28 research outputs found

    DEM investigation of strength and critical state behaviours of sand under axisymmetric stress paths with different shearing modes

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    This paper investigates the strength and critical state (CS) behaviours of sand under axisymmetric stress paths with different shearing modes using discrete element method (DEM). The stress paths include axial compression (AC) and axial extension (AE), and the shearing modes include conventional triaxial (CT) mode and constant mean pressure (CP) mode. A series of dense and loose sand samples are generated for this purpose with confining pressures ranging from 100 kPa to 900 kPa. The CS is achieved for all samples after an axial strain (absolute value) of about 45%. The CS value of deviator stress is unique and independent of the initial packing densities for the samples with a given confining pressure, but the unique deviator stress under AC is generally larger than that under AE. The CS values of the stress ratio are independent of the shearing modes and the confining pressures, but are dependent on the stress paths. The CS friction angle for a given confining pressure is found to be unique and independent of the shearing modes, stress paths and initial packing densities, indicating that Mohr-Coulomb criterion (for axisymmetric conditions, equivalent to Matsuoka criterion) is an appropriate CS strength criterion. The CS value of void ratio is independent of the initial packing densities for a given confining pressure and shearing mode under a given stress path. The differences among the CS values of the mechanical coordination number are found to be attributed to changes in the effective mean pressures

    Boojums and the Shapes of Domains in Monolayer Films

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    Domains in Langmuir monolayers support a texture that is the two-dimensional version of the feature known as a boojum. Such a texture has a quantifiable effect on the shape of the domain with which it is associated. The most noticeable consequence is a cusp-like feature on the domain boundary. We report the results of an experimental and theoretical investigation of the shape of a domain in a Langmuir monolayer. A further aspect of the investigation is the study of the shape of a ``bubble'' of gas-like phase in such a monolayer. This structure supports a texture having the form of an inverse boojum. The distortion of a bubble resulting from this texture is also studied. The correspondence between theory and experiment, while not perfect, indicates that a qualitative understanding of the relationship between textures and domain shapes has been achieved.Comment: replaced with published version, 10 pages, 13 figures include

    Measuring the Effectiveness of Photoresponsive Nanocomposite Coatings on Aircraft Windshields to Mitigate Laser Intensity

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    In 2004, pilots reported 46 laser illumination events to the Federal Aviation Administration (FAA), with the number increasing to approximately 3,600 in 2011. Since that time, the number of reported laser incidents has ranged from 3,500 to 4,000. Previous studies indicate the potential for flight crewmember distraction from bright laser light being introduced to the cockpit. Compositional variations of the photoresponsive nanocomposite coatings were applied to an aircraft windscreen using a modified liquid dispersion/heating curing process. The attenuating effects of the deposited films on laser light intensity were evaluated using an optical power meter and the resultant laser intensity data through treated and untreated windscreens was collected. Data revealed a reduction in laser intensity (36–88%) in the presence of the engineered photoresponsive nanocomposite films. Results lend support of the view that the addition of transparent laser attenuating films applied to aircraft windscreens may improve flight safety, and reduce the risk from distraction or disruption of flight crewmembers’ vision

    Protein kinase C activation disrupts epithelial apical junctions via ROCK-II dependent stimulation of actomyosin contractility

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    <p>Abstract</p> <p>Background</p> <p>Disruption of epithelial cell-cell adhesions represents an early and important stage in tumor metastasis. This process can be modeled <it>in vitro </it>by exposing cells to chemical tumor promoters, phorbol esters and octylindolactam-V (OI-V), known to activate protein kinase C (PKC). However, molecular events mediating PKC-dependent disruption of epithelial cell-cell contact remain poorly understood. In the present study we investigate mechanisms by which PKC activation induces disassembly of tight junctions (TJs) and adherens junctions (AJs) in a model pancreatic epithelium.</p> <p>Results</p> <p>Exposure of HPAF-II human pancreatic adenocarcinoma cell monolayers to either OI-V or 12-O-tetradecanoylphorbol-13-acetate caused rapid disruption and internalization of AJs and TJs. Activity of classical PKC isoenzymes was responsible for the loss of cell-cell contacts which was accompanied by cell rounding, phosphorylation and relocalization of the F-actin motor nonmuscle myosin (NM) II. The OI-V-induced disruption of AJs and TJs was prevented by either pharmacological inhibition of NM II with blebbistatin or by siRNA-mediated downregulation of NM IIA. Furthermore, AJ/TJ disassembly was attenuated by inhibition of Rho-associated kinase (ROCK) II, but was insensitive to blockage of MLCK, calmodulin, ERK1/2, caspases and RhoA GTPase.</p> <p>Conclusion</p> <p>Our data suggest that stimulation of PKC disrupts epithelial apical junctions via ROCK-II dependent activation of NM II, which increases contractility of perijunctional actin filaments. This mechanism is likely to be important for cancer cell dissociation and tumor metastasis.</p

    Intraspecies Variation in the Emergence of Hyperinfectious Bacterial Strains in Nature

