290 research outputs found

    Biphasic anaphylaxis: a systematic review of the literature

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    Conformal Maxwell theory as a singleton field theory on AdS_5, IIB three-branes and duality

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    We examine the boundary conditions associated with extended supersymmetric Maxwell theory in 5-dimensional anti-De Sitter space. Excitations on the boundary are identical to those of ordinary 4-dimensional conformal invariant super electrodynammics. Extrapolations of these excitations give rise to a 5-dimensional topological gauge theory of the singleton type. The possibility of a connection of this phenomenon to the world volume theory of 3-branes in IIB string theory is discussed.Comment: 19 pages, TeX, no figures; v2: misprints corrected, references added, discussion on Chern-Simons couplings revised. v3: References added, misprints corrected and a discussion in section 2 revised. v4: Typos corrected and reference adde

    Focal Adhesion Kinase-mediated Phosphorylation of Beclin1 Protein Suppresses Cardiomyocyte Autophagy and Initiates Hypertrophic Growth

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    Autophagy is an evolutionarily conserved intracellular degradation/recycling system that is essential for cellular homeostasis but is dysregulated in a number of diseases, including myocardial hypertrophy. Although it is clear that limiting or accelerating autophagic flux can result in pathological cardiac remodeling, the physiological signaling pathways that fine-tune cardiac autophagy are poorly understood. Herein, we demonstrated that stimulation of cardiomyocytes with phenylephrine (PE), a well known hypertrophic agonist, suppresses autophagy and that activation of focal adhesion kinase (FAK) is necessary for PE-stimulated autophagy suppression and subsequent initiation of hypertrophic growth. Mechanistically, we showed that FAK phosphorylates Beclin1, a core autophagy protein, on Tyr-233 and that this post-translational modification limits Beclin1 association with Atg14L and reduces Beclin1-dependent autophagosome formation. Remarkably, although ectopic expression of wild-type Beclin1 promoted cardiomyocyte atrophy, expression of a Y233E phosphomimetic variant of Beclin1 failed to affect cardiomyocyte size. Moreover, genetic depletion of Beclin1 attenuated PE-mediated/FAK-dependent initiation of myocyte hypertrophy in vivo. Collectively, these findings identify FAK as a novel negative regulator of Beclin1-mediated autophagy and indicate that this pathway can facilitate the promotion of compensatory hypertrophic growth. This novel mechanism to limit Beclin1 activity has important implications for treating a variety of pathologies associated with altered autophagic flux

    In search of dying radio sources in the local universe

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    Up till now very few dying sources were known, presumably because the dying phase is short at centimeter wavelengths. We therefore have tried to improve the statistics on sources that have ceased to be active, or are intermittently active. The latter sources would partly consist of a fossil radio plasma left over from an earlier phase of activity, plus a recently restarted core and radio jets. Improving the statistics of dying sources will give us a better handle on the evolution of radio sources, in particular the frequency and time scales of radio activity. We have used the WENSS and NVSS surveys, in order to find sources with steep spectral indices, associated with nearby elliptical galaxies. In the cross correlation we presently used only unresolved sources, with flux densities at 1.4 GHz larger than 10 mJy. The eleven candidates thus obtained were observed with the VLA in various configurations, in order to confirm the steepness of the spectra, and to check whether active structures like flat-spectrum cores and jets are present, perhaps at low levels. We estimated the duration of the active and relic phases by modelling the integrated radio spectra using the standard models of spectral evolution. We have found six dying sources and three restarted sources, while the remaining two candidates remain unresolved also with the new VLA data and may be Compact Steep Spectrum sources, with an unusually steep spectrum. The typical age of the active phase, as derived by spectral fits, is in the range 10^7 - 10^8 years. For our sample of dying sources, the age of the relic phase is on average shorter by an order of magnitude than the active phase.Comment: 21 pages, 17 figures, accepted by A&A. For a version with high quality figures, see http://erg.ca.astro.it/preprints/dying2007

    Comparison of next generation sequencing technologies for transcriptome characterization

