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Most drugs or the natural substances reputed to display some biological activity are hydrophobic molecules that demonstrate low bioavailability regardless of their mode of absorption. Resveratrol and its derivatives belong to the chemical group of stilbenes; while stilbenes are known to possess very interesting properties, these are limited by their poor aqueous solubility as well as low bioavailability in animals and humans. Among the substances capable of forming nanomolecular inclusion complexes which can be used for drug delivery, cyclodextrins show spectacular physicochemical and biomedical implications in stilbene chemistry for their possible application in nanomedicine. By virtue of their properties, cyclodextrins have also demonstrated their possible use in green chemistry for the synthesis of stilbene glucosylated derivatives with potential applications in dermatology and cosmetics. Compared to chemical synthesis and genetically modified microorganisms, plant cell or tissue systems provide excellent models for obtaining stilbenes in few g/L quantities, making feasible the production of these compounds at a large scale. However, the biosynthesis of stilbenes is only possible in the presence of the so-called elicitor compounds, the most commonly used of which are cyclodextrins. We also report here on the induction of resveratrol production by cyclodextrins or combinatory elicitation with methyljasmonate in plant cell systems as well as the mechanisms by which they are able to trigger a stilbene response. The present article therefore discusses the role of cyclodextrins in stilbene chemistry both at the physicochemical level as well as the biomedical and biotechnological levels, emphasizing the notion of "easy alliance" between these compounds and stilbenes.

El cáncer colorrectal (CCR) constituye un importante problema de salud siendo uno de los cánceres más comunes a nivel mundial. Se estima una incidencia anual de 1.4 millones de nuevos casos ocasionando 693.900 muertes. En Asia, multitud de países incluyendo China, Japón, Corea del Sur y Singapur, han experimentado un incremento de la incidencia de CCR en las últimas dos décadas. En contraste, la mortalidad se encuentra en descenso en varios países de la Unión Europea, probablemente debido a la introducción de programas de cribado, pero también posiblemente por una mayor eficacia de los tratamientos y del aumento de las tasas de resección. Se ha estimado que el programa de cribado puede reducir la mortalidad en un 40% además de lograr una reducción del coste en el tratamiento. El pronóstico y la supervivencia a largo plazo de estos pacientes están en gran medida limitados por la presencia de metástasis a distancia. El hígado es el órgano más frecuentemente afectado en el CCR.

Covering: 1976 to 2020. Although constituting a limited chemical family, phytostilbenes represent an emblematic group of molecules among natural compounds. Ever since their discovery as antifungal compounds in plants and their ascribed role in human health and disease, phytostilbenes have never ceased to arouse interest for researchers, leading to a huge development of the literature in this field. Owing to this, the number of references to this class of compounds has reached the tens of thousands. The objective of this article is thus to offer an overview of the different aspects of these compounds through a large bibliography analysis of more than 500 articles. All the aspects regarding phytostilbenes will be covered including their chemistry and biochemistry, regulation of their biosynthesis, biological activities in plants, molecular engineering of stilbene pathways in plants and microbes as well as their biotechnological production by plant cell systems.

The observation by scanning tunnelling spectroscopy (STS) of Abrikosov vortex cores in the high-temperature superconductor YBa$_2$Cu$_3$O$_{7-��}$ (Y123) has revealed a robust pair of electron-hole symmetric states at finite subgap energy. Their interpretation remains an open question because theory predicts a different signature in the vortex cores, characterised by a strong zero-bias conductance peak. We present STS data on very homogeneous Y123 at 0.4 K revealing that the subgap features do not belong to vortices: they are actually observed everywhere along the surface with high spatial and energy reproducibility, even in the absence of magnetic field. Detailed analysis and modelling show that these states remain unpaired in the superconducting phase and belong to an incoherent channel which contributes to the tunnelling signal in parallel with the superconducting density of states., Final version with supplementary material

