Seladin-1 (SELective Alzheimer's Disease INdicator-1) is an anti-apoptotic gene, which is down-regulated in brain regions affected by Alzheimer's disease (AD). In addition, seladin-1 catalyzes the conversion of desmosterol into cholesterol. Disruption of cholesterol homeostasis in neurons may increase cell susceptibility to toxic agents. Because the hippocampus and the subventricular zone, which are affected in AD, are the unique regions containing stem cells with neurogenic potential in the adult brain, it might be hypothesized that this multipotent cell compartment is the predominant source of seladin-1 in normal brain. In the present study, we isolated and characterized human mesenchymal stem cells (hMSC) as a model of cells with the ability to differentiate into neurons. hMSC were then differentiated toward a neuronal phenotype (hMSC-n). These cells were thoroughly characterized and proved to be neurons, as assessed by molecular and electrophysiological evaluation. Seladin-1 expression was determined and found to be significantly reduced in hMSC-n compared to undifferentiated cells. Accordingly, the total content of cholesterol was decreased after differentiation. These original results demonstrate for the first time that seladin-1 is abundantly expressed by stem cells and appear to suggest that reduced expression in AD might be due to an altered pool of multipotent cells. © 2006 Elsevier Inc. All rights reserved. Keywords:Seladin-1 Alzheimer's disease Human mesenchymal stem cells

Constraint LTL over clocks is a variant of CLTL, an extension of lineartime temporal logic allowing atomic assertions in a concrete constraint system. Satisfiability of CLTL over clocks is here shown to be decidable by means of a reduction to a decidable SMT (Satisfiability Modulo Theories) problem. The result is a complete Bounded Satisfiability Checking procedure, which has been implemented by using standard SMT solvers. The importance of this technique derives from the possibility of translating various continuous-time metric temporal logics, such as MITL and QTL, into CLTL over clocks itself. Although standard decision procedures of these logics do exist, they have never been realized in practice. Suitable translations into CLTL over clocks have instead allowed us the development of the first prototype tool for deciding MITL and QTL. The paper also reports preliminary, but encouraging, experiments on some significant examples of MITL and QTL formulae.

Reconstruction of the regulatory network is an important step in understanding how organisms control the expression of gene products and therefore phenotypes. Recent studies have pointed out the importance of regulatory network plasticity in bacterial adaptation and evolution. The evolution of such networks within and outside the species boundary is however still obscure. Sinorhizobium meliloti is an ideal species for such study, having three large replicons, many genomes available and a significant knowledge of its transcription factors (TF). Each replicon has a specific functional and evolutionary mark; which might also emerge from the analysis of their regulatory signatures. Here we have studied the plasticity of the regulatory network within and outside the S. meliloti species, looking for the presence of 41 TFs binding motifs in 51 strains and 5 related rhizobial species. We have detected a preference of several TFs for one of the three replicons, and the function of regulated genes was found to be in accordance with the overall replicon functional signature: house-keeping functions for the chromosome, metabolism for the chromid, symbiosis for the megaplasmid. This therefore suggests a replicon-specific wiring of the regulatory network in the S. meliloti species. At the same time a significant part of the predicted regulatory network is shared between the chromosome and the chromid, thus adding an additional layer by which the chromid integrates itself in the core genome. Furthermore, the regulatory network distance was found to be correlated with both promoter regions and accessory genome evolution inside the species, indicating that both pangenome compartments are involved in the regulatory network evolution. We also observed that genes which are not included in the species regulatory network are more likely to belong to the accessory genome, indicating that regulatory interactions should also be considered to predict gene conservation in bacterial pangenomes.

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A crucial aspect of physical human-robot collaboration (HRC) is to maintain a safe common workspace for human operator. However, close proximity between human-robot and unpredictability of human behavior raises serious challenges in terms of safety. This article proposes a risk analysis methodology for collaborative robotic applications, which is compatible with well-known standards in the area and relies on formal verification techniques to automate the traditional risk analysis methods. In particular, the methodology relies on temporal logic-based models to describe the different possible ways in which tasks can be carried out, and on fully automated formal verification techniques to explore the corresponding state space to detect and modify the hazardous situations at early stages of system design.Index Terms-Formal methods, human-robot collaboration (HRC), model-based risk assessment, robot safety, temporal logic. I. INTRODUCTIONH UMAN-ROBOT collaboration (HRC) in industrial settings enhances the flexibility and adaptability of robotic systems for production. Close proximity and hybrid task assignment between humans and robots have substantial impacts on the safety of human operators. Most importantly, shared dynamic environments cannot be effectively supported by static safety analyses. In particular, the hybrid human-robot tasks generate different possible execution workflows. Therefore, various task assignments among humans and robots can also change during operations. In realistic scenarios, the environment can also change, due to mobile resources, tool changing, modification of the layout, and process locations, so that the specifications of the system need to be re-evaluated. The safety of such evolving systems should not be verified as a static property, but rather according to the behavior of the system in actual situations.