3,627 research outputs found

    A leader election algorithm for dynamic networks with causal clocks

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    An algorithm for electing a leader in an asynchronous network with dynamically changing communication topology is presented. The algorithm ensures that, no matter what pattern of topology changes occurs, if topology changes cease, then eventually every connected component contains a unique leader. The algorithm combines ideas from the Temporally Ordered Routing Algorithm for mobile ad hoc networks (Park and Corson in Proceedings of the 16th IEEE Conference on Computer Communications (INFOCOM), pp. 1405–1413 (1997) with a wave algorithm (Tel in Introduction to distributed algorithms, 2nd edn. Cambridge University Press, Cambridge, MA, 2000), all within the framework of a height-based mechanism for reversing the logical direction of communication topology links (Gafni and Bertsekas in IEEE Trans Commun C–29(1), 11–18 1981). Moreover, a generic representation of time is used, which can be implemented using totally-ordered values that preserve the causality of events, such as logical clocks and perfect clocks. A correctness proof for the algorithm is provided, and it is ensured that in certain well-behaved situations, a new leader is not elected unnecessarily, that is, the algorithm satisfies a stability condition.National Science Foundation (U.S.) (0500265)Texas Higher Education Coordinating Board (ARP-00512-0007-2006)Texas Higher Education Coordinating Board (ARP 000512-0130-2007)National Science Foundation (U.S.) (IIS-0712911)National Science Foundation (U.S.) (CNS-0540631)National Science Foundation (U.S.) (Research Experience for Undergraduates (Program) (0649233)

    Site-Specific Cleavage by Topoisomerase 2: A Mark of the Core Centromere.

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    In addition to its roles in transcription and replication, topoisomerase 2 (topo 2) is crucial in shaping mitotic chromosomes and in ensuring the orderly separation of sister chromatids. As well as its recruitment throughout the length of the mitotic chromosome, topo 2 accumulates at the primary constriction. Here, following cohesin release, the enzymatic activity of topo 2 acts to remove residual sister catenations. Intriguingly, topo 2 does not bind and cleave all sites in the genome equally; one preferred site of cleavage is within the core centromere. Discrete topo 2-centromeric cleavage sites have been identified in α-satellite DNA arrays of active human centromeres and in the centromere regions of some protozoans. In this study, we show that topo 2 cleavage sites are also a feature of the centromere in Schizosaccharomyces pombe, the metazoan Drosophila melanogaster and in another vertebrate species, Gallus gallus (chicken). In vertebrates, we show that this site-specific cleavage is diminished by depletion of CENP-I, an essential constitutive centromere protein. The presence, within the core centromere of a wide range of eukaryotes, of precise sites hypersensitive to topo 2 cleavage suggests that these mark a fundamental and conserved aspect of this functional domain, such as a non-canonical secondary structure

    1.6 W continuous-wave Raman laser using low-loss synthetic diamond

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    Low-birefringence (Δn<2x10−6), low-loss (absorption coefficient <0.006cm−1 at 1064nm), single-crystal, synthetic diamond has been exploited in a CW Raman laser. The diamond Raman laser was intracavity pumped within a Nd:YVO4 laser. At the Raman laser wavelength of 1240nm, CW output powers of 1.6W and a slope efficiency with respect to the absorbed diode-laser pump power (at 808nm) of ~18% were measured. In quasi-CW operation, maximum on-time output powers of 2.8W (slope efficiency ~24%) were observed, resulting in an absorbed diode-laser pump power to the Raman laser output power conversion efficiency of 13%

    Continuous-wave Raman laser pumped within a semiconductor disk laser cavity

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    A KGd(WO4)(2) Raman laser was pumped within the cavity of a cw diode-pumped InGaAs semiconductor disk laser (SDL). The Raman laser threshold was reached for 5: 6W of absorbed diode pump power, and output power up to 0.8W at 1143nm, with optical conversion efficiency of 7.5% with respect to the absorbed diode pump power, was demonstrated. Tuning the SDL resulted in tuning of the Raman laser output between 1133 and 1157nm

    Longitudinal relations of television, electronic games, and digital versatile discs with changes in diet in adolescents 1 , 2 , 3

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    BackgroundYouth spend more time with screens than any activity except sleeping. Screen time is a risk factor for obesity, possibly because of the influence of food and beverage advertising on diet.ObjectiveWe sought to assess longitudinal relations of screen time [ie, television, electronic games, digital versatile discs (DVDs)/videos, and total screen time] with the 2-y changes in consumption of foods of low nutritional quality (FLNQ) that are commonly advertised on screens [ie, sugar-sweetened beverages, fast food, sweets, salty snacks, and the sum of these foods (total FLNQ)] and fruit and vegetables.DesignWith the use of 2004, 2006, and 2008 waves of the Growing Up Today Study II, which consisted of a cohort of 6002 female and 4917 male adolescents aged 9-16 y in 2004, we assessed screen time (change and baseline) in relation to the 2-y dietary changes. Regression models included 4604 girls and 3668 boys with complete screen time and diet data on ≄2 consecutive questionnaires.ResultsEach hour-per-day increase in television, electronic games, and DVDs/videos was associated with increased intake of total FLNQ (range: 0.10-0.28 servings/d; P &lt; 0.05). Each hour-per-day increase in total screen time predicted increased intakes of sugar-sweetened beverages, fast food, sweets, and salty snacks (range: 0.02-0.06 servings/d; P &lt; 0.001) and decreased intakes of fruit and vegetables (range: -0.05 to -0.02 servings/d; P &lt; 0.05). Greater screen time at baseline (except electronic games in boys) was associated with subsequent increased intake of total FLNQ, and greater screen time at baseline (except DVDs/videos) was associated with decreased intake of fruit and vegetables (P &lt; 0.05). Across sex and food groups and in sensitivity analyses, television was most consistently associated with dietary changes.ConclusionsIncreases in screen time were associated with increased consumption of foods and beverages of low nutritional quality and decreased consumption of fruit and vegetables. Our results caution against excessive use of screen media, especially television, in youth

    De novo design of bioactive protein switches.

