Bayesian approach to parameter estimation of the generalized pareto distribution

Several methods have been used for estimating the parameters of the generalized Pareto distribution (GPD), namely maximum likelihood (ML), the method of moments (MOM) and the probability-weighted moments (PWM). It is known that for these estimators to exist, certain constraints have to be imposed on the range of the shape parameter,k, of the GPD. For instance, PWM and ML estimators only exist fork>−0.5 andk≤1, respectively. Moreover, and particularly for small sample sizes, the most efficient method to apply in any practical situation highly depends on a previous knowledge of the most likely values ofk. This clearly suggests the use of Bayesian techniques as a way of using prior information onk. In the present work, we address the issue of estimating the parameters of the GPD from a Bayesian point of view. The proposed approach is compared via a simulation study with ML, PWM and also with the elemental percentile method (EPM) which was developed by Castillo and Hadi (1997). The estimation procedure is then applied to two real data sets.     

Mean Square End-to-End Distance of a Semiflexible Polymer on the Bethe Lattice

A combinatorial method to calculate the mean square end-to-end distance R ² of a polymer on a Bethe lattice is used. The case of an anisotropic lattice and semiflexible polymers is considered. The distance on the Cayley tree is defined by embedding the tree on an N-dimensional Euclidean space considering that every bend of the polymer defines a direction orthogonal to all the previous ones. The semiflexible polymer is effectively equivalent to a flexible one if one considers an effective (noninteger) coordination number. Although an analytical calculation is performed, a closed expression for R ² is possible only for the isotropic case. Numerical results are shown for the anisotropic case. Plots of R ² against N for different values of the anisotropy parameter y are shown. The power dependence for N does not depend on the anisotropy as expected, but the linear coefficient increases on increasing the anisotropy. The anisotropy tends to stretch the polymer.     

Impact of high pressure treatment on the structure of montmorillonite

The modification of sodium montmorillonite after a high pressure pasteurization treatment was followed by X-ray diffraction, FTIR spectroscopy and thermogravimetric analysis. Regardless of the treatment intensity (300 and 800 MPa), the structure of montmorillonite was clearly modified. Such changes should be taken into consideration when binging montmorillonite–polymer nanocomposites into contact with food.     

Concomitant use of liquid–liquid batch and continuous plug flow reactors for kinetic model discrimination. Application to the Rh/TPPTS catalysed reduction of the C–C double bond in dimethylitaconate

The biphasic catalytic reduction of the C–C double bond of dimethylitaconate with a water soluble rhodium/triphenylphosphinetrisulphonated sodium salt (TPPTS) complex is investigated. Kinetic studies in a well-mixed batch reactor provide kinetics parameters and an activation energy of 71 kJ mol⁻¹ but cannot discriminate between a first order or a complex kinetic model within the range of substrate concentration where the approximation of linear liquid/liquid partition is respected. Catalytic tests in the centrifugal partition chromatograph (CPC) reactor under steady-state operations in chemical regime and plug flow mode allow discriminating the kinetic models, the complex kinetic rate law being preferred.     

Cold Compaction and Solid-State Sintering of WC-Co-Based Structures: Experiments and Modeling

Cold compaction (200-1900 MPa) and sintering (1250°-1350°C) of cermets based on WC-Co were experimentally studied using die compaction, cold isostatic pressing, sintering, and creep tests. Two different-sized WC powders were used. The cobalt content varied over a range of 10-30 wt%. Cold-compaction behavior has been described by using a Cam-Clay model. Die-wall friction was measured by using green powder compacts that had different aspect ratios. Friction coefficients were 0.28-0.85, depending on the WC particle size and cobalt content. Simple constitutive equations have been used to model the high-temperature behavior (sintering and creep). The constitutive equations were implemented in a finite-element program to model the compaction, ejection, and sintering of bilayer structures that had different cobalt contents. The model can represent the effect of die-wall friction on the average density, as well as deformation inside the green compact. Density gradients were generated; they were revealed during sintering, because the compact does not deform homogeneously. Simulation also can be used to evaluate deformations that are induced by sintering.     

