Clinical pharmacokinetics of mycophenolic acid and its metabolites in solid organ transplant recipient

Mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy and prevention of renal allograft rejection in renal transplant recipients.MPA inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the “de novo” synthesis of purine nucleotides, thus suppressing both T-cell and B-cell proliferation. MPA shows a complex pharmacokinetics with considerable interand intra- patient by between- and within patient variabilities associated to MPA exposure. Several factors may contribute to it. The pharmacokinetic modeling according to the population pharmacokinetic approach with the non-linear mixed effects models has shown to be a powerful tool to describe the relationships between MMF doses and the MPA exposures and also to identify potential predictive patients’ demographic and clinical characteristics for dose tailoring during the post-transplant immunosuppresive treatment.

Clinical pharmacokinetics of mycophenolic acid and its metabolites in solid organ transplant recipient

Mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy and prevention of renal allograft rejection in renal transplant recipients.MPA inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the “de novo” synthesis of purine nucleotides, thus suppressing both T-cell and B-cell proliferation. MPA shows a complex pharmacokinetics with considerable interand intra- patient by between- and within patient variabilities associated to MPA exposure. Several factors may contribute to it. The pharmacokinetic modeling according to the population pharmacokinetic approach with the non-linear mixed effects models has shown to be a powerful tool to describe the relationships between MMF doses and the MPA exposures and also to identify potential predictive patients’ demographic and clinical characteristics for dose tailoring during the post-transplant immunosuppresive treatment.

Solid phase crystallization under continuous heating: kinetic and microstructure scaling laws

The kinetics and microstructure of solid-phase crystallization under continuous heating conditions and random distribution of nuclei are analyzed. An Arrhenius temperature dependence is assumed for both nucleation and growth rates. Under these circumstances, the system has a scaling law such that the behavior of the scaled system is independent of the heating rate. Hence, the kinetics and microstructure obtained at different heating rates differ only in time and length scaling factors. Concerning the kinetics, it is shown that the extended volume evolves with time according to αex = [exp(κCt′)]m+1, where t′ is the dimensionless time. This scaled solution not only represents a significant simplification of the system description, it also provides new tools for its analysis. For instance, it has been possible to find an analytical dependence of the final average grain size on kinetic parameters. Concerning the microstructure, the existence of a length scaling factor has allowed the grain-size distribution to be numerically calculated as a function of the kinetic parameters

Recent Advances in Valorization Methods of Inorganic/Organic Solid, Liquid, and Gas Wastes

The main goal of this special issue was to gather contributions dealing with the latest breakthrough methods for providing value compounds and energy/fuel from waste valorization. Valorization is a relatively new approach in the area of industrial wastes management, a key issue to promote sustainable development. In this field, the recovery of value-added substances, such as antioxidants, proteins, vitamins, and so forth, from the processing of agroindustrial byproducts, is worth mentioning. Another important valorization approach is the use of biogas from waste treatment plants for the production of energy. Several approaches involving physical and chemical processes, thermal and biological processes that ensure reduced emissions and energy consumptions were taken into account. The papers selected for this topical issue represent some of the mostly researched methods that currently promote the valorization of wastes to energy and useful materials ...

Interpolating and sampling sequences in finite Riemann surfaces

We provide a description of the interpolating and sampling sequences on a space of holomorphic functions on a finite Riemann surface, where a uniform growth restriction is imposed on the holomorphic functions.

The number of planar central configurations for the 4-body problem is finite when 3 mass positions are fixed

In the n{body problem a central con guration is formed when the position vector of each particle with respect to the center of mass is a common scalar multiple of its acceleration vector. Lindstrom showed for n = 3 and for n > 4 that if n ? 1 masses are located at xed points in the plane, then there are only a nite number of ways to position the remaining nth mass in such a way that they de ne a central con guration. Lindstrom leaves open the case n = 4. In this paper we prove the case n = 4 using as variables the mutual distances between the particles.

Ecuaciones de recurrencia estocásticas en el cálculo de la prima de reaseguro Finite Risk

RESUMEN: El objetivo de este trabajo es calcular el importe de la prima pura periódica que debe cobrar el reasegurador a la cedente en un reaseguro finite risk en ambiente financiero estocástico. El problema de la convolución de las diferentes variables aleatorias que intervienen en el cálculo de la prima lo hemos solucionado simulando, por Monte-Carlo, trayectorias de siniestralidad para el reasegurador aplicando posteriormente, en cada trayectoria simulada, los criterios de decisión financieros, esperanza, varianza y desviación. En los criterios de la varianza y de la desviación proponemos utilizar una ecuación de recurrencia estocástica para evitar el problema de la dependencia que existe entre los factores de capitalización estocásticos, obteniendo la prima de reaseguro en función del nivel de aversión al riesgo del reasegurador y de la volatilidad del tipo de interés. Palabras clave: Finite risk, ambiente estocástico, ecuación de recurrencia, simulación de Monte-Carlo, prima pura periódica.

