3,104 research outputs found

    Bus Frequency Optimization: When Waiting Time Matters in User Satisfaction

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    Reorganizing bus frequency to cater for the actual travel demand can save the cost of the public transport system significantly. Many, if not all, existing studies formulate this as a bus frequency optimization problem which tries to minimize passengers' average waiting time. However, many investigations have confirmed that the user satisfaction drops faster as the waiting time increases. Consequently, this paper studies the bus frequency optimization problem considering the user satisfaction. Specifically, for the first time to our best knowledge, we study how to schedule the buses such that the total number of passengers who could receive their bus services within the waiting time threshold is maximized. We prove that this problem is NP-hard, and present an index-based algorithm with (11/e)(1-1/e) approximation ratio. By exploiting the locality property of routes in a bus network, we propose a partition-based greedy method which achieves a (1ρ)(11/e)(1-\rho)(1-1/e) approximation ratio. Then we propose a progressive partition-based greedy method to further improve the efficiency while achieving a (1ρ)(11/eε)(1-\rho)(1-1/e-\varepsilon) approximation ratio. Experiments on a real city-wide bus dataset in Singapore verify the efficiency, effectiveness, and scalability of our methods

    Local antiferromagnetic exchange and collaborative Fermi surface as key ingredients of high temperature superconductors

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    Cuprates, ferropnictides and ferrochalcogenides are three classes of unconventional high-temperature superconductors, who share similar phase diagrams in which superconductivity develops after a magnetic order is suppressed, suggesting a strong interplay between superconductivity and magnetism, although the exact picture of this interplay remains elusive. Here we show that there is a direct bridge connecting antiferromagnetic exchange interactions determined in the parent compounds of these materials to the superconducting gap functions observed in the corresponding superconducting materials. High superconducting transition temperature is achieved when the Fermi surface topology matches the form factor of the pairing symmetry favored by local magnetic exchange interactions. Our result offers a principle guide to search for new high temperature superconductors.Comment: 12 pages, 5 figures, 1 table, 1 supplementary materia

    Whole-genome association analysis of treatment response in obsessive-compulsive disorder.

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    Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed

    Activated K-ras and INK4a/Arf Deficiency Cooperate During the Development of Pancreatic Cancer by Activation of Notch and NF-κB Signaling Pathways

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    BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States, suggesting that novel strategies for the prevention and treatment of PDAC are urgently needed. K-ras mutations are observed in >90% of pancreatic cancer, suggesting its role in the initiation and early developmental stages of PDAC. In order to gain mechanistic insight as to the role of mutated K-ras, several mouse models have been developed by targeting a conditionally mutated K-ras(G12D) for recapitulating PDAC. A significant co-operativity has been shown in tumor development and metastasis in a compound mouse model with activated K-ras and Ink4a/Arf deficiency. However, the molecular mechanism(s) by which K-ras and Ink4a/Arf deficiency contribute to PDAC has not been fully elucidated. METHODOLOGY/PRINCIPAL FINDINGS:To assess the molecular mechanism(s) that are involved in the development of PDAC in the compound transgenic mice with activated K-ras and Ink4a/Arf deficiency, we used multiple methods, such as Real-time RT-PCR, western blotting assay, immunohistochemistry, MTT assay, invasion, EMSA and ELISA. We found that the deletion of Ink4a/Arf in K-ras(G12D) expressing mice leads to PDAC, which is in part mediated through the activation of Notch and NF-κB signaling pathways. Moreover, we found down-regulation of miR-200 family, which could also play important roles in tumor development and progression of PDAC in the compound transgenic mice. CONCLUSIONS/SIGNIFICANCE:Our results suggest that the activation of Notch and NF-κB together with the loss of miR-200 family is mechanistically linked with the development and progression of PDAC in the compound K-ras(G12D) and Ink4a/Arf deficient transgenic mice

    Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo.

