2,729 research outputs found

    Criminal Law and Procedure

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    This Article surveys recent developments in criminal procedure and law in Virginia. Because of space limitations, the authors have limited their discussion to the most significant appellate decisions and legislation

    Criminal Law and Procedure

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    This article surveys recent developments in criminal law and procedure in Virginia. Because of space limitations, the authors have limited their discussion to the most significant appellate decisions and legislation

    Modeling and Optimal Design of Machining-Induced Residual Stresses in Aluminium Alloys Using a Fast Hierarchical Multiobjective Optimization Algorithm

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    The residual stresses induced during shaping and machining play an important role in determining the integrity and durability of metal components. An important issue of producing safety critical components is to find the machining parameters that create compressive surface stresses or minimise tensile surface stresses. In this paper, a systematic data-driven fuzzy modelling methodology is proposed, which allows constructing transparent fuzzy models considering both accuracy and interpretability attributes of fuzzy systems. The new method employs a hierarchical optimisation structure to improve the modelling efficiency, where two learning mechanisms cooperate together: NSGA-II is used to improve the model’s structure while the gradient descent method is used to optimise the numerical parameters. This hybrid approach is then successfully applied to the problem that concerns the prediction of machining induced residual stresses in aerospace aluminium alloys. Based on the developed reliable prediction models, NSGA-II is further applied to the multi-objective optimal design of aluminium alloys in a β€˜reverse-engineering’ fashion. It is revealed that the optimal machining regimes to minimise the residual stress and the machining cost simultaneously can be successfully located

    The yeast lgl family member Sro7p is an effector of the secretory Rab GTPase Sec4p

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    Rab guanosine triphosphatases regulate intracellular membrane traffic by binding specific effector proteins. The yeast Rab Sec4p plays multiple roles in the polarized transport of post-Golgi vesicles to, and their subsequent fusion with, the plasma membrane, suggesting the involvement of several effectors. Yet, only one Sec4p effector has been documented to date: the exocyst protein Sec15p. The exocyst is an octameric protein complex required for tethering secretory vesicles, which is a prerequisite for membrane fusion. In this study, we describe the identification of a second Sec4p effector, Sro7p, which is a member of the lethal giant larvae tumor suppressor family. Sec4-GTP binds to Sro7p in cell extracts as well as to purified Sro7p, and the two proteins can be coimmunoprecipitated. Furthermore, we demonstrate the formation of a ternary complex of Sec4-GTP, Sro7p, and the t-SNARE Sec9p. Genetic data support our conclusion that Sro7p functions downstream of Sec4p and further imply that Sro7p and the exocyst share partially overlapping functions, possibly in SNARE regulation

    Transcriptional and Proteomic Analysis of a Ferric Uptake Regulator (Fur) Mutant of Shewanella oneidensis: Possible Involvement of Fur in Energy Metabolism, Transcriptional Regulation, and Oxidative Stress

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    The iron-directed, coordinate regulation of genes depends on the fur (ferric uptake regulator) gene product, which acts as an iron-responsive, transcriptional repressor protein. To investigate the biological function of a fur homolog in the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1, a fur knockout strain (FUR1) was generated by suicide plasmid integration into this gene and characterized using phenotype assays, DNA microarrays containing 691 arrayed genes, and two-dimensional polyacrylamide gel electrophoresis. Physiological studies indicated that FUR1 was similar to the wild-type strain when they were compared for anaerobic growth and reduction of various electron acceptors. Transcription profiling, however, revealed that genes with predicted functions in electron transport, energy metabolism, transcriptional regulation, and oxidative stress protection were either repressed (ccoNQ, etrA, cytochrome b and c maturation-encoding genes, qor, yiaY, sodB, rpoH, phoB, and chvI) or induced (yggW, pdhC, prpC, aceE, fdhD, and ppc) in the fur mutant. Disruption of fur also resulted in derepression of genes (hxuC, alcC, fhuA, hemR, irgA, and ompW) putatively involved in iron uptake. This agreed with the finding that the fur mutant produced threefold-higher levels of siderophore than the wild-type strain under conditions of sufficient iron. Analysis of a subset of the FUR1 proteome (i.e., primarily soluble cytoplasmic and periplasmic proteins) indicated that 11 major protein species reproducibly showed significant (P < 0.05) differences in abundance relative to the wild type. Protein identification using mass spectrometry indicated that the expression of two of these proteins (SodB and AlcC) correlated with the microarray data. These results suggest a possible regulatory role of S. oneidensis MR-1 Fur in energy metabolism that extends the traditional model of Fur as a negative regulator of iron acquisition systems

