Study of the Differential Activity of Thrombin Inhibitors Using Docking, QSAR, Molecular Dynamics, and MM-GBSA

Indexación: Web of Science; Scopus.Non-peptidic thrombin inhibitors (TIs; 177 compounds) with diverse groups at motifs P1 (such as oxyguanidine, amidinohydrazone, amidine, amidinopiperidine), P2 (such as cyano-fluorophenylacetamide, 2-(2-chloro-6-fluorophenyl)acetamide), and P3 (such as phenylethyl, arylsulfonate groups) were studied using molecular modeling to analyze their interactions with S1, S2, and S3 subsites of the thrombin binding site. Firstly, a protocol combining docking and three dimensional quantitative structure-activity relationship was performed. We described the orientations and preferred active conformations of the studied inhibitors, and derived a predictive CoMSIA model including steric, donor hydrogen bond, and acceptor hydrogen bond fields. Secondly, the dynamic behaviors of some selected TIs (compounds 26, 133, 147, 149, 162, and 177 in this manuscript) that contain different molecular features and different activities were analyzed by creating the solvated models and using molecular dynamics (MD) simulations.We used the conformational structures derived from MD to accomplish binding free energetic calculations using MM-GBSA. With this analysis, we theorized about the effect of van der Waals contacts, electrostatic interactions and solvation in the potency of TIs. In general, the contents reported in this article help to understand the physical and chemical characteristics of thrombin-inhibitor complexes. © 2015 Mena-Ulecia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.014277

Análisis de la capacidad de soporte sísmica de fundaciones superficiales

Indexación: Web of Science; Scielo.In the context of engineering practice, the problem of the seismic bearing capacity of shallow foundations has been solved indirectly, either due an increase of the static allowable soil pressures related to the probability of occurrence of the design earthquake or by adopting an equivalent pseudo-static approach. However, during last decades, a series of analytical methods that directly address the problem from the seismic point of view has been developed. This paper presents a parametric comparative analysis of different methods for estimating seismic bearing capacity of shallow strip foundations. Analytical methods, developed in the framework of both limit equilibrium and limit analysis theories, and also simplified design procedures typically used in practice were considered. The results obtained show an important decrease of the bearing foundation capacity with increasing of the maximum earthquake acceleration, which highlights the need to obtain a measure of the reliability associated with both calculation methods and safety factors commonly used for seismic design.En el contexto de la práctica ingenieril, el problema de la capacidad de soporte sísmica de fundaciones superficiales generalmente ha sido resuelto, de modo indirecto, ya sea considerando un incremento en las tensiones admisibles estáticas del suelo, asociado a la probabilidad de ocurrencia de un cierto evento sísmico de diseño, o bien adoptando un enfoque de tipo pseudoestático equivalente. Sin embargo, durante las últimas décadas se han desarrollado una serie de métodos analíticos que abordan directamente el problema desde el punto de vista sísmico. Este artículo presenta un análisis comparativo de tipo paramétrico entre diferentes métodos para estimar la capacidad de soporte sísmica de fundaciones superficiales corridas. Se consideraron métodos analíticos, desarrollados en el contexto de las teorías de equilibrio límite y análisis límite, y también procedimientos de diseño simplificados típicamente utilizados en la práctica. Los resultados obtenidos muestran un importante deterioro de la capacidad de soporte de la fundación en la medida que la aceleración máxima del sismo aumenta, lo cual pone de manifiesto la necesidad de establecer una medida de la confiabilidad asociada a los métodos de cálculo y factores de seguridad comúnmente usados para diseño sísmico.http://ref.scielo.org/kp4j8

Validation of a test assessing functional capacity in stroke survivors: UCSD performance-based skills assessment (UPSA)

Title from PDF of title page, viewed on July 30, 2014Thesis advisor: Joan McDowdVitaIncludes bibliographical references (pages 37-40)Thesis (M.A.)--Dept. of Psychology. University of Missouri--Kansas City, 2014Everyday functioning is an important outcome that is evaluated and targeted in stroke rehabilitation programs. Therefore, it is important to identify assessments of functional capacity that are feasible, acceptable and valid to predict daily life abilities among stroke survivors. The purpose of the present study was to determine the feasibility, acceptability and validity of the UCSD Performance-Based Skills Assessment (UPSA) in a stroke population. Participants were 40 stroke survivors, 22 Caregivers, and 20 Healthy Controls. The UPSA was validated against the Executive Function Performance Test (EFPT), a valid measure of daily functioning in stroke survivors, and Social Participation was measured using the Assessment of Life-Habits Scale (LIFE-H) which was completed by the stroke survivor's caregiver. Significant correlations were found between UPSA total and EPFT total scores, UPSA Communication and EFPT Telephone scores, and UPSA Household Management and EFPT Simple Cooking scores. However, no significant correlation was found between the UPSA Finance and the EFPT Bill Payment scores. Additionally, stroke survivors' Social Participation was significantly predicted by UPSA total scores, controlling for age, education and severity of stroke. Regarding our sensitivity analysis, no differences were found between stroke survivors' and healthy controls' performance in UPSA total scores and domain scores, except in the transportation domain. The UPSA provides advantages for its use in this population including: the limited amount of training needed to administer and score it, its portability, and the time of administration (i.e., 30 minutes). In summary, findings from this study offer preliminary support for the feasibility, acceptability and validity of the UPSA as a performance-based measure of functional capacity in stroke survivors.Abstract -- List of tables -- List of illustrations -- Acknowledgments -- Introduction and background -- Methodology -- Results -- Discussion -- Appendix A - Appendix B -- Reference

