A Method for Developing Model to Text Transformations

In the field of business process development, model transformations play a key role, for example for moving from business process models to either code or inputs for simulation systems, as well as to convert models expressed with notation A into equivalent models expressed with notation B. In the literature, many cases of useful transformations of business process models can be found. However, in general each transformation has been developed in an ad-hoc fashion, at a quite low-level, and its quality is often neglected. To ensure the quality of the transformations is important to apply to them all the well-known software engineering principles and practices, from the requirements definition to the testing activities. For this reason, we propose a method, MeDMoT, for developing non-trivial Model to Text Transformations, which prescribes how to: (1) capture and specify the transformation requirements; (2) design the transformation, (3) implement the transformation and (4) test the transformation. The method has been applied in several case studies, including a transformation of UML business processes into inputs for an agent-based simulator

Maturity of Software Modelling and Model Driven Engineering: a Survey in the Italian Industry

Background: The main claimed advantage of Model-driven engineering is improvement in productivity. However, few information is available about its actual adoption during software development and maintenance in the industry. Objective: The main aim of this work is investigating the level of maturity in the adoption of software models and of Model-driven engineering in the Italian industry. The perspective is that of software engineering researchers. Method: First, we conducted an exploratory personal opinion survey with 155 Italian software professionals. The data were collected with the help of a web-based on-line questionnaire. Then, we conducted focused interviews with three software professionals to interpret doubtful results. Results: Software modelling is a very relevant phenomenon in the Italian industry. Model-Driven techniques are used in the industry, even if (i) only for a limited extent, (ii) despite a quite generalized dissatisfaction about available tools and (iii) despite a generally low experience of the IT personnel in such techniques. Limitations: Generalization of results is limited due to the sample size. Moreover, possible self-exclusion from participants not interested in modelling could have biased the results. Conclusion: Results reinforce existing evidence regarding the usage of software modelling and (partially of) Model-driven engineering in the industry but highlight several aspects of immaturity of the Italian industry

Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration

Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from \u3b2-cells are not yet fully understood. By taking advantage of a tcf7l2 zebrafish mutant line, we first show that these animals are characterized by hyperglycemia and impaired islet development. Moreover, we demonstrate that the zebrafish tcf7l2 gene is highly expressed in the exocrine pancreas, suggesting potential bystander effects on \u3b2-cell growth, differentiation and regeneration. Finally, we describe a peculiar vascular phenotype in tcf7l2 mutant larvae, characterized by significant reduction in the average number and diameter of pancreatic islet capillaries. Overall, the zebrafish Tcf7l2 mutant, characterized by hyperglycemia, pancreatic and vascular defects, and reduced regeneration proves to be a suitable model to study the mechanism of action and the pleiotropic effects of Tcf7l2, the most relevant T2D GWAS hit in human populations

A Smad3 transgenic reporter reveals TGF-beta control of zebrafish spinal cord development

TGF-beta (TGFβ) family mediated Smad signaling is involved in mesoderm and endoderm specification, left-right asymmetry formation and neural tube development. The TGFβ1/2/3 and Activin/Nodal signal transduction cascades culminate with activation of SMAD2 and/or SMAD3 transcription factors and their overactivation are involved in different pathologies with an inflammatory and/or uncontrolled cell proliferation basis, such as cancer and fibrosis. We have developed a transgenic zebrafish reporter line responsive to Smad3 activity. Through chemical, genetic and molecular approaches we have seen that this transgenic line consistently reproduces in vivo Smad3-mediated TGFβ signaling. Reporter fluorescence is activated in phospho-Smad3 positive cells and is responsive to both Smad3 isoforms, Smad3a and 3b. Moreover, Alk4 and Alk5 inhibitors strongly repress the reporter activity. In the CNS, Smad3 reporter activity is particularly high in the subpallium, tegumentum, cerebellar plate, medulla oblongata and the retina proliferative zone. In the spinal cord, the reporter is activated at the ventricular zone, where neuronal progenitor cells are located. Colocalization methods show in vivo that TGFβ signaling is particularly active in neuroD+ precursors. Using neuronal transgenic lines, we observed that TGFβ chemical inhibition leads to a decrease of differentiating cells and an increase of proliferation. Similarly, smad3a and 3b knock-down alter neural differentiation showing that both paralogues play a positive role in neural differentiation. EdU proliferation assay and pH3 staining confirmed that Smad3 is mainly active in post-mitotic, non-proliferating cells. In summary, we demonstrate that the Smad3 reporter line allows us to follow in vivo Smad3 transcriptional activity and that Smad3, by controlling neural differentiation, promotes the progenitor to precursor switch allowing neural progenitors to exit cell cycle and differentiate

Platelet aggregation is affected by nitrosothiols in patients with chronic hepatitis: in vivo and in vitro studies

AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-6 in patients with chronic hepatitis C (CH). METHODS: In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO). RESULTS: In vivo, S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts 150000/microL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen

