The assessment of the damage probability of storage tanks in domino events triggered by fire

An approach aimed to the quantitative assessment of the risk caused by escalation scenarios triggered by fire was developed. Simplified models for the estimation of the vessel time to failure (ttf) with respect to the radiation intensity on the vessel shell were obtained using a multi-level approach to the analysis of vessel wall failure under different fire conditions. Each vessel “time to failure” calculated by this approach for the specific fire scenario of concern was compared to a reference time required for effective mitigation actions and related to the escalation probability. The failure probability of each vessel was correlated to the probability of scenarios involving multiple vessel failure as a consequence of the primary fire, thus allowing a comprehensive assessment of domino scenarios triggered by fire. The application of the methodology to the analysis of several case-studies allowed the estimation of the quantitative contribution of escalation events triggered by fire to the overall individual and societal risk indexes.     

Tocotrienol-rich fraction from palm oil affects gene expression in tumors resulting from MCF-7 cell inoculation in athymic mice

It has recently been shown that tocotrienols are the components of vitamin E responsible for inhibiting the growth of human breast cancer cells in vitro, through an estrogen-independent mechanism. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. To investigate the molecular basis of the effect of tocotrienols, we injected MCF-7 breast cancer cells into athymic nude mice. Mice were fed orally with 1 mg/d of tocotrienol-rich fraction (TRF) for 20 wk. At end of the 20 wk, there was a significant delay in the onset, incidence, and size of the tumors in nude mice supplemented with TRF compared with the controls. At autopsy, the tumor tissue was excised and analyzed for gene expression by means of a cDNA array technique. Thirty out of 1176 genes were significantly affected. Ten genes were down-regulated and 20 genes up-regulated with respect to untreated animals, and some genes in particular were involved in regulating the immune system and its function. The expression of the interferon-inducible transmembrane protein-1 gene was significantly up-regulated in tumors excised from TRF-treated animals compared with control mice. Within the group of genes related to the immune system, we also found that the CD59 glycoprotein precursor gene was up-regulated. Among the functional class of intracellular transducers/effectors/modulators, the c-myc gene was significantly down-regulated in tumors by TRF treatment. Our observations indicate that TRF supplementation significantly and specifically affects MCF-7 cell response after tumor formation in vivo and therefore the host immune function. The observed effect on gene expression is possibly exerted independently from the antioxidant activity typical of this family of molecules.     

Performance analysis of parallel Schwarz preconditioners in the LES of turbulent channel flows

We present a comparative study of parallel Schwarz preconditioners in the solution of linear systems arising in a Large Eddy Simulation (LES) procedure for turbulent plane channel flows. This procedure applies a time-splitting technique to suitably filtered Navier–Stokes equations, in order to decouple the continuity and momentum equations, and uses a semi-implicit scheme for time integration and finite volumes for space discretisation. This approach requires the solution of four sparse linear systems at each time step, accounting for a large part of the overall simulation; hence the linear system solvers are a crucial component in the whole procedure. Several preconditioners are applied in the simulation of a reference test case for the LES community, using discretisation grids of different sizes, with the aim of analysing the effects of different algorithmic choices defining the preconditioners, and identifying the most effective ones for the selected problem. The preconditioners, coupled with the GMRES method, are run within SParC-LES, a recently developed LES code based on the PSBLAS and MLD2P4 libraries for parallel sparse matrix computations and preconditioning.     

Physical exercise, oxidative stress and muscle damage in racehorses

Since it has been suggested that lipid peroxidation following free radical overproduction may be one of the causes of physical exercise-induced myopathies and hemolysis in horses, we looked for the possible relationships between these phenomena and muscle fiber damage. We use a homogeneous group of Maremmana stallions which, after a 3-month training period, underwent a series of physical exercises of increasing intensity. We determined the contents of malondialdehyde (MDA), one of the main lipid peroxidation end-products, and glutathione the substrate of one of the most important free radical scavenger enzymes. We also measured creatine phosphokinase and serum lactate dehydrogenase isoenzyme activities whose modification may be indicative of muscle fiber damage. The results obtained indicated that the physical exercise we adopted was able to modify both MDA and glutathione contents in blood. However, its effect on some LDH isoenzyme activities suggested possible damage to tissues other than muscle.     

Formalizing REST APIs for web-based communication and SIP interworking

This paper proposes an instantaneous recovery route design scheme using multiple coding-aware link protection scenarios to achieve higher link cost reduction in the network. In this scheme, two protection scenarios, namely, (i) traffic splitting (TS), and (ii) two sources and a common destination (2SD) are used to integrate multiple sources and a common destination. The proposed scheme consists of two phases. In the first phase, the proposed scheme determines routes for 2SD and TS scenarios of all possible source-destination pairs to minimize the total link cost. In this phase, the network coding is applied to the common path within each scenario, individually. In the second phase, network coding is applied to the common path between two scenarios (or a scenario pair) in order to enhance the resource saving. This phase develops conditions that select the most appropriate combination of scenario pairs, such as TS–TS, 2SD–2SD, and 2SD–TS for network coding, including their proofs. Using these conditions, a heuristic algorithm is introduced in order to select the most appropriate combination of scenario pairs for further enhancing of resource saving. Simulation results show that the proposed scheme outperforms the conventional 1 + 1 protection scheme, the TS scenario, and the 2SD scenario in terms of link cost reduction in the network.     

A methodology for the quantitative risk assessment of major accidents triggered by seismic events

A procedure for the quantitative risk assessment of accidents triggered by seismic events in industrial facilities was developed. The starting point of the procedure was the use of available historical data to assess the expected frequencies and the severity of seismic events. Available equipment-dependant failure probability models (vulnerability or fragility curves) were used to assess the damage probability of equipment items due to a seismic event. An analytic procedure was subsequently developed to identify, evaluate the credibility and finally assess the expected consequences of all the possible scenarios that may follow the seismic events. The procedure was implemented in a GIS-based software tool in order to manage the high number of event sequences that are likely to be generated in large industrial facilities. The developed methodology requires a limited amount of additional data with respect to those used in a conventional QRA, and yields with a limited effort a preliminary quantitative assessment of the contribution of the scenarios triggered by earthquakes to the individual and societal risk indexes. The application of the methodology to several case-studies evidenced that the scenarios initiated by seismic events may have a relevant influence on industrial risk, both raising the overall expected frequency of single scenarios and causing specific severe scenarios simultaneously involving several plant units.     

Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia

The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms have identified the most immunogenic epitopes from NPM1-mutated protein. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients, potentially contributing to remission maintenance and prolonged survival. Genetically engineered T cells, namely CAR-T or TCR-transduced T cells, directed against NPM1-mutated peptides bound to HLA could prospectively represent a promising therapeutic approach. Although either adoptive or vaccine-based immunotherapies are unlikely to be highly effective in patients with full-blown leukemia, these strategies, potentially in combination with immune-checkpoint inhibitors, could be promising in maintaining remission or preemptively eradicating persistent measurable residual disease, mainly in patients ineligible for allogeneic hematopoietic stem cell transplant (HSCT). Alternatively, neoantigen-specific donor lymphocyte infusion derived from healthy donors and targeting NPM1-mutated protein to selectively elicit graft-versus-leukemia effect may represent an attractive option in subjects experiencing post-HSCT relapse. Future studies are warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies may have potential clinical utility in NPM1-mutated AML patients.