Evaluación de la didáctica y la satisfacción de los estudiantes en una asignatura de historia del derecho

El objetivo de este trabajo es presentar los resultados de una investigación llevada a cabo en la asignatura de Historia del Derecho correspondiente al primer año de la carrera de Licenciatura en Ciencias Jurídicas. Se trata de una investigación exploratoria que vincula la didáctica de la historia con la satisfacción de los estudiantes. Se concluye que existen importantes dificultades en la implementación didáctica de la asignatura, además de insatisfacción de los estudiantes, mala utilización de herramientas tics y la no utilización de fuentes primarias

Giovanni Arrighi, EL LARGO SIGLO XX.

Revisión libro El largo siglo XX

La agresividad y su influencia en el rendimiento escolar en los estudiantes de la I.E. Nº 2075 nivel primario del distrito de Comas, región Lima, 2010

El trabajo de investigación tuvo como objetivo: Determinar el grado de influencia de la agresividad en el rendimiento escolar en los estudiantes de la I.E Nº 2075 nivel primaria del distrito de Comas, Región Lima, 2010. La metodología empleada fue de un nivel correlacional de tipo Sustantiva: Descriptiva - Explicativa, un diseño descriptivo correlacional. Con una población de 90 alumnos, se trabajó con una muestra representativa de 30 alumnos de la I.E Nº 2075 “Cristo Hijo de Dios” de la Ugel Nº04 en el distrito de Comas. Los instrumentos que se aplicaron fueron un cuestionario con 15 preguntas tipo escala de Likert, con el fin de medir las variables de la investigación y que fueron validados por tres expertos. Las principales conclusiones a que se arribaron son: La agresividad es una conducta aprendida en el hogar, la escuela y la sociedad. Derivada de estímulos ambientales y conductuales negativos los cuales han sido adquiridos en el desarrollo de la infancia de cada individuo, por lo que se concluye que siendo una conducta aprendida es susceptible a cambios y modificaciones

Los créditos de consumo y su relación con la morosidad de Edpyme Marcimex, Agencia Junín Distrito Trujillo, año 2016.

La presente investigación tiene por objetivo demostrar la relación que existe entre los créditos de consumo y la morosidad de la Edpyme Marcimex, Agencia Junín. Para realizar esta investigación se aplicó un diseño de contrastación tipo correlacional, utilizando los métodos de análisis, síntesis e inducción - deducción. El proceso de obtención de datos se realizó a través de análisis documental utilizando como instrumento la hoja de registro de datos. Entre los resultados obtenidos se determinó que no existe relación directa entre las políticas de crédito y la morosidad de Edpyme Marcimex, Agencia Junín –Distrito Trujillo, año 2016, lo cual se reflejó en la cartera de clientes y en los expedientes de créditos revisados. El incremento de la morosidad genera provisiones, refinanciamientos y frecuentes castigos de las cuentas, por no aplicarse de manera adecuada la política de créditos. Con el estudio realizado se concluye que en la EDPYME MARCIMEX S.A, no se cumplen adecuadamente las políticas de créditos, tales como: los procesos, metodologías y políticas crediticias, los cuales incrementaron ligeramente la morosidad, al mantener criterios de evaluación y metodologías inexactas que no se basaron en un análisis financiero minucioso, sino que dependieron más de la opinión, percepción y juicio personal de cada evaluador de créditos. Se recomienda mejorar los criterios de evaluación crediticia sobre la base de un análisis financiero minucioso que considere a los indicadores financieros básicos como esenciales para la determinación de un crédito de consumo.The present research has as objective the relation that exists between the credits of consumption and the moroseness of the Edpyme Marcimex, Junín Agency. To carry out this research, a correlational type test was applied, using the analysis, synthesis and induction-deduction methods. The process of obtaining data was done through the documentary analysis applying the record sheet. Among the results obtained, it was concluded that there is no direct relationship between the credit policies and the delinquency of Edpyme Marcimex, Junín Agency -Distrito Trujillo, 2016, which is reflected in the client portfolio and in the records of revised credits. The increase in delinquency generates provisions, refinancing and frequent write-offs of accounts, as the credit policy is not appropriately adapted. It is recommended to modify and improve the credit evaluation criteria based on a minimum financial analysis that considers the basic financial indicators as essential for the determination of a consumer credit.Tesi

