Boundary-crossing identities for diffusions having the time-inversion property

We review and study a one-parameter family of functional transformations, denoted by (S (β)) β∈ℝ, which, in the case β<0, provides a path realization of bridges associated to the family of diffusion processes enjoying the time-inversion property. This family includes Brownian motions, Bessel processes with a positive dimension and their conservative h-transforms. By means of these transformations, we derive an explicit and simple expression which relates the law of the boundary-crossing times for these diffusions over a given function f to those over the image of f by the mapping S (β), for some fixed β∈ℝ. We give some new examples of boundary-crossing problems for the Brownian motion and the family of Bessel processes. We also provide, in the Brownian case, an interpretation of the results obtained by the standard method of images and establish connections between the exact asymptotics for large time of the densities corresponding to various curves of each family

Cr cluster characterization in Cu-Cr-Zr alloy after ECAP processing and aging using SANS and HAADF-STEM

International audienceThe precipitation of nano-sized Cr clusters was investigated in a commercial Cu-1Cr-0.1Zr (wt.%) alloy processed by Equal-Channel Angular Pressing (ECAP) and subsequent aging at 550 °C for 4 hours using small angle neutron scattering (SANS) measurements and high-angle annular dark-field-scanning transmission electron microscopy (HAADF-STEM). The size and volume fraction of nano-sized Cr clusters were estimated using both techniques. These parameters assessed from SANS (d~3.2 nm, Fv~1.1 %) agreed reasonably with those from HAADF-STEM (d ~2.5 nm, Fv~2.3%). Besides nano-sized Cr clusters, HAADF-STEM technique evidenced the presence of rare cuboid and spheroid sub-micronic Cr particles about 380-620 nm mean size. Both techniques did not evidence the presence of intermetallic CuxZry phases within the aging conditions

Exact Asymptotic Results for Persistence in the Sinai Model with Arbitrary Drift

We obtain exact asymptotic results for the disorder averaged persistence of a Brownian particle moving in a biased Sinai landscape. We employ a new method that maps the problem of computing the persistence to the problem of finding the energy spectrum of a single particle quantum Hamiltonian, which can be subsequently found. Our method allows us analytical access to arbitrary values of the drift (bias), thus going beyond the previous methods which provide results only in the limit of vanishing drift. We show that on varying the drift, the persistence displays a variety of rich asymptotic behaviors including, in particular, interesting qualitative changes at some special values of the drift.Comment: 17 pages, two eps figures (included

On Feeding Business Systems with Linked Resources from the Web of Data

Business systems that are fed with data from the Web of Data require transparent interoperability. The Linked Data principles establish that different resources that represent the same real-world entities must be linked for such purpose. Link rules are paramount to transparent interoperability since they produce the links between resources. State-of-the-art link rules are learnt by genetic programming and build on comparing the values of the attributes of the resources. Unfortunately, this approach falls short in cases in which resources have similar values for their attributes, but represent different real-world entities. In this paper, we present a proposal that leverages a genetic programming that learns link rules and an ad-hoc filtering technique that boosts them to decide whether the links that they produce must be selected or not. Our analysis of the literature reveals that our approach is novel and our experimental analysis confirms that it helps improve the F1 score by increasing precision without a significant penalty on recall.Ministerio de Economía y Competitividad TIN2013-40848-RMinisterio de Economía y Competitividad TIN2016- 75394-

Adipocyte ATP-binding cassette G1 promotes triglyceride storage, fat mass growth, and human obesity

