756 research outputs found

    The Sobering Truth: The Seventh Circuit Categorizes Drunk Driving as a Violent Felony

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    The Armed Career Criminal Act ( ACCA ) supplements states’ law enforcement efforts against chronic violent offenders by substantially raising the penalty for armed criminals with past “violent felony” convictions. The ACCA defines the term “violent felony” by giving several specific examples and then adding a catch-all clause. One question that has continued to face courts since the ACCA’s enactment is what constitutes a violent felony under the catch-all clause. The Seventh Circuit recently categorized the offense of drunk driving as a “violent felony” under the catch-all clause and qualified drunk driving as a predicate act subject to recidivist sentence enhancement under the ACCA. In light of drunk driving’s non-violent nature, however, the Seventh Circuit’s expansion of the ACCA’s predicate acts blurs the distinction between crimes of violence and crimes of neglect and allows excessive penalties to be imposed on crimes that Congress did not intend for heightened punishment. This Comment examines the Seventh Circuit’s broad interpretation and concludes that the Seventh Circuit should not have enlarged the ACCA’s predicate acts to include negligent drunk driving

    Quantitative analysis of RET signaling dynamics and crosstalk

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    Most existing studies of receptor signaling are qualitative, which can lead scientists to misinterpret or overlook key information about the extent and timing of key events. To overcome these shortcomings, we have applied quantitative approaches to characterize receptor activation and signaling events. Most signaling studies focus on events occurring at a particular level in the system (e.g., on the membrane, at the level of phosphorylation of intracellular signaling molecules, or at the level of transcription). Instead, we are interested in taking a longitudinal view of signaling by achieving a quantitative understanding of a single signaling pathway from initial stimulation of the receptor by its growth factor (GF) ligand, through to gene expression, and functional cellular responses. As a model system for our studies, we used the growth factor receptor tyrosine kinase, REarranged during Transfection (RET), which requires a ligand and a glycosylphosphatidylinositol-anchored co-receptor for activation. RET mediates the response of cells to members of the glial cell-line derived neurotrophic factor (GDNF) family of neurotrophins, which are important in the development and maintenance of a subset of neuronal cells as well as in other cell types and tissues. We have characterized the molecular mechanisms of RET activation and signaling by pursuing the following four aims: 1) We developed a sensitive and robust luciferase reporter gene assay for RET signaling. 2) We characterized the dynamic relationship between receptor activation and downstream signaling events, including gene transcription and translation of three target genes. 3) We used the reporter gene assay, and other detection approaches, to test and quantify crosstalk between RET and other GF receptors. 4) We developed a FRET reporter system to enable monitoring of the assembly of the activated RET receptor complex on cells, as a means to distinguish between ligand-induced oligomerization and pre-associated oligomer mechanisms. Through these four aims, we have established new methods to quantitatively elucidate mechanisms of GF receptor activation, new insights into how signals are propagated from the receptor to the nucleus and into a functional response, and have established crosstalk between RET and other GF receptor pathways

    Using Jacobi iterations and blocking for solving sparse triangular systems in incomplete factorization preconditioning

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    When using incomplete factorization preconditioners with an iterative method to solve large sparse linear systems, each application of the preconditioner involves solving two sparse triangular systems. These triangular systems are challenging to solve efficiently on computers with high levels of concurrency. On such computers, it has recently been proposed to use Jacobi iterations, which are highly parallel, to approximately solve the triangular systems from incomplete factorizations. The effectiveness of this approach, however, is problem-dependent: the Jacobi iterations may not always converge quickly enough for all problems. Thus, as a necessary and important step to evaluate this approach, we experimentally test the approach on a large number of realistic symmetric positive definite problems. We also show that by using block Jacobi iterations, we can extend the range of problems for which such an approach can be effective. For block Jacobi iterations, it is essential for the blocking to be cognizant of the matrix structure

    Drosophila Bruce Can Potently Suppress Rpr- and Grim-Dependent but Not Hid-Dependent Cell Death

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    Bruce is a large protein (530 kDa) that contains an N-terminal baculovirus IAP repeat (BIR) and a C-terminal ubiquitin conjugation domain (E2) 1, 2. BRUCE upregulation occurs in some cancers and contributes to the resistance of these cells to DNA-damaging chemotherapeutic drugs [2]. However, it is still unknown whether Bruce inhibits apoptosis directly or instead plays some other more indirect role in mediating chemoresistance, perhaps by promoting drug export, decreasing the efficacy of DNA damage-dependent cell death signaling, or by promoting DNA repair. Here, we demonstrate, using gain-of-function and deletion alleles, that Drosophila Bruce (dBruce) can potently inhibit cell death induced by the essential Drosophila cell death activators Reaper (Rpr) and Grim but not Head involution defective (Hid). The dBruce BIR domain is not sufficient for this activity, and the E2 domain is likely required. dBruce does not promote Rpr or Grim degradation directly, but its antiapoptotic actions do require that their N termini, required for interaction with DIAP1 BIR2, be intact. dBruce does not block the activity of the apical cell death caspase Dronc or the proapoptotic Bcl-2 family member Debcl/Drob-1/dBorg-1/Dbok. Together, these results argue that dBruce can regulate cell death at a novel point

    Intentions to reciprocate vendor gifts amongst Malaysian purchasing executives

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    Business gift giving is a universal standard of conduct for most business oorganizations and industries (Beltramini 1992; Brenner and Molander 1977). Organizations use gift as means to show appreciation for past business and to influence the attitudes and behaviours of select, prestigious group of buyers in anticipation of future business (Meredith and Fried, 1977). Vendor gifts may serve as effective means of influencing customers or prospects. This research studied the effect of types of gift (personal or corporate gifts), cost of gift (expensive or inexpensive), and buyer-vendor relationship status (no relationship, moderate or strong) in relation to the buyers' (purchasing executives') feelings of indebtedness, perceived manipulations and intentions to reciprocate vendor's gifts
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