706 research outputs found
Going the Distance with Distance Learning: An analysis of Motivational Factors that Influence E-Learning Course Completion Rates
This research asked the following question: is there a correlation between types of organizational culture and factors influencing knowledge transfer? It hypothesized that organizations scoring high on the cultural factors of openness to change/innovation, and task-oriented organizational growth would be fertile to knowledge transfer. Second, it hypothesized that organizations scoring high on the factors of bureaucratic and competition/confrontation would be infertile to knowledge transfer. The research looked at Air Force squadrons, surveying a representative sample of the 1,495 active-duty squadrons included in the study with a 62-item, 5-point Likert-type instrument. Overall, 51 squadrons were surveyed, and 22 produced usable results. Both squadron and individual results were analyzed and both were similar. Squadron results showed that organizations scoring high on the factors of openness to change/innovation and task-oriented organizational growth appeared to score consistently high on three of the four measures of fertility to knowledge transfer. Organizations scoring high on the factors of competition/confrontation appeared to score consistently low on three of the four measures of fertility to knowledge transfer. The factor bureaucratic produced no significant correlations. In every case, the measure of fertility to knowledge transfer known as partner similarity did not behave as expected. The research concluded that there appears to be a correlation between organizational culture and factors influencing the transfer of knowledge, but concludes that the factors influencing the transfer of knowledge should be further explored, and a longitudinal study performed, before inferring any causal relationship
Correlated X-ray and Optical Variability in Mkn 509
We present results of a 3 year monitoring campaign of the Seyfert 1 galaxy
Markarian 509, using X-ray data from the Rossi X-ray Timing Explorer (RXTE) and
optical data taken by the SMARTS consortium. Both light curves show significant
variations, and are strongly correlated with the optical flux leading the X-ray
flux by 15 days. The X-ray power spectrum shows a steep high-frequency slope of
-2.0, breaking to a slope of -1.0 at at timescale of 34 days. The lag from
optical to X-ray emission is most likely caused by variations in the accretion
disk propagating inward.Comment: 13 pages, 3 figures. Accepted for publication in the Astrophysical
Journa
Improved hatchery and grow-out technology for marine finfish aquaculture in the Asia–Pacific region
This project focussed on improving marine finfish aquaculture production in the Asia-Pacific region by focussing on key constraints: improving hatchery technology to improve the availability of seedstock; evaluating the nutritional needs of groupers to support the development of compounded pellet diets; and improving communication and coordination of marine finfish aquaculture research and development activities in the Asia-Pacific region
Total Synthesis and Antimalarial Activity of 2-(-Hydroxybenzyl)-Prodigiosins, Isoheptylprodigiosin, and Geometric Isomers of Tambjamine MYP1 Isolated from Marine Bacteria.
Highly efficient and straightforward synthetic routes toward the first total synthesis of 2-(-hydroxybenzyl)-prodigiosins (-), isoheptylprodigiosin (), and geometric isomers of tambjamine MYP1 ((/)-) have been developed. The crucial steps involved in these synthetic routes are the construction of methoxy-bipyrrole-carboxaldehydes (MBCs) and a 20-membered macrocyclic core and a regioselective demethylation of MBC analogues. These new synthetic routes enabled us to generate several natural prodiginines - in larger quantity. All of the synthesized natural products exhibited potent asexual blood-stage antiplasmodial activity at low nanomolar concentrations against a panel of parasites, with a great therapeutic index. Notably, prodiginines and - provided curative in vivo efficacy against erythrocytic at 25 mg/kg × 4 days via oral route in a murine model. No overt clinical toxicity or behavioral change was observed in any mice treated with prodiginines and tambjamines
The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach
The calcitonin gene-related peptide (CGRP) receptor is a complex of a calcitonin receptor-like receptor (CLR), which is a family B G-protein-coupled receptor (GPCR) and receptor activity modifying protein 1. The role of the second extracellular loop (ECL2) of CLR in binding CGRP and coupling to Gs was investigated using a combination of mutagenesis and modelling. An alanine scan of residues 271–294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM). These data were used to select probable ECL2-modelled conformations that are involved in agonist binding, allowing the identification of the likely contacts between the peptide and receptor. The implications of the most likely structures for receptor activation are discussed.</jats:p