Dynamics of F=1 87Rb condensates at finite temperatures

We investigate the dynamics of a F=1 spinor Bose-Einstein condensate of 87Rb atoms confined in a quasi-one-dimensional trap both at zero and at finite temperature. At zero temperature, we observe coherent oscillations between populations of the various spin components and the formation of multiple domains in the condensate. We study also finite temperature effects in the spin dynamics taking into account the phase fluctuations in the Bogoliubov-de Gennes framework. At finite T, despite complex multidomain formation in the condensate, population equipartition occurs. The length scale of these spin domains seems to be determined intrinsically by nonlinear interactions.

Solvencia en un Reaseguro Finite Risk

One of the characteristics of the finite risk reinsurance is the existence of an found of experience, which is constituted by the premiums charged by the reinsurer, together with his financial incomes, and his objective is to finance the claims to be satisfied to the insurer in the specified period. The objective of this work is to design a model that allows us to determinate the reserve that the found of experience should have in every annual period in order to guarantee its dynamic solvency, taking into the experience of the claims of the reinsurer"s portfolio and of each insurance company.

Solid-Phase Synthesis of New Trp(Nps)-Containing Dipeptide Derivatives as TRPV1 Channel Blockers

Trp(Nps)-Lys-NH2 derivatives, bearing alkyl or guanidine groups either at the N-terminus or on the Lys side-chain or at both positions were conveniently prepared on solid-phase and evaluated as TRPV1 channel antagonists.

Finite mixture analysis of beauty-contest data using generalised beta distributions

This paper introduces a mixture model based on the beta distribution, without preestablishedmeans and variances, to analyze a large set of Beauty-Contest data obtainedfrom diverse groups of experiments (Bosch-Domenech et al. 2002). This model gives a bettert of the experimental data, and more precision to the hypothesis that a large proportionof individuals follow a common pattern of reasoning, described as iterated best reply (degenerate),than mixture models based on the normal distribution. The analysis shows thatthe means of the distributions across the groups of experiments are pretty stable, while theproportions of choices at dierent levels of reasoning vary across groups.

Kumar's algorithm for solving Toeplitz systems of equations over finite fields

Adaptació de l'algorisme de Kumar per resoldre sistemes d'equacions amb matrius de Toeplitz sobre els reals a cossos finits en un temps 0 (n log n).

Volcanoes of l-isogenies of elliptic curves over finite fields: the case l=3

This paper is devoted to the study of the volcanoes of l-isogenies of elliptic curves over a finite field, focusing on their height as well as on the location of curves across its different levels. The core of the paper lies on the relationship between the l-Sylow subgroup of an elliptic curve and the level of the volcano where it is placed. The particular case l = 3 is studied in detail, giving an algorithm to determine the volcano of 3-isogenies of a given elliptic curve. Experimental results are also provided.

Protein oligomers studied by solid-state NMR the case of the full-length nucleoid-associated protein histone-like nucleoid structuring protein

Members of the histone-like nucleoid structuring protein (H-NS) family play roles both as architectural proteins and as modulators of gene expression in Gram-negative bacteria. The H-NS protein participates in modulatory processes that respond to environmental changes in osmolarity, pH, or temperature. H-NS oligomerization is essential for its activity. Structural models of different truncated forms are available. However, high-resolution structural details of full-length H-NS and its DNA-bound state have largely remained elusive. We report on progress in characterizing the biologically active H-NS oligomers with solid-state NMR. We compared uniformly ((13)C,(15)N)-labeled ssNMR preparations of the isolated N-terminal region (H-NS 1-47) and full-length H-NS (H-NS 1-137). In both cases, we obtained ssNMR spectra of good quality and characteristic of well-folded proteins. Analysis of the results of 2D and 3D (13)C-(13)C and (15)N-(13)C correlation experiments conducted at high magnetic field led to assignments of residues located in different topological regions of the free full-length H-NS. These findings confirm that the structure of the N-terminal dimerization domain is conserved in the oligomeric full-length protein. Small changes in the dimerization interface suggested by localized chemical shift variations between solution and solid-state spectra may be relevant for DNA recoginition.

Technical Note: Dissolved organic matter fluorescence a finite mixture approach to deconvolve excitation-emission matrices

The analysis of the shape of excitation-emission matrices (EEMs) is a relevant tool for exploring the origin, transport and fate of dissolved organic matter (DOM) in aquatic ecosystems. Within this context, the decomposition of EEMs is acquiring a notable relevance. A simple mathematical algorithm that automatically deconvolves individual EEMs is described, creating new possibilities for the comparison of DOM fluorescence properties and EEMs that are very different from each other. A mixture model approach is adopted to decompose complex surfaces into sub-peaks. The laplacian operator and the Nelder-Mead optimisation algorithm are implemented to individuate and automatically locate potential peaks in the EEM landscape. The EEMs of a simple artificial mixture of fluorophores and DOM samples collected in a Mediterranean river are used to describe the model application and to illustrate a strategy that optimises the search for the optimal output.