Computer Modelling and Simulations of Enzymes and their Mechanisms

Although the tremendous catalytic power of enzymes is widely recognized, their exact mechanisms of action are still a source of debate. In order to elucidate the origin of their power, it is necessary to look at individual residues and atoms, and establish their contribution to ligand binding, activation, and reaction. Given the present limitations of experimental techniques, only computational tools allow for such detailed analysis. During my PhD studies I have applied a variety of computational methods, reviewed in Chapter 2, to the study of two enzymes: DfrB dihydrofolate reductase (DHFR) and methyltetrahydrofolate: corrinoid/iron-sulfur protein methyltransferase (MeTr). ¶ ..

Addressing MEP Labor Shortages and Methods to Attract Young Adults into The Trades

The mechanical, electrical, and plumbing (MEP) fields require a large skilled workforce. In recent years, companies have experienced shortages of skilled employees. These shortages arise from many causes, a root cause identified is the decrease of young adults pursuing MEP careers. This project focuses on the reasons young adults are reluctant to enter these careers, such as misconceptions or lack of knowledge on MEP careers. A pool of twelve MEP companies was surveyed regarding their experiences with the causes of labor shortages and the short-term mitigation methods used. They were also asked about their perspective on the lack of young adults in their industry and the importance of attracting young talent. The responses indicated how crucial it is to attract young adults to the MEP fields, and that an efficient way to do so is by informing them on what they are and their associated benefits. In response to the survey outcome, a brochure and PowerPoint were developed. They will be presented in high schools for the purpose of informing students about the MEP industries. Through the PowerPoint and brochure, students in high school can learn about the MEP fields, potentially sparking interest to pursue a career in these trades

Velocity dispersion estimates of APM galaxy clusters

We present 83 new galaxy radial velocities in the field of 18 APM clusters with redshifts between 0.06 and 0.13. The clusters have Abell identifications and the galaxies were selected within 0.75 h$^{-1}$Mpc in projection from their centers. We derive new cluster velocity dispersions for 13 clusters using our data and published radial velocities. We analyze correlations between cluster velocity dispersions and cluster richness counts as defined in Abell and APM catalogs. The correlations show a statistically significant trend although with a large scatter suggesting that richness is a poor estimator of cluster mass irrespectively of cluster selection criteria and richness definition. We find systematically lower velocity dispersions in the sample of Abell clusters that do not fulfill APM cluster selection criteria suggesting artificially higher Abell richness counts due to contamination by projection effects in this subsample.Comment: Accepted for publication in MNRA

Local Luminous Infrared Galaxies. III. Co-evolution of Black Hole Growth and Star Formation Activity?

Local luminous infrared (IR) galaxies (LIRGs) have both high star formation rates (SFR) and a high AGN (Seyfert and AGN/starburst composite) incidence. Therefore, they are ideal candidates to explore the co-evolution of black hole (BH) growth and star formation (SF) activity, not necessarily associated with major mergers. Here, we use Spitzer/IRS spectroscopy of a complete volume-limited sample of local LIRGs (distances of <78Mpc). We estimate typical BH masses of 3x10^7 M_sun using [NeIII]15.56micron and optical [OIII]5007A gas velocity dispersions and literature stellar velocity dispersions. We find that in a large fraction of local LIRGs the current SFR is taking place not only in the inner nuclear ~1.5kpc region, as estimated from the nuclear 11.3micron PAH luminosities, but also in the host galaxy. We next use the ratios between the SFRs and BH accretion rates (BHAR) to study whether the SF activity and BH growth are contemporaneous in local LIRGs. On average, local LIRGs have SFR to BHAR ratios higher than those of optically selected Seyferts of similar AGN luminosities. However, the majority of the IR-bright galaxies in the RSA Seyfert sample behave like local LIRGs. Moreover, the AGN incidence tends to be higher in local LIRGs with the lowest SFRs. All this suggests that in local LIRGs there is a distinct IR-bright star forming phase taking place prior to the bulk of the current BH growth (i.e., AGN phase). The latter is reflected first as a composite and then as a Seyfert, and later as a non-LIRG optically identified Seyfert nucleus with moderate SF in its host galaxy.Comment: Accepted for publication in Ap

Why Is Aedes aegypti Moving South in South America?

