1,069 research outputs found

    Investigating Ligand-Modulation of GPCR Activation Pathways

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    Please Think Of Me

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    Illustration of woman\u27s face; Photograph of Tommy Dorseyhttps://scholarsjunction.msstate.edu/cht-sheet-music/12308/thumbnail.jp

    Content-based microarray search using differential expression profiles

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    <p>Abstract</p> <p>Background</p> <p>With the expansion of public repositories such as the Gene Expression Omnibus (GEO), we are rapidly cataloging cellular transcriptional responses to diverse experimental conditions. Methods that query these repositories based on gene expression content, rather than textual annotations, may enable more effective experiment retrieval as well as the discovery of novel associations between drugs, diseases, and other perturbations.</p> <p>Results</p> <p>We develop methods to retrieve gene expression experiments that differentially express the same transcriptional programs as a query experiment. Avoiding thresholds, we generate differential expression profiles that include a score for each gene measured in an experiment. We use existing and novel dimension reduction and correlation measures to rank relevant experiments in an entirely data-driven manner, allowing emergent features of the data to drive the results. A combination of matrix decomposition and <it>p</it>-weighted Pearson correlation proves the most suitable for comparing differential expression profiles. We apply this method to index all GEO DataSets, and demonstrate the utility of our approach by identifying pathways and conditions relevant to transcription factors Nanog and FoxO3.</p> <p>Conclusions</p> <p>Content-based gene expression search generates relevant hypotheses for biological inquiry. Experiments across platforms, tissue types, and protocols inform the analysis of new datasets.</p

    A Method of Drusen Measurement Based on the Geometry of Fundus Reflectance

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    BACKGROUND: The hallmarks of age-related macular degeneration, the leading cause of blindness in the developed world, are the subretinal deposits known as drusen. Drusen identification and measurement play a key role in clinical studies of this disease. Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method. METHODS: An interactive semi-automated procedure was developed to level the macular background reflectance for the purpose of morphometric analysis of drusen. 12 color fundus photographs of patients with age-related macular degeneration and drusen were analyzed. After digitizing the photographs, the underlying background pattern in the green channel was leveled by an algorithm based on the elliptically concentric geometry of the reflectance in the normal macula: the gray scale values of all structures within defined elliptical boundaries were raised sequentially until a uniform background was obtained. Segmentation of drusen and area measurements in the central and middle subfields (1000 μm and 3000 μm diameters) were performed by uniform thresholds. Two observers using this interactive semi-automated software measured each image digitally. The mean digital measurements were compared to independent stereo fundus gradings by two expert graders (stereo Grader 1 estimated the drusen percentage in each of the 24 regions as falling into one of four standard broad ranges; stereo Grader 2 estimated drusen percentages in 1% to 5% intervals). RESULTS: The mean digital area measurements had a median standard deviation of 1.9%. The mean digital area measurements agreed with stereo Grader 1 in 22/24 cases. The 95% limits of agreement between the mean digital area measurements and the more precise stereo gradings of Grader 2 were -6.4 % to +6.8 % in the central subfield and -6.0 % to +4.5 % in the middle subfield. The mean absolute differences between the digital and stereo gradings 2 were 2.8 +/- 3.4% in the central subfield and 2.2 +/- 2.7% in the middle subfield. CONCLUSIONS: Semi-automated, supervised drusen measurements may be done reproducibly and accurately with adaptations of commercial software. This technique for macular image analysis has potential for use in clinical research

    First Measurement of pi e -> pi e gamma Pion Virtual Compton Scattering

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    Pion Virtual Compton Scattering (VCS) via the reaction pi e --> pi e gamma was observed in the Fermilab E781 SELEX experiment. SELEX used a 600 GeV/c pi- beam incident on target atomic electrons, detecting the incident pi- and the final state pi-, electron and gamma. Theoretical predictions based on chiral perturbation theory are incorporated into a Monte Carlo simulation of the experiment and are compared to the data. The number of reconstructed events (9) and their distribution with respect to the kinematic variables (for the kinematic region studied) are in reasonable accord with the predictions. The corresponding pi- VCS experimental cross section is sigma=38.8+-13 nb, in agreement with the theoretical expectation sigma=34.7 nb.Comment: 10 pages, 12 figures, 4 tables, 25 references, SELEX home page is http://fn781a.fnal.gov/, revised July 21, 2002 in response to journal referee Comment

    Statistics of gravitational lenses in the clumpy Universe

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    We evaluate the effect of small scale inhomogeneities on large scale observations within the statistics of gravitationally lensed quasars. At this aim, we consider a cosmological model whose large scale properties (dynamics, matter distribution) are the same as in Friedmann-Lemaitre models, but whose matter distribution is locally inhomogeneous. We use the well known Dyer-Roder distances to allow a simple analytical expression of the optical depth, and pay particular attention on the different role played by the different notions of distances (filled beam angular diameter distance and Dyer-Roder distances) when calculating this quantity, following the prescription from Ehlers & Schneider for a coherent formalism. We find that the expected number of gravitationally lensed quasars is a decreasing function of the clumpiness parameter.Comment: 11 pages, 9 figures. MNRAS, in pres

    Purpose vs performance : what does marine protected area success look like?

