465 research outputs found

    Annual Survey of Virginia Law: Construction Law

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    This article reviews recent legislation and judicial decisions in Virginia affecting owners, contractors, and design professionals in the construction context. The discussion includes amendments to the Code of Virginia promulgated by the General Assembly in the 1992 and 1993 legislative sessions, as well as important cases dealing with construction law issues decided by Virginia\u27s state and federal courts in 1992 and the first half of 1993

    Evaluation of protection in a mouse model after vaccination with Mycobacterium avium subsp. paratuberculois protein cocktails

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    Whole-cell vaccines successfully reduce signs of clinical disease and fecal shedding of Mycobacterium avium subsp. paratuberculosis (MAP), however, these vaccines have some limitations. The present study was conducted to identify MAP proteins that might be candidates for the development of an improved vaccine. MAP proteins were screened for immunogenicity in naturally infected cattle and selected based upon reactivity in the interferon- (IFN-) and Western blot assays. Proteins (MAP1087, MAP1204, MAP1272c, and MAP2077c) were arrayed into 4 overlapping cocktails containing 3 proteins each. The efficacy of the proteins within these cocktails as vaccine candidates was evaluated by subcutaneous immunization of mice, followed by challenge with live, virulent MAP. All MAP protein cocktails significantly reduced the recovery of live MAP from the ileum, while cocktails 1 and 3 reduced colonization in the liver. No significant differences were seen in the mesenteric lymph node or spleen, however, cocktail 1 reduced viable MAP in the mesenteric lymph node compared to other treatments. Stimulation of splenocytes upregulated antigen-specific IFN- and IL-23 secretion in all treatment groups, regardless of vaccination. Interestingly, IL-4 was moderately downregulated for vaccinates compared to control infected mice. An increase in total CD25 expression was noted for 3 of the 4 vaccinate groups upon stimulation of splenocytes with a whole-cell sonicate of MAP, with this effect becoming more significant within CD4CD25+ and CD8CD25+ subpopulations. The present study demonstrated that MAP proteins are useful as vaccine candidates to reduce MAP tissue burden

    Electro-Magnetic Nucleon Form Factors and their Spectral Functions in Soliton Models

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    It is demonstrated that in simple soliton models essential features of the electro-magnetic nucleon form factors observed over three orders of magnitude in momentum transfer tt are naturally reproduced. The analysis shows that three basic ingredients are required: an extended object, partial coupling to vector mesons, and relativistic recoil corrections. We use for the extended object the standard skyrmion, one vector meson propagator for both isospin channels, and the relativistic boost to the Breit frame. Continuation to timelike tt leads to quite stable results for the spectral functions in the regime from the 2- or 3-pion threshold to about two rho masses. Especially the onset of the continuous part of the spectral functions at threshold can be reliably determined and there are strong analogies to the results imposed on dispersion theoretic approaches by the unitarity constraint.Comment: 24 pages, (RevTeX), 5 PS-figures; Data points in fig.2 and corresponding references added. Final version, to be published in Z.Physik

    Knowledge-based gene expression classification via matrix factorization

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    Motivation: Modern machine learning methods based on matrix decomposition techniques, like independent component analysis (ICA) or non-negative matrix factorization (NMF), provide new and efficient analysis tools which are currently explored to analyze gene expression profiles. These exploratory feature extraction techniques yield expression modes (ICA) or metagenes (NMF). These extracted features are considered indicative of underlying regulatory processes. They can as well be applied to the classification of gene expression datasets by grouping samples into different categories for diagnostic purposes or group genes into functional categories for further investigation of related metabolic pathways and regulatory networks. Results: In this study we focus on unsupervised matrix factorization techniques and apply ICA and sparse NMF to microarray datasets. The latter monitor the gene expression levels of human peripheral blood cells during differentiation from monocytes to macrophages. We show that these tools are able to identify relevant signatures in the deduced component matrices and extract informative sets of marker genes from these gene expression profiles. The methods rely on the joint discriminative power of a set of marker genes rather than on single marker genes. With these sets of marker genes, corroborated by leave-one-out or random forest cross-validation, the datasets could easily be classified into related diagnostic categories. The latter correspond to either monocytes versus macrophages or healthy vs Niemann Pick C disease patients.Siemens AG, MunichDFG (Graduate College 638)DAAD (PPP Luso - Alem˜a and PPP Hispano - Alemanas

    The influence of tumor regression, solar elastosis, and patient age on pathologists\u27 interpretation of melanocytic skin lesions.

