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Involvement of Bruton's tyrosine kinase in FcepsilonRI-dependent mast cell degranulation and cytokine production.
We investigated the role of Bruton's tyrosine kinase (Btk) in FcepsilonRI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcepsilonRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcepsilonRI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in FcepsilonRI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild-type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of FcepsilonRI signal transduction in mast cells
High Energy Neutrinos from Quasars
We review and clarify the assumptions of our basic model for neutrino
production in the cores of quasars, as well as those modifications to the model
subsequently made by other workers. We also present a revised estimate of the
neutrino background flux and spectrum obtained using more recent empirical
studies of quasars and their evolution. We compare our results with other
thoeretical calculations and experimental upper limits on the AGN neutrino
background flux. We also estimate possible neutrino fluxes from the jets of
blazars detected recently by the EGRET experiment on the Compton Gamma Ray
Observatory. We discuss the theoretical implications of these estimates.Comment: 14 pg., ps file (includes figures), To be published in Space Science
Review
High Energy Gamma-Ray Emission From Blazars: EGRET Observations
We will present a summary of the observations of blazars by the Energetic
Gamma Ray Experiment Telescope (EGRET) on the Compton Gamma Ray Observatory
(CGRO). EGRET has detected high energy gamma-ray emission at energies greater
than 100 MeV from more that 50 blazars. These sources show inferred isotropic
luminosities as large as ergs s. One of the most
remarkable characteristics of the EGRET observations is that the gamma-ray
luminosity often dominates the bolometric power of the blazar. A few of the
blazars are seen to exhibit variability on very short time-scales of one day or
less. The combination of high luminosities and time variations seen in the
gamma-ray data indicate that gamma-rays are an important component of the
relativistic jet thought to characterize blazars. Currently most models for
blazars involve a beaming scenario. In leptonic models, where electrons are the
primary accelerated particles, gamma-ray emission is believed to be due to
inverse Compton scattering of low energy photons, although opinions differ as
to the source of the soft photons. Hardronic models involve secondary
production or photomeson production followed by pair cascades, and predict
associated neutrino production.Comment: 16 pages, 7 figures, style files included. Invited review paper in
"Observational Evidence for Black Holes in the Universe," 1999, ed. S. K.
Chakrabarti (Dordrecht: Kluwer), 215-23
Catalytic Roles of Flexible Regions at the Active Site of Ribulose-Bisphosphate Carboxylase/Oxygenase (Rubisco)
Chemical and mutagenesis studies of Rubisco have identified Lys329 and Glu48 as active-site residues that are located in distinct, interacting domains from adjacent subunits. Crystallographic analyses have shown that Lys329 is the apical residue in a 12-residue flexible loop (loop 6) of the {Beta},{alpha}-barrel domain of the active site and that Glu48 resides at the end of helix B of the N-terminal domain of the active site. When phosphorylated ligands are bound by the enzyme, loop 6 adopts a closed conformation and, in concert with repositioning of helix B, thereby occludes the active site from the external environment. In this closed conformation, the {gamma}-carboxylate of Glu48 and the {epsilon}-amino group of Lys329 engage in intersubunit electrostatic interaction. By use of appropriate site-directed mutants of Rhodospirillum rubrum Rubisco, we are addressing several issues: the catalytic roles of Lys329 and Glu48, the functional significance of the intersubunit salt bridge comprised of these two residues, and the roles of loop 6 and helix B in stabilizing labile reaction intermediates. Characterization of novel products derived from misprocessing of D-ribulose-1,5-bisphosphate (RuBP) by the mutant proteins have illuminated the structure of the key intermediate in the normal oxygenase pathway
GLAST: Understanding the High Energy Gamma-Ray Sky
We discuss the ability of the GLAST Large Area Telescope (LAT) to identify,
resolve, and study the high energy gamma-ray sky. Compared to previous
instruments the telescope will have greatly improved sensitivity and ability to
localize gamma-ray point sources. The ability to resolve the location and
identity of EGRET unidentified sources is described. We summarize the current
knowledge of the high energy gamma-ray sky and discuss the astrophysics of
known and some prospective classes of gamma-ray emitters. In addition, we also
describe the potential of GLAST to resolve old puzzles and to discover new
classes of sources.Comment: To appear in Cosmic Gamma Ray Sources, Kluwer ASSL Series, Edited by
K.S. Cheng and G.E. Romer
Using Genomic Sequencing for Classical Genetics in E. coli K12
We here develop computational methods to facilitate use of 454 whole genome shotgun sequencing to identify mutations in Escherichia coli K12. We had Roche sequence eight related strains derived as spontaneous mutants in a background without a whole genome sequence. They provided difference tables based on assembling each genome to reference strain E. coli MG1655 (NC_000913). Due to the evolutionary distance to MG1655, these contained a large number of both false negatives and positives. By manual analysis of the dataset, we detected all the known mutations (24 at nine locations) and identified and genetically confirmed new mutations necessary and sufficient for the phenotypes we had selected in four strains. We then had Roche assemble contigs de novo, which we further assembled to full-length pseudomolecules based on synteny with MG1655. This hybrid method facilitated detection of insertion mutations and allowed annotation from MG1655. After removing one genome with less than the optimal 20- to 30-fold sequence coverage, we identified 544 putative polymorphisms that included all of the known and selected mutations apart from insertions. Finally, we detected seven new mutations in a total of only 41 candidates by comparing single genomes to composite data for the remaining six and using a ranking system to penalize homopolymer sequencing and misassembly errors. An additional benefit of the analysis is a table of differences between MG1655 and a physiologically robust E. coli wild-type strain NCM3722. Both projects were greatly facilitated by use of comparative genomics tools in the CoGe software package (http://genomevolution.org/)
Оценка качества образования на основе компетентностного подхода
В работе представлен практический опыт оценки качества образования в новом формате компетентностного подход
How to construct and use a simple device to prevent the formation of precipitates when using Sudan Black B for histology
Leadership after virtue: MacIntyre’s critique of management reconsidered
MacIntyre argues that management embodies emotivism, and thus is inherently amoral and manipulative. His claim that management is necessarily Weberian is, at best, outdated, and the notion that management aims to be neutral and value free is incorrect. However, new forms of management, and in particular the increased emphasis on leadership which emerged after MacIntyre’s critique was published, tend to support his central charge. Indeed, charismatic and transformational forms of leadership seem to embody emotivism to a greater degree than do more Weberian, bureaucratic forms of management, so MacIntyre’s central contention about our emotivistic culture seems to be well-founded. Having criticised the details but defended the essence of MacIntyre’s critique of management, this paper sketches a MacIntyrean approach to management and leadership by highlighting the affinities between MacIntyre’s political philosophy and Greenleaf’s concept of servant leadership
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