346 research outputs found

    Stochastic Online Shortest Path Routing: The Value of Feedback

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    This paper studies online shortest path routing over multi-hop networks. Link costs or delays are time-varying and modeled by independent and identically distributed random processes, whose parameters are initially unknown. The parameters, and hence the optimal path, can only be estimated by routing packets through the network and observing the realized delays. Our aim is to find a routing policy that minimizes the regret (the cumulative difference of expected delay) between the path chosen by the policy and the unknown optimal path. We formulate the problem as a combinatorial bandit optimization problem and consider several scenarios that differ in where routing decisions are made and in the information available when making the decisions. For each scenario, we derive a tight asymptotic lower bound on the regret that has to be satisfied by any online routing policy. These bounds help us to understand the performance improvements we can expect when (i) taking routing decisions at each hop rather than at the source only, and (ii) observing per-link delays rather than end-to-end path delays. In particular, we show that (i) is of no use while (ii) can have a spectacular impact. Three algorithms, with a trade-off between computational complexity and performance, are proposed. The regret upper bounds of these algorithms improve over those of the existing algorithms, and they significantly outperform state-of-the-art algorithms in numerical experiments.Comment: 18 page

    Multiple sclerosis and psychiatric disorders : comorbidity and sibling risk in a nationwide Swedish cohort

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    Background: Psychiatric disorders are known to be prevalent in Multiple Sclerosis (MS). Objective: To study comorbidity between MS and bipolar disorder, schizophrenia and depression in a nation-wide cohort and to determine whether shared genetic liability underlies the putative association. Methods: We identified ICD-diagnosed patients with MS (n=16,467), bipolar disorder (n=30,761), schizophrenia (n= 22,781) and depression (n=172,479) in the Swedish National Patient Register and identified their siblings in the Multi-Generation Register. The risk of MS was compared in psychiatric patients and in matched unexposed individuals. Shared familial risk between MS and psychiatric disorders was estimated by sibling comparison. Results: The risk of MS was increased in patients with bipolar disorder (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.6-2.2, p<0.0001) and depression (HR 1.9, 95% CI 1.7-2.0, p<0.0001). MS risk in schizophrenia was decreased (HR 0.6, 95% CI 0.4-0.9, p=0.005). The association between having a sibling with a psychiatric disorder and developing MS was not significant. Conclusion: We found a strong positive association between MS and bipolar disorder and depression that could not be explained by genetic liability. The unexpected negative association between MS and schizophrenia might be spurious or indicate possible protective mechanisms that warrant further exploration.Stockholm County CouncilThe Swedish Research CouncilKarolinska InstitutetAccepte

    Cerebrospinal fluid microglia and neurodegenerative markers in twins concordant and discordant for psychotic disorders

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    International audienceThe jacket type offshore wind turbine transfers efficiently the horizontal load applied on the wind turbine to an axial load on the four piles of its foundation. The axial behaviour of one single pile of the foundation is investigated in a geotechnical centrifuge. The model pile, tested under a 100 g centrifuge acceleration, is designed to represent a cast-in-place pile with a 1.8 m diameter and a 40 m embedded length. The pile, installed in dense Fontainebleau sand, is instrumented with a load sensor at its end to measure the tip resistance. By subtracting the total load applied on the pile, its shaft capacity is also calculated. Different axial loading paths are applied: i) monotonic loadings in compression and tension to obtain ultimate capacities and ii) cyclic loadings which represent a more realistic loading path applied by the jacket during its life time in order to observe the tip and shaft capacities reductions

    Full genome re-sequencing reveals a novel circadian clock mutation in Arabidopsis

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    Map based cloning in Arabidopsis thaliana can be a difficult and time-consuming process, specifically if the phenotype is subtle and scoring labour intensive. Here, we have re-sequenced the 120-Mb genome of a novel Arabidopsis clock mutant early bird (ebi-1) in Wassilewskija (Ws-2). We demonstrate the utility of sequencing a backcrossed line in limiting the number of SNPs considered. We identify a SNP in the gene AtNFXL-2 as the likely cause of the ebi-1 phenotype

    Sub-millimeter Observations of Giant Molecular Clouds in the Large Magellanic Cloud: Temperature and Density as Determined from J=3-2 and J=1-0 transitions of CO

