148 research outputs found

    Fault Trees from Data: Efficient Learning with an Evolutionary Algorithm

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    Cyber-physical systems come with increasingly complex architectures and failure modes, which complicates the task of obtaining accurate system reliability models. At the same time, with the emergence of the (industrial) Internet-of-Things, systems are more and more often being monitored via advanced sensor systems. These sensors produce large amounts of data about the components' failure behaviour, and can, therefore, be fruitfully exploited to learn reliability models automatically. This paper presents an effective algorithm for learning a prominent class of reliability models, namely fault trees, from observational data. Our algorithm is evolutionary in nature; i.e., is an iterative, population-based, randomized search method among fault-tree structures that are increasingly more consistent with the observational data. We have evaluated our method on a large number of case studies, both on synthetic data, and industrial data. Our experiments show that our algorithm outperforms other methods and provides near-optimal results.Comment: This paper is an extended version of the SETTA 2019 paper, Springer-Verla

    Substrate Adhesion Regulates Sealing Zone Architecture and Dynamics in Cultured Osteoclasts

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    The bone-degrading activity of osteoclasts depends on the formation of a cytoskeletal-adhesive super-structure known as the sealing zone (SZ). The SZ is a dynamic structure, consisting of a condensed array of podosomes, the elementary adhesion-mediating structures of osteoclasts, interconnected by F-actin filaments. The molecular composition and structure of the SZ were extensively investigated, yet despite its major importance for bone formation and remodelling, the mechanisms underlying its assembly and dynamics are still poorly understood. Here we determine the relations between matrix adhesiveness and the formation, stability and expansion of the SZ. By growing differentiated osteoclasts on micro-patterned glass substrates, where adhesive areas are separated by non-adhesive PLL-g-PEG barriers, we show that SZ growth and fusion strictly depend on the continuity of substrate adhesiveness, at the micrometer scale. We present a possible model for the role of mechanical forces in SZ formation and reorganization, inspired by the current data

    How Linear Tension Converts to Curvature: Geometric Control of Bone Tissue Growth

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    This study investigated how substrate geometry influences in-vitro tissue formation at length scales much larger than a single cell. Two-millimetre thick hydroxyapatite plates containing circular pores and semi-circular channels of 0.5 mm radius, mimicking osteons and hemi-osteons respectively, were incubated with MC3T3-E1 cells for 4 weeks. The amount and shape of the tissue formed in the pores, as measured using phase contrast microscopy, depended on the substrate geometry. It was further demonstrated, using a simple geometric model, that the observed curvature-controlled growth can be derived from the assembly of tensile elements on a curved substrate. These tensile elements are cells anchored on distant points of the curved surface, thus creating an actin “chord” by generating tension between the adhesion sites. Such a chord model was used to link the shape of the substrate to cell organisation and tissue patterning. In a pore with a circular cross-section, tissue growth increases the average curvature of the surface, whereas a semi-circular channel tends to be flattened out. Thereby, a single mechanism could describe new tissue growth in both cortical and trabecular bone after resorption due to remodelling. These similarities between in-vitro and in-vivo patterns suggest geometry as an important signal for bone remodelling

    Vicrostatin – An Anti-Invasive Multi-Integrin Targeting Chimeric Disintegrin with Tumor Anti-Angiogenic and Pro-Apoptotic Activities

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    Similar to other integrin-targeting strategies, disintegrins have previously shown good efficacy in animal cancer models with favorable pharmacological attributes and translational potential. Nonetheless, these polypeptides are notoriously difficult to produce recombinantly due to their particular structure requiring the correct pairing of multiple disulfide bonds for biological activity. Here, we show that a sequence-engineered disintegrin (called vicrostatin or VCN) can be reliably produced in large scale amounts directly in the oxidative cytoplasm of Origami B E. coli. Through multiple integrin ligation (i.e., αvβ3, αvβ5, and α5β1), VCN targets both endothelial and cancer cells significantly inhibiting their motility through a reconstituted basement membrane. Interestingly, in a manner distinct from other integrin ligands but reminiscent of some ECM-derived endogenous anti-angiogenic fragments previously described in the literature, VCN profoundly disrupts the actin cytoskeleton of endothelial cells (EC) inducing a rapid disassembly of stress fibers and actin reorganization, ultimately interfering with EC's ability to invade and form tubes (tubulogenesis). Moreover, here we show for the first time that the addition of a disintegrin to tubulogenic EC sandwiched in vitro between two Matrigel layers negatively impacts their survival despite the presence of abundant haptotactic cues. A liposomal formulation of VCN (LVCN) was further evaluated in vivo in two animal cancer models with different growth characteristics. Our data demonstrate that LVCN is well tolerated while exerting a significant delay in tumor growth and an increase in the survival of treated animals. These results can be partially explained by potent tumor anti-angiogenic and pro-apoptotic effects induced by LVCN