In this work, preconditioners for the iterative solution by Krylov methods of the linear systems arising at each Newton iteration are studied. The preconditioner is defined by means of a Broyden-type rank-one update of a given initial preconditioner, at each nonlinear iteration, as described in where convergence properties of the scheme are theoretically proved. This acceleration is employed in the solution of the nonlinear system of algebraic equations arising from the finite element discretization of two-phase flow model in porous media. We report numerical results of the application of this approach when the initial preconditioner is chosen to be the incomplete LU decomposition of the Jacobian matrix at the initial nonlinear stage. It is shown that the proposed acceleration reduces the number of linear iterations needed to achieve convergence. Also, the cost of computing the preconditioner is reduced as this operation is made only once at the beginning of the Newton iteration.

Root-to-shoot signalling via xylem sap is an important mechanism by which plants respond to stress. This signalling could be mediated by alteration in the concentrations of inorganic and/or organic molecules. The effect of salt stress on the contents of xylem sap in Brassica olarecea has been analysed by mass spectrometry in order to quantify these changes. Subcellular location of arabinogalactan proteins (AGPs) by immunogold labelling and peroxidase isozymes was also analysed by isoelectrofocusing. The xylem sap metabolome analysis demonstrated the presence of many organic compounds such as sugars, organic acids and amino acids. Of these, amino acid concentrations, particularly that of glutamine, the major amino acid in the sap, were substantially reduced by salt stress. The xylem sap proteome analysis demonstrated the accumulation of enzymes involved in xylem differentiation and lignification, such as cystein proteinases, acid peroxidases, and a putative hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyl transferase under salt stress. The peroxidase isozyme pattern showed that salt stress induced a high accumulation of an acid isoform. These results suggest that xylem differentiation and lignification is induced by salt stress. The combination of different methods to analyse the xylem sap composition provides new insights into mechanisms in plant development and signalling under salt stress.

The first paper on isogeometric analysis appeared only five years ago [1], and the first book appeared last year [2]. Progress has been rapid. Isogeometric analysis has been applied to a wide variety of problems in solids, fluids and fluid-structure interactions. Superior accuracy to traditional finite elements has been demonstrated in all cases. In addition, it has been shown that isogeometric analysis provides an efficient framework for the design through analysis paradigm. In this contribution we present two examples which illustrate the potential of T-splines, a powerful generalization of NURBS, the CAD industry standard. The first example utilizes T-splines for a problem of propagating cracks. Smoothly turning discontinuities can be introduced in T-splines through local knot insertion. The possibility of enhancing a T-spline basis with discontinuities makes isogeometric finite elements suitable for the capturing of discontinuities, in particular, cracks. From an implementation point of view, the concept of Bézier extraction [3] allows for a unified approach to NURBS and T-splines, and will allow this approach to be extended to T-splines of arbitrary topology. The second example demonstrates the enabling power of T-splines in a design through analysis framework. A trimless T-spline automotive bumper is generated and then used directly in an LS-DYNA vibrations analysis [4]. T-splines can describe shapes of arbitrary topological complexity while maintaining a smooth analysis-suitable basis. This makes them an attractive alternative to classical finite elements for many problems of engineering interest. For such problems, the isogeometric paradigm can be invoked thus eliminating the analysis costs associated with geometry clean-up, defeaturing and mesh generation. The two numerical simulations considered in this work demonstrate the capability of the T-spline basis to meet the stringent needs of analysis while providing the flexibility to overcome design through analysis bottlenecks. Specifically, T-splines were found to give efficient discretizations in terms of the number of degrees of freedom and the required computational effort. We anticipate that T-splines and isogeometric analysis will continue to provide efficient solutions to many important problems in computational mechanics.

