2,878 research outputs found

    Foreword

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    Vertical plane response of surface ships in close proximity towing

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    The purpose of this thesis is to analyze the vertical plane response of surface ships in close proximity towing. The problem is formulated by using the heave and pitch equations of motion in regular waves. The vertical motion of the leading and trailing ship attachment points is calculated. The relative motion between these points is then matched through a notional spring/damper model of the connection. This allows calculation of the complete response amplitude operators for the two ships in terms of their relative motion and connection force. Parametric studies are conducted in terms of connection spring and damper characteristics, speed, and sea direction. Regular wave results are extended in standard fully developed random seas. A notional example provides insight into future studies necessary to validate the close-proximity towing concept.http://archive.org/details/verticalplaneres109451099

    Producing facial composite sketches in remote cognitive interviews:a preliminary investigation

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    Justice systems around the world are increasingly turning to videoconferencing as a means to reduce delays and reduce costs in legal processes. This preliminary research examined whether interviewing a witness remotely - without physical co-presence of the witness and interviewer - could facilitate the production of quality facial composite sketches of suspects. In Study 1, 42 adults briefly viewed a photograph of a face. The next day they participated in Cognitive Interviews with a forensic artist, conducted either face-to-face or remotely via videoconference. In Study 2, 20 adults participated in videoconferenced interviews, and we manipulated the method by which they viewed the developing sketch. In both studies, independent groups of volunteers rated the likeness of the composites to the original photographs. The data suggest that remote interviews elicited effective composites; however, in Study 1 these composites were considered poorer matches to the photographs than were those produced in face-to-face interviews. The differences were small, but significant. Participants perceived several disadvantages to remote interviewing, but also several advantages including less pressure and better concentration. The results of Study 2 suggested that different sketch presentation methods offered different benefits. We propose that remote interviewing could be a useful tool for investigators in certain circumstances

    Direct observations of the kinetics of migrating T-cells suggest active retention by endothelial cells with continual bidirectional migration.

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    The kinetics and regulatory mechanisms of T-cell migration through endothelium have not been fully defined. In experimental filter-based assays in vitro, transmigration of lymphocytes takes hours, compared to minutes in vivo. We cultured endothelial cell (EC) monolayers on filters, solid substrates or collagen gels, and treated them with tumour necrosis factor-α (TNF), interferon-γ (IFN), or both, prior to analysis of lymphocyte migration in the presence or absence of flow. Peripheral blood lymphocytes (PBL), CD4+ cells or CD8+ cells, took many hours to migrate through EC-filter constructs for all cytokine treatments. However, direct microscopic observations of EC-filters which had been mounted in a flow chamber showed that PBL crossed the endothelial monolayer in minutes and were highly motile in the subendothelial space. Migration through EC was also observed on clear plastic, with or without flow. After brief settling without flow, PBL and isolated CD3+ or CD4+ cells all crossed EC in minutes, but the numbers of migrated cells varied little with time. Close observation revealed that lymphocytes continuously migrated back and forth across endothelium. Under flow, migration kinetics and the proportions migrating back and forth were little altered. On collagen gels, PBL again crossed EC in minutes and migrated back and forth, but showed little penetration of the gel over hours.In contrast, neutrophils migrated efficiently through EC and into gels. These observations suggest a novel model for lymphoid migration, in which endothelial cells support migration but retain lymphocytes (as opposed to neutrophils), and additional signal(s) are required for onward migration

    Treatment recommendations for psoriatic arthritis

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    Objective: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion. Methods: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire. Results: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective. Conclusions: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available

    Cell lineage-specific mitochondrial resilience during mammalian organogenesis

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    Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments

    Categorizing the severity of paralytic shellfish poisoning outbreaks in the Gulf of Maine for forecasting and management

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    Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 103 (2014): 277-287, doi:10.1016/j.dsr2.2013.03.027.Development of forecasting systems for harmful algal blooms (HABs) has been a long-standing research and management goal. Significant progress has been made in the Gulf of Maine, where seasonal bloom forecasts are now being issued annually using Alexandrium fundyense cyst abundance maps and a population dynamics model developed for that organism. Thus far these forecasts have used terms such as “significant”, “moderately large” or “moderate” to convey the extent of forecasted paralytic shellfish poisoning (PSP) outbreaks. In this study, historical shellfish harvesting closure data along the coast of the Gulf of Maine were used to derive a series of bloom severity levels that are analogous to those used to define major storms like hurricanes or tornados. Thirty-four years of PSP-related shellfish closure data for Maine, Massachusetts and New Hampshire were collected and mapped to depict the extent of coastline closure in each year. Due to fractal considerations, different methods were explored for measuring length of coastline closed. Ultimately, a simple procedure was developed using arbitrary straight-line segments to represent specific sections of the coastline. This method was consistently applied to each year’s PSP toxicity closure map to calculate the total length of coastline closed. Maps were then clustered together statistically to yield distinct groups of years with similar characteristics. A series of categories or levels was defined (“Level 1: Limited”, “Level 2: Moderate”, and “Level 3: Extensive”) each with an associated range of expected coastline closed, which can now be used instead of vague descriptors in future forecasts. This will provide scientifically consistent and simply defined information to the public as well as resource managers who make decisions on the basis of the forecasts.Research support provided through the Woods Hole Center for Oceans and Human Health, National Science Foundation (NSF) Grants OCE-0430724, and OCE-0911031; and National Institute of Environmental Health Sciences (NIEHS) Grant 1-P50-ES012742-01, the ECOHAB Grant program through NOAA Grant NA06NOS4780245, and the PCM HAB Grant program through NOAA Grant NA11NOS4780023

