured data would be to gauge if the model developed as part of this work could replicate commercially used direct and indirect technology in general and not to achieve perfect fits with measured data. Results We found that the simulated image quality metrics such as MTF, NNPS, and DQE were in reasonable agreement with experimental data. To demonstrate the imaging performance of the three DM/DBT systems, we integrated the detector models with the VICTRE pipeline and simulated DM images of a fatty breast model containing a spiculated mass and a calcium oxalate cluster. In general, we found that the images generated using the indirect model appeared more blurred with a different noise texture and contrast as compared to the systems with direct detectors. Conclusions We have presented computational models of three commercially available FDA‐approved DM/DBT systems, which implement both direct and indirect detector technology. The updated versions of the MC‐GPU codes that can be used to replicate three systems are available in open source format through GitHub.

Sengupta, Aunnasha↗

Quantifying Uncertainties in Heat Capacity Measurements of Molten Salts Determined Using Differential Scanning Calorimetry

Uncertainty in specific heat capacity values of a molten salt determined by using differential scanning calorimetry (DSC) was assessed based on the precision of replicate measurements of heat flows used in the calculation and effects of corrections that are commonly made to heat flow measurements. The ratio method of determining heat capacity was applied using the results of replicate heat flow measurements made with two empty cells, a sapphire reference material, and three samples of a doped NaCl-UCl 3 salt mixture. Replicate measurements with empty cells were used to quantify the effects of system instabilities and sensitivities on the measured heat flows of sapphire and salt. The combined effects of uncertainties in individual heat flow measurements made with blank cells using this system were quantified to be 2.6 μV based on isothermal holds before and after the scan, with cell placement adding the greatest uncertainty. This value was used as the tolerance for accepting background-corrected heat flows measured with sapphire and salt to calculate the specific heat capacity. The acceptable heat flows measured for sapphire and salt over the temperature range of 540 to 725 °C resulted in calculated specific heat capacity values ranging from 0.53 to 0.91 J g −1 K −1 with an overall average value of 0.70 J g −1 K −1 and an uncertainty of 0.22 J g −1 K −1 at the 99 % confidence level. The combined uncertainty in the specific heat capacity masked detection of any effect of temperature or salt composition that occurred.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

The Influence of Sliding and Contact Severity on the Generation of White Etching Cracks

White etching cracks (WECs) have been identified as the dominant mechanism of premature failure for bearings within wind turbine gearboxes. Though WECs have been observed in the field for over a decade, the exact mechanisms which lead to this failure are still debated, and benchtop replication has proven difficult. In previously published work, WECs have been replicated only through the use of component level test rigs, where complete bearings are tested. In these tests, the factors that are thought to drive the formation of WECs, such as slide-to-roll ratio (SRR) and lubricant film thickness, cannot not be easily altered or controlled. In this paper, WECs have been replicated on a three rings on roller, benchtop test rig, which allowed for a direct investigation into the influence that SRR magnitude, sliding direction, and the lubricant film thickness have on surface failures and WEC generation. It was determined that WEC were formed in samples that experienced -30% SRR at various lubrication conditions, however, at lower levels of negative SRR and positive SRR up to 30% no white-etching cracks were observed.

17 WIND ENERGY↗

Genome-wide association studies of bark texture in Populus trichocarpa

Plants have developed bark as a defense barrier to deal with environmental stresses, such as pathogen invasion, drought, and UV radiation. Bark is composed of dead differentiated cells and is formed when radial expansion pushes the cortex and epidermis outward creating secondary meristem. However, the genetic control of this complex phenotype is generally unknown. Here, we use association mapping to define the genomic regions associated with natural variation in bark texture (BT) in Populus trichocarpa. Clonally replicated provenance trials of P. trichocarpa were studied for BT collected across three sites, multiple years, and (2–3) biological replicates per site. Forty-one genomic intervals containing SNPs significantly associated with BT were detected that were highly reproducible across sites, years, and replicates. A list of candidate genes within these regions with related putative function was identified. A total of 98 genes were considered candidate genes due to significance and putative function with connection to the phenotype. Association mapping using low coverage sequencing allowed us to detect narrow genomic intervals (1–20 kb) with high reproducibility and shared candidate genes. For example, a membrane-associated apoptosis protein and a wall-associated receptor kinase (PR5K-like) protein, which both are involved in radial growth and tissue differentiation, lie within significant trait-associated region. Here, two copies of root hair defective3 genes, transmembrane protein in Populus differentiating xylem and phloem, were also significantly associated with BT and co-located with major quantitative trait locus (QTL) for BT, bark thickness, and diameter from our previous study suggesting an important role in radial growth.

59 BASIC BIOLOGICAL SCIENCES↗

Stronger activation of SREBP-1a by nucleus-localized HBx

We previously showed that hepatitis B virus (HBV) X protein activates the sterol regulatory element-binding protein-1a (SREBP-1a). Here we examined the role of nuclear localization of HBx in this process. In comparison to the wild-type and cytoplasmic HBx, nuclear HBx had stronger effects on SREBP-1a and fatty acid synthase transcription activation, intracellular lipid accumulation and cell proliferation. Furthermore, nuclear HBx could activate HBV enhancer I/X promoter and was more effective on up-regulating HBV mRNA level in the context of HBV replication than the wild-type HBx, while the cytoplasmic HBx had no effect. Our results demonstrate the functional significance of the nucleus-localized HBx in regulating host lipogenic pathway and HBV replication. - Highlights: • Nuclear HBx is more effective on activating SREBP-1a and FASN transcription. • Nuclear HBx is more effective on enhancing intracellular lipid accumulation. • Nuclear HBx is more effective on enhancing cell proliferation. • Nuclear HBx up-regulates HBV enhancer I/X promoter activity. • Nuclear HBx increases HBV mRNA level in the context of HBV replication.

60 APPLIED LIFE SCIENCES↗