On optimal smoothing of density estimators obtained from orthogonal polynomial expansion methods

We discuss the application of orthogonal polynomials to the estimation of probability density functions, particularly with regard to accessing features of a portfolio’s profit/loss distribution. Such expansions are given by the sum of known orthogonal polynomials multiplied by an associated weight function. However, naive applications of expansion methods are flawed. The shape of the estimator’s tail can undulate under the influence of the constituent polynomials in the expansion, and it can even exhibit regions of negative density. This paper presents techniques to remedy these flaws and improve the quality of risk estimation.We show that by targeting a smooth density that is sufficiently close to the target density, we can obtain expansion-based estimators that do not have the shortcomings of equivalent naive estimators. In particular, we apply optimization and smoothing techniques that place greater weight on the tails than on the body of the distribution. Numerical examples using both real and simulated data illustrate our approach. We further outline how our techniques can apply to a wide class of expansion methods and indicate opportunities to extend to the multivariate case, where distributions of individual component risk factors in a portfolio can be accessed for the purpose of risk management

Behavioural variability, physical activity, rumination time, and milk characteristics of dairy cattle in response to regrouping

We gratefully thank the farm staff and the Lely Farm Management Support Ireland and UK manager, Mr Bas Van Santen, for technical assistance and data retrieval from the Lely T4C software database and Dr Sharon Mitchell for assistance with the laboratory analyses. This work has already been published as part of a PhD thesis (Marumo et al. (2021a)).Peer reviewe

Modelo experimental de lesão pulmonar aguda para estudo de manobras de recrutamento alveolar

O artigo não apresenta resumo

Safety and efficacy of an attenuated heartwater (Ehrlichia ruminantium) vaccine administered by the intramuscular route in cattle, sheep and Angora goats

Please read abstract in the article.Red Meat Research and Development Trust of South Africa; Mohair South Africa LTD; Technology Innovation Agency, South Africa; Agricultural Research Council, South Africa.http://www.elsevier.com/locate/vaccinehj2021Veterinary Tropical Disease

Direct Sensing of Endothelial Oxidants by Vascular Endothelial Growth Factor Receptor-2 and c-Src

BACKGROUND: ADPH oxidase-derived reactive oxygen species (ROS) play important roles in redox homeostasis and signal transduction in endothelial cells (ECs). We previously demonstrated that c-Src plays a key role in VEGF-induced, ROS-dependent selective activation of PI3K-Akt but not PLCγ-1-ERK1/2 signaling pathways. The aim of the present study was to understand how VEGFR-2-c-Src signaling axis 'senses' NADPH oxidase-derived ROS levels and couples VEGF activation of c-Src to the redox state of ECs. METHODOLOGY/PRINCIPAL FINDINGS: Using biotinylated probe that detects oxidation of cysteine thiol (cys-OH) in intracellular proteins, we demonstrate that VEGF induced oxidative modification in c-Src and VEGFR-2, and that reduction in ROS levels using siRNA against p47(phox) subunit of Rac1-dependent NADPH oxidase inhibited this phenomenon. Co-immunoprecipitation studies using human coronary artery ECs (HCAEC) showed that VEGF-induced ROS-dependent interaction between VEGFR-2 and c-Src correlated with their thiol oxidation status. Immunofluorescence studies using antibodies against internalized VEGFR-2 and c-Src demonstrated that VEGF-induced subcellular co-localization of these tyrosine kinases were also dependent on NADPH oxidsase-derived ROS. CONCLUSION/SIGNIFICANCE: These results demonstrate that VEGF induces cysteine oxidation in VEGFR-2 and c-Src in an NADPH oxidase-derived ROS-dependent manner, suggesting that VEGFR-2 and c-Src can 'sense' redox levels in ECs. The data also suggest that thiol oxidation status of VEGFR-2 and c-Src correlates with their ability to physically interact with each other and c-Src activation. Taken together, these findings suggest that prior to activating downstream c-Src-PI3K-Akt signaling pathway, VEGFR-2-c-Src axis requires an NADPH oxidase-derived ROS threshold in ECs

Association between Catechol-O-Methyltrasferase Val108/158Met Genotype and Prefrontal Hemodynamic Response in Schizophrenia

BACKGROUND:"Imaging genetics" studies have shown that brain function by neuroimaging is a sensitive intermediate phenotype that bridges the gap between genes and psychiatric conditions. Although the evidence of association between functional val108/158met polymorphism of the catechol-O-methyltransferase gene (COMT) and increasing risk for developing schizophrenia from genetic association studies remains to be elucidated, one of the most topical findings from imaging genetics studies is the association between COMT genotype and prefrontal function in schizophrenia. The next important step in the translational approach is to establish a useful neuroimaging tool in clinical settings that is sensitive to COMT variation, so that the clinician could use the index to predict clinical response such as improvement in cognitive dysfunction by medication. Here, we investigated spatiotemporal characteristics of the association between prefrontal hemodynamic activation and the COMT genotype using a noninvasive neuroimaging technique, near-infrared spectroscopy (NIRS). METHODOLOGY/PRINCIPAL FINDINGS:Study participants included 45 patients with schizophrenia and 60 healthy controls matched for age and gender. Signals that are assumed to reflect regional cerebral blood volume were monitored over prefrontal regions from 52-channel NIRS and compared between two COMT genotype subgroups (Met carriers and Val/Val individuals) matched for age, gender, premorbid IQ, and task performance. The [oxy-Hb] increase in the Met carriers during the verbal fluency task was significantly greater than that in the Val/Val individuals in the frontopolar prefrontal cortex of patients with schizophrenia, although neither medication nor clinical symptoms differed significantly between the two subgroups. These differences were not found to be significant in healthy controls. CONCLUSIONS/SIGNIFICANCE:These data suggest that the prefrontal NIRS signals can noninvasively detect the impact of COMT variation in patients with schizophrenia. NIRS may be a promising candidate translational approach in psychiatric neuroimaging