Short synthesis and anti-rhinoviral activity of imidazo[1,2-a]pyridines: the effect of acyl groups at 3-position

Various 2-amino-3-acyl-6-[(E)-1-phenyl-2-N-methylcarbamoylvinyl]-imidazo[1,2-a]pyridines, structurally related to Enviroxime were prepared to determine the effect of acyl groups on the antirhinoviral activity. A short and efficient means for the construction of the imidazo nucleus as well as biological evaluation of the final compounds are disclosed.This research was supported by a CDTI program (Plan concertado 96/0036) and the Spanish Farma III programme (Ministerio de Industria y Ministerio de Sanidad). We are also grateful to the Lilly Rhinovirus Action Group for their advice and interest in this work

Mapeo de procesos dentro del área de programas del Organismo de Nutrición Infantil

El PAP es una experiencia de aprendizaje y de contribución social integrada por estudiantes, profesores, actores sociales y responsables de las organizaciones, que de manera colaborativa construir sus conocimientos para dar respuestas a problemáticas de un contexto específico y en un tiempo delimitado. Por tanto, la experiencia PAP supone un proceso en lógica de proyecto, así como de un estilo de trabajo participativo y recíproco entre los involucrados. La organización donde se trabajará el proyecto PAP es en el Organismo de Nutrición Infantil, con el que se tuvo el primer acercamiento con la organización el miércoles 9 de febrero. Durante la reunión que se tuvo se definió el contexto actual de la organización y se presentaron los distintos proyectos a desarrollar, dependiendo de la carrera y los intereses de los miembros del equipo. Este documento abarcará el proyecto realizado por los estudiantes de ingeniería industrial, el cual consta del mapeo y documentación de procesos de un área de importancia especificada por el ONI.ITESO, A.C

Capacitación para mapeo de procesos BPMN en el Organismo de Nutrición Infantil

Mapeo y Documentación de Procesos II: Plan de capacitación para la elaboración de BPMN y auditoría de procesos. En este Proyecto se dará seguimiento al mapeo de procesos realizado por el equipo durante el PAP I. En esta ocasión, se elaborará un plan de capacitación para que la organización sea capaz de Mapear y Auditar los procesos restantes. Esto con el objetivo de que ONI pueda terminar de realizar los diagramas BPMN 1 de los procesos faltantes que no podrán ser elaborados por el mismo equipo del PAP. Utilizando la misma metodología seguida por el equipo en el PAP I, se generarán las guías, formatos, documentos y material de apoyo necesarios para capacitar al personal elegido por ONI. Se realizarán tres sesiones de capacitación para la elaboración de diagramas BPMN, las cuales abarcarán: • La introducción al mapeo de procesos y el software a utilizar: BIZAGI. • Notaciones utilizadas: tipos y diferencias. • Ejemplos prácticos y el mapeo del Proceso de uso de ONI Móvil. Por último, se realizará un material de apoyo audiovisual que servirá como guía para poder auditar los procesos que se mapeen. Esta guía se tomará en cuenta como la cuarta sesión de capacitación. Los resultados esperados de este proyecto es que ONI uente con los conocimientos y habilidades necesarios para continuar con el mapeo de procedimientos de la Organización. Se espera que el personal seleccionado para las capacitaciones sea capaz de mapear el proceso: Entrega de ONI fórmula con implementación de ONI Móvil.ITESO, A.C

Mechanisms of refractive index modification during femtosecond laser writing of waveguides in alkaline lead-oxide silicate glass

3 pages, 3 figures.We report on the mechanisms responsible for the formation of optical waveguides upon femtosecond laser irradiation of an alkaline lead-oxide silicate glass. MicroRaman spectroscopy and nonlinear fluorescence were employed to probe the local glass network structure and the formation of optically active defects respectively. At low laser pulse energies, the laser modified region is formed by a single light guiding region, whereas for pulses above 14 µJ the modified region is formed by a central dark zone, which does not guide light, accompanied by light guiding zones located in the surrounding of the dark one. This behavior is different from that observed in common silica glass systems but agrees with recent results obtained in phosphate and heavy metal oxide glasses. However, our results show that, unlike the latter glass, local densification of the glass occurs in the whole laser modified region, i.e., in the dark and the guiding zones. The suppression of light guiding in the dark region is explained by a high density of absorbing color centers.This work was partially supported by CICYT (Spain) under Project No. DPI2002-00151. One of the authors (V.D.B.) acknowledges the financial support of the CSIC and the European Social Fund through an I3P Ph.D. fellowship. Another author (P.L.-A. acknowledges funding from the Spanish Government ( the Ramón y Cajal program and Grant No. TIC2003-07485).Peer reviewe

Early imaging and molecular changes with neoadjuvant bevacizumab in stage ii/iii breast cancer

This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2–C5). Tumour proliferation and hypoxic status were evaluated using18F-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT)-and18F-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre-and post-bevacizumab vascular changes were evaluated using dynamic contrastenhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (p = 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

On soil-structure interaction in large non-slender partially buried structures

This paper addresses the seismic analysis of a deeply embedded non-slender structure hosting the pumping unit of a reservoir. The dynamic response in this type of problems is usually studied under the assumption of a perfectly rigid structure using a sub-structuring procedure (three-step solution) proposed specifically for this hypothesis. Such an approach enables a relatively simple assessment of the importance of some key factors influencing the structural response. In this work, the problem is also solved in a single step using a direct approach in which the structure and surrounding soil are modelled as a coupled system with its actual geometry and flexibility. Results indicate that, quite surprisingly, there are significant differences among prediction using both methods. Furthermore, neglecting the flexibility of the structure leads to a significant underestimation of the spectral accelerations at certain points of the structure

