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

Toxicity and protective effects of cerium oxide nanoparticles (Nanoceria) depending on their preparation method, particle size, cell type, and exposure route

Nanoceria (cerium oxide nanoparticles) toxicity is currently a concern because of its use in motor vehicles in order to reduce carbon monoxide (CO), nitrogen oxides (NOx), and hydrocarbons in exhaust gases. In addition, many questions arise with respect to its biomedical applications exploiting its potential to protect cells against irradiation and oxidative stress. Indeed, toxicology studies on nanoceria report results that seem contradictory, demonstrating toxic effects in some studies, protective effects in others, and sometimes little or no effect at all. The variability in the experimental setups and particle characterization makes these studies difficult to compare and the toxicity of newly developed nanoceria materials challenging to predict. This microreview aims to compare the toxicity of nanoceria in terms of preparation method, particle size, concentration, host organism, and exposure method

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

On some Features of the Grain and Subgrain Size in a Cu-Cr-Zr Alloy After ECAP Processing and Aging

A Cu-1Cr-0.1Zr alloy has been subjected to ECAP processing via route Bc and aging at 250-800°C. Electron BackScatter diffraction (EBSD), Transmission Electron Microscopy (TEM) and X-Ray Diffraction Line Profile Analysis (XRDLPA) techniques have been used to unveil some peculiarities of the grain and subgrain structure with a special emphasis on the comparison of the grain size estimated by the three techniques. For the alloy ECAP processed and aged up to 16 passes, the grain size (from EBSD, 0.2 < d < 5 μm), subgrain size (from TEM, d ~ 0.75 μm) and “apparent” average crystallite size (from XRDLPA, d < 0.25 μm) are manifestly different. The results were compared to the published data and analyzed based on the fundamental aspects of these techniques

Optimal Stopping in Levy Models, for Non-Monotone Discontinuous Payoffs

We give short proofs of general theorems about optimal entry and exit problems in Levy models, when payoff streams may have discontinuities and be non-monotone. As applications, we consider exit and entry problems in the theory of real options, and an entry problem with an embedded option to exit

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

Scholarly publishing depends on peer reviewers

The peer-review crisis is posing a risk to the scholarly peer-reviewed journal system. Journals have to ask many potential peer reviewers to obtain a minimum acceptable number of peers accepting reviewing a manuscript. Several solutions have been suggested to overcome this shortage. From reimbursing for the job, to eliminating pre- publication reviews, one cannot predict which is more dangerous for the future of scholarly publishing. And, why not acknowledging their contribution to the final version of the article published? PubMed created two categories of contributors: authors [AU] and collaborators [IR]. Why not a third category for the peer-reviewer

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

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.</p