Heterocycle-based bifunctional organocatalysts in asymmetric synthesis

Different chiral bifunctional organocatalysts derived from trans-cyclohexane-1,2-diamine bearing different types of guanidine units able to form-hydrogen bonding activation have been designed. Conformational rigid 2-aminobenzimidazoles bearing a tertiary amino group have been used in enantioselective Michael type reactions of activated methylene compounds to nitroalkenes. The C2 symmetric bis(2-aminobenzimidazole) derivatives the appropriate organocatalyst for the conjugate addition of 1,3-dicarbonyl compounds to maleimides as well as for the SN1 reaction of benzylic alcohols with carbon nucleophiles. 2-Aminobenzimidazoles bearing a primary amino group have shown excellent catalytic activity in the Michael reaction of aldehydes to maleimides and nitroalkenes. Diastereomeric 2-aminopyrimidines bearing a prolinamide unit have been incorporated in the trans-cyclohexane-1,2-diamine scaffold and have been used for the inter- and intra-molecular direct aldol reaction under solvent-free conditions. For the Michael reaction of aldehydes with maleimides the primary amine 2-aminopyrimidine has shown excellent efficiency as organocatalyst. The bifunctional character of these organocatalysts has been demonstrated by means of DFT calculations.The Spanish Ministerio de Ciencia e Innovación (MICINN) (projects CTQ2010-20387, and Consolider Ingenio 2010, CSD2007-00006), the Spanish Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC), FEDER, the Generalitat Valenciana (PROMETEO 2009/039 and PROMETEOII/2014/017), the Basque Government (GV Grant IT-291-07), the FP7 Marie Curie Actions of the European Commission via the ITN ECHONET network (MCITN-2012-316379) and the Universities of Alicante and Basque Country are gratefully acknowledged for financial support. We also thank for technical and human support provided by IZO-SGI SGIker of UPV-EHU and European funding (ERDF and ESF)

Pyrimidine-Derived Prolinamides as Recoverable Bifunctional Organocatalysts for Enantioselective Inter- and Intramolecular Aldol Reactions under Solvent-Free Conditions

Chiral L-prolinamides 2 containing the (R,R)- and (S,S)-trans-cyclohexane-1,2-diamine scaffold and a 2-pyrimidinyl unit are synthesized and used as general organocatalysts for intermolecular and intramolecular aldol reactions with 1,6-hexanedioic acid as a co-catalyst under solvent-free conditions. The intermolecular reaction between ketone–aldehyde and aldehyde–aldehyde must be performed under wet conditions with catalyst (S,S)-2b at 10 °C, which affords anti-aldols with high regio-, diastereo-, and enantioselectivities. For the Hajos–Parrish–Eder–Sauer–Wiechert reaction, both diastereomers of catalyst 2 give similar results at room temperature in the absence of water to give the corresponding Wieland–Miescher ketone and derivatives. Both types of reactions were scaled up to 1 g, and the organocatalysts were recovered by extractive workup and reused without any appreciable loss in activity. DFT calculations support the stereochemical results of the intermolecular process and the bifunctional role played by the organocatalyst by providing a computational comparison of the H-bonding networks occurring with catalysts 2a and 2b.The Spanish Ministerio de Ciencia e Innovación (MICINN) (projects CTQ2010-20387 and Consolider Ingenio 2010, CSD2007-00006), the Spanish Ministerio de Economia y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC), Fondos Europeos para el Desarrollo Regional (FEDER), Generalitat Valenciana (PROMETEO 2009/039 and PROMETEOII/2014/017), the Basque Government (GV Grant IT-291-07), the European Commission, FP7 Marie Curie Actions through the ITN ECHONET network (MCITN-2012-316379), the University of Alicante, and the University of the Basque Country are gratefully acknowledged for financial support

Cationic exchange in nanosized ZnFe2O4 spinel revealed by experimental and simulated near-edge absorption structure

The non-equilibrium cation site occupancy in nanosized zinc ferrites (6-13 nm) with different degree of inversion (0.2 to 0.4) was investigated using Fe and Zn K-edge x-ray absorption spectroscopy XANES and EXAFS, and magnetic measurements. The very good agreement between experimental and ab-initio calculations on the Zn K-edge XANES region clearly show the large Zn2+(A)--Zn2+[B] transference that takes place in addition to the well-identified Fe3+[B]--Fe3+(A) one, without altering the long-range structural order. XANES spectra features as a function of the spinel inversion were shown to depend on the configuration of the ligand shells surrounding the absorbing atom. This XANES approach provides a direct way to sense cationic inversion in these spinel compounds. We also demonstrated that a mechanical crystallization takes place on nanocrystalline spinel that causes an increase of both grain and magnetic sizes and, simultaneously, generates a significant augment of the inversion.Comment: 5 pages, 5 eps figures, uses revtex4, corrected table