Objetivo: analizar los posibles factores pronósticos de supervivencia en tumores estromales gastrointestinales c-kit positivo (GIST), tras citorreducción óptima R0. Pacientes y método: estudio de 35 pacientes intervenidos en nuestra Unidad desde enero 2002 a febrero 2007, con tumores del estroma gastrointestinal CD117/c-kit positivo en los que se alcanzó citorreducción quirúrgica sin residuo tumoral macroscópico. Una base de datos prospectiva nos proporcionó las distintas variables analizadas, de carácter demográfico, anatómico, clínico, histopatológico e inmunohistoquímico, entre otras. El análisis de la supervivencia actuarial se realizó según el método de Kaplan-Meier y el análisis multivariante mediante el método de regresión múltiple de Cox. Resultados: la supervivencia global a 5 años fue del 77%, con una supervivencia media de 52 meses. El riesgo de malignidad según la clasificación de Fletcher y el tamaño tumoral mayor de 10 cm, influyeron significativamente de forma negativa sobre la supervivencia de los pacientes, tras el análisis univariante realizado (p < 0,05). La actividad proliferativa Ki-67 mayor del 50% fue la única covariable con significación estadística en el análisis multivariante. El 20% de los tumores recurrieron. Sólo 3 pacientes metastáticos recibieron tratamiento adyuvante con mesilato de imatinib, todos ellos con Ki-67 > 50% y vivos en la actualidad. Conclusiones: el índice proliferativo Ki-67 podría representar un excelente marcador pronóstico de supervivencia en aquellos pacientes con tumores del estroma gastrointestinal c-kit positivo. Su confirmación y el punto de corte adecuado deberían ser objeto de futuros estudios prospectivos, así como su posible utilidad para seleccionar pacientes candidatos al tratamiento con mesilato de imatinib. Objective: to analyze the different factors predictive of survival associated with optimal R0-cytoreduction in c-kit-positive gastrointestinal stromal tumors. Methods: thirty-five patients were operated on in our Oncological Surgery Department from January 2002 to February 2007 because of CD117/c-kit-positive gastrointestinal stromal tumors, and an optimal surgical cytoreduction was obtained without macroscopical residual disease. Demographic, anatomical, clinical, pathological, and immunohistochemical variables were analyzed from a specific database. Survival and multivariate analyses were developed using Kaplan-Meier and multiple Cox regression models, respectively. Results: five-year overall survival was 77% with a mean survival of 52 months. Risk of malignant behaviour according to Fletcher's classification and tumor size higher than 10 cm had a significantly negative influence on overall survival in the univariate analysis (p < 0.05). Proliferative Ki-67 activity higher than 50% was the only statistically significant variable in the multivariate analysis. Twenty percent of tumors recurred. Only 3 patients with metastatic disease received adjuvant treatment with imatinib mesylate, all of them with Ki-67 > 50% and currently alive. Conclusions: the poliferative Ki-67 index could represent an excellent predictive factor for survival in patients with c-kit-positive stromal gastrointestinal tumors. Confirmation and an adequate cut-off level should be the main objectives for future prospective studies, mostly focused on the appropriate selection of optimal candidates to imatinib-mesylate-based treatment.

A continuos time dynamic control system of the "Level IV Fugacity Model" is presented and applied to selected organic chemicals in evaluative environments system. In order to illustrate the numerical solution by this model a discretization is used to calculate the fugacity, concentration and fugacity settling time for a set of three insecticides applied in a hypothetical three compartmental environmental system. The model employs the fugacity concept and treats three bulk compartments: air, water and bottom sediment. Input to the model consists of a description of the environmental, the physical-chemical and reaction properties of the chemical, and emission rates. Expressions in matrix form are included for emissions, advections, reactions, and inter-phase transference. An algorithm to determine the values of the fugacities, concentrations and fugacity settling time is given. Made available in DSpace on 2019-12-18T18:27:06Z (GMT). No. of bitstreams: 1 ParaibaLevelIV.pdf: 5754733 bytes, checksum: a8303bde8dff8d69bef2c362013f23a1 (MD5) Previous issue date: 1999