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    It is not known whether patient age or tumor characteristics such as tumor regression or solar elastosis influence pathologists\u27 interpretation of melanocytic skin lesions (MSLs). We undertook a study to determine the influence of these factors, and to explore pathologist\u27s characteristics associated with the direction of diagnosis. To meet our objective, we designed a cross-sectional survey study of pathologists\u27 clinical practices and perceptions. Pathologists were recruited from diverse practices in 10 states in the United States. We enrolled 207 pathologist participants whose practice included the interpretation of MSLs. Our findings indicated that the majority of pathologists (54.6%) were influenced toward a less severe diagnosis when patients were70 years of age, or by the presence of tumor regression or solar elastosis (58.5%, 71.0%, and 57.0%, respectively). Generally, pathologists with dermatopathology board certification and/or a high caseload of MSLs were more likely to be influenced, whereas those with more years\u27 experience interpreting MSL were less likely to be influenced. Our findings indicate that the interpretation of MSLs is influenced by patient age, tumor regression, and solar elastosis; such influence is associated with dermatopathology training and higher caseload, consistent with expertise and an appreciation of lesion complexity

    Measurement of the lateral distribution function of UHECR air showers with the Pierre Auger Observatory

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    We describe how the lateral distribution function (LDF) is measured using the large sample of events recorded with the surface detector (SD) array and with a small sample observed with the fluorescence detectors (FD). For hybrid events, in which SD and FD measurements of the same shower are available, the core position is much better constrained than for SD-onlyevents, thus providing an important cross-check on the LDF determined from SD measurements alone. [Segmento extraído de la ponencia]Facultad de Ciencias Exacta

    Consistent Treatment of Relativistic Effects in Electrodisintegration of the Deuteron

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    The influence of relativistic contributions to deuteron electrodisintegration is systematically studied in various kinematic regions of energy and momentum transfer. As theoretical framework the equation-of-motion and the unitarily equivalent S-matrix approaches are used. In a (p/M)-expansion, all leading order relativistic π\pi-exchange contributions consistent with the Bonn OBEPQ model are included. In addition, static heavy meson exchange currents including boost terms, γπρ/ω\gamma\pi\rho/\omega-currents, and Δ\Delta-isobar contributions are considered. Sizeable effects from the various relativistic two-body contributions, mainly from π\pi-exchange, have been found in inclusive form factors and exclusive structure functions for a variety of kinematic regions.Comment: 41 pages revtex including 15 postscript figure

    Lysosome-mediated processing of chromatin in senescence

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    Cellular senescence is a stable proliferation arrest, a potent tumor suppressor mechanism, and a likely contributor to tissue aging. Cellular senescence involves extensive cellular remodeling, including of chromatin structure. Autophagy and lysosomes are important for recycling of cellular constituents and cell remodeling. Here we show that an autophagy/lysosomal pathway processes chromatin in senescent cells. In senescent cells, lamin A/C–negative, but strongly γ-H2AX–positive and H3K27me3-positive, cytoplasmic chromatin fragments (CCFs) budded off nuclei, and this was associated with lamin B1 down-regulation and the loss of nuclear envelope integrity. In the cytoplasm, CCFs were targeted by the autophagy machinery. Senescent cells exhibited markers of lysosomal-mediated proteolytic processing of histones and were progressively depleted of total histone content in a lysosome-dependent manner. In vivo, depletion of histones correlated with nevus maturation, an established histopathologic parameter associated with proliferation arrest and clinical benignancy. We conclude that senescent cells process their chromatin via an autophagy/lysosomal pathway and that this might contribute to stability of senescence and tumor suppression
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