A screen for transcription factor targets of glycogen synthase kinase-3 highlights an inverse correlation of NFκB and androgen receptor signaling in prostate cancer

This is an open-access article distributed under the terms of the Creative Commons Attribution License.Expression of Glycogen Synthase Kinase-3 (GSK-3) is elevated in prostate cancer and its inhibition reduces prostate cancer cell proliferation, in part by reducing androgen receptor (AR) signaling. However, GSK-3 inhibition can also activate signals that promote cell proliferation and survival, which may preclude the use of GSK-3 inhibitors in the clinic. To identify such signals in prostate cancer, we screened for changes in transcription factor target DNA binding activity in GSK-3-silenced cells. Among the alterations was a reduction in AR DNA target binding, as predicted from previous studies, and an increase in NFκB DNA target binding. Consistent with the latter, gene silencing of GSK-3 or inhibition using the GSK-3 inhibitor CHIR99021 increased basal NFκB transcriptional activity. Activation of NFκB was accompanied by an increase in the level of the NFκB family member RelB. Conversely, silencing RelB reduced activation of NFκB by CHIR99021. Furthermore, the reduction of prostate cancer cell proliferation by CHIR99021 was potentiated by inhibition of NFκB signaling using the IKK inhibitor PS1145. Finally, stratification of human prostate tumor gene expression data for GSK3 revealed an inverse correlation between NFκB-dependent and androgen-dependent gene expression, consistent with the results from the transcription factor target DNA binding screen. In addition, there was a correlation between expression of androgen-repressed NFκB target genes and reduced survival of patients with metastatic prostate cancer. These findings highlight an association between GSK-3/AR and NFκB signaling and its potential clinical importance in metastatic prostate cancer.This study was funded by grants from the Spanish Ministry of Science and Innovation (SAF 2008-00768; SAF2011-30494), the Prostate Cancer Research Foundation (now PCUK) and the Department of Industry, Tourism and Trade (Etortek) and Department of Innovation Technology of the Government of the Autonomous Community of the Basque Country.Peer Reviewe

Material y técnica de la exploración subterránea

Descripción del tipo de material utilizado normalmente en espeleología y de las técnicas básicas utilizadas en exploraciones subterráneas

Winograd technique. About one case

Una de las técnicas quirúrgicas de elección para las onicocriptosis severas es el Winograd. En el presente artículo presentamos el caso de un varón de 17 años, afecto de onicocriptosis severa, con los rodetes ungueales hipertróficos al que sometimos a cirugía ungueal con resultados satisfactorios tanto para él como para los profesionales que llevamos a cabo la intervención.One of the surgical techniques of election for the severe onicocriptosis is the Winograd. In the present article we presents the clinical case of a man of 17 years old, affected of severe onicocriptosis, with the nails fols hypertrophied who underwent to nail surgery with satisfactory results for him as for the professionals as much who we carried out the intervention

Distribution of macro- and micronutrient intakes in relation to the meal pattern of third- and fourth-grade schoolchilderen in the city of Quetzaltenango, Guatemala

Objective: Our objective was to assess the distribution of energy, macro- and micronutrient intakes by meal (breakfast, lunch, dinner and combined snacks) in a cross-sectional sample of schoolchildren. Design: Cross-sectional dietary survey in schoolchildren. Setting: Twelve private and public schools in the urban setting of Quetzaltenango, Guatemala. Subjects: A total of 449 schoolchildren (from higher and lower socio-economic strata) were enrolled in the study. Methods: Each child completed a single, pictorial 24 h prospective diary and a face-to-face interview to check completeness and estimate portion sizes. Estimated daily intakes were examined by mealtime as: (i) absolute intakes; (ii) relative nutrient distribution; and (iii) critical micronutrient density (i.e. nutrient density in relation to the WHO Recommended Nutrient Intakes/median age-specific Guatemalan energy requirements). Results: The daily distribution of energy intake was 24 % at breakfast, 30 % at lunch, 23 % at dinner and 23 % among snacks. Lunch was also the leading meal for macronutrients, providing 35 % of proteins, 27 % of fat and 30 % of carbohydrate. The distribution of selected micronutrients did not follow the pattern of energy, insofar as lunch provided relatively more vitamin C and Zn, whereas breakfast led in terms of vitamins A and D, thiamin, riboflavin, folate, Ca and Fe. Conclusions: Meal-specific distribution of energy, macro- and micronutrients provides a unique and little used perspective for evaluation of children's habitual intake, and may provide guidance to strategies to improve dietary balance in an era of coexisting energy overnutrition and micronutrient inadequacy. © The Authors 2008

