1,602 research outputs found

    The ChIP-seq-defined networks of Bcl-3 gene binding support its required role in skeletal muscle atrophy

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    NF-kappaB transcriptional activation is required for skeletal muscle disuse atrophy. We are continuing to study how the activation of NF-kB regulates the genes that encode the protein products that cause atrophy. Using ChIP-sequencing we found that Bcl-3, an NF-kB transcriptional activator required for atrophy, binds to the promoters of a number of genes whose collective function describes two major aspects of muscle wasting. By means of bioinformatics analysis of ChIP-sequencing data we found Bcl-3 to be directing transcription networks of proteolysis and energy metabolism. The proteolytic arm of the Bcl-3 networks includes many E3 ligases associated with proteasomal protein degradation, including that of the N-end rule pathway. The metabolic arm appears to be involved in organizing the change from oxidative phosphorylation to glycolysis in atrophying muscle. For one gene, MuRF1, ChIP-sequencing data identified the location of Bcl-3 and p50 binding in the promoter region which directed the creation of deletant and base-substitution mutations of MuRF1 promoter constructs to determine the effect on gene transcription. The results provide the first direct confirmation that the NF-kB binding site is involved in the muscle unloading regulation of MuRF1. Finally, we have combined the ChIP-sequencing results with gene expression microarray data from unloaded muscle to map several direct targets of Bcl-3 that are transcription factors whose own targets describe a set of indirect targets for NF-kB in atrophy. ChIP-sequencing provides the first molecular explanation for the finding that Bcl3 knockout mice are resistant to disuse muscle atrophy. Mapping the transcriptional regulation of muscle atrophy requires an unbiased analysis of the whole genome, which we show is now possible with ChIP-sequencing.R01 AR041705 - NIAMS NIH HHS; R01 AR060217 - NIAMS NIH HHS; AR041705 - NIAMS NIH HHS; AR060217 - NIAMS NIH HH

    Fuzzy Weighted Average: Analytical Solution

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    An algorithm is presented for the computation of analytical expressions for the extremal values of the α-cuts of the fuzzy weighted average, for triangular or trapeizoidal weights and attributes. Also, an algorithm for the computation of the inverses of these expressions is given, providing exact membership functions of the fuzzy weighted average. Up to now, only algorithms exist for the computation of the extremal values of the α-cuts for a fixed value of α. To illustrate the power of our algorithms, they are applied to several examples from the literature, providing exact membership functions in each case

    Comparison of Computational and Experimental Aerodynamics: Results for a WMU Solar Car Model

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    Three-dimensional numerical simulations using FLUENT [1] were performed to model the airflow over the Sunseeker, an award-winning solar car that was designed and built at Western Michigan University. Converged numerical solutions on three different grids are reported and compared with the available experimental data, which include the lift and the drag coefficients. Also reported are the results obtained by using the second-order upwinding discretization on one of the grids. The comparison shows that the computed lift coefficients agree well with the experimental data for all the three grids and the different orders of numerical methods, indicating that the pressure field is well captured. The agreement with the data for drag coefficient varies, which appears to suggest a higher degree of dependency on the grid distributions than that for the lift coefficient. These results are discussed in terms of their implications for the simulations of similar low-drag vehicles

    Preparative Synthesis of dTDP-L-Rhamnose Through Combined Enzymatic Pathways

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    dTDP-L-rhamnose, an important precursor of O-antigen, was prepared on a large scale from dTMP by executing an one-pot reaction in which six enzymes are involved. Two enzymes, dTDP-4-keto-6-deoxy-D-glucose 3,5-epimerase and dTDP-4-keto-rhamnose reductase, responsible for the conversion of dTDP-4-keto-6-deoxy- D-glucose to dTDP-L-rhamnose, were isolated from their putative sequences in the genome of Mesorhizobium loti, functionally expressed in Escherichia coli, and their enzymatic activities were identified. The two enzymes were combined with an enzymatic process for dTDP-4- keto-6-deoxy-D-glucose involving TMP kinase, acetate kinase, dTDP-glucose synthase, and dTDP-glucose 4,6- dehydratase, which allowed us to achieve a preparative scale synthesis of dTDP-L-rhamnose using dTMP and glucose-1-phosphate as starting materials. About 82% yield of dTDP-L-rhamnose was obtained based on initial dTMP concentration at 20 mM dTMP, 1 mM ATP, 10 mM NADH, 60 mM acetyl phosphate, and 80 mM glucose-1- phosphate. From the reaction with 20 ml volume, approximately 180 mg of dTDP-L-rhamnose was obtained in an overall yield of 60% after two-step purification, that is, anion exchange chromatography and gel filtration for desalting. The purified product was identifiedbyHPLC, ESI-MS,andNMR,showingabout95%purity

    Numerical and Experimental Analysis of the Powder Flow Streams in the Laser Aided Material Deposition Process

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    Axial powder stream concentration between the nozzle end and the deposition point is an important process parameter in the laser aided material deposition process. The powder concentration is greatly influenced by the nozzle geometry in use. This paper describes the numerical and experimental analysis of this important parameter in relation to the coaxial nozzle. The experiments are performed with the different nozzle geometries to generate various flow patterns of the gravity fed powder in a cold stream. The results of the experimental analysis are compared with the numerical simulation and found justified. These results are used in concluding the significance of important nozzle parameters for various powder concentration modes.Mechanical Engineerin

    Critical temperature for quenching of pair correlations

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    The level density at low spin in the 161,162-Dy and 171,172-Yb nuclei has been extracted from primary gamma rays. The nuclear heat capacity is deduced within the framework of the canonical ensemble. The heat capacity exhibits an S-formed shape as a function of temperature, which is interpreted as a fingerprint of the phase transition from a strongly correlated to an uncorrelated phase. The critical temperature for the quenching of pair correlations is found at Tc=0.50(4) MeV.Comment: 8 pages including 4 figures, different method to extract Tc, different figures, text partly rewritte

    Liouvillian gap and out-of-equilibrium dynamics of a sunburst Kitaev ring: from local to uniform dissipation

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    We consider an open quantum system composed of a (1+1)(1+1)-dimensional Kitaev ring coupled with the environment via nn particle-loss dissipators in a \textit{sunburst} geometry. We describe the out-of-equilibrium dynamics of the whole apparatus in terms of Lindblad master equations and focus on the scaling behavior of the Liovillian gap Δλ\Delta_\lambda with the system size LL. We unveil different regimes, which depend primarily on the number of dissipation sources considered in the large-size limit and the dissipation strength ww, which may be either fixed or attenuated to zero as w∼1/Lw\sim1/L. In the second part, we develop a dynamic Finite-Size Scaling framework close to Continuous Quantum Transitions to monitor the time evolution of the critical correlations and the entanglement entropy, emphasizing the role of Δλ\Delta_\lambda in this regime.Comment: 14 pages, 14 figure

    Experimental Investigation of Laser Metal Deposition of Functionally Graded Copper and Steel

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    Laser metal deposition is an emerging technology for producing fully dense metallic parts. This process shows a promising future for the deposition of functionally graded steel - copper alloys. Good thermal conductivity of copper and a high wear resistance of steel can be achieved in dies and cores. However, to accomplish this, there are many issues to be resolved, such as the formation of an undesirable phase, solidification cracking, porosity at the interface and difference in thermal coefficient of expansion between steel and copper. The influences of process variables, such as laser power, laser scan speed, composition, powder flow rate, on the success of the process, should be studied.Mechanical Engineerin
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