An Experience on Formal Analysis of a high-level graphical SOA Design

Abstract: In this paper, we present the experience gained with the participation in a case study in which a novel high-level design language (UML4SOA) was used to produce a service-oriented system design, to be model checked with respect to the intended requirements and automatically translated into executable BPEL code. This experience, beyond revealing several uncertainties in the language definition, and several flaws in the designed model, has been useful to better understand the hidden risks of apparently intuitive graphical designs, when these are not backed up by a precise and rigorous semantics. The adoption of a rigorous or formal semantics for these notations, and the adoption of formal verification methods allow the full exploration of designs which otherwise risk to become simple to draw and update, but difficult to really understand in all their hidden ramifications. Automatic formal model generation from high level graphical designs is not only desirable but also pragmatically feasible e.g. using appropriate model transformation techniques. This is particularly valuable in the context of agile development approaches which are based on rapid and continuous updates of the system designs

Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells

AbstractRecent studies indicate that mesenchymal stromal cell (MSC) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMP) expression and activity in different cells of the muscle tissue. MSCs in co-culture with C2C12 cells or their conditioned medium (MSC-CM) up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-1 and -2 and with increased cell motility. In the single muscle fiber experiments, MSC-CM administration increased MMP-2/9 expression in Pax-7+ satellite cells and stimulated their mobilization, differentiation and fusion. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts. The treatment with SB-3CT, a potent MMP inhibitor, prevented in these cells, the decrease of α-smooth actin and type-I collagen expression induced by MSC-CM, suggesting that MSC-CM could attenuate the fibrogenic response through mechanisms mediated by MMPs. Our results indicate that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration

Co-Transplantation of endothelial progenitor cells and pancreatic islets to induce long-lasting normoglycemia in streptozotocin-treated diabetic rats

Graft vascularization is a crucial step to obtain stable normoglycemia in pancreatic islet transplantation. Endothelial progenitor cells (EPCs) contribute to neoangiogenesis and to the revascularization process during ischaemic events and play a key role in the response to pancreatic islet injury. In this work we co-transplanted EPCs and islets in the portal vein of chemically-induced diabetic rats to restore islet vascularization and to improve graft survival. Syngenic islets were transplanted, either alone or with EPCs derived from green fluorescent protein (GFP) transgenic rats, into the portal vein of streptozotocin-induced diabetic rats. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests were performed. Real time-PCR was carried out to evaluate the gene expression of angiogenic factors. Diabetic-induced rats showed long-lasting (6 months) normoglycemia upon co-transplantation of syngenic islets and EPCs. After 3–5 days from transplantation, hyperglycaemic levels dropped to normal values and lasted unmodified as long as they were checked. Further, glucose tolerance tests revealed the animals' ability to produce insulin on-demand as indexed by a prompt response in blood glucose clearance. Graft neovascularization was evaluated by immunohistochemistry: for the first time the measure of endothelial thickness revealed a donor-EPC-related neovascularization supporting viable islets up to six months after transplant. Our results highlight the importance of a newly formed viable vascular network together with pancreatic islets to provide de novo adequate supply in order to obtain enduring normoglycemia and prevent diabetes-related long-term health hazards

A Logical Verification Methodology for Service-Oriented Computing

We introduce a logical verification methodology for checking behavioural properties of service-oriented computing systems. Service properties are described by means of SocL, a branching-time temporal logic that we have specifically designed to express in an effective way distinctive aspects of services, such as, e.g., acceptance of a request, provision of a response, and correlation among service requests and responses. Our approach allows service properties to be expressed in such a way that they can be independent of service domains and specifications. We show an instantiation of our general methodology that uses the formal language COWS to conveniently specify services and the expressly developed software tool CMC to assist the user in the task of verifying SocL formulae over service specifications. We demonstrate feasibility and effectiveness of our methodology by means of the specification and the analysis of a case study in the automotive domain

Mesenchymal stromal cells and their paracrine factors regulate MMP-2 and MMP-9/ TIMP-2 balance in skeletal myoblasts and fibroblasts: new insights into the potential role of MSC-cell therapy in muscle regenerative medicine

Recent studies showed that mesenchymal stromal cell (MSCs) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are still poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMPs) expression and activity in different cells of the muscle tissue. It was found that MSCs in co-culture with C2C12 cells up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-2. Similar results were obtained upon incubation of conditioned medium from MSCs (MSC-CM) or in experiments where MSCs were separated from myoblasts by polycarbonate membranes, enabling diffusion of soluble factors while preventing the physical contact between the two cell types, suggesting that MSCs regulated MMP/TIMP balance in skeletal myoblasts by paracrine factors. In the single muscle fibre experiments, MSC-CM administration increased MMP-2 and MMP-9 expression in Pax-7+ satellite cells and stimulated their mobilization, differentiation and fusion into multinucleated myotubes. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts, as detected by reduced expression of α-smooth actin and type-I collagen in the fibroblasts incubated with MSC-CM. These findings add novel information on the effects of MSCs on the skeletal muscle healing, suggesting that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration

10 simple rules to create a serious game, illustrated with examples from structural biology

Serious scientific games are games whose purpose is not only fun. In the field of science, the serious goals include crucial activities for scientists: outreach, teaching and research. The number of serious games is increasing rapidly, in particular citizen science games, games that allow people to produce and/or analyze scientific data. Interestingly, it is possible to build a set of rules providing a guideline to create or improve serious games. We present arguments gathered from our own experience ( Phylo , DocMolecules , HiRE-RNA contest and Pangu) as well as examples from the growing literature on scientific serious games

Mesenchymal Stem Cell-Based Immunomodulation in Allogeneic Heterotopic Heart-Lung Transplantation

Mesenchymal stem cells are able to differentiate in various cell lineages and they have shown immunomodulatory properties in vitro, altering the cytokine secretion profile of T helper, T effector and dendritic cells and stimulating natural killer cells towards an anti-inflammatory and tolerant phenotype. In vivo they prolong skin allograft survival and may decrease graft-versus-host disease after hematopoietic stem cell transplants. In this work we studied the effects of mesenchymal stem cell treatment in an allogeneic heterotopic heart-lung transplant model. The following experimental groups were formed: A) Control B) Immunosuppressive therapy (Cyclosporine A) C) Mesenchymal stem-cell intravenous infusion D) Mesenchymal stem-cell infusion plus immunosuppressive treatment. The infusion of mesenchymal stem cells improved the mean graft survival up to 14.5±3.7 days with respect to the control group (3±0.6 days). Treatment with Cyclosporine A plus mesenchymal stem cells (group D) produced a mean survival time of 18.25±4.9 days, and was not significantly different to the results for group B (21.75±3.5 days). Furthermore, in the immunosuppressive treatment and the mesenchymal stem cell treatment, histological analysis revealed a reduction in the grade of rejection in heart and lung grafts. This decrease was most significant in group D. In conclusion, mesenchymal stem cells alone or in combination with Cyclosporine A were able to prolong graft survival time. These data suggest that, in vivo, mesenchymal stem cells retain their ability, already shown in vitro, to suppress lymphocyte activation and proliferation