1,035 research outputs found

    CART Raman Lidar Aerosol and Water Vapor Measurements in the Vicinity of Clouds

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    Aerosol and water vapor profiles acquired by the Raman lidar instrument located at the Climate Research Facility (CRF) at Southern Great Plains (SGP) provide data necessary to investigate the atmospheric variability in the vicinity of clouds near the top of the planetary boundary layer (PBL). Recent CARL upgrades and modifications to the routine processing algorithms afforded the necessarily high temporal and vertical data resolutions for these investigations. CARL measurements are used to investigate the behavior of aerosol backscattering and extinction and their correlation with water vapor and relative humidity

    Initial indicators of effectiveness for a high school drug prevention program

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    All Stars, Sr. is a comprehensive high school health education supplement designed to prevent high-risk behaviors among adolescents. The program includes topics such as personal health, nutrition, interpersonal relationships, and stress, with a special emphasis on drug prevention. Effective research-based programs that target late onset prevention and early cessation of high-risk behaviors among high school students are not yet widely available. All Stars, Sr. fills this need by providing high schools with a program that promotes positive change in research-based mediating variables. The purpose of this study was to conduct an initial evaluation of All Stars, Sr. to examine program effects on drug use as well as mediating variables related to other high-risk behaviors. Six suburban high schools in North Carolina were randomly assigned to treatment and comparison conditions. Immediate pre- and posttest surveys were used to evaluate program effects. Results indicate that students exposed to All Stars, Sr. became increasingly likely to view drug use, poor nutrition, and stress as not fitting with their desired future lives. Additionally, students who participated in All Stars, Sr. were significantly less likely to have smoked cigarettes, and they demonstrated a trend toward less drunkenness than comparison students

    Use of a targeted, combinatorial next-generation sequencing approach for the study of bicuspid aortic valve

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    BACKGROUND: Bicuspid aortic valve (BAV) is the most common type of congenital heart disease with a population prevalence of 1-2%. While BAV is known to be highly heritable, mutations in single genes (such as GATA5 and NOTCH1) have been reported in few human BAV cases. Traditional gene sequencing methods are time and labor intensive, while next-generation high throughput sequencing remains costly for large patient cohorts and requires extensive bioinformatics processing. Here we describe an approach to targeted multi-gene sequencing with combinatorial pooling of samples from BAV patients. METHODS: We studied a previously described cohort of 78 unrelated subjects with echocardiogram-identified BAV. Subjects were identified as having isolated BAV or BAV associated with coarctation of aorta (BAV-CoA). BAV cusp fusion morphology was defined as right-left cusp fusion, right non-coronary cusp fusion, or left non-coronary cusp fusion. Samples were combined into 19 pools using a uniquely overlapping combinatorial design; a given mutation could be attributed to a single individual on the basis of which pools contained the mutation. A custom gene capture of 97 candidate genes was sequenced on the Illumina HiSeq 2000. Multistep bioinformatics processing was performed for base calling, variant identification, and in-silico analysis of putative disease-causing variants. RESULTS: Targeted capture identified 42 rare, non-synonymous, exonic variants involving 35 of the 97 candidate genes. Among these variants, in-silico analysis classified 33 of these variants as putative disease-causing changes. Sanger sequencing confirmed thirty-one of these variants, found among 16 individuals. There were no significant differences in variant burden among BAV fusion phenotypes or isolated BAV versus BAV-CoA. Pathway analysis suggests a role for the WNT signaling pathway in human BAV. CONCLUSION: We successfully developed a pooling and targeted capture strategy that enabled rapid and cost effective next generation sequencing of target genes in a large patient cohort. This approach identified a large number of putative disease-causing variants in a cohort of patients with BAV, including variants in 26 genes not previously associated with human BAV. The data suggest that BAV heritability is complex and polygenic. Our pooling approach saved over $39,350 compared to an unpooled, targeted capture sequencing strategy