Colonies of Aedes aegypti have been reported at increasingly southern locations. Is this feature a manifestation of climate change or the result of the mosquito’s adaptation? Answering the question requires the testing and comparison of results produced under different, competing, hypotheses. We address the problem using “AedesBA”, a detailed model of the mosquito Aedes aegypti that has been under development for about 20 years. The aim of the model is to promote understanding. We incorporate the recently discovered biological behavior of this mosquito: diapause. Namely, this is the laying of resistance eggs when the day light shortens, entering into the unfavorable season for reproduction in temperate climates, as described from laboratory experiments. When the model is challenged to answer the questions posed, it suggests that climate change, as experienced during the time of the field records, does not explain the observations. Furthermore, the standard climate change argument does not support a detailed analysis. In contrast, we find that while diapause is not expected to be a trait that is selected by natural conditions in a subtropical climate (simulations for Resistencia, AR), within temperate climates such as in Buenos Aires city (AR), there is pressure favoring the selection of the trait. As we move southward (the cities of Dolores, Azul, Tandil, and Mar del Plata), the pressure increases, while the probability of Aedes aegypti to become established in them decreases, being in accordance with the field observations. The model shows in addition that the field-observable effects of diapause depend on weather variables, especially precipitation, and the dynamics of the nutritional resources in the breeding sites.Fil: Alonso, Lucas Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones en Energía no Convencional. Universidad Nacional de Salta. Facultad de Ciencias Exactas. Departamento de Física. Instituto de Investigaciones en Energía no Convencional; ArgentinaFil: Romeo Aznar, Victoria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Solari, Hernan Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentin

Two essential light chains regulate the MyoA lever arm to promote Toxoplasma gliding motility

Key to the virulence of apicomplexan parasites is their ability to move through tissue and to invade and egress from host cells. Apicomplexan motility requires the activity of the glideosome, a multicomponent molecular motor composed of a type XIV myosin, MyoA. Here we identify a novel glideosome component, essential light chain 2 (ELC2), and functionally characterize the two essential light chains (ELC1 and ELC2) of MyoA in Toxoplasma. We show that these proteins are functionally redundant but are important for invasion, egress, and motility. Molecular simulations of the MyoA lever arm identify a role for Ca2+ in promoting intermolecular contacts between the ELCs and the adjacent MLC1 light chain to stabilize this domain. Using point mutations predicted to ablate either the interaction with Ca2+ or the interface between the two light chains, we demonstrate their contribution to the quality, displacement, and speed of gliding Toxoplasma parasites. Our work therefore delineates the importance of the MyoA lever arm and highlights a mechanism by which this domain could be stabilized in order to promote invasion, egress, and gliding motility in apicomplexan parasites

G4.5 Pamam Dendrimer-Risperidone: Biodistribution and Behavioral Changes in In Vivo Model

Dendritic polymers are considered as emerging and outstanding carriers as modern medicinal systems due to their derivatisable branched architecture and possibility to modify them in numerous ways. Here, G4.5 PAMAM dendrimers were obtained as carriers of the antipsychotic drug risperidone. Despite their extensive applicability in the pharmaceutical field, the use of dendrimers as carriers in biological systems is constrained due to their inherent associated toxicity. The biocompatibility of dendrimers and dendrimer-risperidone complexes was evaluated in vivo for biological performance. To this end, the pharmacokinetics and biodistribution after oral treatment of free risperidone and dendrimer-risperidone complexes were studied in healthy mice. Also, the behavioral changes such as locomotion, aggression, dominance in male and female mice were evaluated both after a single dose and after daily therapy for 8 days. Also, in vivo effects of risperidone and dendrimer-risperidone complexes on the locomotion of zebrafish larvae were explored. The data obtained suggest that the unmetabolized risperidone complexes increase the arrival to the brain after 90 minutes. On the other hand, behavioral studies showed an increase in the potency of the drug in animals treated with the complexesFil: Prieto, Maria Jimena. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: del Rio Zabala, Nahuel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Marotta, Cristian Hernán. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Bichara, Darío Román. Fundación Instituto Leloir; ArgentinaFil: Simonetta, Sergio Hernan. Fundación Instituto Leloir; ArgentinaFil: Chiaramoni, Nadia Silvia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Alonso, Silvia del Valle. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentin

Resultados óptimos demandan herramientas de mayor precisión: el aporte de Mínimos Cuadrados Parciales (PLS)

