Structure-activity relationships based on 3D-QSAR CoMFA/CoMSIA and design of aryloxypropanol-amine agonists with selectivity for the human β3-adrenergic receptor and anti-obesity and anti-diabetic profiles

Indexación: Scopus.Acknowledgments: This work was supported by FONDECYT No. 11130701. We would also like to thank fDoTr CthLeafbr efeora vthaeil afrbeilei tayvoafiltahbeilsitoyf towfa trheer seoqfutwireadret orecqaulciureladt etothcealAcuDla(thet ttph:e/ A/dDt c(lhatbt.pw:/e/dbstc.cloabm.w/seobfst.wcoamre/-stoofotlws aarned-tools and http://teqip.jdvu.ac.in/QSAR_Tools/). SDG. Conflicts of Interest: The authors declare no conflict of interest. Conflicts of Interest: The authors declare no conflict of interest.The wide tissue distribution of the adrenergic β3 receptor makes it a potential target for the treatment of multiple pathologies such as diabetes, obesity, depression, overactive bladder (OAB), and cancer. Currently, there is only one drug on the market, mirabegron, approved for the treatment of OAB. In the present study, we have carried out an extensive structure-activity relationship analysis of a series of 41 aryloxypropanolamine compounds based on three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques. This is the first combined comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) study in a series of selective aryloxypropanolamines displaying anti-diabetes and anti-obesity pharmacological profiles. The best CoMFA and CoMSIA models presented values of r2 ncv = 0.993 and 0.984 and values of r2 test = 0.865 and 0.918, respectively. The results obtained were subjected to extensive external validation (q2, r2, r2 m, etc.) and a final series of compounds was designed and their biological activity was predicted (best pEC50 = 8.561). © 2018 by the authors.https://www.mdpi.com/1420-3049/23/5/119

Parallel Evolution of Quasi-separatrix Layers and Active Region Upflows

Persistent plasma upflows were observed with Hinode's EUV Imaging Spectrometer (EIS) at the edges of active region (AR) 10978 as it crossed the solar disk. We analyze the evolution of the photospheric magnetic and velocity fields of the AR, model its coronal magnetic field, and compute the location of magnetic null-points and quasi-sepratrix layers (QSLs) searching for the origin of EIS upflows. Magnetic reconnection at the computed null points cannot explain all of the observed EIS upflow regions. However, EIS upflows and QSLs are found to evolve in parallel, both temporarily and spatially. Sections of two sets of QSLs, called outer and inner, are found associated to EIS upflow streams having different characteristics. The reconnection process in the outer QSLs is forced by a large-scale photospheric flow pattern which is present in the AR for several days. We propose a scenario in which upflows are observed provided a large enough asymmetry in plasma pressure exists between the pre-reconnection loops and for as long as a photospheric forcing is at work. A similar mechanism operates in the inner QSLs, in this case, it is forced by the emergence and evolution of the bipoles between the two main AR polarities. Our findings provide strong support to the results from previous individual case studies investigating the role of magnetic reconnection at QSLs as the origin of the upflowing plasma. Furthermore, we propose that persistent reconnection along QSLs does not only drive the EIS upflows, but it is also responsible for a continuous metric radio noise-storm observed in AR 10978 along its disk transit by the Nan\c{c}ay Radio Heliograph.Comment: 29 pages, 10 figure

How Can Active Region Plasma Escape into the Solar Wind from below a Closed Helmet Streamer?

Recent studies show that active-region (AR) upflowing plasma, observed by the EUV-Imaging Spectrometer (EIS), onboard Hinode, can gain access to open field-lines and be released into the solar wind (SW) via magnetic-interchange reconnection at magnetic null-points in pseudo-streamer configurations. When only one bipolar AR is present on the Sun and it is fully covered by the separatrix of a streamer, such as AR 10978 in December 2007, it seems unlikely that the upflowing AR plasma can find its way into the slow SW. However, signatures of plasma with AR composition have been found at 1 AU by Culhane et al. (2014) apparently originating from the West of AR 10978. We present a detailed topology analysis of AR 10978 and the surrounding large-scale corona based on a potential-field source-surface (PFSS) model. Our study shows that it is possible for the AR plasma to get around the streamer separatrix and be released into the SW via magnetic reconnection, occurring in at least two main steps. We analyse data from the Nan\c{c}ay Radioheliograph (NRH) searching for evidence of the chain of magnetic reconnections proposed. We find a noise storm above the AR and several varying sources at 150.9 MHz. Their locations suggest that they could be associated with particles accelerated during the first-step reconnection process and at a null point well outside of the AR. However, we find no evidence of the second-step reconnection in the radio data. Our results demonstrate that even when it appears highly improbable for the AR plasma to reach the SW, indirect channels involving a sequence of reconnections can make it possible.Comment: 26 pages, 10 figures. appears in Solar Physics, 201

Seed Size and Its Relationship with Crop Establishment, Productivity and Nutritive Value in Genotypes of Maize for Silage

For a high dry matter (DM) yield of forage maize an adequate population of plants is required, which is related to germination, vigour, and seed size (Ellis, 1992). The objective of the present study was to investigate seed size and its relationship to establishment, productive and nutritional potential of silage maize, which has not before been reported in the literature