    Ground Vibration Testing Options for Space Launch Vehicles

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    New NASA launch vehicles will require development of robust systems in a fiscally-constrained environment. NASA, Department of Defense (DoD), and commercial space companies routinely conduct ground vibration tests as an essential part of math model validation and launch vehicle certification. Although ground vibration testing must be a part of the integrated test planning process, more affordable approaches must also be considered. A study evaluated several ground vibration test options for the NASA Constellation Program flight test vehicles, Orion-1 and Orion-2, which concluded that more affordable ground vibration test options are available. The motivation for ground vibration testing is supported by historical examples from NASA and DoD. The approach used in the present study employed surveys of ground vibration test subject-matter experts that provided data to qualitatively rank six test options. Twenty-five experts from NASA, DoD, and industry provided scoring and comments for this study. The current study determined that both element-level modal tests and integrated vehicle modal tests have technical merits. Both have been successful in validating structural dynamic math models of launch vehicles. However, element-level testing has less overall cost and schedule risk as compared to integrated vehicle testing. Future NASA launch vehicle development programs should anticipate that some structural dynamics testing will be necessary. Analysis alone will be inadequate to certify a crew-capable launch vehicle. At a minimum, component and element structural dynamic tests are recommended for new vehicle elements. Three viable structural dynamic test options were identified. Modal testing of the new vehicle elements and an integrated vehicle test on the mobile launcher provided the optimal trade between technical, cost, and schedule

    Apatites in Gale Crater

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    ChemCam is an active remote sensing instrument suite that has operated successfully on MSL since landing Aug. 6th, 2012. It uses laser pulses to remove dust and to analyze rocks up to 7 m away. Laser-induced breakdown spectroscopy (LIBS) obtains emission spectra of materials ablated from the samples in electronically excited states. The intensities of the emission lines scale with the abundances of the related element. ChemCam is sensitive to most major rock-forming elements as well as to a set of minor and trace elements such as F, Cl, Li, P, Sr, Ba, and Rb. The measured chemical composition can then be used to infer the mineralogical composition of the ablated material. Here, we report a summary of inferred apatite detections along the MSL traverse at Gale Crater. We present the geologic settings of these findings and derive some interpretations about the formation conditions of apatite in time and space

    The impact of ocean acidification on the functional morphology of foraminifera

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    This work was supported by the NERC UK Ocean Acidification Research Programme grant NE/H017445/1. WENA acknowledges NERC support (NE/G018502/1). DMP received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions.Culturing experiments were performed on sediment samples from the Ythan Estuary, N. E. Scotland, to assess the impacts of ocean acidification on test surface ornamentation in the benthic foraminifer Haynesina germanica. Specimens were cultured for 36 weeks at either 380, 750 or 1000 ppm atmospheric CO2. Analysis of the test surface using SEM imaging reveals sensitivity of functionally important ornamentation associated with feeding to changing seawater CO2 levels. Specimens incubated at high CO2 levels displayed evidence of shell dissolution, a significant reduction and deformation of ornamentation. It is clear that these calcifying organisms are likely to be vulnerable to ocean acidification. A reduction in functionally important ornamentation could lead to a reduction in feeding efficiency with consequent impacts on this organism’s survival and fitness.Publisher PDFPeer reviewe

    Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays

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    <p>Abstract</p> <p>Background</p> <p>Array-based comparative genomic hybridization (aCGH) is a high-throughput method for measuring genome-wide DNA copy number changes. Current aCGH methods have limited resolution, sensitivity and reproducibility. Microarrays for aCGH are available only for a few organisms and combination of aCGH data with expression data is cumbersome.</p> <p>Results</p> <p>We present a novel method of using commercial oligonucleotide expression microarrays for aCGH, enabling DNA copy number measurements and expression profiles to be combined using the same platform. This method yields aCGH data from genomic DNA without complexity reduction at a median resolution of approximately 17,500 base pairs. Due to the well-defined nature of oligonucleotide probes, DNA amplification and deletion can be defined at the level of individual genes and can easily be combined with gene expression data.</p> <p>Conclusion</p> <p>A novel method of gene resolution analysis of copy number variation (graCNV) yields high-resolution maps of DNA copy number changes and is applicable to a broad range of organisms for which commercial oligonucleotide expression microarrays are available. Due to the standardization of oligonucleotide microarrays, graCNV results can reliably be compared between laboratories and can easily be combined with gene expression data using the same platform.</p

