STPA Based Approach for a Resilience Assessment at an Early Design Stage of a Cruise Ship

Several definitions and approaches have been proposed to study resilience in different fields like materials, ecology, psychology and infrastructures. A general definition, applicable also to human-made or engineered systems, describes resilience as the ability to maintain capability in case of disruption. Thanks to its systemic, top-down approach, STAMP (System-Theoretic Accident Model and Processes) has been already identified in literature as a very effective and \u201cconductive\u201d reference when reasoning about the possible need of resilience of a complex system. The STAMP-based tool named STPA (System Theoretic Process Analysis) establishes the following steps: identify system accidents, hazards; draw functional control structure; identify unsafe control actions (UCAs); identify accident scenarios; formulate decisions and recommendations. It focuses on what actually is in the hands of the system designer and operator i.e. the possibility to take action on hazards that can be eliminated or controlled. In this paper an approach to design resilience into a cruise vessel will be proposed. An application case will be developed considering the specific hazard of dead ship condition i.e. of energy black-out on board. In case of navigation close to the shore and in heavy weather condition, this situation can rapidly evolve into a loss. The ship energy production and delivery system, both for the propulsion and for the hotel services, will be considered. Running the procedure up to the level of UCAs enables the identification of the possible disruptive events capable to degrade the operational performance of the system. Starting from this point, suggestions will be discussed for a selected UCA, able to prevent or mitigate it. A metric for ship resilience will be proposed as well with the aim to allow comparisons among different design solutions

Life cycle performance assessment tool development and application with a focus on maintenance aspects

Ships are among the most complex systems in the world. The always increasing interest in environmental aspects, the evolution of technologies and the introduction of new rule constraints in the maritime field have compelled the innovation of the ship design approach. At an early design stage, there is the need to compare different design solutions, also in terms of environmental performance, building and operative costs over the whole ship life cycle. In this context, the Life Cycle Performance Assessment (LCPA) tool allows an integrated design approach merging the evaluation of both costs and environmental performances on a comparative basis, among different design solutions. Starting from the first tool release, this work aims to focus on the maintenance of the propulsion system, developing a flexible calculation method for maintenance costs prediction, based on the ship operational profiles and the selected technical solution. After the improvement, the whole LCPA tool has been applied on a research vessel to evaluate, among different propulsion layout solutions, the one with the more advantageous performance in terms of costs during the whole vessel operating life. The identification of the best design solution is strictly dependent on the selection criterion and the point of view of the interested parties using the LCPA tool, e.g., the shipbuilder or the ship-owner

A Novel Form of Chondrocyte Stress is Triggered by a COMP Mutation Causing Pseudoachondroplasia

Pseudoachondroplasia (PSACH) results from mutations in cartilage oligomeric matrix protein (COMP) and the p.D469del mutation within the type III repeats of COMP accounts for approximately 30% of PSACH. To determine disease mechanisms of PSACH in vivo, we introduced the Comp D469del mutation into the mouse genome. Mutant animals were normal at birth but grew slower than their wild-type littermates and developed short-limb dwarfism. In the growth plates of mutant mice chondrocyte columns were reduced in number and poorly organized, while mutant COMP was retained within the endoplasmic reticulum (ER) of cells. Chondrocyte proliferation was reduced and apoptosis was both increased and spatially dysregulated. Previous studies on COMP mutations have shown mutant COMP is co-localized with chaperone proteins, and we have reported an unfolded protein response (UPR) in mouse models of PSACH-MED (multiple epiphyseal dysplasia) harboring mutations in Comp (T585M) and Matn3, Comp etc (V194D). However, we found no evidence of UPR in this mouse model of PSACH. In contrast, microarray analysis identified expression changes in groups of genes implicated in oxidative stress, cell cycle regulation, and apoptosis, which is consistent with the chondrocyte pathology. Overall, these data suggest that a novel form of chondrocyte stress triggered by the expression of mutant COMP is central to the pathogenesis of PSACH. Hum Mutat 33:218–231, 2012. © 2011 Wiley Periodicals, Inc