Composite system well-being evaluation based on non-sequential Monte Carlo simulation

The reliability evaluation of composite power systems has historically been assessed using deterministic and probabilistic criteria and methods. The well-being approach was recently proposed in order to combine deterministic criteria with probabilistic methods and evaluates the system by healthy, marginal and risky states. This paper presents an efficient method for composite system well-being evaluation based on non-sequential Monte Carlo simulation. It is assumed that the system is coherent, and the frequency and duration indices are calculated by the conditional probability method. The system adequacy is evaluated by a non-linear power flow solved by the Newton–Raphson method and by an optimal power flow solved by the Interior Points method. Results are presented for the IEEE-RTS system with a constant load and with a variable load curve. It is demonstrated that the proposed method, as well as the assumed hypothesis, are valid and provide an efficient alternative for the well-being analysis of large scale power systems.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Life and Death of Immature Neurons in the Juvenile and Adult Primate Amygdala

In recent years, a large population of immature neurons has been documented in the paralaminar nucleus of the primate amygdala. A substantial fraction of these immature neurons differentiate into mature neurons during postnatal development or following selective lesion of the hippocampus. Notwithstanding a growing number of studies on the origin and fate of these immature neurons, fundamental questions about the life and death of these neurons remain. Here, we briefly summarize what is currently known about the immature neurons present in the primate ventral amygdala during development and in adulthood, as well as following selective hippocampal lesions. We provide evidence confirming that the distribution of immature neurons extends to the anterior portions of the entorhinal cortex and layer II of the perirhinal cortex. We also provide novel arguments derived from stereological estimates of the number of mature and immature neurons, which support the view that the migration of immature neurons from the lateral ventricle accompanies neuronal maturation in the primate amygdala at all ages. Finally, we propose and discuss the hypothesis that increased migration and maturation of neurons in the amygdala following hippocampal dysfunction may be linked to behavioral alterations associated with certain neurodevelopmental disorders.     

Anti-Inflammatory Effect of Very High Dose Local Vessel Wall Statin Administration: Poly(L,L-Lactide) Biodegradable Microspheres with Simvastatin for Drug Delivery System (DDS)

Atherosclerosis involves an ongoing inflammatory response of the vascular endothelium and vessel wall of the aorta and vein. The pleiotropic effects of statins have been well described in many in vitro and in vivo studies, but these effects are difficult to achieve in clinical practice due to the low bioavailability of statins and their first-pass metabolism in the liver. The aim of this study was to test a vessel wall local drug delivery system (DDS) using PLA microstructures loaded with simvastatin. Wistar rats were fed high cholesterol chow as a model. The rat vessels were chemically injured by repeated injections of perivascular paclitaxel and 5-fluorouracil. The vessels were then cultured and treated by the injection of several concentrations of poly(L,L-lactide) microparticles loaded with the high local HMG-CoA inhibitor simvastatin (0.58 mg/kg) concentration (SVPLA). Histopathological examinations of the harvested vessels and vital organs after 24 h, 7 days and 4 weeks were performed. Microcirculation in mice as an additional test was performed to demonstrate the safety of this approach. A single dose of SVPLA microspheres with an average diameter of 6.4 μm and a drug concentration equal to 8.1% of particles limited the inflammatory reaction of the endothelium and vessel wall and had no influence on microcirculation in vivo or in vitro. A potent pleiotropic (anti-inflammatory) effect of simvastatin after local SVPLA administration was observed. Moreover, significant concentrations of free simvastatin were observed in the vessel wall (compared to the maximum serum level). In addition, it appeared that simvastatin, once locally administered as SVPLA particles, exerted potent pleiotropic effects on chemically injured vessels and presented anti-inflammatory action. Presumably, this effect was due to the high local concentrations of simvastatin. No local or systemic side effects were observed. This approach could be useful for local simvastatin DDSs when high, local drug concentrations are difficult to obtain, or systemic side effects are present.