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    BACKGROUND Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases. METHODS To identify generalized vitiligo susceptibility loci, we conducted a genomewide association study. We genotyped 579,146 single-nucleotide polymorphisms (SNPs) in 1514 patients with generalized vitiligo who were of European-derived white (CEU) ancestry and compared the genotypes with publicly available control genotypes from 2813 CEU persons. We then tested 50 SNPs in two replication sets, one comprising 677 independent CEU patients and 1106 CEU controls and the other comprising 183 CEU simplex trios with generalized vitiligo and 332 CEU multiplex families. RESULTS We detected significant associations between generalized vitiligo and SNPs at several loci previously associated with other autoimmune diseases. These included genes encoding major-histocompatibility-complex class I molecules (P=9.05×10−23) and class II molecules (P=4.50×10−34), PTPN22 (P=1.31×10−7), LPP (P=1.01×10−11), IL2RA (P=2.78×10−9), UBASH3A (P=1.26×10−9), and C1QTNF6 (P=2.21×10−16). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07×10−15) and GZMB (P=3.44×10−8), and in a locus containing TYR (P=1.60×10−18), encoding tyrosinase. CONCLUSIONS We observed associations between generalized vitiligo and markers implicating multiple genes, some associated with other autoimmune diseases and one (TYR) that may mediate target-cell specificity and indicate a mutually exclusive relationship between susceptibility to vitiligo and susceptibility to melanoma

    Conductive Carbon Microfibers Derived from Wet-Spun Lignin/Nanocellulose Hydrogels

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    We introduce an eco-friendly process to dramatically simplify carbon microfiber fabrication from biobased materials. The microfibers are first produced by wet-spinning in aqueous calcium chloride solution, which provides rapid coagulation of the hydrogel precursors comprising wood-derived lignin and 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO)-oxidized cellulose nanofibrils (TOCNF). The thermomechanical performance of the obtained lignin/TOCNF filaments is investigated as a function of cellulose nanofibril orientation (wide angle X-ray scattering (WAXS)), morphology (scanning electron microscopy (SEM)), and density. Following direct carbonization of the filaments at 900 degrees C, carbon microfibers (CMFs) are obtained with remarkably high yield, up to 41%, at lignin loadings of 70 wt % in the precursor microfibers (compared to 23% yield for those produced in the absence of lignin). Without any thermal stabilization or graphitization steps, the morphology, strength, and flexibility of the CMFs are retained to a large degree compared to those of the respective precursors. The electrical conductivity of the CMFs reach values as high as 103 S cm(-1), making them suitable for microelectrodes, fiber-shaped supercapacitors, and wearable electronics. Overall, the cellulose nanofibrils act as structural elements for fast, inexpensive, and environmentally sound wet-spinning while lignin endows CMFs with high carbon yield and electrical conductivity

    Perfluorinated alkyl substances (PFASs) in northern Spain municipal solid waste landfill leachates

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    Landfill leachates have been recognized as significant secondary sources of poly- and perfluoroalkyl substances (PFASs). This study presents data on the occurrence and concentration of 11 perfluoroalkyl carboxylates (PFCAs) and 5 perfluoroalkyl sulfonates (PFSAs) in leachates from 4 municipal solid waste landfill sites located across northern Spain. To the best of our knowledge, this is the first report of the presence of PFASs in Spanish landfill leachates. Two of the landfill sites applied on-site treatment using membrane bioreactors (MBR), and its effect on PFASs occurrence is also reported. Total PFASs (∑PFASs) in raw leachates reached 1378.9 ng/L, while in treated samples ∑PFASs was approximately two-fold (3162.3 ng/L). PFCAs accounted for the majority of the detected PFASs and perfluorooctanoic acid (PFOA) was the dominant compound in raw leachates (42.6%), followed by shorter chain PFHxA (30.1%), PFPeA and PFBA. The age of the sites might explain the PFASs pattern found in raw leachates as all of them were stabilized leachates. However, PFASs profile was different in treated samples where the most abundant compound was PFHxA (26.5%), followed by linear perfluorobutane sulfonate (L-PFBS) (18.7%) and PFOA (17.7%). The overall increase of the PFASs content as well as the change in the PFASs profile after the MBR treatment, could be explained by the possible degradation of PFASs precursors such as fluorotelomer alcohols or fluorotelomer sulfonates. Using the volume of leachates generated in the landfill sites, that served 1.8 million people, the discharge of 16 ∑PFASs contained in the landfill leachates was estimated as 1209 g/year.The authors thank financial support from the Spanish Ministry of Economy and Competitiveness (Project CTM2013-44081-R)
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