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    We have carried out sub-mm 12CO(J=3-2) observations of 6 giant molecular clouds (GMCs) in the Large Magellanic Cloud (LMC) with the ASTE 10m sub-mm telescope at a spatial resolution of 5 pc and very high sensitivity. We have identified 32 molecular clumps in the GMCs and revealed significant details of the warm and dense molecular gas with n(H2) \sim 1035^{3-5} cm3^{-3} and Tkin \sim 60 K. These data are combined with 12CO(J=1-0) and 13CO(J=1-0) results and compared with LVG calculations. We found that the ratio of 12CO(J=3-2) to 12CO(J=1-0) emission is sensitive to and is well correlated with the local Halpha flux. We interpret that differences of clump propeties represent an evolutionary sequence of GMCs in terms of density increase leading to star formation.Type I and II GMCs (starless GMCs and GMCs with HII regions only, respectively) are at the young phase of star formation where density does not yet become high enough to show active star formation and Type III GMCs (GMCs with HII regions and young star clusters) represents the later phase where the average density is increased and the GMCs are forming massive stars. The high kinetic temperature correlated with \Halpha flux suggests that FUV heating is dominant in the molecular gas of the LMC.Comment: 74 pages, including 41 figures, accepted for publication in ApJ

    Exploring the Biochemical Foundations of a Successful GLUT1-Targeting Strategy to BNCT: Chemical Synthesis and In Vitro Evaluation of the Entire Positional Isomer Library of ortho-Carboranylmethyl-Bearing Glucoconjugates

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    Boron neutron capture therapy (BNCT) is a noninvasive binary therapeutic modality applicable to the treatment of cancers. While BNCT offers a tumor-targeting selectivity that is difficult to match by other means, the last obstacles preventing the full harness of this potential come in the form of the suboptimal boron delivery strategies presently used in the clinics. To address these challenges, we have developed delivery agents that target the glucose transporter GLUT1. Here, we present the chemical synthesis of a number of ortho-carboranylmethyl-substituted glucoconjugates and the biological assessment of all positional isomers. Altogether, the study provides protocols for the synthesis and structural characterization of such glucoconjugates and insights into their essential properties, for example, cytotoxicity, GLUT1-affinity, metabolism, and boron delivery capacity. In addition to solidifying the biochemical foundations of a successful GLUT1-targeting approach to BNCT, we identify the most promising modification sites in d-glucose, which are critical in order to further develop this strategy toward clinical use.Peer reviewe

    Project Status of the Polish Synchrotron Radiation Facility Solaris

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    Abstract in Undetermined The Polish synchrotron radiation facility Solaris is being built at the Jagiellonian University in Krakow. The project is based on an identical copy of the 1.5 GeV storage ring being concurrently built for the MAX IV project in Lund, Sweden. A general description of the facility is given together with a status of activities. Unique features associated with Solaris are outlined, such as infrastructure, the injector and operational characteristics

    Assessment of the EarlyCDT-Lung test as an early biomarker of lung cancer in ever-smokers: A retrospective nested case-control study in two prospective cohorts

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    The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample <3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT-Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT-Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI: 0.34-2.30) for a moderate risk EarlyCDT-Lung test result and 1.09 (95% CI: 0.48-2.47) for a high-risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI: 4.6-14) and overall specificity was 92% (95% CI: 87-96) when considering a high-risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI: 7.2-32.1) in subjects with blood drawn up to 1 year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT-Lung test in identifying the high-risk subjects in ever-smokers for lung cancer screening in the EPIC and NSHDS cohorts

    The Expression of BAFF, APRIL and TWEAK Is Altered in Eczema Skin but Not in the Circulation of Atopic and Seborrheic Eczema Patients

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    The TNF family cytokines BAFF (B-cell activating factor of the TNF family) and APRIL (a proliferation-inducing ligand) are crucial survival factors for B-cell development and activation. B-cell directed treatments have been shown to improve atopic eczema (AE), suggesting the involvement of these cytokines in the pathogenesis of AE. We therefore analyzed the expression of these TNF cytokines in AE, seborrheic eczema (SE) and healthy controls (HC). The serum/plasma concentration of BAFF, APRIL and a close TNF member TWEAK (TNF-like weak inducer of apoptosis) was measured by ELISA. The expression of these cytokines and their receptors in skin was analyzed by quantitative RT-PCR and immunofluorescence. Unlike other inflammatory diseases including autoimmune diseases and asthma, the circulating levels of BAFF, APRIL and TWEAK were not elevated in AE or SE patients compared with HCs and did not correlate with the disease severity or systemic IgE levels in AE patients. Interestingly, we found that the expression of these cytokines and their receptors was altered in positive atopy patch test reactions in AE patients (APT-AE) and in lesional skin of AE and SE patients. The expression of APRIL was decreased and the expression of BAFF was increased in eczema skin of AE and SE, which could contribute to a reduced negative regulatory input on B-cells. This was found to be more pronounced in APT-AE, the initiating acute stage of AE, which may result in dysregulation of over-activated B-cells. Furthermore, the expression levels of TWEAK and its receptor positively correlated to each other in SE lesions, but inversely correlated in AE lesions. These results shed light on potential pathogenic roles of these TNF factors in AE and SE, and pinpoint a potential of tailored treatments towards these factors in AE and SE
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