Observational models of requirements evolution

Requirements Evolution is one of the main issues that affect development activities as well as system features (e.g., system dependability). Although researchers and practitioners recognise the importance of requirements evolution, research results and experience are still patchy. This points out a lack of methodologies that address requirements evolution. This thesis investigates the current understanding of requirements evolution and explores new directions in requirements evolution research. The empirical analysis of industrial case studies highlights software requirements evolution as an important issue. Unfortunately, traditional requirements engineering methodologies provide limited support to capture requirements evolution. Heterogeneous engineering provides a comprehensive account of system requirements. Heterogeneous engineering stresses a holistic viewpoint that allows us to understand the underlying mechanisms of evolution of socio-technical systems. Requirements, as mappings between socio-technical solutions and problems, represent an account of the history of socio-technical issues arising and being solved within industrial settings. The formal extension of a heterogeneous account of requirements provides a framework to model and capture requirements evolution. The application of the proposed framework provides further evidence that it is possible to capture and model evolutionary information about requirements. The discussion of scenarios of use stresses practical necessities for methodologies addressing requirements evolution. Finally, the identification of a broad spectrum of evolutions in socio-technical systems points out strong contingencies between system evolution and dependability. This thesis argues that the better our understanding of socio-techn..

Nuclear Reprogramming in Mouse Primordial Germ Cells: Epigenetic Contribution

The unique capability of germ cells to give rise to a new organism, allowing the transmission of primary genetic information from generation to generation, depends on their epigenetic reprogramming ability and underlying genomic totipotency. Recent studies have shown that genome-wide epigenetic modifications, referred to as “epigenetic reprogramming”, occur during the development of the gamete precursors termed primordial germ cells (PGCs) in the embryo. This reprogramming is likely to be critical for the germ line development itself and necessary to erase the parental imprinting and setting the base for totipotency intrinsic to this cell lineage. The status of genome acquired during reprogramming and the associated expression of key pluripotency genes render PGCs susceptible to transform into pluripotent stem cells. This may occur in vivo under still undefined condition, and it is likely at the origin of the formation of germ cell tumors. The phenomenon appears to be reproduced under partly defined in vitro culture conditions, when PGCs are transformed into embryonic germ (EG) cells. In the present paper, I will try to summarize the contribution that epigenetic modifications give to nuclear reprogramming in mouse PGCs

The Beginning of Meiosis in Mammalian Female Germ Cells: A Never-Ending Story of Intrinsic and Extrinsic Factors

Meiosis is the unique division of germ cells resulting in the recombination of the maternal and paternal genomes and the production of haploid gametes. In mammals, it begins during the fetal life in females and during puberty in males. In both cases, entering meiosis requires a timely switch from the mitotic to the meiotic cell cycle and the transition from a potential pluripotent status to meiotic differentiation. Revealing the molecular mechanisms underlying these interrelated processes represents the essence in understanding the beginning of meiosis. Meiosis facilitates diversity across individuals and acts as a fundamental driver of evolution. Major differences between sexes and among species complicate the understanding of how meiosis begins. Basic meiotic research is further hindered by a current lack of meiotic cell lines. This has been recently partly overcome with the use of primordial-germ-cell-like cells (PGCLCs) generated from pluripotent stem cells. Much of what we know about this process depends on data from model organisms, namely, the mouse; in mice, the process, however, appears to differ in many aspects from that in humans. Identifying the mechanisms and molecules controlling germ cells to enter meiosis has represented and still represents a major challenge for reproductive medicine. In fact, the proper execution of meiosis is essential for fertility, for maintaining the integrity of the genome, and for ensuring the normal development of the offspring. The main clinical consequences of meiotic defects are infertility and, probably, increased susceptibility to some types of germ-cell tumors. In the present work, we report and discuss data mainly concerning the beginning of meiosis in mammalian female germ cells, referring to such process in males only when pertinent. After a brief account of this process in mice and humans and an historical chronicle of the major hypotheses and progress in this topic, the most recent results are reviewed and discussed

Identification of side population cells in mouse primordial germ cells and prenatal testis