Identification of gastric cancer from speckle patterns

Speckle technique is based on the light intensity distribution randomly formed when a laser light is reflected on a rough surface, creating a pattern of illuminated grains (constructively) and dark (destructive) on scales of 1 μm. When the samples are displaced or deformed, the speckle pattern is altered. In this paper we present speckle patterns obtained from samples of gastric mucosa that is physically altered for the carcinogenesis process. Biopsies were studied with different diagnoses and were grouped according to the characteristics of speckle patterns. Speckle patterns were obtained by illuminating the samples with green laser. Morphological parameters of the speckle patterns reveal existence of 3 descriptors: the average grain size, hydraulic radius and the radio of the Weddel disc, which showed a high, intermediate and low value. The comparison shows agreement between the histopathological diagnosis and the values obtained by the speckle technique, making this technique emerge as a new classification system for quantitative diagnosis of precancerous lesions.Facultad de Ingenierí

Identification of gastric cancer from speckle patterns

Speckle technique is based on the light intensity distribution randomly formed when a laser light is reflected on a rough surface, creating a pattern of illuminated grains (constructively) and dark (destructive) on scales of 1 μm. When the samples are displaced or deformed, the speckle pattern is altered. In this paper we present speckle patterns obtained from samples of gastric mucosa that is physically altered for the carcinogenesis process. Biopsies were studied with different diagnoses and were grouped according to the characteristics of speckle patterns. Speckle patterns were obtained by illuminating the samples with green laser. Morphological parameters of the speckle patterns reveal existence of 3 descriptors: the average grain size, hydraulic radius and the radio of the Weddel disc, which showed a high, intermediate and low value. The comparison shows agreement between the histopathological diagnosis and the values obtained by the speckle technique, making this technique emerge as a new classification system for quantitative diagnosis of precancerous lesions.Facultad de Ingenierí

Fluctuaciones minerales en pastos de clima frío Colombiano: II kikuyo (Pennisetum clandestinum, Hochst), anual y estacional.

El experimento se llevó a cabo en la Hacienda Piedra Gorda, municipio de Ubaté (Cundinamarca), situado a 2600 m.s.n.m. con una temperatura promedia de 13,5° C; desde Octubre de 1980 a Marzo de 1982, correspondiendo a un periodo de lluvia y dos de sequía. Se utilizó ci pasto kikuyo sometido a pastoreo en franjas con ganado Holstein en levante y producción (7,7 L/día) con una carga de 2,5 cabezas/ha. Las muestras de pasto se tomaron a mano, de las porciones que los animales estaban consumiendo y que una vez secados y molidos se determinaron las concentraciones de proteína cruda y de los macro y micro elementos. La proteína cruda presentó contenidos de 14,6% a 16,2%, suficientes para no menoscabar ci consumo de alimento por parte de los animales. Los contenidos de calcio en la época de lluvias y sequia fueron de 0,51% y 0,79%, respectivamente, niveles que Ilenan los requerimientos de este nutriente para ci ganado lechero del área bajo estudio. Los macroelementos fósforo, magnesio, azufre y sodio se encuentran en niveles deficitarios en el forraje- Mientras que ci potasio, hierro y manganeso están por encima del nivel normal y posiblemente ocasionaban imbalances en los niveles de magnesio y cobre provocando problemas metabólicos en el ganado.This experiment was carried out at the Piedras Gordas Farm, Ubaté (Cundinarnarca) valley, located at 2600 inabove sea level, with a mean temperature of 13,5 0 C, from October 1980 to March 1982, corresponding to one period of wet season and two periods of dry season. Kikuyu grass was used under rotational grazing with 2.5 Ilolstein cows per hectare and 7,7 L/day of milk production. The gtass samples were taken by hand from the areas and fractions that the animal were grazing. Those samples were dried at 60° by 48 hr, ground and kept until the chemical determinations were made. The crude Protein content were 14,6%and 16,19% for dry and wet season, respectively, with enough concentration to guarantee the fulfillment of the animal requirements. The Ca content in wet and dry season were 0,51% and 0,79% respectively, enough for animals in lactating period and during the year. The P, Mg, S and Na were in low concentration during the year in kikuyu grass. However the K, Fe and Mn were at vcry.high levels and could have been producing metabolic interferences to Mg and Cu. In paddocks with kikuyu grass will be possible to found serious deficiencies of Cu and Zn.Ganado de leche-Ganadería lech

Oxygen vacancy related distortions in rutile TiO_2 nanoparticles: a combined experimental and theoretical study

The effects of doubly ionized oxygen vacancies [(V_O)ˆ(2+)]on the electronic structure and charge distribution in rutile TiO_2 are studied by combining first-principles calculations based on density functional theory and experimental results from x-ray photoelectron and x-ray absorption measurements carried out in synchrotron facilities on rutile TiO_2 nanoparticles. The generalized gradient approximation of the Perdew-Burke-Ernzerhof functional has demonstrated its suitability for the analysis of the [(V_O)ˆ(2+)]defects in rutile TiO_2. It has been found that the presence of empty electronic states at the conduction band shifted ̴1 eV from t_(2g) and e_(g) states can be associated with local distortions induced by [(V_O)ˆ(2+)]defects, in good agreement with Gauss-Lorentzian band deconvolution of experimental O K-edge spectra. The asymmetry of t(2g) and e(g) bands at the O-K edge has been associated with [(V_O)ˆ(2+)], which can enrich the understanding of studies where the presence of these defects plays a key role, as in the case of doped TiO_2