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© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. The coupled task scheduling problem aims to schedule a set of jobs, each with at least two tasks and there is an exact delay period between two consecutive tasks, on a set of machines to optimize a performance criterion. We study the problem of scheduling a set of coupled jobs to be processed on a single machine with the objective of minimizing the makespan, which is known to be strongly NP-hard. We obtain competitive lower bounds for the problem through different procedures, including solving 0-1 knapsack problems. We obtain an upper bound by applying a heuristic algorithm. We then propose a binary search heuristic algorithm for the coupled task scheduling problem. We perform extensive computational experiments and show that the proposed method is able to obtain quality solutions. The results also indicate that the proposed solution method outperforms the standard exact solver Gurobi.

Background: Several recent studies have shown that mitochondrial DNA mutations lead to major disabilities and premature death in carriers. More than 150 mutations in human mitochondrial DNA (mtDNA) genes have been associated with a wide spectrum of disorders. Varicocele, one of the causes of infertility in men wherein abnormal inflexion and distension of veins of the pampiniform plexus is observed within spermatic cord, can increase reactive oxygen species (ROS) production in semen and cause oxidative stress and sperm dysfunction in patients. Given that mitochondria are the source of ROS production in cells, the aim of this study was to scan nine mitochondrial genes (MT-COX2, MT-tRNALys , MT-ATP8, MT-ATP6, MT-COX3, MT-tRNAGly , MT-ND3, MT-tRNAArg and MT-ND4L) for mutations in infertile patients with varicocele. Materials and Methods: In this cross-sectional study, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing were used to detect and identify point mutations respectively in 9 mitochondrial genes in 72 infertile men with varicocele and 159 fertile men. In brief, the samples showing altered electrophoretic patterns of DNA in the SSCP gel were sent for DNA sequencing to identify the exact nucleotide variation. Results: Ten type nucleotide variants were detected exclusively in mitochondrial DNA of infertile men. These include six novel nucleotide changes and four variants previously reported for other disorders. Conclusion: Mutations in mitochondrial genes may affect respiratory complexes in combination with environmental risk factors. Therefore these nucleotide variants probably lead to impaired ATP synthesis and mitochondrial function ultimately interfering with sperm motility and infertility.

Background: Ischemic injury during organ transplantation increases the risk of acute and chronic rejections by promoting alloimmune responses. Measurement of neutrophil gelatinase-associated lipocalin (NGAL) immediately after kidney transplantation may be promising for early detection of ischemic injuries to allograft. Objective: This study assessed possible predictive values of plasma NGAL levels during first hours after kidney transplantation for graft loss within the first 3 months after transplantation. Methods: 45 kidney transplant recipients were classified into those without graft loss or with graft loss during 3 months after transplantation. Plasma NGAL levels were measured before and at 2, 6, 12, 24 and 96 hours after transplantation. Serum creatinine concentration was assessed daily during hospitalization and at 1, 2, and 3 months post-transplantation. Results: Serum creatinine and plasma NGAL levels were consistently higher in patients with graft loss compared with those without graft loss. At 2, 24, and 96 hours after transplantation, plasma NGAL concentration was significantly higher in patients who developed allograft loss within 3 months post-transplantation. The cutoff point of plasma NGAL at 2, 24, and 96 hours after transplantation for prediction of graft loss was 304.5 ng/mL (sensitivity of 71.4%, and specificity of 73.7%), 207.8 ng/mL(sensitivity of 85.7%, and specificity of 60.5%), and 184 ng/mL (sensitivity of 85.7%, and specificity of 71.1%), respectively. Conclusion: Plasma NGAL levels at 2, 24, and 96 hours after transplantation can predict 3-month graft loss with fair sensitivity and specificity.

© 2015 The Authors. Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. © The Author 2015.

Background: Because of some insult to kidney during transplantation, assessment of kidney function after the procedure is essential. It would be ideal to find a marker better than creatinine to early predict the acute kidney injury. Objective: To compare with creatinine the predictive value of serum neutrophil gelatinase-associated lipocalin (NGAL) in detecting kidney recovery after renal transplantation. Methods: We studied 33 patients who received kidney transplantation (deceased [n=20] and live [n=13]) during a 6-month period in 2010. Serum NGAL and creatinine, hemoglobin, and blood glucose were measured at 0, 12, 24, 48, and 72 hours after transplantation. The need for dialysis and kidney function in one week were studied. Results: There were 16 men and 17 women with the mean±SD age of 36.3±12.2 (range: 14–58) years. Of the studied patients, 6 had delayed graft function (DGF; hemodialysis within the first week of transplant); 9 had slow graft function (SGF; serum creatinine reduction from transplantation to day 7

Let G be a nite group. The prime graph Γ(G) of G is de ned as follows. The vertices of Γ(G) are the primes dividing the order of G and two distinct vertices p, p′ are joined by an edge if G has an element of order pp′. Let L = Dn(q) have disconnected prime graph and q ∈ {2; 5}. In this paper, we determine nite groups G with the same prime graph as L, i.e. Γ(G) = Γ(L).Keywords: Prime graph, simple group, recognition, quasirecognitionQuaestiones Mathematicae 36(2013), 517-535

Development of myotubes from chick embryo breast muscle myoblasts has been shown to occur in the combined presence of insulin, and both the low and high molecular weight components (LMW, HMW) of chick embryo extract. We report here that alanine, or pyruvate, will replace the LMW component with serine enhancing this effect. In addition, extracts of embryonic kidneys were the most active of five embryonic tissues tested in replacing the LMW component, which led to the finding that cortisol is active in promoting both the development of myotubes and the expression of creatine phosphokinase activity, a muscle-specific indicator of myogenesis. Since it was observed that myoblasts are highly glycolytic, it may be that pyruvate is limiting, suggesting that some aspect of oxidative metabolism is also limiting in these cells.