777 research outputs found

    T-cell antigenic sites tend to be amphipathic structures.

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    An epidemiological study of burglary offenders: trends and predictors of self-reported arrests for burglary in the United States, 2002-2013

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    Burglary is serious property crime with a relatively high incidence and has been shown to be variously associated with other forms of criminal behavior. Unfortunately, an epidemiological understanding of burglary and its correlates is largely missing from the literature. Using public-use data collected between 2002 and 2013 as part of the National Survey on Drug Use and Health (NSDUH), the current study compared those who self-reported burglary arrest in the prior 12 months with and without criminal history. The unadjusted prevalence estimates of self-reported burglary arrest were statistically different for those with a prior arrest history (4.7%) compared with those without an arrest history (0.02%) which is a 235-fold difference. Those with an arrest history were more likely to report lower educational attainment, to have lower income, to have moved more than 3 times in the past 5 years, and to use alcohol, tobacco, illicit drugs, and engage in binge drinking. Moreover, those with prior arrest histories were younger and more likely to be male. There is considerable heterogeneity among burglars with criminal history indicating substantially greater behavioral risk

    Data Perturbation Independent Diagnosis and Validation of Breast Cancer Subtypes Using Clustering and Patterns

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    Molecular stratification of disease based on expression levels of sets of genes can help guide therapeutic decisions if such classifications can be shown to be stable against variations in sample source and data perturbation. Classifications inferred from one set of samples in one lab should be able to consistently stratify a different set of samples in another lab. We present a method for assessing such stability and apply it to the breast cancer (BCA) datasets of Sorlie et al. 2003 and Ma et al. 2003. We find that within the now commonly accepted BCA categories identified by Sorlie et al. Luminal A and Basal are robust, but Luminal B and ERBB2+ are not. In particular, 36% of the samples identified as Luminal B and 55% identified as ERBB2+ cannot be assigned an accurate category because the classification is sensitive to data perturbation. We identify a ā€œcore clusterā€ of samples for each category, and from these we determine ā€œpatternsā€ of gene expression that distinguish the core clusters from each other. We find that the best markers for Luminal A and Basal are (ESR1, LIV1, GATA-3) and (CCNE1, LAD1, KRT5), respectively. Pathways enriched in the patterns regulate apoptosis, tissue remodeling and the immune response. We use a different dataset (Ma et al. 2003) to test the accuracy with which samples can be allocated to the four disease subtypes. We find, as expected, that the classification of samples identified as Luminal A and Basal is robust but classification into the other two subtypes is not

    945-65 Effect of Left Anterior Hemiblock on the Sensitivity of Exercise Stress Tests

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    We had observed a relatively high frequency of false negative stress electrocardiograms compared with SPECT thallium scintigraphy in patients with LAHB.PurposeTo assess the effect of LAHB on the sensitivity of exercise induced ST depressions for ischemia compared with SPECT thallium scintigraphyMethodsA 5ā€“year retrospective analysis of all treadmill thallium stress tests performed in our exercise laboratory was performed. Patients with LBBB, RBBB, IVCD, LVH or <85% of maximal HR were excluded.Study groupn=25 (16 M, 9 F, ages 35ā€“87)Matched controlsn=18.Results(1) The sensitivity of ST depressions for ischemia in the study group was 30% compared with 71%in the control group, the specificities were 90% and 75% respectively.(2) There was no significant association between presence of ischemia on ECG and on SPECT thallium scans in the study group, while an association was found in the control group (p<0.01).ConclusionsThe sensitivity of exercise stress tests for ischemia is low in the presence left anterior hemiblock

    A preliminary DTI study showing no brain structural change associated with adolescent cannabis use

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    Analyses were performed on brain MRI scans from individuals who were frequent cannabis users (N = 10; 9 males, 1 female, mean age 21.1 Ā± 2.9, range: 18ā€“27) in adolescence and similar age and sex matched young adults who never used cannabis (N = 10; 9 males, 1 female, mean age of 23.0 Ā± 4.4, range: 17ā€“30). Cerebral atrophy and white matter integrity were determined using diffusion tensor imaging (DTI) to quantify the apparent diffusion coefficient (ADC) and the fractional anisotropy (FA). Whole brain volumes, lateral ventricular volumes, and gray matter volumes of the amygdala-hippocampal complex, superior temporal gyrus, and entire temporal lobes (excluding the amygdala-hippocampal complex) were also measured. While differences existed between groups, no pattern consistent with evidence of cerebral atrophy or loss of white matter integrity was detected. It is concluded that frequent cannabis use is unlikely to be neurotoxic to the normal developing adolescent brain

    A unifying mathematical framework for experimental TCR-pMHC kinetic constants

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    Receptor binding and triggering are central in Immunology as T cells activated through their T cell receptors (TCR) by protein antigens orchestrate immune responses. In order to understand receptor-ligand interactions, many groups working with different experimental techniques and assays have generated a vast body of knowledge during the last decades. However, in recent years a type of assays, referred to as two-dimensional or membrane-to-membrane, has questioned our current understanding of the role of different kinetic constants (for instance, on- versus off-rate constants) on TCR-ligand interaction and subsequent T cell activation. Here we present a general mathematical framework that provides a unifying umbrella to relate fundamental and effective (or experimentally determined) kinetic constants, as well as describe and compare state-of-the-art experimental methods. Our framework is able to predict the correlations between functional output, such as 1/EC50, and effective kinetic constants for a range of different experimental assays (in two and three dimensions). Furthermore, our approach can be applied beyond Immunology, and serve as a ā€œtranslation methodā€ for the biochemical characterization of receptor-ligand interactions

    A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes

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    Peptides that are antigenic for T lymphocytes are ligands for two receptors, the class I or II glycoproteins that are encoded by genes in the major histocompatibility complex, and the idiotypic / chain T-cell antigen receptor1ā€“9. That a peptide must bind to an MHC molecule to interact with a T-cell antigen receptor is the molecular basis of the MHC restriction of antigen-recognition by T lymphocytes10,11. In such a trimolecular interaction the amino-acid sequence of the peptide must specify the contact with both receptors: agretope residues bind to the MHC receptor and epitope residues bind to the T-cell antigen receptor12,13. From a compilation of known antigenic peptides, two algorithms have been proposed to predict antigenic sites in proteins. One algorithm uses linear motifs in the sequence14, whereas the other considers peptide conformation and predicts antigenicity for amphipathic -helices15,16. We report here that a systematic delimitation of an antigenic site precisely identifies a predicted pentapeptide motif as the minimal antigenic determinant presented by a class I MHC molecule and recognized by a cytolytic T lymphocyte clone

    Psychopathy and Violent Misconduct in a Sample of Violent Young Offenders

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    Purpose: Most prior research on psychopathy and institutional misconduct/violence occurs with adult samples and comparatively less is known about the nature of this relationship among serious, violent juvenile offenders. Methods: A subsample of 159 male serious and violent offenders interviewed in custody facilities in British Columbia, Canada as part of the Vancouver Longitudinal Study of Incarcerated Young Offenders were used. Bivariate, AUC-ROC, and Poisson regression models examined the association between psychopathy and violent misconduct and exposure to violence with different specifications and separately for Caucasian and Aboriginal youth. Results: Overall, psychopathic youth evince more misconduct, are more violent, and break more institutional rules than their less psychopathic peers; however, the effects are relatively small, and ROC-AUC models reveal generally unimpressive classification accuracy. Conclusions: Although psychopathy is a risk factor for violent misconduct, its effects are measurement-variant (e.g., total scores, factor scores, and item scores) and differ for Caucasian and Aboriginal serious offenders
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