    Characterization of an Ex Vivo Equine Endometrial Tissue Culture Model Using Next-Generation RNA-Sequencing Technology

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    SIMPLE SUMMARY: Notwithstanding extensive research into fertility problems in mares, pregnancy rates have remained low mainly because of endometrial inflammation (endometritis). In the field of equine research, endometrial explants have been used to carry out in vitro studies of the mare’s endometrium. However, there has been no wide-ranging assessment of relative stability of this model over time. The aim of this study was to perform an in-depth transcriptomic assessment of endometrial explants over a culture period of 72 h and assess if they are representative of the whole mare. Explants at 24 h demonstrated significant changes when compared to biopsies at 0 h as expected. Even though gene expression changes were seen between 24 and 48 h of culture, prior to this window changes were dominated by the effects of explanting and culture and subsequently, transcription was generally compromised. Our results, therefore have defined the optimal period when explants can be used to study equine endometritis and how the endometrium is modulated during inflammation. It highlights the use of abattoir derived samples to understand the physiology and pathophysiology of the equine endometrium, negating the need to collect repeated uterine biopsies from living mares. ABSTRACT: Persistent mating-induced endometritis is a major cause of poor fertility rates in the mare. Endometritis can be investigated using an ex vivo equine endometrial explant system which measures uterine inflammation using prostaglandin F(2α) as a biomarker. However, this model has yet to undergo a wide-ranging assessment through transcriptomics. In this study, we assessed the transcriptomes of cultured endometrial explants and the optimal temporal window for their use. Endometrium harvested immediately post-mortem from native pony mares (n = 8) were sampled (0 h) and tissue explants were cultured for 24, 48 and 72 h. Tissues were stored in RNALater, total RNA was extracted and sequenced. Differentially expressed genes (DEGs) were defined using DESeq2 (R/Bioconductor). Principal component analysis indicated that the greatest changes in expression occurred in the first 24 h of culture when compared to autologous biopsies at 0 h. Fewer DEGs were seen between 24 and 48 h of culture suggesting the system was more stable than during the first 24 h. No genes were differentially expressed between 48 and 72 h but the low number of background gene expression suggested that explant viability was compromised after 48 h. ESR1, MMP9, PTGS2, PMAIP1, TNF, GADD45B and SELE genes were used as biomarkers of endometrial function, cell death and inflammation across tissue culture timepoints. STRING assessments of gene ontology suggested that DEGs between 24 and 48 h were linked to inflammation, immune system, cellular processes, environmental information processing and signal transduction, with an upregulation of most biomarker genes at 24 h. Taken together our observations indicated that 24–48 h is the optimal temporal window when the explant model can be used, as explants restore microcirculation, perform wound healing and tackle inflammation during this period. This key observation will facilitate the appropriate use of this as a model for further research into the equine endometrium and potentially the progression of mating-induced endometritis to persistent inflammation between 24 and 48 h

    The gut mycobiome of the Human Microbiome Project healthy cohort

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    Background: Most studies describing the human gut microbiome in healthy and diseased states have emphasized the bacterial component, but the fungal microbiome (i.e., the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. To date, human gut mycobiome studies have primarily been disease centric or in small cohorts of healthy individuals. To contribute to existing knowledge of the human mycobiome, we investigated the gut mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene. Results: Three hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal fungal diversity was significantly lower in comparison to bacterial diversity. Yeast dominated the samples, comprising eight of the top 15 most abundant genera. Specifically, fungal communities were characterized by a high prevalence of Saccharomyces, Malassezia, and Candida, with S. cerevisiae, M. restricta, and C. albicans operational taxonomic units (OTUs) present in 96. 8, 88.3, and 80.8% of samples, respectively. There was a high degree of inter- and intra-volunteer variability in fungal communities. However, S. cerevisiae, M. restricta, and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided greater resolution of the relatively low abundance mycobiome constituents. Conclusions: Compared to bacterial communities, the human gut mycobiome is low in diversity and dominated by yeast including Saccharomyces, Malassezia, and Candida. Both inter- and intra-volunteer variability in the HMP cohort were high, revealing that unlike bacterial communities, an individual’s mycobiome is no more similar to itself over time than to another person’s. Nonetheless, several fungal species persisted across a majority of samples, evidence that a core gut mycobiome may exist. ITS2 sequencing data provided greater resolution of the mycobiome membership compared to metagenomic and 18S rRNA gene sequencing data, suggesting that it is a more sensitive method for studying the mycobiome of stool samples

    The Volume of some Non-spherical Horizons and the AdS/CFT Correspondence

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    We calculate the volumes of a large class of Einstein manifolds, namely Sasaki-Einstein manifolds which are the bases of Ricci-flat affine cones described by polynomial embedding relations in C^n. These volumes are important because they allow us to extend and test the AdS/CFT correspondence. We use these volumes to extend the central charge calculation of Gubser (1998) to the generalized conifolds of Gubser, Shatashvili, and Nekrasov (1999). These volumes also allow one to quantize precisely the D-brane flux of the AdS supergravity solution. We end by demonstrating a relationship between the volumes of these Einstein spaces and the number of holomorphic polynomials (which correspond to chiral primary operators in the field theory dual) on the corresponding affine cone.Comment: 25 pp, LaTeX, 1 figure, v2: refs adde
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