A hybrid model for human-factor analysis of engine-room fires on ships: HFACS-PV&FFTA

In this study, an analysis of fire-explosion accidents in ship engine rooms was conducted. For analysis, a hybrid method including the Human Factors Analysis and Classification System (HFACS) and fuzzy fault tree analysis (FFTA) was used. Using the HFACS method, the factors in the formation of engine-room fires were classified according to a hierarchical structure. The possible accident scenarios and probabilities were calculated using the FFTA method. In this study, it was observed that fire-explosion accidents were concentrated in ships over 20 years old and that mechanical fatigue affected accident formation. In particular, when the increased hot surfaces due to the operation of a ship's engines while it is in motion are combined with oil/fuel leakage, fire-related accidents become inevitable. Failure to provide proper insulation also triggers the occurrence of accidents. It has been observed that some of such accidents occur because the materials used in maintenance and repair work are not original to the ship. During this study, the causes of accidents were examined to prevent fire-related accidents from occurring in engine rooms, and suggestions were made to prevent similar accidents from happening in the future

Structure, chemistry, and charge transfer resistance of the interface between Li7La3Zr2O12 electrolyte and LiCoO2 cathode

All-solid-state batteries promise significant safety and energy density advantages over liquid-electrolyte batteries. The interface between the cathode and the solid electrolyte is an important contributor to charge transfer resistance. Strong bonding of solid oxide electrolytes and cathodes requires sintering at elevated temperatures. Knowledge of the temperature dependence of the composition and charge transfer properties of this interface is important for determining the ideal sintering conditions. To understand the interfacial decomposition processes and their onset temperatures, model systems of LiCoO2 (LCO) thin films deposited on cubic Al-doped Li7La3Zr2O12 (LLZO) pellets were studied as a function of temperature using interface-sensitive techniques. X-ray photoelectron spectroscopy (XPS), secondary ion mass spectroscopy (SIMS), and energy-dispersive X-ray spectroscopy (EDS) data indicated significant cation interdiffusion and structural changes starting at temperatures as low as 300°C. La2Zr2O7 and Li2CO3 were identified as decomposition products after annealing at 500°C by synchrotron X-ray diffraction (XRD). X-ray absorption spectroscopy (XAS) results indicate the presence of also LaCoO3, in addition to La2Zr2O7 and Li2CO3. Based on electrochemical impedance spectroscopy, and depth profiling of the Li distribution upon potentiostatic hold experiments on symmetric LCO|LLZO|LCO cells, the interfaces exhibited significantly increased impedance, up to 8 times that of the as-deposited samples after annealing at 500°C. Our results indicate that lower-temperature processing conditions, shorter annealing time scales, and CO2-free environments are desirable for obtaining ceramic cathode-electrolyte interfaces that enable fast Li transfer and high capacity

Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2

Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits. The S1 site lies within a key negative regulatory region (NRR) of the receptor, which contains three highly conserved Lin12/Notch repeats and a heterodimerization domain (HD) that interact to prevent premature signaling in the absence of ligands. Because the role of S1 cleavage in Notch signaling remains unresolved, we investigated the effect of S1 cleavage on the structure, surface trafficking and ligand-mediated activation of human Notch1 and Notch2, as well as on ligand-independent activation of Notch1 by mutations found in human leukemia.The X-ray structure of the Notch1 NRR after furin cleavage shows little change when compared with that of an engineered Notch1 NRR lacking the S1-cleavage loop. Likewise, NMR studies of the Notch2 HD domain show that the loop containing the S1 site can be removed or cleaved without causing a substantial change in its structure. However, Notch1 and Notch2 receptors engineered to resist S1 cleavage exhibit unexpected differences in surface delivery and signaling competence: S1-resistant Notch1 receptors exhibit decreased, but detectable, surface expression and ligand-mediated receptor activation, whereas S1-resistant Notch2 receptors are fully competent for cell surface delivery and for activation by ligands. Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity.S1 cleavage has distinct effects on the surface expression of Notch1 and Notch2, but is not generally required for physiologic or pathophysiologic activation of Notch proteins. These findings are consistent with models for receptor activation in which ligand-binding or T-ALL-associated mutations lead to conformational changes of the NRR that permit metalloprotease cleavage

Atomic picture of ligand migration in toluene 4-monooxygenase

Computational modeling combined with mutational and activity assays was used to underline the substrate migration pathways in toluene 4-monooxygenase, a member of the important family of bacterial multicomponent monooxygenases (BMMs). In all structurally defined BMM hydroxylases, several hydrophobic cavities in the α-subunit map a preserved path from the protein surface to the diiron active site. Our results confirm the presence of two pathways by which different aromatic molecules can enter/escape the active site. While the substrate is observed to enter from both channels, the more hydrophilic product is withdrawn mainly from the shorter channel ending at residues D285 and E214. The long channel ends in the vicinity of S395, whose variants have been seen to affect activity and specificity. These mutational effects are clearly reproduced and rationalized by the in silico studies. Furthermore, the combined computational and experimental results highlight the importance of residue F269, which is located at the intersection of the two channels.This work has been funded by the EU projects INDOX (KBBE20137613549) and ERC 2009Adg25027PELE (to V.G) and the Spanish Ministry of Education and Science project CTQ201348287 (to V.G).Peer ReviewedPostprint (author's final draft

European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

Background: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. Design: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts’ consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. Conclusion: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer

Understanding the roles of gingival beta-defensins

Gingival epithelium produces β-defensins, small cationic peptides, as part of its contribution to the innate host defense against the bacterial challenge that is constantly present in the oral cavity. Besides their functions in healthy gingival tissues, β-defensins are involved in the initiation and progression, as well as restriction of periodontal tissue destruction, by acting as antimicrobial, chemotactic, and anti-inflammatory agents. In this article, we review the common knowledge about β-defensins, coming from in vivo and in vitro monolayer studies, and present new aspects, based on the experience on three-dimensional organotypic culture models, to the important role of gingival β-defensins in homeostasis of the periodontium

Searches for new physics using the t(t)over-bar invariant mass distribution in pp collisions at √s=8 TeV

This is the pre-print version of the final published paper that is available from the link belowSearches for anomalous top quark-antiquark production are presented, based on pp collisions at √s=8  TeV . The data, corresponding to an integrated luminosity of 19:7 fb^-1, were collected with the CMS detector at the LHC. The observed tt invariant mass spectrum is found to be compatible with the standard model prediction. Limits on the production cross section times branching fraction probe, for the first time, a region of parameter space for certain models of new physics not yet constrained by precision measurements

Short-Term Price Overreaction: Identification, Testing, Exploitation

This paper examines short-term price reactions after one-day abnormal price changes and whether they create exploitable profit opportunities in various financial markets. A t-test confirms the presence of overreactions and also suggests that there is an "inertia anomaly", i.e. after an overreaction day prices tend to move in the same direction for some time. A trading robot approach is then used to test two trading strategies aimed at exploiting the detected anomalies to make abnormal profits. The results suggest that a strategy based on counter-movements after overreactions does not generate profits in the FOREX and the commodity markets, but it is profitable in the case of the US stock market. By contrast, a strategy exploiting the "inertia anomaly" produces profits in the case of the FOREX and the commodity markets, but not in the case of the US stock market