170 research outputs found

    Analisi del comportamento dinamico di supporti antishock per applicazioni navali

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    Formal Verification of Security Protocol Implementations: A Survey

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    Automated formal verification of security protocols has been mostly focused on analyzing high-level abstract models which, however, are significantly different from real protocol implementations written in programming languages. Recently, some researchers have started investigating techniques that bring automated formal proofs closer to real implementations. This paper surveys these attempts, focusing on approaches that target the application code that implements protocol logic, rather than the libraries that implement cryptography. According to these approaches, libraries are assumed to correctly implement some models. The aim is to derive formal proofs that, under this assumption, give assurance about the application code that implements the protocol logic. The two main approaches of model extraction and code generation are presented, along with the main techniques adopted for each approac

    po 237 the pro oncogenic transcription factor stat3 regulates ca2 release and apoptosis from the endoplasmic reticulum via interaction with the ca2 channel ip3r3

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    Introduction Signal Transducer and Activator of Transcription (STAT) 3 is an oncogenic transcription factor found constitutively activated in several tumours, where it exerts its functions both as a canonical transcription factor and as a non-canonical regulator of energy metabolism and mitochondrial functions. These two activities rely on different post-translational activating events; the phosphorylation on Y705 is involved in nuclear activities, while that on S727 is relevant for mitochondrial functions. Mitochondrial STAT3 increases aerobic glycolysis and decreases ROS production, partly by interacting with the Electron Transfer Complexes (ETC). Material and methods By means of cell fractionations, we tested STAT3 localization to the Endoplasmic Reticulum (ER) in breast cancer cell lines dependent or not on STAT3 activity. We then measured Ca2+ release and apoptotic response in the same cells. The physical interaction between inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) and STAT3 was demonstrated by co-IP either of the endogenous proteins or of their truncated/mutated forms, while STAT3 role in the degradation of IP3R3 was tested by serum starvation and refeeding experiments, followed by WB. Results and discussions We describe here the previously undetected abundant localization of STAT3 also to the ER. In this cellular compartment IP3R3, a Ca2+ channel that allows Ca2+ release from the ER and the mitochondrial associated membranes (MAMs) in response to IP3, regulates the balance between mitochondrial activation and Ca2+-triggered apoptosis. We observed that STAT3 within the ER physically interacts with IP3R3 and, via its phosphorylation on S727, it down-regulates Ca2+ release and apoptosis. Indeed, STAT3 silencing enhances both ER Ca2+ release and sensitivity to apoptosis following oxidative stress in STAT3-dependent mammary tumour cells, correlating with increased IP3R3 levels. In line with this, basal-like breast tumours, which frequently display constitutively active STAT3, show an inverse correlation between IP3R3 and STAT3 protein levels. Conclusion Our results indicate that S727-phosphorylated STAT3 contribute to mammary tumour aggressiveness, also by localising to the ER and regulating Ca2+ fluxes. STAT3-mediated enhanced IP3R3 degradation leads to decreased Ca2+ release and thus to resistance to apoptosis. This new non-canonical STAT3 role appears to be particularly relevant in basal-like breast cancers, adding a new mechanisms through which STAT3 exerts its well established pro-oncogenic anti-apoptotic role

    Numerical and experimental investigation of a lightweight bonnet for pedestrian safety

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    A topic of great consideration in current vehicle development in Europe is pedestrian protection. The enforcement of a new regulation trying to decrease the injuries to head, pelvis, and leg of pedestrian impacted by cars, is imposing great changes in vehicles' front design. In the present work a design solution for the bonnet, which is the main body part interacting with the human head during a car to pedestrian collision, is proposed. This solution meets the stiffness and safety targets, takes into account the manufacturing and recyclability requirements and gives a relevant contribution to vehicle lightweight. Thus this proposed solution puts in evidence that safety and lightweight are not incompatible targets. The amount of potential injury to the pedestrian head is evaluated, as prescribed by the standard test procedures, by means of a headform launched on the bonnet. However, the standard approach based on the head injury criterion (HIC) value only is reported to be largely unsatisfactory: therefore, a new experimental methodology for the measurement of the translational and the rotational accelerations has been developed, and the experimental results are reported. This would be a starting point for the evolution of currently adopted injury criteria to increase the safety of the vulnerable road user
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