Sequential design of computer experiments for the estimation of a probability of failure

This paper deals with the problem of estimating the volume of the excursion set of a function $f:\mathbb{R}^d \to \mathbb{R}$ above a given threshold, under a probability measure on $\mathbb{R}^d$ that is assumed to be known. In the industrial world, this corresponds to the problem of estimating a probability of failure of a system. When only an expensive-to-simulate model of the system is available, the budget for simulations is usually severely limited and therefore classical Monte Carlo methods ought to be avoided. One of the main contributions of this article is to derive SUR (stepwise uncertainty reduction) strategies from a Bayesian-theoretic formulation of the problem of estimating a probability of failure. These sequential strategies use a Gaussian process model of $f$ and aim at performing evaluations of $f$ as efficiently as possible to infer the value of the probability of failure. We compare these strategies to other strategies also based on a Gaussian process model for estimating a probability of failure.Comment: This is an author-generated postprint version. The published version is available at http://www.springerlink.co

Diode and final-focus simulations for DARHT

Beam dynamics calculations for the injector and final-focus region of a 4 kA, 20 MeV linear induction accelerator are presented. The injector is a low-emittance 4 MeV thermionic or photocathode diode designed to produce four 70 ns pulses over 2 {micro}sec. Due to the long total pule length, the authors have kept the field stress to < 200 kV/cm over the cathode electrode, and to {approx} 50 kV/cm on the radial insulator stacks. The normalized edge emittance produced by the diode is only {approx} 0.019 cm-rad. In the final-focus region, the authors have modeled the effect of ion emission from the target. The intense electric field of the beam at the 1-mm-diameter focal spot produces substantial ion velocities, and, if the space-charge-limited current density can be supplied, significant focal spot degradation may occur due to ion space-charge. Calculations for the existing Integrated Test Stand, which has a larger focal spot, show that the effect should be observable for H{sup +} and C{sup +} ion species. The effect is lessened if there is insufficient ion density on the target to supply the space-charge-limited current density, or if the ion charge-to-mass ratio is sufficiently small

Active Brownian Particles. From Individual to Collective Stochastic Dynamics

We review theoretical models of individual motility as well as collective dynamics and pattern formation of active particles. We focus on simple models of active dynamics with a particular emphasis on nonlinear and stochastic dynamics of such self-propelled entities in the framework of statistical mechanics. Examples of such active units in complex physico-chemical and biological systems are chemically powered nano-rods, localized patterns in reaction-diffusion system, motile cells or macroscopic animals. Based on the description of individual motion of point-like active particles by stochastic differential equations, we discuss different velocity-dependent friction functions, the impact of various types of fluctuations and calculate characteristic observables such as stationary velocity distributions or diffusion coefficients. Finally, we consider not only the free and confined individual active dynamics but also different types of interaction between active particles. The resulting collective dynamical behavior of large assemblies and aggregates of active units is discussed and an overview over some recent results on spatiotemporal pattern formation in such systems is given.Comment: 161 pages, Review, Eur Phys J Special-Topics, accepte

Estimates of energy fluence at the focal plane in beams undergoing neutralized drift compression

The authors estimate the energy fluence (energy per unit area) at the focal plane of a beam undergoing neutralized drift compression and neutralized solenoidal final focus, as is being carried out in the Neutralized Drift Compression Experiment (NDCX) at LBNL. In these experiments, in order to reach high beam intensity, the beam is compressed longitudinally by ramping the beam velocity (i.e. introducing a velocity tilt) over the course of the pulse, and the beam is transversely focused in a high field solenoid just before the target. To remove the effects of space charge, the beam drifts in a plasma. The tilt introduces chromatic aberrations, with different slices of the original beam having different radii at the focal plane. The fluence can be calculated by summing the contribution from the various slices. They develop analytic formulae for the energy fluence for beams that have current profiles that are initially constant in time. They compare with envelope and particle-in-cell calculations. The expressions derived are useful for predicting how the fluence scales with accelerator and beam parameters

β-Lactamase cleavable antimicrobial peptide–drug conjugates

Antimicrobial resistance attracts a considerable amount of attention as it threatens the efficiency of current antibacterial treatments. Besides a more considerate use of current antibiotics to slow down the spread of antimicrobial resistance, there is ample need for new therapeutic avenues to treat already resistant strains. Here, we describe the use of a cleavable peptide–drug conjugate to target bacteria with diverse resistance strategies. The conjugate consists of three main components: a β-lactamase cleavable linker, a positively charged stapled antimicrobial peptide, and an antibiotic. The linker ensures selective cleavage and provides the prospect of lowering systemic toxicity of the conjugate. The positively charged peptide targets the negatively charged bacterial membrane, and stapling pre-organises it in a helical structure. Finally, the drug provides another, distinct mode of action to the peptide, which should overall reduce the development of resistance. A series of peptides was prepared and the most promising one was then developed into a stapled conjugate. The factors affecting the activity of this conjugate were investigated, proving cleavage by β-lactamase and superior potency compared to the non-cleavable control, as shown by its minimal inhibitory concentrations