Caracterización estructural de un bosque pantanoso sin intervención antrópica en la comuna de Pitrufquén, Chile

The swampy forests of the Central - South zone of Chile are distributed between the regions from Coquimbo to Los Lagos (30 ° - 41 ° 28 'S). In the La Araucanía region, the marsh forests called Pitrantos or pitra-forests stand out, dominated by Blepharocalyx cruckshanksii and Myrceugenia exsucca. Currently, pitrants are under permanent stress from anthropic activities and could become extinct ecosystems before being scientifically known. The objective of this work is to structurally characterize a swamp forest without anthropic intervention in the commune of Pitrufquén, Chile. For this, a 300 m2 rectangular plot was established in the study area where the tree species was recorded, the height and DBH of all latizal-type individuals were measured, the number of seedlings of each species was counted and, finally, the number of seedlings was counted in 50 subplots of 1 m2, distributed within the same sampling plot. The swamp forest established in the study site is made up of nine tree species, all broadleaf, evergreen and native; the most abundant Myrceugenia exsucca with 11,928 individuals per hectare; followed by Drimys winteri with 5,952 individuals and maximum total heights of 20 and 18 meters, respectively. It has a typical structure in terms of the altitude and length where it is established, and it is regenerating with its own species at an advanced successional dynamics.Los bosques pantanosos de la zona Centro - Sur de Chile se distribuyen entre las regiones de Coquimbo a Los Lagos (30°- 41°28´ S). Destacan en la región de La Araucanía los bosques pantanosos denominados Pitrantos, dominados por Blepharocalyx cruckshanksii y Myrceugenia exsucca. Actualmente, los pitrantos se encuentran bajo el permanente estrés de las actividades antrópicas y podrían convertirse en ecosistemas extintos antes de ser científicamente conocidos. El objetivo de este trabajo es caracterizar estructuralmente un bosque pantanoso sin intervención antrópica en la comuna de Pitrufquén, Chile. Para esto, se estableció en el área de estudio una parcela rectangular de 300 m2 en donde se registró la especie arbórea, se midió la altura y el DAP de todos los individuos de tipo latizal, se contó el número de brinzales de cada especie y, finalmente, se contabilizó el número de plántulas en 50 subparcelas de 1 m2, distribuidas dentro de la misma parcela de muestreo. El bosque pantanoso establecido en el sitio de estudio se encuentra conformado por nueve especies arbóreas, todas latifoliadas, perennifolias y nativas; la más abundante Myrceugenia exsucca con 11.928 individuos por hectárea; seguida por Drimys winteri con 5.952 individuos y alturas totales máximas de 20 y 18 metros, respectivamente. Posee una estructura típica en cuanto a la altitud y longitud en donde se establece, y se encuentra regenerando con especies propias a una avanzada dinámica sucesional

Predictors of performance-based measures of instrumental activities of daily living in stroke survivors

Title from PDF of title page, viewed on August 22, 2016Dissertation advisor: Joan McDowdVitaIncludes bibliographical references (pages 70-80)Thesis (Ph.D.)--Department of Psychology. University of Missouri--Kansas City, 2016The aim of this dissertation was to investigate the relationship between cognitive domains/executive functions and performance on measures of Instrumental Activities of Daily Living (IADLs) in stroke survivors. Fifty-two stroke survivors completed assessments of immediate memory, visuospatial/constructional skills, language, attention, delayed memory, executive functions (i.e., inhibition and flexibility, concept-formation and problem solving, abstract thinking, deductive thinking, and verbal abstraction), and two performance-based measures of IADLs. Results indicated significant correlations between the UCSD Performance-based Skills Assessment (UPSA), a measure of IADLS, and immediate memory, visuospatial/constructional skills, language, delayed memory, and executive functions (i.e., concept formation and problem solving, flexibility of thinking, and verbal abstraction). In regards to the Executive Function Performance Test (EFPT), the second measure of IADLs, significant correlations were found between the EFPT and visuospatial/constructional skills, language, delayed memory, and executive functions (i.e., concept formation and problem solving, and flexibility of thinking). Hierarchical multiple regressions demonstrated that only language significantly predicted UPSA total scores and no cognitive domains and executive functions significantly predicted EFPT total scores. These results have several implications. For example, cognitive domains and executive functions are important in predicting a stroke survivors’ level of functioning, and not as individual predictors but rather as a set of cognitive abilities. Limitations of this study and future research directions are discussed.Introduction -- Methodology -- Results -- Discussion -- Appendix A. Tables 1-10 -- Appendix B. Figures 1-2