The role of ATP-binding Cassette G1 (ABCG1) transporter in human pathophysiology is still largely unknown. Indeed, beyond its role in mediating free cholesterol efflux to HDL, ABCG1 transporter equally promotes lipid accumulation in a triglyceride (TG)-rich environment through regulation of the bioavailability of Lipoprotein Lipase (LPL).As both ABCG1 and LPL are expressed in adipose tissue, we hypothesize that ABCG1 is implicated in adipocyte TG storage and could be then a major actor in adipose tissue fat accumulation.Silencing of Abcg1 expression by RNAi in 3T3-L1 preadipocytes compromised LPL-dependent TG accumulation during initial phase of differentiation. Generation of stable Abcg1 Knockdown 3T3-L1 adipocytes revealed that Abcg1 deficiency reduces TG storage and diminishes lipid droplet size through inhibition of Pparγ expression. Strikingly, local inhibition of adipocyte Abcg1 in adipose tissue from mice fed a high fat diet led to a rapid decrease of adiposity and weight gain. Analysis of two frequent ABCG1 SNPs (rs1893590 (A/C) and rs1378577 (T/G)) in morbidly obese individuals indicated that elevated ABCG1 expression in adipose tissue was associated with an increased PPARγ expression and adiposity concomitant to an increased fat mass and BMI (haplotype AT&gt;GC). The critical role of ABCG1 regarding obesity was further confirmed in independent populations of severe obese and diabetic obese individuals.For the first time, this study identifies a major role of adipocyte ABCG1 in adiposity and fat mass growth and suggests that adipose ABCG1 might represent a potential therapeutic target in obesity

American Step-Up and Step-Down Default Swaps under Levy Models

This paper studies the valuation of a class of default swaps with the embedded option to switch to a different premium and notional principal anytime prior to a credit event. These are early exercisable contracts that give the protection buyer or seller the right to step-up, step-down, or cancel the swap position. The pricing problem is formulated under a structural credit risk model based on Levy processes. This leads to the analytic and numerical studies of several optimal stopping problems subject to early termination due to default. In a general spectrally negative Levy model, we rigorously derive the optimal exercise strategy. This allows for instant computation of the credit spread under various specifications. Numerical examples are provided to examine the impacts of default risk and contractual features on the credit spread and exercise strategy.Comment: 35 pages, 5 figure

Valsartan Improves Adipose Tissue Function in Humans with Impaired Glucose Metabolism: A Randomized Placebo-Controlled Double-Blind Trial

<div><h3>Background</h3><p>Blockade of the renin-angiotensin system (RAS) reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT) function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans. Therefore, we examined whether 26-wks treatment with the angiotensin II type 1 receptor blocker valsartan affects AT function in humans with impaired glucose metabolism (IGM).</p> <h3>Methodology/Principal Findings</h3><p>We performed a randomized, double-blind, placebo-controlled parallel-group study, in which 38 subjects with IGM were treated with valsartan (VAL, 320 mg/d) or placebo (PLB) for 26 weeks. Before and after treatment, an abdominal subcutaneous AT biopsy was collected for measurement of adipocyte size and AT gene/protein expression of angiogenesis/capillarization, adipogenesis, lipolytic and inflammatory cell markers. Furthermore, we evaluated fasting and postprandial AT blood flow (ATBF) (¹³³Xe wash-out), systemic inflammation and insulin sensitivity (hyperinsulinemic-euglycemic clamp). VAL treatment markedly reduced adipocyte size (<em>P</em><0.001), with a shift toward a higher proportion of small adipocytes. In addition, fasting (<em>P</em> = 0.043) and postprandial ATBF (<em>P</em> = 0.049) were increased, whereas gene expression of angiogenesis/capillarization, adipogenesis and macrophage infiltration markers in AT was significantly decreased after VAL compared with PLB treatment. Interestingly, the change in adipocyte size was associated with alterations in insulin sensitivity and reduced AT gene expression of macrophage infiltration markers. VAL did not alter plasma monocyte-chemoattractant protein (MCP)-1, TNF-α, adiponectin and leptin concentrations.</p> <h3>Conclusions/Significance</h3><p>26-wks VAL treatment markedly reduced abdominal subcutaneous adipocyte size and AT macrophage infiltration markers, and increased ATBF in IGM subjects. The VAL-induced decrease in adipocyte size was associated with reduced expression of macrophage infiltration markers in AT. Our findings suggest that interventions targeting the RAS may improve AT function, thereby contributing to a reduced risk of developing cardiovascular disease and type 2 diabetes.</p> <h3>Trial Registration</h3><p>Trialregister.nl NTR721 (ISRCTN Registry: ISRCTN<a href="http://www.controlled-trials.com/isrctn/pf/42786336">42786336</a>)</p> </div

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk

GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies