Dynamic Kinetic Resolution of Hetero biaryl Ketones by Zinc- Catalyzed Asymmetr ic Hydrosil ylation

Adiastereo- and highly enantioselective dynamic kinetic resolution (DKR) of configurationally labile hetero- biaryl ketones is described. The DKR proceeds by zinc- catalyze dhydrosilylation of the carbonyl group ,thus leading to secondary alcohols bearing axial and central chirality .The strategy relies on the labilization of the stereogenic axis that takes place thanks to aLewis acid–base interaction between anitrogen atom in the heterocycle and the ketone carbonyl group .The synthetic utility of the methodology is demonstrated through stereospecific transformations into either N,N-ligands or appealing axially chiral, bifunctional thiourea organocata- lysts.Ministerio de Ciencia e Innovación (Grants CTQ2016-76908-C2-1-P, CTQ2016-76908-C2-2-P, contract RYC-2013-12585)European FEDER FundsJunta de Andalucía (Grant 2012/FQM 10787)European Union - Marie Skłodowska-Curie (COFUND—Grant Agreement n 8 8 291780

A Dynamic Kinetic Asymmetric Heck Reaction for the Simultaneous Generation of Central and Axial Chirality

A highly diastereo- and enantioselective, scalable Pd-catalyzed dynamic kinetic asymmetric Heck reaction of heterobiaryl sulfonates with electron-rich olefins is described. The coupling of 2,3-dihydrofuran or N-boc protected 2,3-dihydropyrrole with a variety of quinoline, quinazoline, phthalazine, and picoline derivatives takes place with simultaneous installation of central and axial chirality, reaching excellent diastereo- and enantiomeric excesses when in situ formed [Pd0/DM-BINAP] was used as the catalyst, with loadings reduced down to 2 mol % in large scale reactions. The coupling of acyclic, electron-rich alkenes can also be performed using a [Pd0/Josiphos ligand] to obtain axially chiral heterobiaryl α-substituted alkenes in high yields and enantioselectivities. Products from Boc-protected 2,3-dihydropyrrole can be easily transformed into N,N ligands or appealing axially chiral, bifunctional proline-type organocatalysts. Computational studies suggest that a β-hydride elimination is the stereocontrolling step, in agreement with the observed stereochemical outcome of the reaction.Ministerio de Ciencia e Innovación (Grants CTQ2016-76908-C2-1-P; CTQ2016-76908-C2-2-P; CTQ2016-78083-P; RYC-2013-12585)European Commission (FEDER Programme)Junta de Andalucía (Grant 2012/FQM 10787)Universidad de Sevilla (Grant No. 1800511201)European Union - Marie Skłodowska-Curie (COFUND—Grant Agreement nº 291780

A family of complex potentials with real spectrum

We consider a two-parameter non hermitean quantum-mechanical hamiltonian that is invariant under the combined effects of parity and time reversal transformation. Numerical investigation shows that for some values of the potential parameters the hamiltonian operator supports real eigenvalues and localized eigenfunctions. In contrast with other PT symmetric models, which require special integration paths in the complex plane, our model is integrable along a line parallel to the real axis.Comment: Six figures and four table

Fractional-order operators: Boundary problems, heat equations

The first half of this work gives a survey of the fractional Laplacian (and related operators), its restricted Dirichlet realization on a bounded domain, and its nonhomogeneous local boundary conditions, as treated by pseudodifferential methods. The second half takes up the associated heat equation with homogeneous Dirichlet condition. Here we recall recently shown sharp results on interior regularity and on $L_p$-estimates up to the boundary, as well as recent H\"older estimates. This is supplied with new higher regularity estimates in $L_2$-spaces using a technique of Lions and Magenes, and higher $L_p$-regularity estimates (with arbitrarily high H\"older estimates in the time-parameter) based on a general result of Amann. Moreover, it is shown that an improvement to spatial $C^\infty$-regularity at the boundary is not in general possible.Comment: 29 pages, updated version, to appear in a Springer Proceedings in Mathematics and Statistics: "New Perspectives in Mathematical Analysis - Plenary Lectures, ISAAC 2017, Vaxjo Sweden

Structural stabilization of botulinum neurotoxins by tyrosine phosphorylation

AbstractTyrosine phosphorylation of botulinum neurotoxins augments their proteolytic activity and thermal stability, suggesting a substantial modification of the global protein conformation. We used Fourier-transform infrared (FTIR) spectroscopy to study changes of secondary structure and thermostability of tyrosine phosphorylated botulinum neurotoxins A (BoNT A) and E (BoNT E). Changes in the conformationally-sensitive amide I band upon phosphorylation indicated an increase of the α-helical content with a concomitant decrease of less ordered structures such as turns and random coils, and without changes in β-sheet content. These changes in secondary structure were accompanied by an increase in the residual amide II absorbance band remaining upon H-D exchange, consistent with a tighter packing of the phosphorylated proteins. FTIR and differential scanning calorimetry (DSC) analyses of the denaturation process show that phosphorylated neurotoxins denature at temperatures higher than those required by non-phosphorylated species. These findings indicate that tyrosine phosphorylation induced a transition to higher order and that the more compact structure presumably imparts to the phosphorylated neurotoxins the higher catalytic activity and thermostability

Aging impairs the hepatic subcellular distribution of ChREBP in response to fasting/feeding in rats: Implications on hepatic steatosis