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    Salmonella is a principal health concern because of its endemic prevalence in food and water supplies, the rise in incidence of multi-drug resistant strains, and the emergence of new strains associated with increased disease severity. Insights into pathogen emergence have come from animal-passage studies wherein virulence is often increased during infection. However, these studies did not address the prospect that a select subset of strains undergo a pronounced increase in virulence during the infective process- a prospect that has significant implications for human and animal health. Our findings indicate that the capacity to become hypervirulent (100-fold decreased LD50) was much more evident in certain S. enterica strains than others. Hyperinfectious salmonellae were among the most virulent of this species; restricted to certain serotypes; and more capable of killing vaccinated animals. Such strains exhibited rapid (and rapidly reversible) switching to a less-virulent state accompanied by more competitive growth ex vivo that may contribute to maintenance in nature. The hypervirulent phenotype was associated with increased microbial pathogenicity (colonization; cytotoxin production; cytocidal activity), coupled with an altered innate immune cytokine response within infected cells (IFN-ÎČ; IL-1ÎČ; IL-6; IL-10). Gene expression analysis revealed that hyperinfectious strains display altered transcription of genes within the PhoP/PhoQ, PhoR/PhoB and ArgR regulons, conferring changes in the expression of classical virulence functions (e.g., SPI-1; SPI-2 effectors) and those involved in cellular physiology/metabolism (nutrient/acid stress). As hyperinfectious strains pose a potential risk to human and animal health, efforts toward mitigation of these potential food-borne contaminants may avert negative public health impacts and industry-associated losses

    Early immune factors associated with the development of post-acute sequelae of SARS-CoV-2 infection in hospitalized and non-hospitalized individuals

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    BackgroundInfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that can persist for weeks to years following initial viral infection. Clinical manifestations of PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms of PASC and its associated symptoms, the acute biological drivers of PASC are still unknown.MethodsWe enrolled 494 patients with COVID-19 at their initial presentation to a hospital or clinic and followed them longitudinally to determine their development of PASC. From 341 patients, we conducted multi-omic profiling on peripheral blood samples collected shortly after study enrollment to investigate early immune signatures associated with the development of PASC.ResultsDuring the first week of COVID-19, we observed a large number of differences in the immune profile of individuals who were hospitalized for COVID-19 compared to those individuals with COVID-19 who were not hospitalized. Differences between individuals who did or did not later develop PASC were, in comparison, more limited, but included significant differences in autoantibodies and in epigenetic and transcriptional signatures in double-negative 1 B cells, in particular.ConclusionsWe found that early immune indicators of incident PASC were nuanced, with significant molecular signals manifesting predominantly in double-negative B cells, compared with the robust differences associated with hospitalization during acute COVID-19. The emerging acute differences in B cell phenotypes, especially in double-negative 1 B cells, in PASC patients highlight a potentially important role of these cells in the development of PASC

    Content and performance of the MiniMUGA genotyping array: A new tool to improve rigor and reproducibility in mouse research

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    The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost-effective, informative, and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole-genome sequencing. Here, we describe the content and performance of a new iteration of the Mouse Universal Genotyping Array (MUGA), MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: (1) chromosomal sex determination, (2) discrimination between substrains from multiple commercial vendors, (3) diagnostic SNPs for popular laboratory strains, (4) detection of constructs used in genetically engineered mice, and (5) an easy-to-interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA, we genotyped 6899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays, both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived, and recombinant inbred lines. Here, we also report the detection of a substantial number of XO and XXY individuals across a variety of sample types, new markers that expand the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. We provide preliminary evidence that the array can be used to identify both partial sex chromosome duplication and mosaicism, and that diagnostic SNPs can be used to determine how long inbred mice have been bred independently from the relevant main stock. We conclude that MiniMUGA is a valuable platform for genetic QC, and an important new tool to increase the rigor and reproducibility of mouse research

    Data Descriptor: A global multiproxy database for temperature reconstructions of the Common Era

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    Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python.(TABLE)Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013').This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product.This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike

    Research of the farmland protection based on food security —A case study of Anshan City in Liaoning Province, China

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    The quantity and quality of farmland is the key factor determining grain production capacity, so protecting farmland has become the key to guaranteeing food security. I take Anshan City in Liaoning Province as the study area which has its own particularity in terms of protecting farmland. Based on the prediction of population, coupled with the relevant data concerning farmland area, the per unit area yield of grain, the prediction and analysis of the balance of supply and demand of farmland in Anshan City are conducted. The results show that in the year 2010, the maximum supply amount of farmland that the city can offer is 239000 hm2, and in the year 2020 the maximum supply amount of farmland that the city can offer will be 238000hm2; in the year 2010, the maximum demand amount of farmland is 204186.02 hm2, and in the year 2020 the maximum supply amount of farmland will be 226409.61hm2. So the supply amount of farmland that the city can offer can meet the need of grain production objective. Some problems concerning farmland protection are pointed out in order to provide beneficial exploration of the farmland protection based on the model of food security
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