    ChIP-Seq and RNA-Seq Reveal an AmrZ-Mediated Mechanism for Cyclic di-GMP Synthesis and Biofilm Development by Pseudomonas aeruginosa

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    The transcription factor AmrZ regulates genes important for P. aeruginosa virulence, including type IV pili, extracellular polysaccharides, and the flagellum; however, the global effect of AmrZ on gene expression remains unknown, and therefore, AmrZ may directly regulate many additional genes that are crucial for infection. Compared to the wild type strain, a ΔamrZ mutant exhibits a rugose colony phenotype, which is commonly observed in variants that accumulate the intracellular second messenger cyclic diguanylate (c-di-GMP). Cyclic di-GMP is produced by diguanylate cyclases (DGC) and degraded by phosphodiesterases (PDE). We hypothesized that AmrZ limits the intracellular accumulation of c-di-GMP through transcriptional repression of gene(s) encoding a DGC. In support of this, we observed elevated c-di-GMP in the ΔamrZ mutant compared to the wild type strain. Consistent with other strains that accumulate c-di-GMP, when grown as a biofilm, the ΔamrZ mutant formed larger microcolonies than the wild-type strain. This enhanced biofilm formation was abrogated by expression of a PDE. To identify potential target DGCs, a ChIP-Seq was performed and identified regions of the genome that are bound by AmrZ. RNA-Seq experiments revealed the entire AmrZ regulon, and characterized AmrZ as an activator or repressor at each binding site. We identified an AmrZ-repressed DGC-encoding gene (PA4843) from this cohort, which we named AmrZ dependent cyclase A (adcA). PAO1 overexpressing adcA accumulates 29-fold more c-di-GMP than the wild type strain, confirming the cyclase activity of AdcA. In biofilm reactors, a ΔamrZ ΔadcA double mutant formed smaller microcolonies than the single ΔamrZ mutant, indicating adcA is responsible for the hyper biofilm phenotype of the ΔamrZ mutant. This study combined the techniques of ChIP-Seq and RNA-Seq to define the comprehensive regulon of a bifunctional transcriptional regulator. Moreover, we identified a c-di-GMP mediated mechanism for AmrZ regulation of biofilm formation and chronicity

    Induction of Group IVC Phospholipase A2 in Allergic Asthma: Transcriptional Regulation by TNF-α in Bronchoepithelial Cells

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    Airway inflammation in allergen-induced asthma is associated with eicosanoid release. These bioactive lipids exhibit anti- and pro-inflammatory activities with relevance to pulmonary pathophysiology. We hypothesized that sensitization/challenge using an extract from the ubiquitous fungus, Aspergillus fumigatus (Af), in a mouse model of allergic asthma would result in altered phospholipase gene expression, thus modulating the downstream eicosanoid pathway. We observed the most significant induction in the group IVC phospholipase A2 (cPLA2γ or PLA2G4C). Our results infer that Af extract can induce cPLA2γ levels directly in eosinophils while induction in lung epithelial cells is most likely a consequence of TNF-α secretion by Af-activated macrophages. The mechanism of TNF-α-dependent induction of cPLA2γ gene expression was elucidated through a combination of promoter deletions, ChIP and overexpression studies in human bronchoepithelial cells, leading to the identification of functionally relevant CRE, NF-κB and E-box promoter elements. ChIP analysis demonstrated that RNA polymerase II, c-Jun/ATF-2, p65/p65 and USF1/USF2 complexes are recruited to the cPLA2γ enhancer/promoter in response to TNF-α with overexpression and dominant negative studies implying a strong level of cooperation and interplay between these factors. Overall, our data link cytokine-mediated alterations in cPLA2γ gene expression with allergic asthma and outline a complex regulatory mechanism
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