Optimal paths in multi-stage stochastic decision networks

This paper deals with the search of optimal paths in a multi-stage stochastic decision network as a first application of the deterministic approximation approach proposed by Tadei et al. (2019). In the network, the involved utilities are stage-dependent and contain random oscillations with an unknown probability distribution. The problem is modeled as a sequential choice of nodes in a graph layered into stages, in order to find the optimal path value in a recursive fashion. It is also shown that an optimal path solution can be derived by using a Nested Multinomial Logit model, which represents the choice probability at the different stages. The accuracy and efficiency of the proposed method are experimentally proved on a large set of randomly generated instances. Moreover, insights on the calibration of a critical parameter of the deterministic approximation are also provided

XX males SRY negative: a confirmed cause of infertility

BACKGROUND: SOX9 is a widely expressed transcription factor playing several relevant functions during development and essential for testes differentiation. It is considered to be the direct target gene of the protein encoded by SRY and its overexpression in an XX murine gonad can lead to male development in the absence of Sry. Recently, a family was reported with a 178 kb duplication in the gene desert region ending about 500 kb upstream of SOX9 in which 46,XY duplicated persons were completely normal and fertile whereas the 46,XX ones were males who came to clinical attention because of infertility. METHODS AND RESULTS: We report a family with two azoospermic brothers, both 46,XX, SRY negative, having a 96 kb triplication 500 kb upstream of SOX9. Both subjects have been analyzed trough oligonucleotide array-CGH and the triplication was confirmed and characterised through qPCR, defining the minimal region of amplification upstream of SOX9 associated with 46,XX infertile males, SRY negative. CONCLUSIONS: Our results confirm that even in absence of SRY, complete male differentiation may occur, possibly driven by overexpression of SOX9 in the gonadal ridge, as a consequence of the amplification of a gene desert region. We hypothesize that this region contains gonadal specific long-range regulation elements whose alteration may impair the normal sex development. Our data show that normal XX males, with alteration in copy number or, possibly, in the critical sequence upstream to SOX9 are a new category of infertility inherited in a dominant way with expression limited to the XX background