Pore geometry as a control on rock strength

This study was funded via RJW's University of Leicester start-up fund, as part of AAB's PhD project. We thank Don Swanson and Mike Poland at HVO, Hawai'i, for their help and advice during fieldwork planning and sample collection in the Koa'e fault system, and the National Park Service for granting a research permit to collect rock samples. Sergio Vinciguerra is thanked for access to the Rock Mechanics and Physics lab at the British Geological Survey and Audrey Ougier-Simonin is thanked for her help preparing samples and advice during testing. We thank Mike Heap (EOST Strasbourg) and an anonymous reviewer for their detailed and careful comments that greatly improved the manuscript.Peer reviewedPostprin

Analysis of Different Types of Regret in Continuous Noisy Optimization

The performance measure of an algorithm is a crucial part of its analysis. The performance can be determined by the study on the convergence rate of the algorithm in question. It is necessary to study some (hopefully convergent) sequence that will measure how "good" is the approximated optimum compared to the real optimum. The concept of Regret is widely used in the bandit literature for assessing the performance of an algorithm. The same concept is also used in the framework of optimization algorithms, sometimes under other names or without a specific name. And the numerical evaluation of convergence rate of noisy algorithms often involves approximations of regrets. We discuss here two types of approximations of Simple Regret used in practice for the evaluation of algorithms for noisy optimization. We use specific algorithms of different nature and the noisy sphere function to show the following results. The approximation of Simple Regret, termed here Approximate Simple Regret, used in some optimization testbeds, fails to estimate the Simple Regret convergence rate. We also discuss a recent new approximation of Simple Regret, that we term Robust Simple Regret, and show its advantages and disadvantages.Comment: Genetic and Evolutionary Computation Conference 2016, Jul 2016, Denver, United States. 201

Endothelial ADAM10 utilization defines a molecular pathway of vascular injury in mice with bacterial sepsis

The endothelium plays a critical role in the host response to infection and has been a focus of investigation in sepsis. While it is appreciated that intravascular thrombus formation, severe inflammation, and loss of endothelial integrity impair tissue oxygenation during sepsis, the precise molecular mechanisms that lead to endothelial injury remain poorly understood. We demonstrate here that endothelial ADAM10 was essential for the pathogenesis of Staphylococcus aureus sepsis, contributing to α-toxin-mediated (Hla-mediated) microvascular thrombus formation and lethality. As ADAM10 is essential for endothelial development and homeostasis, we examined whether other major human sepsis pathogens also rely on ADAM10-dependent pathways in pathogenesis. Mice harboring an endothelium-specific knockout of ADAM10 were protected against lethal Pseudomonas aeruginosa and Streptococcus pneumoniae sepsis, yet remained fully susceptible to group B streptococci and Candida albicans sepsis. These studies illustrate a previously unknown role for ADAM10 in sepsis-associated endothelial injury and suggest that understanding pathogen-specific divergent host pathways in sepsis may enable more precise targeting of disease

On the Prior Sensitivity of Thompson Sampling

The empirically successful Thompson Sampling algorithm for stochastic bandits has drawn much interest in understanding its theoretical properties. One important benefit of the algorithm is that it allows domain knowledge to be conveniently encoded as a prior distribution to balance exploration and exploitation more effectively. While it is generally believed that the algorithm's regret is low (high) when the prior is good (bad), little is known about the exact dependence. In this paper, we fully characterize the algorithm's worst-case dependence of regret on the choice of prior, focusing on a special yet representative case. These results also provide insights into the general sensitivity of the algorithm to the choice of priors. In particular, with $p$ being the prior probability mass of the true reward-generating model, we prove $O(\sqrt{T/p})$ and $O(\sqrt{(1-p)T})$ regret upper bounds for the bad- and good-prior cases, respectively, as well as \emph{matching} lower bounds. Our proofs rely on the discovery of a fundamental property of Thompson Sampling and make heavy use of martingale theory, both of which appear novel in the literature, to the best of our knowledge.Comment: Appears in the 27th International Conference on Algorithmic Learning Theory (ALT), 201

Relational und dimensional: heuristische Dimensionen in der Situationsanalyse am Beispiel von Care-Praktiken und ihrer Materialität

Die Berücksichtigung von Materialität ist ein wesentlicher Bestandteil der Sozialwissenschaften des 21. Jahrhunderts. Für die empirische Sozialforschung ergeben sich daraus methodologische und methodische Herausforderungen, insbesondere in Bezug auf nicht-menschliche Akteur*innen und deren Körperlichkeit. Dies erfordert spezifische Analyseverfahren. Die Situationsanalyse mit ihrer Fokusverschiebung auf die Relationalität von heterogenen Akteur*innen, die eine Handlungssituation generieren, bietet dazu eine entsprechende Möglichkeit. Im vorliegenden Beitrag gehen wir auf der Basis zweier empirischer Projekte zu Care-Praktiken im medizinischen Bereich der Frage der Multidimensionalität von materiellen Beziehungen nach. Die Beispiele beziehen sich zum einen auf das Einschläfern von Pferden in der Tiermedizin und zum anderen auf automatisierte Technologien bei der Behandlung von Typ-1-Diabetes. Im Zentrum der Analyse steht die Materialität des Beziehungsgeflechts. Wir schlagen vor, den Werkzeugkasten der Situationsanalyse um ein dimensionalisierendes Relations-Mapping zu erweitern, indem die Beziehungen zwischen Elementen in Dimensionen unterteilt werden. In den Beispielen nutzen wir eine Dimensionalisierung, bei der wir uns an der Care-Theorie orientieren. Die Verwendung von unterschiedlichen Farben im Mapping macht die Multidimensionalität der Situation erst sichtbar und ermöglicht es, der Komplexität der materiellen und körperlichen Beziehungen analytisch mehr Raum zu geben.The consideration of materiality is an essential component of the social sciences of the 21st century. For empirical social research, this poses methodological challenges, especially concerning non-human actors and their corporeality. Therefore, specific analytical strategies are required. Situational analysis, focusing on the relationality of heterogeneous actors generating a situation, offers one such possibility. In this article, we explore the multidimensionality and relationality of materiality through two empirical projects about care practices in the medical field. Examples are euthanizing of horses in veterinary medicine and automated technologies in managing type 1 diabetes. In the analysis, we focus on the materiality of the relational network. We propose to extend the situation analysis toolbox by adding dimensionalizing relational mapping, where we categorize the relations between elements into dimensions. In the examples, we use a dimensionalization inspired by care theory. The use of different colors in the mapping practice highlights the multidimensionality of the situation and gives more analytical space to the complexity of the material and embodied connections