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    Allosteric regulation of protein function is widespread in biology, but is challenging for de novo protein design as it requires the explicit design of multiple states with comparable free energies. Here we explore the possibility of designing switchable protein systems de novo, through the modulation of competing inter- and intramolecular interactions. We design a static, five-helix 'cage' with a single interface that can interact either intramolecularly with a terminal 'latch' helix or intermolecularly with a peptide 'key'. Encoded on the latch are functional motifs for binding, degradation or nuclear export that function only when the key displaces the latch from the cage. We describe orthogonal cage-key systems that function in vitro, in yeast and in mammalian cells with up to 40-fold activation of function by key. The ability to design switchable protein functions that are controlled by induced conformational change is a milestone for de novo protein design, and opens up new avenues for synthetic biology and cell engineering

    Probiotic \u3ci\u3eBifidobacterium\u3c/i\u3e strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics

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    Background: One way to improve both the ecological performance and functionality of probiotic bacteria is by combining them with a prebiotic in the form of a synbiotic. However, the degree to which such synbiotic formulations improve probiotic strain functionality in humans has not been tested systematically. Our goal was to use a randomized, double-blind, placebo-controlled, parallel-arm clinical trial in obese humans to compare the ecological and physiological impact of the prebiotic galactooligosaccharides (GOS) and the probiotic strains Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous to the human gut) when used on their own or as synbiotic combinations. After 3 weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA gene sequencing were performed on fecal samples to assess changes in the microbiota. Intestinal permeability was determined by measuring sugar recovery in urine by GC after consumption of a sugar mixture. Serum-based endotoxin exposure was also assessed. Results: IVS-1 reached significantly higher cell numbers in fecal samples than BB-12 (P \u3c 0.01) and, remarkably, its administration induced an increase in total bifidobacteria that was comparable to that of GOS. Although GOS showed a clear bifidogenic effect on the resident gut microbiota, both probiotic strains showed only a non-significant trend of higher fecal cell numbers when administered with GOS. Post-aspirin sucralose:lactulose ratios were reduced in groups IVS-1 (P = 0.050), IVS-1 + GOS (P = 0.022), and GOS (P = 0.010), while sucralose excretion was reduced with BB-12 (P = 0.002) and GOS (P = 0.020), indicating improvements in colonic permeability but no synergistic effects. No changes in markers of endotoxemia were observed. Conclusion: This study demonstrated that “autochthony” of the probiotic strain has a larger effect on ecological performance than the provision of a prebiotic substrate, likely due to competitive interactions with members of the resident microbiota. Although the synbiotic combinations tested in this study did not demonstrate functional synergism, our findings clearly showed that the pro- and prebiotic components by themselves improved markers of colonic permeability, providing a rational for their use in pathologies with an underlying leakiness of the gut

    Effects of Changes in Adiposity and Physical Activity on Preadolescent Insulin Resistance: The Australian LOOK Longitudinal Study

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    BACKGROUND In a previous longitudinal analysis of our cohort as 8 to 10 year-olds, insulin resistance (IR) increased with age, but was not modified by changes in percent body fat (%BF), and was only responsive to changes in physical activity (PA) in boys. We aimed to determine whether these responses persisted as the children approached adolescence. METHODS In this prospective cohort study, 256 boys and 278 girls were assessed at ages 8, 10 and 12 years for fasting blood glucose and insulin, %BF (dual energy X-ray absorptiometry); PA (7-day pedometers), fitness (multistage run); and pubertal development (Tanner stage). RESULTS From age 8 to 12 years, the median homeostatic model of IR (HOMA-IR) doubled in boys and increased 250% in girls. By age 12, 23% of boys and 31% of girls had elevated IR, as indicated by HOMA-IR greater than 3. Longitudinal relationships, with important adjustments for covariates body weight, PA, %BF, Tanner score and socioeconomic status showed that, on average, for every 1 unit reduction of %BF, HOMA-IR was lowered by 2.2% (95% CI 0.04-4) in girls and 1.6% (95% CI 0-3.2) in boys. Furthermore, in boys but not girls, HOMA-IR was decreased by 3.5% (95%CI 0.5-6.5) if PA was increased by 2100 steps/day. CONCLUSION Evidence that a quarter of our apparently healthy 12 year-old Australians possessed elevated IR suggests that community-based education and prevention strategies may be warranted. Responsiveness of IR to changes in %BF in both sexes during late preadolescence and to changes in PA in the boys provides a specific basis for targeting elevated IR. That body weight was a strong covariate of IR, independent of %BF, points to the importance of adjusting for weight in correctly assessing these relationships in growing children.Financial support was provided by the Commonwealth Education Trust (London, UK), the Board of Trustees and The Canberra Hospital Salaried Staff Specialists Private Practice Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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