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    Marine protected areas (MPAs) are an increasingly deployed spatial management tool. MPAs are primarily designed for biodiversity conservation, with their success commonly measured using a narrow suite of ecological indicators. However, for MPAs to achieve their biodiversity conservation goals they require community support, which is dependent on wider social, economic and political factors. Despite this, research into the human dimensions of MPAs continues to lag behind our understanding of ecological responses to MPA protection. Here, we explore stakeholders’ perceptions of what MPA success is. We conducted a series of semi-structured interviews and focus groups with a diverse group of stakeholders local to a South Australian MPA. What constitutes success varied by stakeholder group, and stakeholders’ stated understanding of the purpose of the MPA differed from how they would choose to measure the MPA’s success. Indeed, all interviewees stated that the primary purpose of the MPA was ecological, yet almost all (>90%) would measure the success of the MPA using social and economic measures, either exclusively or in conjunction with ecological ones. Many respondents also stated that social and economic factors were key to the MPA achieving ongoing/future success. Respondents generated a large range of novel socio-economic measures of MPA success, many of which could be incorporated into monitoring programs for relatively little additional cost. These findings also show that success is not straightforward and what constitutes success depends on who you ask. Even where an MPA’s primary ecological purpose is acknowledged by stakeholders, stakeholders are likely to only consider the MPA a success if its designation also demonstrates social and economic benefits to their communities. To achieve local stakeholder support MPAs and associated monitoring programs need to be designed for a variety of success criteria in mind, criteria which reflect the priorities and needs of the adjacent communities as well as national and international conservation objectives

    Modelling in vivo skeletal muscle ageing in vitro using three-dimensional bioengineered constructs

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    Degeneration of skeletal muscle (SkM) with age (sarcopenia) is a major contributor to functional decline, morbidity and mortality. Methodological implications often make it difficult to embark on interventions in already frail and diseased elderly individuals. Using in vitro three-dimensional (3D) bioengineered skeletal muscle constructs that model aged phenotypes and incorporate a representative extracellular matrix (collagen), are under tension, and display morphological and transcript expression of mature skeletal muscle may more accurately characterize the SkM niche. Furthermore, an in vitro model would provide greater experimental manipulation with regard to gene, pharmacological and exercise (mechanical stretch / electrical stimulation) therapies and thus strategies for combating muscle wasting with age. The present study utilized multiple population-doubled (MPD) murine myoblasts compared with parental controls (CON), previously shown to have an aged phenotype in monolayer cultures (Sharples et al., 2011), seeded into 3D type I collagen matrices under uniaxial tension. 3D bioengineered constructs incorporating MPD cells had reduced myotube size and diameter vs. CON constructs. MPD constructs were characterized by reduced peak force development over 24 h after cell seeding, reduced transcript expression of remodelling matrix metalloproteinases, MMP2 and MMP9, with reduced differentiation / hypertrophic potential shown by reduced IGF-I, IGF-IR, IGF-IEa, MGF mRNA. Increased IGFBP2 and myostatin in MPD vs. CON constructs also suggested impaired differentiation / reduced regenerative potential. Overall, 3D bioengineered skeletal muscle constructs represent an in vitro model of the in vivo cell niche with MPD constructs displaying similar characteristics to ageing / atrophied muscle in vivo, thus potentially providing a future test bed for therapeutic interventions to contest muscle degeneration with age

    Evaluation of immunoglobulin purification methods and their impact on quality and yield of antigen-specific antibodies

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    <p>Abstract</p> <p>Background</p> <p>Antibodies are the main effectors against malaria blood-stage parasites. Evaluation of functional activities in immune sera from Phase 2a/b vaccine trials may provide invaluable information in the search for immune correlates of protection. However, the presence of anti-malarial-drugs, improper collection/storage conditions or concomitant immune responses against other pathogens can contribute to non-specific anti-parasite activities when the sera/plasma are tested <it>in vitro</it>. Purification of immunoglobulin is a standard approach for reducing such non-specific background activities, but the purification method itself can alter the quality and yield of recovered Ag-specific antibodies.</p> <p>Methods</p> <p>To address this concern, various immunoglobulin (Ig) purification methods (protein G Sepharose, protein A/G Sepharose, polyethylene glycol and caprylic acid-ammonium sulphate precipitation) were evaluated for their impact on the quality, quantity and functional activity of purified rabbit and human Igs. The recovered Igs were analysed for yield and purity by SDS-PAGE, for quality by Ag-specific ELISAs (determining changes in titer, avidity and isotype distribution) and for functional activity by <it>in vitro </it>parasite growth inhibition assay (GIA).</p> <p>Results</p> <p>This comparison demonstrated that overall polyethylene glycol purification of human serum/plasma samples and protein G Sepharose purification of rabbit sera are optimal for recovering functional Ag-specific antibodies.</p> <p>Conclusion</p> <p>Consequently, critical consideration of the purification method is required to avoid selecting non-representative populations of recovered Ig, which could influence interpretations of vaccine efficacy, or affect the search for immune correlates of protection.</p
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