Diseases of dragon fruit (Hylocereus species): Etiology and current management options

© 2019 Elsevier Ltd More than seven billion people compete for food to survive. Agriculture has increased the production of staple crops, through plant breeding and biotechnology, in arable areas that are now becoming limited due to industrialization. With staple crops becoming a common diet and with people getting the same nutrients from these foods, wild, exotic and underutilized edible plants are being explored as supplements or alternatives. One potential plant is dragon fruit or pitahaya. This vine cactus plant is water-efficient, rich in betalains and antioxidants, has medicinal benefits and is a source of income to growers. However, dragon fruit production faces significant challenges. Among these, losses due to diseases play a significant role in fruit-yield reduction and profitability. This paper provides a comprehensive review of dragon fruit diseases, their associated pathogens, distribution, and their current management options. We conclude that anthracnose, fruit and stem rot, stem canker and the cactus viral disease are among the most frequently reported diseases of dragon fruit and actions are needed to address the growing problems associated with these diseases as effective, sustainable and practical management strategies are yet to be identified

Regional innovation and spillover effects of foreign direct investment in China: a threshold approach

Using a data set on twenty-nine Chinese provinces for the period 1985–2008, this paper establishes a threshold model to analyse the relationship between spillover effects of foreign direct investment (FDI) and regional innovation in China. There is clear evidence of double-threshold effects of regional innovation on productivity spillovers from FDI. Specifically, only when the level of regional innovation reaches the minimum innovation threshold will FDI in the region begin to produce positive productivity spillovers. Furthermore, positive productivity spillovers from FDI will be substantial only when the level of regional innovation attains a higher threshold. The double threshold divides Chinese provinces into three super-regions in terms of innovation, with most provinces positioned within the middle-level innovation super-region. Policy implications are discussed

La dirección de centros educativos en Iberoamérica : reflexiones y experiencias

La presente aportación recoge la visión de más de veinticinco especialistas de doce países iberoamericanos sobre aspectos de la dirección de centros educativos. Su presentación exige unas reflexiones tanto sobre la temática como sobre el contenido. En relación con la temática, la dirección, entendida como sistema de dinamización, apoyo y acompañamiento a la actuación pedagógica e institucional, lejos de estar en crisis, se considera cada vez más necesaria. Los centros de formación y los profesores se enfrentan a situaciones nuevas, diversas y complejas, consecuencia de una realidad más dinámica, de una sociedad más exigente y de unos usuarios más conscientes de la calidad de servicios que precisan. La nueva situación hace pertinente que las respuestas educativas tengan en cuenta la complejidad de los fenómenos y sean diferenciadas en función del contexto y de los destinatarios, resaltando la necesidad y conveniencia de toma de decisiones fundamentadas y de apoyos vinculados a su desarrollo. El desarrollo de la temática de dirección que se aborda en el presente texto recoge aportaciones de diversa naturaleza. Por una parte, aquellas que han venido trabajando cuatro equipos con profesionales de diferentes países durante seis meses; por otra, recoge otras tres complementarias realizadas también por equipos de especialistas. Su realización se vincula al encuentro de especialistas de la Red de Apoyo a la Gestión Educativa (Red AGE: http://www.redage.org) realizado en el mes de junio de 2010 en la ciudad de Santiago de Chile. Allí, los representantes de las organizaciones miembro presentaron y debatieron sobre la situación actual de la dirección escolar en sus respectivos países, que constituyen la base sobre la que se han realizado las aportaciones definitivas que recoge el presente texto. Se cubre así un propósito fundamental de la Red AGE, como es el de fomentar el intercambio de experiencias, la profesionalización de los directivos y la promoción del conocimiento sobre administración y gestión educativa. La finalidad última es la de mejorar el funcionamiento de las instituciones formativas (y, a través de ellas, de los sistemas formativos), procurando sean de calidad y un instrumento para el cambio profesional y social