Relevance, benefits, and problems of software modelling and model driven techniques—A survey in the Italian industry

Context Claimed benefits of software modelling and model driven techniques are improvements in productivity, portability, maintainability and interoperability. However, little effort has been devoted at collecting evidence to evaluate their actual relevance, benefits and usage complications. Goal The main goals of this paper are: (1) assess the diffusion and relevance of software modelling and MD techniques in the Italian industry, (2) understand the expected and achieved benefits, and (3) identify which problems limit/prevent their diffusion. Method We conducted an exploratory personal opinion survey with a sample of 155 Italian software professionals by means of a Web-based questionnaire on-line from February to April 2011. Results Software modelling and MD techniques are very relevant in the Italian industry. The adoption of simple modelling brings common benefits (better design support, documentation improvement, better maintenance, and higher software quality), while MD techniques make it easier to achieve: improved standardization, higher productivity, and platform independence. We identified problems, some hindering adoption (too much effort required and limited usefulness) others preventing it (lack of competencies and supporting tools). Conclusions The relevance represents an important objective motivation for researchers in this area. The relationship between techniques and attainable benefits represents an instrument for practitioners planning the adoption of such techniques. In addition the findings may provide hints for companies and universitie

Prostate volume index and prostatic chronic inflammation have an effect on tumor load at baseline random biopsies in patients with normal DRE and PSA values less than 10\u2009ng/ml: results of 564 consecutive cases

Background: To assess the association of prostate volume index (PVI), defined as the ratio of the central transition zone volume (CTZV) to the peripheral zone volume (PZV), and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA) load in patients presenting with normal digital rectal exam (DRE) and prostate-specific antigen (PSA) <= 10 ng/ml at baseline random biopsies. Methods: Parameters evaluated included age, PSA, total prostate volume (TPV), PSA density (PSAD), PVI and PCI. All patients underwent 14 core transperineal randomized biopsies. We considered small and high PCA load patients with no more than three (limited tumor load) and greater than three (extensive tumor load) positive biopsy cores, respectively. The association of factors with the risk of PCA was evaluated by logistic regression analysis, utilizing different multivariate models. Results: 564 Caucasian patients were included. PCA and PCI were detected in 242 (42.9%) and 129 (22.9%) cases, respectively. On multivariate analysis, PVI and PCI were independent predictors of the risk of detecting limited or extensive tumor load. The risk of detecting extensive tumor load at baseline biopsies was increased by PSAD above the median and third quartile as well as PVI <= 1 [odds ratio (OR)=1.971] but decreased by PCI (OR=0.185; 95% CI: 0.088-0.388). Conclusions: Higher PVI and the presence of PCI predicted decreased PCA risk in patients presenting with normal DRE, and a PSA <= 10 ng/ml at baseline random biopsy. In this subset of patients, a PVI <= or >1 is able to differentiate patients with PCA or PCI

High surgeon volume and positive surgical margins can predict the risk of biochemical recurrence after robot-assisted radical prostatectomy

Background: The aim of this study was to determine whether any clinical factors are independent predictors of positive surgical margins (PSM), and to assess the association of PSM and biochemical recurrence (BR) after robot-assisted radical prostatectomy (RARP). Methods: The population included cases with negative surgical margins (control group) and patients with PSM (study group). Tumor grade was evaluated according to the International Society of Urologic Pathology (ISUP) system. A logistic regression model assessed the independent association of factors with the risk of PSM. The risk of BR was assessed by Cox\u2019s multivariate proportional hazards. Results: A total of 732 consecutive patients were evaluated. Extend pelvic lymph node dissection (ePLND) was performed in 342 cases (46.7%). Overall, 192 cases (26.3%) had PSM. The risk of PSM was positively associated with the percentage of biopsy positive cores (BPC; odds ratio, OR = 1.012; p = 0.004), extracapsular extension (pT3a; OR=2.702; p < 0.0001), invasion of seminal vesicle (pT3b; OR = 2.889; p < 0.0001), but inversely with body mass index (OR = 0.936; p = 0.021), and high surgeon volume (OR = 0.607; p = 0.006). Independent clinical factors associated with the risk of BR were baseline prostate-specific antigen (PSA; hazard ratio, HR = 1.064; p = 0.004), BPC (HR = 1.015; p = 0.027), ISUP biopsy grade group (BGG) 2/3 (HR = 2.966; p = 0.003), and BGG 4/5 (HR = 3.122; p = 0.022). Pathologic factors associated with the risk of BR were ISUP group 4/5 (HR = 3.257; p = 0.001), pT3b (HR = 2.900; p = 0.003), and PSM (HR = 2.096; p = 0.045). Conclusions: In our cohort, features related to host, tumor, and surgeon volume are associated with the risk of PSM, which is also an independent parameter predicting BR after RARP. The surgical volume of the operating surgeon is an independent factor that decreases the risk of PSM, and, as such, the risk of BR