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    <p>Abstract</p> <p>Background</p> <p>We have developed a simulation approach to help determine the optimal mixture of sequencing methods for most complete and cost effective transcriptome sequencing. We compared simulation results for traditional capillary sequencing with "Next Generation" (NG) ultra high-throughput technologies. The simulation model was parameterized using mappings of 130,000 cDNA sequence reads to the <it>Arabidopsis </it>genome (NCBI Accession SRA008180.19). We also generated 454-GS20 sequences and <it>de novo </it>assemblies for the basal eudicot California poppy (<it>Eschscholzia californica</it>) and the magnoliid avocado (<it>Persea americana</it>) using a variety of methods for cDNA synthesis.</p> <p>Results</p> <p>The <it>Arabidopsis </it>reads tagged more than 15,000 genes, including new splice variants and extended UTR regions. Of the total 134,791 reads (13.8 MB), 119,518 (88.7%) mapped exactly to known exons, while 1,117 (0.8%) mapped to introns, 11,524 (8.6%) spanned annotated intron/exon boundaries, and 3,066 (2.3%) extended beyond the end of annotated UTRs. Sequence-based inference of relative gene expression levels correlated significantly with microarray data. As expected, NG sequencing of normalized libraries tagged more genes than non-normalized libraries, although non-normalized libraries yielded more full-length cDNA sequences. The <it>Arabidopsis </it>data were used to simulate additional rounds of NG and traditional EST sequencing, and various combinations of each. Our simulations suggest a combination of FLX and Solexa sequencing for optimal transcriptome coverage at modest cost. We have also developed ESTcalc <url>http://fgp.huck.psu.edu/NG_Sims/ngsim.pl</url>, an online webtool, which allows users to explore the results of this study by specifying individualized costs and sequencing characteristics.</p> <p>Conclusion</p> <p>NG sequencing technologies are a highly flexible set of platforms that can be scaled to suit different project goals. In terms of sequence coverage alone, the NG sequencing is a dramatic advance over capillary-based sequencing, but NG sequencing also presents significant challenges in assembly and sequence accuracy due to short read lengths, method-specific sequencing errors, and the absence of physical clones. These problems may be overcome by hybrid sequencing strategies using a mixture of sequencing methodologies, by new assemblers, and by sequencing more deeply. Sequencing and microarray outcomes from multiple experiments suggest that our simulator will be useful for guiding NG transcriptome sequencing projects in a wide range of organisms.</p

    Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease

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    Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4+ T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DP–restricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4+ T cells in CBD. These peptides possess aspartic and glutamic acid residues at p4 and p7, respectively, that surround the putative Be-binding site and cooperate with HLA-DP2 in Be coordination. Endogenous plexin A peptides and proteins, which share the core motif and are expressed in lung, also stimulate these TCRs. Be-loaded HLA-DP2–mimotope and HLA-DP2–plexin A4 tetramers detected high frequencies of CD4+ T cells specific for these ligands in all HLA-DP2+ CBD patients tested. Thus, our findings identify the first ligand for a CD4+ T cell involved in metal-induced hypersensitivity and suggest a unique role of these peptides in metal ion coordination and the generation of a common antigen specificity in CBD

    The Amborella genome: an evolutionary reference for plant biology

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    The nuclear genome sequence of Amborella trichopoda, the sister species to all other extant angiosperms, will be an exceptional resource for plant genomics

    Noncommutative Sp(2,R) Gauge Theories - A Field Theory Approach to Two-Time Physics

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    Phase-space and its relativistic extension is a natural space for realizing Sp(2,R) symmetry through canonical transformations. On a Dx2 dimensional covariant phase-space, we formulate noncommutative field theories, where Sp(2,R) plays a role as either a global or a gauge symmetry group. In both cases these field theories have potential applications, including certain aspects of string theories, M-theory, as well as quantum field theories. If interpreted as living in lower dimensions, these theories realize Poincare' symmetry linearly in a way consistent with causality and unitarity. In case Sp(2,R) is a gauge symmetry, we show that the spacetime signature is determined dynamically as (D-2,2). The resulting noncommutative Sp(2,R) gauge theory is proposed as a field theoretical formulation of two-time physics: classical field dynamics contains all known results of `two-time physics', including the reduction of physical spacetime from D to (D-2) dimensions, with the associated `holography' and `duality' properties. In particular, we show that the solution space of classical noncommutative field equations put all massless scalar, gauge, gravitational, and higher-spin fields in (D-2) dimensions on equal-footing, reminiscent of string excitations at zero and infinite tension limits.Comment: 32 pages, LaTe

    Superconformal symmetry and maximal supergravity in various dimensions

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    In this paper we explore the relation between conformal superalgebras with 64 supercharges and maximal supergravity theories in three, four and six dimensions using twistorial oscillator techniques. The massless fields of N=8 supergravity in four dimensions were shown to fit into a CPT-self-conjugate doubleton supermultiplet of the conformal superalgebra SU(2,2|8) a long time ago. We show that the fields of maximal supergravity in three dimensions can similarly be fitted into the super singleton multiplet of the conformal superalgebra OSp(16|4,R), which is related to the doubleton supermultiplet of SU(2,2|8) by dimensional reduction. Moreover, we construct the ultra-short supermultiplet of the six-dimensional conformal superalgebra OSp(8*|8) and show that its component fields can be organized in an on-shell superfield. The ultra-short OSp(8*|8) multiplet reduces to the doubleton supermultiplet of SU(2,2|8) upon dimensional reduction. We discuss the possibility of a chiral maximal (4,0) six-dimensional supergravity theory with USp(8) R-symmetry that reduces to maximal supergravity in four dimensions and is different from six-dimensional (2,2) maximal supergravity, whose fields cannot be fitted into a unitary supermultiplet of a simple conformal superalgebra. Such an interacting theory would be the gravitational analog of the (2,0) theory.Comment: 54 pages, PDFLaTeX, Section 5 and several references added. Version accepted for publication in JHE
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