4,727 research outputs found

    Neighbor-Specific BGP: More Flexible Routing Policies While Improving Global Stability

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    Please Note: This document was written to summarize and facilitate discussion regarding (1) the benefits of changing the way BGP selects routes to selecting the most preferred route allowed by export policies, or more generally, to selecting BGP routes on a per-neighbor basis, (2) the safety condition that guarantees global routing stability under the Neighbor-Specific BGP model, and (3) ways of deploying this model in practice. A paper presenting the formal model and proof of the stability conditions was published at SIGMETRICS 2009 and is available online

    Phosphorylation of the Neurospora Clock Protein FREQUENCY Determines its Degradation Rate and Strongly Influences the Period Length of the Circadian Clock

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    Under free running conditions, FREQUENCY (FRQ) protein, a central component of the Neurospora circadian clock, is progressively phosphorylated, becoming highly phosphorylated before its degradation late in the circadian day. To understand the biological function of FRQ phosphorylation, kinase inhibitors were used to block FRQ phosphorylation in vivo and the effects on FRQ and the clock observed. 6-dimethylaminopurine (a general kinase inhibitor) is able to block FRQ phosphorylation in vivo, reducing the rate of phosphorylation and the degradation of FRQ and lengthening the period of the clock in a dose-dependent manner. To confirm the role of FRQ phosphorylation in this clock effect, phosphorylation sites in FRQ were identified by systematic mutagenesis of the FRQ ORF. The mutation of one phosphorylation site at Ser-513 leads to a dramatic reduction of the rate of FRQ degradation and a very long period (\u3e30 hr) of the clock. Taken together, these data strongly suggest that FRQ phosphorylation triggers its degradation, and the degradation rate of FRQ is a major determining factor for the period length of the Neurospora circadian clock

    Working Memory Network Connectivity and Inhibitory Control in Cocaine Use

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    Support exists for inhibitory control and working memory deficits among cocaine users. Existing literature suggests that working memory is central in successful inhibitory control, and that working memory processes may be best captured by examining network connectivity. This study examined whether working memory network connectivity mediates the relationship between group (cocaine users versus controls) and working memory performance, and group and inhibitory control performance. Participants completed working memory and inhibitory control tasks during functional magnetic resonance imaging. Cocaine users demonstrated poorer inhibitory control performance and reduced activation during the working memory task compared to controls. Working memory network connectivity did not account for group differences in working memory or inhibitory control performance. Specific connectivity between the right insula and inferior frontal gyrus and the right precuneus and inferior parietal lobule were significantly related to working memory and inhibitory performance, respectively, suggesting the role of attention and default mode network regulation.Master of Art

    Dynamic GATA4 enhancers shape the chromatin landscape central to heart development and disease.

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    How stage-specific enhancer dynamics modulate gene expression patterns essential for organ development, homeostasis and disease is not well understood. Here, we addressed this question by mapping chromatin occupancy of GATA4--a master cardiac transcription factor--in heart development and disease. We find that GATA4 binds and participates in establishing active chromatin regions by stimulating H3K27ac deposition, which facilitates GATA4-driven gene expression. GATA4 chromatin occupancy changes markedly between fetal and adult heart, with a limited binding sites overlap. Cardiac stress restored GATA4 occupancy to a subset of fetal sites, but many stress-associated GATA4 binding sites localized to loci not occupied by GATA4 during normal heart development. Collectively, our data show that dynamic, context-specific transcription factors occupancy underlies stage-specific events in development, homeostasis and disease

    Child Neglect and Its Association With Subsequent Juvenile Drug and Alcohol Offense

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    This study presents empirical findings about the association between childhood neglect and adolescents’ subsequent involvement with drug and alcohol related offense from a sample of 251 neglected children and their community matched control (N = 502) from a 17-year period longitudinal data set. Findings confirmed that neglected children were at greater risk to be arrested for later juvenile drug and alcohol offenses than non-neglected children. Being male, White and the presence of domestic violence also significantly contributed to elevated risks of being arrested for juvenile drug and alcohol violations for neglected children. Implications for practice and future research are discussed
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