© 2015 Elsevier Inc. All rights reserved. Aging is associated with alterations of lipid metabolism and increased prevalence of non alcoholic hepatic steatosis.Nevertheless, themechanisms bywhich fat is accumulated in the liver during aging remain incompletely understood. In the present study, we investigated potential alterations that might contribute to the development of hepatic steatosis with aging. To this end, we analyzed the expression and the subcellular localization of key transcriptional factors involved in lipid metabolism such as ChREBP, Foxo1, Foxa2 and SREBP-1c in the liver of 3- and 24-month oldWistar rats. In addition, we studied the intracellular redistribution of ChREBP in response to fasting/refeeding transition. Old rats were characterized by hepatic steatosis, low serum ketone body levels and postprandial hyperinsulinemia. These observations were paralleled by the cytoplasmic localization and decreased expression of Foxa2, while ChREBP expression was markedly up-regulated and mainly localized in the nucleus. Consequently, the expression of lipogenic and β-oxidation genes was up-regulated or downregulated, respectively. Besides, the intracellular redistribution of ChREBP in response to fasting/refeeding transition was also impaired in old animals. Additionally, a negative correlation between serum ketone body levels and the nuclear localization of ChREBP was observed only in adult but not in old rats. Taken together, these data suggest that an age-related dysfunctional adaptation of ChREBP, in response to changes in the nutritional state, might contribute to the development of liver steatosis with aging.Junta de Comunidades de Castilla-La Mancha (JCCM), BFU2012- 39705-C03-01 from Ministerio de Ciencia e Innovación, and S2010/BMC2423 from Comunidad de Madrid, Spain. A.S. was supported by FPU predoctoral fellowship from Ministerio de Educación y Ciencia (MEC), Spain, and B.B. was supported by CONACyT predoctoral fellowship from México. The Centre of Molecular Biology “Severo Ochoa” is the recipient of institutional aid from the Ramón Areces FoundationPeer Reviewe

Sistema de b-learning en Farmacología (I): pilotando

Siguiendo el espíritu renovador derivado de la implementación del Espacio Europeo de Educación Superior y utilizando el entorno del Campus Virtual de la UCM (WebCT), se han desarrollado las bases para la implantación de un sistema de b-learning. Los estudiantes de “Farmacología, Farmacia y Terapéutica” de la Licenciatura de Veterinaria podrán consultar, organizado por módulos temáticos, material didáctico para aprender de forma activa los contenidos de esta asignatura troncal. Las herramientas que conforman este sistema presentan diversas finalidades y formatos: formativas (guiones, presentaciones, vídeos, problemas); comunicativas (foro de intercambio de ideas, dudas e iniciativas y avisos); y evaluadoras (autoevaluaciones para los alumnos y encuestas sobre la utilidad de la propia herramienta). La idea es que los estudiantes sean los gestores de su propio aprendizaje. Para ello, cuentan con el apoyo de una herramienta virtual (Aula Virtual de Farmacología), con actividades docentes presenciales (seminarios y tutorías) y con herramientas de evaluación de los conocimientos adquiridos.Following the innovative spirit derived from implementation of the European Higher Education Area and using an online learning environment (Campus Virtual-UCM), the bases for the implantation of a b-learning system have been developed. The students of "Pharmacology, Pharmacy and Therapeutic" of the Veterinary Medicine degree will be able to consult, organized by thematic modules, educational material to learn in an active way the contents of this core subject. The tools that shape this system present diverse purposes and formats: formatives (scripts, presentations, videos, problems); communicatives (forum to exchanging of ideas, doubts or initiatives and notices); assessments (autoevaluations for the pupils and surveys on the usefulness of the own tool). The idea is that students are the managers of their own learning. For it, they have the support of a virtual tool (Virtual Classroom of Pharmacology), face-to-face educational activities (seminars, tutorials) and tools of evaluation of the acquired knowledge

Geodetic Research on Deception Island and its Environment (South Shetland Islands, Bransfield Sea and Antarctic Peninsula) During Spanish Antarctic Campaigns (1987-2007)

Since 1987, Spain has been continuously developing several scientific projects, mainly based on Earth Sciences, in Geodesy, Geochemistry, Geology or Volcanology. The need of a geodetic reference frame when doing hydrographic and topographic mapping meant the organization of the earlier campaigns with the main goals of updating the existing cartography and of making new maps of the area. During this period of time, new techniques arose in Space Geodesy improving the classical methodology and making possible its applications to other different fields such as tectonic or volcanism. Spanish Antarctic Geodetic activities from the 1987/1988 to 2006/2007 campaigns are described as well as a geodetic and a levelling network are presented. The first network, RGAE, was designed and established to define a reference frame in the region formed by the South Shetlands Islands, the Bransfield Sea and the Antarctic Peninsula whereas the second one, REGID, was planned to control the volcanic activity in Deception Island. Finally, the horizontal and vertical deformation models are described too, as well as the strategy which has been followed when computing an experimental geoid

ff-minimal surface and manifold with positive mm-Bakry-\'{E}mery Ricci curvature

In this paper, we first prove a compactness theorem for the space of closed embedded $f$-minimal surfaces of fixed topology in a closed three-manifold with positive Bakry-\'{E}mery Ricci curvature. Then we give a Lichnerowicz type lower bound of the first eigenvalue of the $f$-Laplacian on compact manifold with positive $m$-Bakry-\'{E}mery Ricci curvature, and prove that the lower bound is achieved only if the manifold is isometric to the $n$-shpere, or the $n$-dimensional hemisphere. Finally, for compact manifold with positive $m$-Bakry-\'{E}mery Ricci curvature and $f$-mean convex boundary, we prove an upper bound for the distance function to the boundary, and the upper bound is achieved if only if the manifold is isometric to an Euclidean ball.Comment: 15 page