    †Kenyaichthyidae fam. nov and †Kenyaichthys gen. nov - First Record of a Fossil Aplocheiloid Killifish (Teleostei, Cyprinodontiformes)

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    The extant Cyprinodontiformes (killifishes) with their two suborders Cyprinodontoidei and Aplocheiloidei represent a diverse and well-studied group of fishes. However, their fossil record is comparatively sparse and has so far yielded members of the Cyprinodontoidei only. Here we report on cyprinodontiform fossils from the upper Miocene Lukeino Formation in the Tugen Hills of the Central Rift Valley of Kenya, which represent the first fossil record of an aplocheiloid killifish. A total of 169 specimens - mostly extraordinarily well preserved and a sample of ten extant cyprinodontiform species were studied on the basis of morphometrics, meristics and osteology. A phylogenetic analysis using PAUP was also conducted for the fossils. Both the osteological data and the phylogenetic analysis provide strong evidence for the assignment of the fossils to the Aplocheiloidei, and justify the definition of the new family dagger Kenyaichthyidae, the new genus dagger Kenyaichthys and the new species dagger K. kipkechi sp. nov. The phylogenetic analysis unexpectedly places dagger Kenyaichthys gen. nov. in a sister relationship to the Rivulidae (a purely Neotropical group),a probable explanation might be lack of available synapomorphies for the Rivulidae, Nothobranchiidae and Aplocheilidae. The specimens of dagger K. kipkechi sp. nov. show several polymorphic characters and large overlap in meristic traits, which justifies their interpretation as a species flock in statu nascendi. Patterns of variation in neural and haemal spine dimensions in the caudal vertebrae of dagger Kenyaichthys gen. nov. and the extant species studied indicate that some previously suggested synapomorphies of the Cyprinodontoidei and Aplocheiloidei need to be revised

    Reduction in Local Ozone Levels in Urban São Paulo Due to a Shift from Ethanol to Gasoline Use

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    It has been proposed that lower NOx emission fuels such as ethanol can mitigate air pollution from vehicles burning oil-based hydrocarbons. Yet, existing modeling and laboratory studies, even those seeking to simulate the same environment, vary in their predictions of how gasoline/ethanol blends affect atmospheric pollutant concentrations, including ozone. Importantly, ambient concentrations have not been evaluated during an actual – as opposed to hypothetical – shift in fuel mix in a real-world environment. Here, we report the first such study, for the subtropical megacity of São Paulo, Brazil. We combine detailed street-hour level data on regulated pollutant concentrations, meteorology, and traffic with fuel shares from a consumer demand model to compare concentrations across subsamples that differ only in the fuel mix but are otherwise similar in meteorology, anthropogenic activity, and biogenic emissions. As the gasoline share of the bi-fuel light-duty vehicle fleet rose by 62 percentage points, we estimate a robust and statistically significant reduction of about 20% in ozone concentrations, and less precise increases in NO and CO concentrations. We propose that our “model-free” analysis potentially accounts for the interaction between anthropogenic and biogenic emissions and caution that successful strategies against ozone pollution require knowledge of the local chemistry and analysis beyond the presently monitored pollutants, most notably fine particles

    Pollinator-flower interactions in gardens during the COVID-19 pandemic lockdown of 2020

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    During the main COVID-19 global pandemic lockdown period of 2020 an impromptu set of pollination ecologists came together via social media and personal contacts to carry out standardised surveys of the flower visits and plants in gardens. The surveys involved 67 rural, suburban and urban gardens, of various sizes, ranging from 61.18° North in Norway to 37.96° South in Australia, resulting in a data set of 25,174 rows, with each row being a unique interaction record for that date/site/plant species, and comprising almost 47,000 visits to flowers, as well as records of flowers that were not visited by pollinators, for over 1,000 species and varieties belonging to more than 460genera and 96plant families. The more than 650 species of flower visitors belong to 12 orders of invertebrates and four of vertebrates. In this first publication from the project, we present a brief description of the data and make it freely available for any researchers to use in the future, the only restriction being that they cite this paper in the first instance. The data generated from these global surveys will provide scientific evidence to help us understand the role that private gardens (in urban, rural and suburban areas) can play in conserving insect pollinators and identify management actions to enhance their potential

    A global experiment on motivating social distancing during the COVID-19 pandemic

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    Significance Communicating in ways that motivate engagement in social distancing remains a critical global public health priority during the COVID-19 pandemic. This study tested motivational qualities of messages about social distancing (those that promoted choice and agency vs. those that were forceful and shaming) in 25,718 people in 89 countries. The autonomy-supportive message decreased feelings of defying social distancing recommendations relative to the controlling message, and the controlling message increased controlled motivation, a less effective form of motivation, relative to no message. Message type did not impact intentions to socially distance, but people’s existing motivations were related to intentions. Findings were generalizable across a geographically diverse sample and may inform public health communication strategies in this and future global health emergencies. Abstract Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges
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