Measurement of the neutron magnetic form factor from inclusive quasielastic scattering of polarized electrons from polarized 3He

We report a measurement of the asymmetry in spin-dependent quasielastic scattering of longitudinally polarized electrons from a polarized 3He target. The neutron magnetic form factor GMn has been extracted from the measured asymmetry based on recent PWIA calculations using spin-dependent spectral functions. Our determination of GMn at Q2=0.19 (GeV/c)2 agrees with the dipole parametrization. This experiment represents the first measurement of the neutron magnetic form factor using spin-dependent electron scattering

Desempenho de cabras em lactação alimentadas com dietas com diferentes níveis de fibra oriundas de forragem com maturidade avançada

Objetivou-se com este trabalho avaliar o efeito de diferentes teores de fibra em detergente neutro oriunda da forragem com maturidade avançada sobre o consumo, a digestibilidade da matéria seca e de nutrientes, o balanço de nitrogênio, a produção de leite, a eficiência de utilização da energia metabolizável e o comportamento ingestivo de cabras em lactação. Foram distribuídas cinco cabras em delineamento em quadrado latino 5 × 5 utilizando-se teores crescentes de fibra em detergente neutro oriunda da forragem como variável independente. As concentrações de fibra em detergente neutro oriunda da foragem utilizadas foram 20, 28, 35, 43 e 49%. Os consumos de matéria seca, de nutrientes e de energia líquida reduziram com o aumento de fibra na ração. No entanto, o consumo de fibra em detergente foi crescente, indicando capacidade de acomodação desse componente nutritivo pelos animais. O teor de fibra influenciou os coeficientes de digestibilidade da matéria seca, matéria orgânica, proteína bruta e dos carboidratos não-fibrosos, contudo, a digestibilidade da fibra em detergente neutro não foi influenciada pelas dietas. O nível de fibra em detergente neutro oriunda da forragem não influenciou os constituintes do leite (gordura, proteína e lactose). O teor de fibra oriunda da forragem teve efeito quadrático sobre a produção de leite (corrigida e não corrigida para 4% de gordura), em kg/dia, com maiores produções obtidas com o teor de 28% de fibra. A eficiência de utilização da energia metabolizável não foi influenciada pelas variações nas dietas. O teor de fibra em detergente neutro oriunda da forragem influencia o comportamento ingestivo de cabras em lactação, aumentando os tempos de ruminação e mastigação e diminuindo o tempo em ócio dos animais.The objective of this study was to evaluate the different contents of neutral detergent fiber from forage at advanced maturity on intake, digestibility of the dry matter and of nutrients, nitrogen balance, milk production, efficiency metabolizable energy use and the ingestive behavior of lactating goats. Five dairy goats were distributed in 5 × 5 Latin square by using increasing contents of neutral detergent fiber from forage as independent variable. Concentrations of neutral detergent fiber from forage used were 20, 28, 35, 43 and 49%. The intakes of dry matter, of nutrients and of net energy were reduced with the increase of fiber to the ration. However the intake of neutral detergent fiber was increasing, indicating the capacity of accommodation of this nutrient by the animals. Fiber content influenced digestibility coefficients of dry matter, organic matter, crude protein and non-fibrous carbohydrates but digestibility of neutral detergent fiber was not influenced by the diets. Level of neutral detergent fiber from forage did not influence milk constituents (fat, protein and lactose). Content of fiber from the forage had a quadratic effect on milk production (corrected and not corrected for 4% of fat) in kg.day-1, with greater productions obtained with the content of 28% of fiber. Efficiency of use of the metabolizable energy was not influenced by the variations of the diets. Content of neutral detergent fiber from forage influences ingestive behavior of goats in lactation, increasing the time of rumination and chewing and reducing iddle time of the animals

A proof of the Geroch-Horowitz-Penrose formulation of the strong cosmic censor conjecture motivated by computability theory

In this paper we present a proof of a mathematical version of the strong cosmic censor conjecture attributed to Geroch-Horowitz and Penrose but formulated explicitly by Wald. The proof is based on the existence of future-inextendible causal curves in causal pasts of events on the future Cauchy horizon in a non-globally hyperbolic space-time. By examining explicit non-globally hyperbolic space-times we find that in case of several physically relevant solutions these future-inextendible curves have in fact infinite length. This way we recognize a close relationship between asymptotically flat or anti-de Sitter, physically relevant extendible space-times and the so-called Malament-Hogarth space-times which play a central role in recent investigations in the theory of "gravitational computers". This motivates us to exhibit a more sharp, more geometric formulation of the strong cosmic censor conjecture, namely "all physically relevant, asymptotically flat or anti-de Sitter but non-globally hyperbolic space-times are Malament-Hogarth ones". Our observations may indicate a natural but hidden connection between the strong cosmic censorship scenario and the Church-Turing thesis revealing an unexpected conceptual depth beneath both conjectures.Comment: 16pp, LaTeX, no figures. Final published versio