Multiple Local and Recent Founder Effects of TGM1 in Spanish Families

<div><h3>Background</h3><p>Mutations in the <em>TGM1</em> gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ∼46%, ∼21% and ∼13% of all <em>TGM1</em> gene mutations, respectively. Moreover, these mutations were reported only once outside of Galicia, pointing to the existence of historical episodes of local severe genetic drift in this region.</p> <h3>Methodology/Principal Findings</h3><p>In order to determine whether these mutations were inherited from a common ancestor in the Galician population, and to estimate the number of generations since their initial appearance, we carried out a haplotype-based analysis by way of genotyping 21 SNPs within and flanking the <em>TGM1</em> gene and 10 flanking polymorphic microsatellite markers spanning a region of 12 Mb. Two linkage disequilibrium based methods were used to estimate the time to the most recent common ancestor (TMRCA), while a Bayesian-based procedure was used to estimate the age of the two mutations. Haplotype reconstruction from unphased genotypes of all members of the affected pedigrees indicated that all carriers for each of the two mutations harbored the same haplotypes, indicating common ancestry.</p> <h3>Conclusions/Significance</h3><p>In good agreement with the documentation record and the census, both mutations arose between 2,800–2,900 years ago (y.a.), but their TMRCA was in the range 600–1,290 y.a., pointing to the existence of historical bottlenecks in the region followed by population growth. This demographic scenario finds further support on a Bayesian Coalescent Analysis based on <em>TGM1</em> haplotypes that allowed estimating the occurrence of a dramatic reduction of effective population size around 900–4,500 y.a. (95% highest posterior density) followed by exponential growth.</p> </div

Novel compound shows in vivo anthelmintic activity in gerbils and sheep infected by Haemonchus contortus

8 páginas, 2 figuras, 2 tablas.The control of gastrointestinal nematodes in livestock is becoming increasingly difficult due to the limited number of available drugs and the rapid development of anthelmintic resistance. Therefore, it is imperative to develop new anthelmintics that are effective against nematodes. Under this context, we tested the potential toxicity of three compounds in mice and their potential anthelmintic efficacy in Mongolian gerbils infected with Haemonchus contortus. The compounds were selected from previous in vitro experiments: two diamine (AAD-1 and AAD-2) and one benzimidazole (2aBZ) derivatives. 2aBZ was also selected to test its efficacy in sheep. In Mongolian gerbils, the benzimidazole reduced the percentage of pre-adults present in the stomach of gerbils by 95% at a dose of 200 mg/kg. In sheep, there was a 99% reduction in the number of eggs shed in faeces after 7 days at a dose of 120 mg/kg and a 95% reduction in the number of worm adults present in the abomasum. In conclusion, 2aBZ could be considered a promising candidate for the treatment of helminth infections in small ruminants. © 2022, The Author(s).Financial support came from MINECO: RETOS (AGL2016-79813-C2-1R/2R) and MICINN/AEI (PID2020- 119035RB-100). EVG was funded by FPU17/00627, FPU17/05346; VCGA, MAB, MCP and LGP are recipients of Junta de Castilla y León (JCyL) (LE082-18, LE051-18, LE135-19, LE096-20, respectively) and MMV by the Spanish “Ramon y Cajal” Programme (Ministerio de Economía y competitividad; MMV, RYC-2015-18368).Peer reviewe

Revista del Consejo Superior de Investigaciones Científicas

Alimentación del meloncillo Herpestes ichneumon y de la gineta Genetta genetta en la Reserva Biológica de Doñana, S.O. de la Península Ibérica.Determinación de la edad en Rana perezi Seoane, 1885. Aplicación al análisis del crecimiento somático de poblaciones.Influencias ambientales en la variación del tamaño, forma y peso de los huevos de la collalba rubia (Oenanthe hispanica L.)Características de un coro de sapos corredores (Bufo calamita) en el sureste de España.Estrategias alimentarias del ciervo (Cervus elaphus L.) en Montes de ToledoDistribución de los quirópteros de la provincia de Orense (Noroeste de España).Ecología trófica del lince ibérico en Doñana durante un periodo secoDesarrollo larvario de la rana común (Rana perezi) (anura: ranidae) en charcas temporales del noroeste de la Península Ibérica.Régimen alimenticio del mirlo común (Turdus merula) en el sureste de la Península Ibérica durante el periodo otoño-invierno.Reproducción del gorrión molinero (Passer montanus) en las Islas Canarias.Relación entre la cobertura vegetal y la distribución de nidos en las colonias de pagaza piconegraPeer reviewe

T-Duality and Penrose limits of spatially homogeneous and inhomogeneous cosmologies

Penrose limits of inhomogeneous cosmologies admitting two abelian Killing vectors and their abelian T-duals are found in general. The wave profiles of the resulting plane waves are given for particular solutions. Abelian and non-abelian T-duality are used as solution generating techniques. Furthermore, it is found that unlike in the case of abelian T-duality, non-abelian T-duality and taking the Penrose limit are not commutative procedures.Comment: 16 pages, 4 figures. Discussion on non-abelian T-duality expande