La regresión PLS (Partial Least Squares) es un método estadístico multivariante recientemente generalizado. Combina y generaliza conceptos de análisis de Componentes Principales y de análisis de Regresión Lineal Múltiple y resulta particularmente útil cuando se desea predecir un conjunto de variables dependientes (Y) desde un conjunto (relativamente grande y posiblemente correlacionadas) de variables predictoras (X). También resuelve con propiedad el problema de multicolinealidad, que generalmente se supera eliminando las variables que la causan o transformándolas, solución aplicable si la permanencia del set de variables X no es requerida, o sea cuando necesidades de explicación y predicción no inhiban tal procedimiento. Es apto asimismo cuando el problema requiere considerar relaciones múltiples y cruzadas, y que todas ellas se den simultáneamente o cuando existen variables que no se puedan medir directamente (no observables) no obstante ser necesarias para desarrollar la teoría. El presente trabajo considera específicamente esta metodología, la describe e interpreta en su concepción y hace explícito su potencial aporte a través de su aplicación a dos casos simplificados1 que permiten comparar los resultados con los obtenidos mediante el empleo de otra técnica

ATRIBUCIÓN DE RENDIMIENTOS DE FONDOS DE INVERSIÓN CON BENCHMARK ÍNDICE MERVAL

Return attribution analysis is used to identify and measure components of investment portfolios’ excess returns (alphas). It allows for comparisons among portfolio managers performance, conducted within a class of funds following the same benchmark. The use of a benchmark in this type of peer analysis is necessary to group investments with similar risk profiles. Studying sources of alpha, the analyst strives to detect portfolio managers’ skills in exploit market imperfections to consistently beat the benchmark performance in one or more allocation decisions. This paper follows Brinston &amp; Fachler’s methodology (1985) to conduct a return attribution exercise among mutual funds benchmarked against the Merval Index, listed in the Argentine capital markets. The model assumes a top-down decision process, with weighting allocations in term of regional exposure and economic sector allocations being decided before the selection of individual securities or stock picking. The exercise covers four quarters of 2015 and represents the initial approach of an ongoing project to apply this methodology to additional periods and other sectors of the Argentine stock market. In this preliminary analysis we find that, despite the informational inefficiency of an underdeveloped stock market, fund managers are not showing advantages form access to better information, nor showing distinctive skills to outperform the benchmark in one or more of the allocation decisions considered. Further analysis covering additional periods will be instrumental in explaining local managers’ behavior and relative skill.La atribución de performance de carteras consiste en descomponer sus rendimientos en exceso del registrado en su benchmark –alfas. Tal separación en componentes o fuentes de rendimiento activo, es empleado para evaluar los efectos de las decisiones tomadas por los gestores de carteras, y así comparar su habilidad relativa para explotar imperfecciones de mercado, a nivel de elección entre clases de activos, y a nivel de selección de activos particulares dentro de cada clase. El presente trabajo desarrolla un ejercicio de atribución de performance sobre los fondos de inversión de renta variable que emplean como benchmark al índice Merval. Para ello se emplea el modelo de Brinston y Bachler (1985), asumiendo un proceso decisorio por parte de los gestores de cartera, que primero determina la exposición a factores generales, y en última instancia elige acciones particulares dentro de las exposiciones definidas en las instancias anteriores. El ejercicio abarca los trimestres del año 2015 (actualización en curso). Entre los hallazgos de este análisis inicial se observa la dificultad de los gestores de fondos en obtener rendimientos en exceso de su benchmark. En particular, más allá de las limitaciones que impone un índice con poca diversificación y amplitud, no se detecta la presencia de gestores de cartera con habilidad para detectar sectores y/o activos que superen la performance del índice benchmark. Actualizaciones en la aplicación de la metodología empleada servirán para complementar el análisis de la habilidad relativa de los gestores de carteras en términos de obtención de alfas positivos

Sistema web para la Gestión de pedidos en el Restaurante ‘Zari’, Chimbote 2023

En la presente investigación, tuvo como objetivo mejorar la gestión de pedidos del restaurante ‘Zari’ de la ciudad de Chimbote en al año 2023 mediante la implementación de un sistema web. El tipo de investigación fue Aplicada y con diseño Preexperimental. La muestra poblacional fue de 25 pedidos en un rango de semanal. La metodología empleada para el desarrollo de la solución fue XP, el lenguaje de programación fue PHP y la base de datos MySQL. Como resultados se obtuvo: Para el indicador 1 “Tiempo promedio de registro de información de pedidos” hubo una reducción del 73.8%, para el indicador 2 “Tiempo promedio de procesamiento de información de los pedidos” hubo una reducción del 70.7% y para el indicador 3 “Tiempo promedio de la generación de reportes hubo una reducción del 90.1%. Como conclusión general se tuvo que, en base a los tres (3) indicadores evaluados, se logró mejorar de forma significativa la gestión de pedidos con la solución planteada