Probing Reactivity and Substrate Specificity of Both Subunits of the Dimeric \u3ci\u3eMycobacterium tuberculosis\u3c/i\u3e FabH Using alkyl-CoA Disulfide Inhibitors and acyl-CoA Substrates
The dimeric Mycobacterium tuberculosis FabH (mtFabH) catalyses a Claisen-type condensation between an acyl-CoA and malonyl-acyl carrier protein (ACP) to initiate the Type II fatty acid synthase cycle. To analyze the initial covalent acylation of mtFabH with acyl-CoA, we challenged it with mixture of C6-C20 acyl-CoAs and the ESI-MS analysis showed reaction at both subunits and a strict specificity for C12 acyl CoA. Crystallographic and ESI-MS studies of mtFabH with a decyl-CoA disulfide inhibitor revealed a decyl chain bound in acyl-binding channels of both subunits through disulfide linkage to the active site cysteine. These data provide the first unequivocal evidence that both subunits of mtFabH can react with substrates or inhibitor. The discrepancy between the observed C12 acyl-CoA substrate specificity in the initial acylation step and the higher catalytic efficiency of mtFabH for C18-C20 acyl-CoA substrates in the overall mtFabH catalyzed reaction suggests a role for M. tuberculosis ACP as a specificity determinant in this reaction
A computational model for microbial colonisation of an antifouling surface
Biofouling of marine surfaces such as ship hulls is a major industrial problem. Antifouling (AF) paints delay the onset of biofouling by releasing biocidal chemicals. We present a computational model for microbial colonization of a biocide-releasing AF surface. Our model accounts for random arrival from the ocean of microorganisms with different biocide resistance levels, biocide-dependent proliferation or killing, and a transition to a biofilm state. Our computer simulations support a picture in which biocide-resistant microorganisms initially form a loosely attached layer that eventually transitions to a growing biofilm. Once the growing biofilm is established, immigrating microorganisms are shielded from the biocide, allowing more biocide-susceptible strains to proliferate. In our model, colonization of the AF surface is highly stochastic. The waiting time before the biofilm establishes is exponentially distributed, suggesting a Poisson process. The waiting time depends exponentially on both the concentration of biocide at the surface and the rate of arrival of resistant microorganisms from the ocean. Taken together our results suggest that biofouling of AF surfaces may be intrinsically stochastic and hence unpredictable, but immigration of more biocide-resistant species, as well as the biological transition to biofilm physiology, may be important factors controlling the time to biofilm establishment
Separate Entrance and Exit Portals for Ligand Traffic in Mycobacterium tuberculosis FabH
SummaryMycobacterium tuberculosis FabH initiates type II fatty acid synthase-catalyzed formation of the long chain (C16–C22) acyl-coenzyme A (CoA) precursors of mycolic acids, which are major constituents of the bacterial cell envelope. Crystal structures of M. tuberculosis FabH (mtFabH) show the substrate binding site to be a buried, extended L-shaped channel with only a single solvent access portal. Entrance of an acyl-CoA substrate through the solvent portal would require energetically unfavorable reptational threading of the substrate to its reactive position. Using a class of FabH inhibitors, we have tested an alternative hypothesis that FabH exists in an “open” form during substrate binding and product release, and a “closed” form in which catalysis and intermediate steps occur. This hypothesis is supported by mass spectrometric analysis of the product profile and crystal structures of complexes of mtFabH with these inhibitors
Alkyl-CoA Disulfides as Inhibitors and Mechanistic Probes for FabH Enzymes
SummaryThe first step of the reaction catalyzed by the homodimeric FabH from a dissociated fatty acid synthase is acyl transfer from acyl-CoA to an active site cysteine. We report that C1 to C10 alkyl-CoA disulfides irreversibly inhibit Escherichia coli FabH (ecFabH) and Mycobacterium tuberculosis FabH with relative efficiencies that reflect these enzymes' differential acyl-group specificity. Crystallographic and kinetic studies with MeSSCoA show rapid inhibition of one monomer of ecFabH through formation of a methyl disulfide conjugate with this cysteine. Reaction of the second subunit with either MeSSCoA or acetyl-CoA is much slower. In the presence of malonyl-ACP, the acylation rate of the second subunit is restored to that of the native ecFabH. These observations suggest a catalytic model in which a structurally disordered apo-ecFabH dimer orders on binding either the first substrate, acetyl-CoA, or the inhibitor MeSSCoA, and is restored to a disordered state on binding of malonyl-ACP
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