A Philosophy of “Doing” in the Digital

Playing in counterpoint with the general theoretical orientation of the book, this chapter does not focus its attention on the recording and archiving capabilities of the digital medium. Instead, it proposes an understanding of the digital medium that focuses on its disclosing various forms of “doing.” Gualeni’s chapter begins by offering an understanding of “doing in the digital” that methodologically separates “doing as acting” from “doing as making.” After setting its theoretical framework, the chapter discusses an “interactive thought experiment” designed by the author that is analyzed as a digital artifact leveraging both dimensions of “doing in the digital” for philosophical purposes. In extreme synthesis, one could say that this chapter is about several kinds of soups

Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma

The accrual of myeloid-derived suppressor cells (MDSCs) represents a major obstacle to effective immunotherapy in cancer patients, but the mechanisms underlying this process in the human setting remain elusive. Here, we describe a set of microRNAs (miR-146a, miR-155, miR-125b, miR-100, let-7e, miR-125a, miR-146b, miR-99b) that are associated with MDSCs and with resistance to treatment with immune checkpoint inhibitors in melanoma patients. The miRs were identified by transcriptional analyses as being responsible for the conversion of monocytes into MDSCs (CD14+HLA-DRneg cells) mediated by melanoma extracellular vesicles (EVs) and were shown to recreate MDSC features upon transfection. In melanoma patients, these miRs are increased in circulating CD14+ monocytes, plasma and tumor samples, where they correlate with the myeloid cell infiltrate. In plasma, their baseline level clusters with the clinical efficacy of CTLA-4 or PD-1 blockade. Hence, MDSC-related miRs represent an indicator of MDSC activity in cancer patients and a potential blood marker of a poor immunotherapy outcome

Increased classical endoplasmic reticulum stress is sufficient to reduce chondrocyte proliferation rate in the growth plate and decrease bone growth

Copyright: © 2015 Kung et al. Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH). The majority of these diseases feature classical endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITgcog) was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tgcog) in chondrocytes. The skeletal and histological phenotypes of these ColIITgcog mice were characterised. The expression and intracellular retention of Tgcog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2á and spliced Xbp1. ColIITgcog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole

About necessary and sufficient conditions to design safe ships: the appropriate ship design process

Focus of this paper is the evidence of strong interconnection between safety rules and design process especially for passenger ships. A change in the methodological approach for the safety framework might imply a strong renewal course also of the decision making process during the ship design, keeping in mind its unique peculiarities. After a general discussion about some open issues relevant to performance-based rules implementation, some considerations are given about specific points raised by the \u201cSafe Return to Port\u201d capability in relation with the ship design process. Finally, the high level of flexibility in principle guaranteed by performance-based assessment is discussed in relation with the difficulty to implement the design process as an optimization procedure, due to large amount of information involved and the complexity of problem in terms of objective functions and constraints

Different Ballast Configurations for a 78\u2019 Racer Cruiser Sailing Yacht: a Case Study With Particular Attention To The Stability Performance

In the field of sailing yacht design, there is a growing interest and application towards solutions for righting moment enhancement, to be exploited when a superior capacity to counter-balance wind effect is required. The typical solution adopted to provide such increase in performance is the use of ballast systems, mainly represented by the water ballast tanks or the canting keel. In the first case the effect is obtained by transversal shift of ballast water, loaded/unloaded on board on purpose. In the latter, the keel is able to cant for a definite angle range in order to transfer a significant weight far from the symmetry plan. During the design process both systems need to be attentively examined with the aim to find the best solution in terms of interference with the yacht arrangement. In the paper, an application study will be presented for a 78\u2019 Racer-Cruiser sailing yacht and different design solutions will be compared. A particular attention will be paid to the stability performance. Furthermore, for sake of completeness, a lifting keel configuration will also be considered and commented in terms of stability