In mammals, the stem cells of spermatogenesis are derived from an embryonic cell population called primordial germ cells (PGCs). Spermatogonial stem cells displaying the "side population" (SP) phenotype have been identified in the immature and adult mouse testis, but noting is known about the expression of the SP phenotype during prenatal development of germ cells. The SP phenotype, defined as the ability of cells to efflux fluorescent dyes such as Hoechst, is common to several stem/progenitor cell types. In the present study, we analyzed and characterized the Hoechst SP via cytofluorimetric analysis of disaggregated gonads at different time points during embryonic development in mice. To directly test the hypothesis that the SP phenotype is a feature of germ cell lineage, experiments were performed on transgenic animals expressing enhanced green fluorescent protein (EGFP) under the control of the Oct4 promoter, to identify early germ cells up to PGCs. We found that prenatal gonads contain a fraction of SP cells at each stage analyzed, and the percentage of cells in the SP fraction decreases as development proceeds. Surprisingly, more than 50% of the PGCs displayed the SP phenotype at 11.5 dpc (days post coitum). The percentage of germ cells with the SP phenotype decreased steadily with development, to less than 1% at 18.5 dpc. Cytofluorimetric analysis along with immunocytochemistry performed on sorted cells indicated that the SP fraction of prenatal gonads, as in the adult testis, was heterogeneous, being composed of both somatic and germ cells. Both cell types expressed the ABC transporters Abcg2, Abcb1a, Abcb1b and Abcc1. These findings provide evidence that the SP phenotype is a common feature of PGCs and identifies a subpopulation of fetal testis cells including prospermatogonia whose differentiation fate remains to be investigated. © 2011 UBC Press

Operando Structural Characterization of the E-ALD Process Ultra-Thin Films Growth

Spanning from nanoelectronics to new solar energy materials, technological development in the recent years requested highly controlled nanostructured surfaces, ultra-thin films, and 2D structured materials. In general, although very favorable from a full life cycle assessment (FLCA) standpoint, electrodeposition hardly allows to obtain the high order required by recent technologies. In particular cases, the electrodeposition enables the deposition of atomic layers by means of surface limited reactions (SLRs). By exploiting SLRs, it is possible to define layer-by-layer deposition scheme of different atomic layers; we refer to these schemes as electrochemical atomic layer deposition (E-ALD) and when the growth of the film is epitaxial with the substrate, the techniques are called electrochemical atomic layer epitaxy (ECALE). Aiming at characterizing structure and growth of materials grown by means of E-ALD, surface analysis techniques apply better. In particular, surface X-ray diffraction (SXRD) with high brilliance synchrotron sources enables the operando structural analysis in electrochemical environment. In recent years, several works on the operando surface characterization by means of SXRD have been reported. Thanks to novelties in the field of operando SXRD experiments, semiconducting systems were studied, such as single and multilayer of CdS and Cu2S

Solvable Set/Hyperset Contexts: III. A Tableau System for a Fragment of Hyperset Theory

We propose a decision procedure for a fragment of the hyperset theory, HMLSS, which takes inspiration from a tableau saturation strategy presented in [3] for the fragment MLSS of well-founded set theory. The procedure alternates deduction and model checking steps, driving the correct application of otherwise very liberal rules, thus significantly speeding up the process of discovering a satisfying assignment of a given HMLSS-formula or proving that no such assignment exists

The ovarian reserve as target of insulin/IGF and ROS in metabolic disorder-dependent ovarian dysfunctions

It is known for a long time that metabolic disorders can cause ovarian dysfunctions and affect a woman's fertility either by direct targeting follicular cells and/or the oocytes or by indirect interference with the pituitary-hypothalamic axis, resulting in dysfunctional oogenesis. Such disorders may also influence the efficiency of the embryo implantation and the quality of the embryo with permanent effects on the fertility and health of the offspring. Thanks to the expanding knowledge on the molecular mechanisms governing oogenesis and folliculogenesis in mammals, we are beginning to understand how such disorders can negatively affect this process and consequently fertility in women. In the present review, we point out and discuss how the disturbance of insulin/IGF-dependent signalling and increased reactive oxygen species (ROS) level in the ovary typically associated to metabolic disorders such as type II diabetes and obesity can dysregulate the dynamics of the ovarian reserve and/or impair the survival and competence of the oocytes

Reprogramming Human Female Adipose Mesenchymal Stem Cells into Primordial Germ Cell-Like Cells

In the last two decades, considerable progress has been made in the derivation of mammalian germ cells from pluripotent stem cells such as Embryonic Stem Cells (ESCs) and induced Pluripotent Stem Cells (iPSCs). The pluripotent stem cells are generally first induced into pre-gastrulating endoderm/mesoderm-like status and then specified into putative primordial germ cells (PGCs) termed PGC-like cells (PGCLCs) which possess the potential to generate oocytes and sperms. Adipose-derived mesenchymal stromal cells (ASCs) are multipotent cells, having the capacity to differentiate into cell types such as adipocytes, osteocytes and chondrocytes. Since no information is available about the capability of female human ASCs (hASCs) to generate PGCLCs, we compared protocols to produce such cells from hASCs themselves or from hASC-derived iPSCs. The results showed that, providing pre-induction into a peri-gastrulating endoderm/mesoderm-like status, hASCs can generate PGCLCs. This process, however, shows a lower efficiency than when hASC-derived iPSCs are used as starting cells. Although hASCs possess multipotency and express mesodermal genes, direct induction into PGCLCs resulted less efficient