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We aimed to analyze the role of the common genetic variants located in the PIN1 locus, a relevant prolyl isomerase required to control the proliferation of spermatogonial stem cells and the integrity of the blood–testis barrier, in the genetic risk of developing male infertility due to a severe spermatogenic failure (SPGF). Genotyping was performed using TaqMan genotyping assays for three PIN1 taggers (rs2287839, rs2233678 and rs62105751). The study cohort included 715 males diagnosed with SPGF and classified as suffering from non-obstructive azoospermia (NOA, n = 505) or severe oligospermia (SO, n = 210), and 1058 controls from the Iberian Peninsula. The allelic frequency differences between cases and controls were analyzed by the means of logistic regression models. A subtype specific genetic association with the subset of NOA patients classified as suffering from the Sertoli cell-only (SCO) syndrome was observed with the minor alleles showing strong risk effects for this subset (ORaddrs2287839 = 1.85 (1.17–2.93), ORaddrs2233678 = 1.62 (1.11–2.36), ORaddrs62105751 = 1.43 (1.06–1.93)). The causal variants were predicted to affect the binding of key transcription factors and to produce an altered PIN1 gene expression and isoform balance. In conclusion, common non-coding single-nucleotide polymorphisms located in PIN1 increase the genetic risk to develop SCO. [ABSTRACT FROM AUTHOR]

This article considers the problem of designing a two-level network where the upper level consists of a backbone ring network connecting the so-called hub nodes, and the lower level is formed by access ring networks that connect the non-hub nodes to the hub nodes. There is a fixed cost for each type of link, and a facility opening cost associated to each hub. The number of nodes in each access ring is bounded, and the number of access rings connected to a hub is limited to [ABSTRACT FROM AUTHOR]

Efficient algorithms for the economic lot-sizing problem with storage capacity are proposed. On the one hand, for the cost structure consisting of general linear holding and ordering costs and fixed setup costs, an O T 2 dynamic programming algorithm is introduced, where T is the number of time periods. The new approach induces an accurate partition of the planning horizon, discarding most of the infeasible solutions. Moreover, although there are several algorithms based on dynamic programming in the literature also running in quadratic time, even considering more general cost structures and assumptions, the new solution uses a geometric technique to speed up the algorithm for a class of subproblems generated by dynamic programming, which can now be solved in linearithmic time. To be precise, the computational results show that the average occurrence percentage of this class of subproblems ranges between 13% and 45%, depending on both the total number of periods and the percentage of storage capacity availability. Furthermore, this percentage significantly increases from 13% to 35% as the capacity availability decreases. This reveals that the usage of the geometric technique is predominant under restrictive storage capacities. Specifically, when the percentage of capacity availability is below 50%, the average running times are on average 100 times faster than those when this percentage is above 50%. On the other hand, an O T on-line array searching method in Monge arrays can be used when the costs are non-speculative costs. [ABSTRACT FROM AUTHOR]