Extension parallel to the rift zone during segmented fault growth: application to the evolution of the NE Atlantic

The mechanical interaction of propagating normal faults is known to influence the linkage geometry of first-order faults, and the development of second-order faults and fractures, which transfer displacement within relay zones. Here we use natural examples of growth faults from two active volcanic rift zones (Koa`e, island of Hawai`i, and Krafla, northern Iceland) to illustrate the importance of horizontal-plane extension (heave) gradients, and associated vertical axis rotations, in evolving continental rift systems. Second-order extension and extensional-shear faults within the relay zones variably resolve components of regional extension, and components of extension and/or shortening parallel to the rift zone, to accommodate the inherently three-dimensional (3-D) strains associated with relay zone development and rotation. Such a configuration involves volume increase, which is accommodated at the surface by open fractures; in the subsurface this may be accommodated by veins or dikes oriented obliquely and normal to the rift axis. To consider the scalability of the effects of relay zone rotations, we compare the geometry and kinematics of fault and fracture sets in the Koa`e and Krafla rift zones with data from exhumed contemporaneous fault and dike systems developed within a > 5×104 km2 relay system that developed during formation of the NE Atlantic margins. Based on the findings presented here we propose a new conceptual model for the evolution of segmented continental rift basins on the NE Atlantic margins

Structural basis for membrane attack complex inhibition by CD59

CD59 is an abundant immuno-regulatory receptor that protects human cells from damage during complement activation. Here we show how the receptor binds complement proteins C8 and C9 at the membrane to prevent insertion and polymerization of membrane attack complex (MAC) pores. We present cryo-electron microscopy structures of two inhibited MAC precursors known as C5b8 and C5b9. We discover that in both complexes, CD59 binds the pore-forming β-hairpins of C8 to form an intermolecular β-sheet that prevents membrane perforation. While bound to C8, CD59 deflects the cascading C9 β-hairpins, rerouting their trajectory into the membrane. Preventing insertion of C9 restricts structural transitions of subsequent monomers and indirectly halts MAC polymerization. We combine our structural data with cellular assays and molecular dynamics simulations to explain how the membrane environment impacts the dual roles of CD59 in controlling pore formation of MAC, and as a target of bacterial virulence factors which hijack CD59 to lyse human cells

Bayesian Best-Arm Identification for Selecting Influenza Mitigation Strategies

Pandemic influenza has the epidemic potential to kill millions of people. While various preventive measures exist (i.a., vaccination and school closures), deciding on strategies that lead to their most effective and efficient use remains challenging. To this end, individual-based epidemiological models are essential to assist decision makers in determining the best strategy to curb epidemic spread. However, individual-based models are computationally intensive and it is therefore pivotal to identify the optimal strategy using a minimal amount of model evaluations. Additionally, as epidemiological modeling experiments need to be planned, a computational budget needs to be specified a priori. Consequently, we present a new sampling technique to optimize the evaluation of preventive strategies using fixed budget best-arm identification algorithms. We use epidemiological modeling theory to derive knowledge about the reward distribution which we exploit using Bayesian best-arm identification algorithms (i.e., Top-two Thompson sampling and BayesGap). We evaluate these algorithms in a realistic experimental setting and demonstrate that it is possible to identify the optimal strategy using only a limited number of model evaluations, i.e., 2-to-3 times faster compared to the uniform sampling method, the predominant technique used for epidemiological decision making in the literature. Finally, we contribute and evaluate a statistic for Top-two Thompson sampling to inform the decision makers about the confidence of an arm recommendation

Structure and Melting of Two-Species Charged Clusters in a Parabolic Trap

We consider a system of charged particles interacting with an unscreened Coulomb repulsion in a two-dimensional parabolic confining trap. The static charge on a portion of the particles is twice as large as the charge on the remaining particles. The particles separate into a shell structure with those of greater charge situated farther from the center of the trap. As we vary the ratio of the number of particles of the two species, we find that for certain configurations, the symmetry of the arrangement of the inner cluster of singly-charged particles matches the symmetry of the outer ring of doubly-charged particles. These matching configurations have a higher melting temperature and a higher thermal threshold for intershell rotation between the species than the nonmatching configurations.Comment: 4 pages, 6 postscript figure