    Improving a Dental School\u27s Clinic Operations Using Lean Process Improvement

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    The term lean production, also known as Lean, describes a process of operations management pioneered at the Toyota Motor Company that contributed significantly to the success of the company. Although developed by Toyota, the Lean process has been implemented at many other organizations, including those in health care, and should be considered by dental schools in evaluating their clinical operations. Lean combines engineering principles with operations management and improvement tools to optimize business and operating processes. One of the core concepts is relentless elimination of waste (non-value-added components of a process). Another key concept is utilization of individuals closest to the actual work to analyze and improve the process. When the medical center of the University of Kentucky adopted the Lean process for improving clinical operations, members of the College of Dentistry trained in the process applied the techniques to improve inefficient operations at the Walk-In Dental Clinic. The purpose of this project was to reduce patients\u27 average in-the-door-to-out-the-door time from over four hours to three hours within 90 days. Achievement of this goal was realized by streamlining patient flow and strategically relocating key phases of the process. This initiative resulted in patient benefits such as shortening average in-the-door-to-out-the-door time by over an hour, improving satisfaction by 21%, and reducing negative comments by 24%, as well as providing opportunity to implement the electronic health record, improving teamwork, and enhancing educational experiences for students. These benefits were achieved while maintaining high-quality patient care with zero adverse outcomes during and two years following the process improvement project

    Development and Performance of the Nanoworkbench: A Four Tip STM for Electrical Conductivity Measurements Down to Sub-micrometer Scales

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    A multiple-tip ultra-high vacuum (UHV) scanning tunneling microscope (MT-STM) with a scanning electron microscope (SEM) for imaging and molecular-beam epitaxy growth capabilities has been developed. This instrument (nanoworkbench) is used to perform four-point probe conductivity measurements at micrometer spatial dimension. The system is composed of four chambers, the multiple-tip STM/SEM chamber, a surface analysis and preparation chamber, a molecular-beam epitaxy chamber and a load-lock chamber for fast transfer of samples and probes. The four chambers are interconnected by a unique transfer system based on a sample box with integrated heating and temperature-measuring capabilities. We demonstrate the operation and the performance of the nanoworkbench with STM imaging on graphite and with four-point-probe conductivity measurements on a silicon-on-insulator (SOI) crystal. The creation of a local FET, whose dimension and localization are respectively determined by the spacing between the probes and their position on the SOI surface, is demonstrated.Comment: 39 pages, 15 figure

    A separable domain of the p150 subunit of human Chromatin Assembly Factor-1 promotes protein and chromosome associations with nucleoli

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    Chromatin Assembly Factor-1 (CAF-1) is a three-subunit protein complex conserved throughout eukaryotes that deposits histones during DNA synthesis. Here, we present a novel role for the human p150 subunit in regulating nucleolar macromolecular interactions. Acute depletion of p150 causes redistribution of multiple nucleolar proteins and reduces nucleolar association with several repetitive element-containing loci. Notably, a point mutation in a SUMO-interacting motif (SIM) within p150 abolishes nucleolar associations, whereas PCNA or HP1 interaction sites within p150 are not required for these interactions. Additionally, acute depletion of SUMO-2 or the SUMO E2 ligase Ubc9 reduces alpha-satellite DNA association with nucleoli. The nucleolar functions of p150 are separable from its interactions with the other subunits of the CAF-1 complex, because an N-terminal fragment of p150 (p150N) that cannot interact with other CAF-1 subunits is sufficient for maintaining nucleolar chromosome and protein associations. Therefore, these data define novel functions for a separable domain of the p150 protein, regulating protein and DNA interactions at the nucleolus

    The Clp1/Cdc14 phosphatase contributes to the robustness of cytokinesis by association with anillin-related Mid1

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    Cdc14 phosphatases antagonize cyclin-dependent kinase–directed phosphorylation events and are involved in several facets of cell cycle control. We investigate the role of the fission yeast Cdc14 homologue Clp1/Flp1 in cytokinesis. We find that Clp1/Flp1 is tethered at the contractile ring (CR) through its association with anillin-related Mid1. Fluorescent recovery after photobleaching analyses indicate that Mid1, unlike other tested CR components, is anchored at the cell midzone, and this physical property is likely to account for its scaffolding role. By generating a mutation in mid1 that selectively disrupts Clp1/Flp1 tethering, we reveal the specific functional consequences of Clp1/Flp1 activity at the CR, including dephosphorylation of the essential CR component Cdc15, reductions in CR protein mobility, and CR resistance to mild perturbation. Our evidence indicates that Clp1/Flp1 must interact with the Mid1 scaffold to ensure the fidelity of Schizosaccharomyces pombe cytokinesis
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