87 research outputs found

    Ethyl anthracene-9-carboxyl­ate

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    In the title compound, C17H14O2, the COO group and the anthracene fragment form a dihedral angle of 76.00 (19)°. The torsion angle around the O—Csp 3 bond of the ester group is 108.52 (18)°. The crystal structure is stabilized by C—H⋯O inter­actions and edge-to-face arene inter­actions with C—H⋯(ring centroid) distances in the range 2.75–2.84 Å

    An integrated workflow for robust alignment and simplified quantitative analysis of NMR spectrometry data

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    <p>Abstract</p> <p>Background</p> <p>Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique to reveal and compare quantitative metabolic profiles of biological tissues. However, chemical and physical sample variations make the analysis of the data challenging, and typically require the application of a number of preprocessing steps prior to data interpretation. For example, noise reduction, normalization, baseline correction, peak picking, spectrum alignment and statistical analysis are indispensable components in any NMR analysis pipeline.</p> <p>Results</p> <p>We introduce a novel suite of informatics tools for the quantitative analysis of NMR metabolomic profile data. The core of the processing cascade is a novel peak alignment algorithm, called hierarchical Cluster-based Peak Alignment (CluPA). The algorithm aligns a target spectrum to the reference spectrum in a top-down fashion by building a hierarchical cluster tree from peak lists of reference and target spectra and then dividing the spectra into smaller segments based on the most distant clusters of the tree. To reduce the computational time to estimate the spectral misalignment, the method makes use of Fast Fourier Transformation (FFT) cross-correlation. Since the method returns a high-quality alignment, we can propose a simple methodology to study the variability of the NMR spectra. For each aligned NMR data point the ratio of the between-group and within-group sum of squares (BW-ratio) is calculated to quantify the difference in variability between and within predefined groups of NMR spectra. This differential analysis is related to the calculation of the F-statistic or a one-way ANOVA, but without distributional assumptions. Statistical inference based on the BW-ratio is achieved by bootstrapping the null distribution from the experimental data.</p> <p>Conclusions</p> <p>The workflow performance was evaluated using a previously published dataset. Correlation maps, spectral and grey scale plots show clear improvements in comparison to other methods, and the down-to-earth quantitative analysis works well for the CluPA-aligned spectra. The whole workflow is embedded into a modular and statistically sound framework that is implemented as an R package called "speaq" ("spectrum alignment and quantitation"), which is freely available from <url>http://code.google.com/p/speaq/</url>.</p

    COMPASS identifies T-cell subsets correlated with clinical outcomes.

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    Advances in flow cytometry and other single-cell technologies have enabled high-dimensional, high-throughput measurements of individual cells as well as the interrogation of cell population heterogeneity. However, in many instances, computational tools to analyze the wealth of data generated by these technologies are lacking. Here, we present a computational framework for unbiased combinatorial polyfunctionality analysis of antigen-specific T-cell subsets (COMPASS). COMPASS uses a Bayesian hierarchical framework to model all observed cell subsets and select those most likely to have antigen-specific responses. Cell-subset responses are quantified by posterior probabilities, and human subject-level responses are quantified by two summary statistics that describe the quality of an individual's polyfunctional response and can be correlated directly with clinical outcome. Using three clinical data sets of cytokine production, we demonstrate how COMPASS improves characterization of antigen-specific T cells and reveals cellular 'correlates of protection/immunity' in the RV144 HIV vaccine efficacy trial that are missed by other methods. COMPASS is available as open-source software

    Polyethylene thickness is a risk factor for wear necessitating insert exchange

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    PURPOSE: The aim of this observational study was to investigate the optimal minimal polyethylene (PE) thickness in total knee arthroplasty (TKA) and identify other risk factors associated with revision of the insert due to wear. METHODS: A total of 84 TKA were followed for 11-16 years. All patients received the same prosthesis design (Interax; Howmedica/ Stryker) with halfbearings: separate PE-inserts medially and laterally. Statistical analysis comprised Cox-regression to correct for confounding. RESULTS: Eight knees (9.5%) had been revised due to thinning inserts and an additional patient is scheduled for revision. PE thickness, diagnosis, BMI and weight are risk factors for insert exchange. For each millimetre decrease in PE thickness, the risk of insert exchange increases 3.0 times, which remains after correction for age, gender, weight, diagnosis and femoral-tibial angle. Insert exchange was 4.73 times more likely in OA-patients compared to RA-patients. For every unit increase in BMI and weight the risk for insert exchange increases 1.40 times and 1.14 times, respectively. CONCLUSIONS: In conclusion we therefore advise against the use of thin PE inserts in modular TKA and recommend PE inserts with a minimal 8-mm thickness.Optimising joint reconstruction management in arthritis and bone tumour patient

    LDL Receptor Knock-Out Mice Are a Physiological Model Particularly Vulnerable to Study the Onset of Inflammation in Non-Alcoholic Fatty Liver Disease

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    Non-alcoholic steatohepatitis (NASH) involves steatosis combined with inflammation, which can progress into fibrosis and cirrhosis. Exploring the molecular mechanisms of NASH is highly dependent on the availability of animal models. Currently, the most commonly used animal models for NASH imitate particularly late stages of human disease. Thus, there is a need for an animal model that can be used for investigating the factors that potentiate the inflammatory response within NASH. We have previously shown that 7-day high-fat-high-cholesterol (HFC) feeding induces steatosis and inflammation in both APOE2ki and Ldlr(-/-) mice. However, it is not known whether the early inflammatory response observed in these mice will sustain over time and lead to liver damage. We hypothesized that the inflammatory response in both models is sufficient to induce liver damage over time.APOE2ki and Ldlr(-/-) mice were fed a chow or HFC diet for 3 months. C57Bl6/J mice were used as control.Surprisingly, hepatic inflammation was abolished in APOE2ki mice, while it was sustained in Ldlr(-/-) mice. In addition, increased apoptosis and hepatic fibrosis was only demonstrated in Ldlr(-/-) mice. Finally, bone-marrow-derived-macrophages of Ldlr(-/-) mice showed an increased inflammatory response after oxidized LDL (oxLDL) loading compared to APOE2ki mice.Ldlr(-/-) mice, but not APOE2ki mice, developed sustained hepatic inflammation and liver damage upon long term HFC feeding due to increased sensitivity for oxLDL uptake. Therefore, the Ldlr(-/-) mice are a promising physiological model particularly vulnerable for investigating the onset of hepatic inflammation in non-alcoholic steatohepatitis

    Dutch guideline on total hip prosthesis

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    Contains fulltext : 97840.pdf (publisher's version ) (Open Access
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