139 research outputs found

    New complexity results for parallel identical machine scheduling problems with preemption, release dates and regular criteria

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    In this paper, we are interested in parallel identical machine scheduling problems with preemption and release dates in case of a regular criterion to be minimized. We show that solutions having a permutation flow shop structure are dominant if there exists an optimal solution with completion times scheduled in the same order as the release dates, or if there is no release date. We also prove that, for a subclass of these problems, the completion times of all jobs can be ordered in an optimal solution. Using these two results, we provide new results on polynomially solvable problems and hence refine the boundary between P and NP for these problems

    Фізико-хімічна геотехнологія

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    Розглянуто принципові засади геотехнологічного видобування різнома- нітних корисних копалин. Викладено питання розкриття та підготовки родовищ за допомогою свердловинної розробки, проаналізовано способи буріння і кріп- лення геотехнологічних свердловин, а такж застосоване обладнання. Розкрито сутність технологічних процесів, які виконуються при диспергуванні гірських порід, розчиненні солей, вилуговуванні металів, підземній виплавці сірки і га- зифікації вугілля, видобуванні в’язкої нафти та сланцьового газу. Навчальний посібник призначений для студентів, які навчаються за спе- ціальністю «Розробка родовищ та видобування корисних копалин», а також для студентів інших спеціальностей гірничих вузів і факультетів та інженерно- технічних працівників підприємств і проектних організацій гірничовидобувних галузей промисловості України

    Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene

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    To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (Fundació ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P=0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio=1.31; confidence interval 95% (1.19-1.44); P=9.74 × 10 - 9)

    Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

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    Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

    MiR-137-derived polygenic risk: effects on cognitive performance in patients with schizophrenia and controls

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    Variants at microRNA-137 (MIR137), one of the most strongly associated schizophrenia risk loci identified to date, have been associated with poorer cognitive performance. As microRNA-137 is known to regulate the expression of ~1900 other genes, including several that are independently associated with schizophrenia, we tested whether this gene set was also associated with variation in cognitive performance. Our analysis was based on an empirically derived list of genes whose expression was altered by manipulation of MIR137 expression. This list was cross-referenced with genome-wide schizophrenia association data to construct individual polygenic scores. We then tested, in a sample of 808 patients and 192 controls, whether these risk scores were associated with altered performance on cognitive functions known to be affected in schizophrenia. A subgroup of healthy participants also underwent functional imaging during memory (n=108) and face processing tasks (n=83). Increased polygenic risk within the empirically derived miR-137 regulated gene score was associated with significantly lower performance on intelligence quotient, working memory and episodic memory. These effects were observed most clearly at a polygenic threshold of P=0.05, although significant results were observed at all three thresholds analyzed. This association was found independently for the gene set as a whole, excluding the schizophrenia-associated MIR137 SNP itself. Analysis of the spatial working memory fMRI task further suggested that increased risk score (thresholded at P=10−5) was significantly associated with increased activation of the right inferior occipital gyrus. In conclusion, these data are consistent with emerging evidence that MIR137 associated risk for schizophrenia may relate to its broader downstream genetic effects
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