Algoritmo de tipo búsqueda tabú para un problema de programación de horarios universitarios vespertinos

En este estudio se presenta un modelo de programación no lineal en variables enteras para un problema de programación de horarios universitarios vespertinos y se propone un algoritmo para su solución. El problema consiste en programar asignaturas en un horizonte de planificación considerando profesores, aulas, alumnos, días y un conjunto de restricciones, buscando minimizar la penalidad de no satisfacer los requerimientos de profesores, el número de cambios de sala y el número de periodos libres entre cursos. Se propone un modelo matemático y una implementación de un algoritmo de tipo búsqueda tabú. Para evaluar la efectividad del algoritmo se utilizaron casos de prueba con datos reales del Instituto IPEGE (Chile), en los que el algoritmo es capaz de obtener soluciones factibles en un tiempo razonable. Los parámetros de dicho algoritmo fueron calibrados con los casos de prueba, para posteriormente evaluar su desempeño. Se muestra que este obtuvo mejores soluciones que el método manual

Algoritmo de tipo búsqueda tabú para un problema de programación de horarios universitarios vespertinos

En este estudio se presenta un modelo de programación no lineal en variables enteras para un problema de programación de horarios universitarios vespertinos y se propone un algoritmo para su solución. El problema consiste en programar asignaturas en un horizonte de planificación considerando profesores, aulas, alumnos, días y un conjunto de restricciones, buscando minimizar la penalidad de no satisfacer los requerimientos de profesores, el número de cambios de sala y el número de periodos libres entre cursos. Se propone un modelo matemático y una implementación de un algoritmo de tipo búsqueda tabú. Para evaluar la efectividad del algoritmo se utilizaron casos de prueba con datos reales del Instituto IPEGE (Chile), en los que el algoritmo es capaz de obtener soluciones factibles en un tiempo razonable. Los parámetros de dicho algoritmo fueron calibrados con los casos de prueba, para posteriormente evaluar su desempeño. Se muestra que este obtuvo mejores soluciones que el método manual

A tabu search algorithm for an evening university timetabling problem

En este estudio se presenta un modelo de programación no lineal en variables enteras para un problema de programación de horarios universitarios vespertinos y se propone un algoritmo para su solución. El problema consiste en programar asignaturas en un horizonte de planificación considerando profesores, aulas, alumnos, días y un conjunto de restricciones, buscando minimizar la penalidad de no satisfacer los requerimientos de profesores, el número de cambios de sala y el número de periodos libres entre cursos. Se propone un modelo matemático y una implementación de un algoritmo de tipo búsqueda tabú. Para evaluar la efectividad del algoritmo se utilizaron casos de prueba con datos reales del Instituto IPEGE (Chile), en los que el algoritmo es capaz de obtener soluciones factibles en un tiempo razonable. Los parámetros de dicho algoritmo fueron calibrados con los casos de prueba, para posteriormente evaluar su desempeño. Se muestra que este obtuvo mejores soluciones que el método manual.This study presents a model of non-linear integer programming for an evening university timetabling problem and proposes an algorithm for its solution. The problem consists of programming subjects over a planning horizon considering teachers, classrooms, students, days and a set of constraints, trying to minimize the penalty of unsatisfied requirements of teachers, the number of changes of classrooms and the numbers of free periods between courses. A mathematical model is proposed beside the implementation of tabu search algorithm. Test cases are proposed to evaluate the effectiveness of the algorithm, which have real data obtained from IPEGE Institute (Chile), where the algorithm could obtain feasible solutions within a reasonable time. The parameters of the algorithm were calibrated with the test cases to later evaluate its performance, showing that it obtained better solutions than the manual method by an average of 66,5 % and it is about 62,7 % of lower bound calculate

Estudio de la senescencia linfocitaria T en pacientes con lesión de médula espinal crónica

La Lesión de Médula Espinal (LME) es una patología grave que causa un daño que conduce a cambios irreversibles en el sistema nervioso central, provocando con ello una elevada discapacidad y morbilidad en las personas que la padecen, así como disminución en su esperanza de vida. Como consecuencia del daño primario en la médula espinal se desencadena un proceso inflamatorio en el que interviene el sistema inmunológico (SI), que mantiene este estado inflamatorio de forma prolongada en el tiempo. Se han demostrado alteraciones en el sistema inmune tanto innato como adaptativo, durante una primera fase aguda, y existen diferentes estudios que demuestran que estas alteraciones se mantienen durante una fase crónica de la enfermedad. En otras patologías de base inmunológica se ha evidenciado una senescencia prematura del SI como consecuencia de este estado inflamatorio crónico. La hipótesis de este trabajo establece que los pacientes con LME presentan un estado de envejecimiento prematuro del SI, y concretamente del compartimento linfocitario T. Se realiza una caracterización de los linfocitos T cooperadores (Th) y citotóxicos (Tc) en células mononucleares de sangre periférica (PBMCs), obtenidas de muestras de sangre de pacientes con LME en estado crónico y controles sanos. Los resultados obtenidos muestran alteraciones en el compartimento linfocitario T de pacientes con LME crónica, con un estado linfocitario altamente diferenciado, una pequeña disminución del receptor coestimulador CD28, una disminución de la población de linfocitos T no activados apoptóticos, un aumento de la población de linfocitos T activados apoptóticos y un aumento de las células T reactivas específicas contra MBP. Esto se traduce en un envejecimiento del SI en estos pacientes con LME, que podría provocar una disfunción inmunitaria que conllevara la aparición de infecciones y predispusiera al desarrollo de una enfermedad autoinmun

Expression of Inducible Nitric Oxide Synthase (iNOS) in Microglia of the Developing Quail Retina

Inducible nitric oxide synthase (iNOS), which produce large amounts of nitric oxide (NO), is induced in macrophages and microglia in response to inflammatory mediators such as LPS and cytokines. Although iNOS is mainly expressed by microglia that become activated in different pathological and experimental situations, it was recently reported that undifferentiated amoeboid microglia can also express iNOS during normal development. The aim of this study was to investigate the pattern of iNOS expression in microglial cells during normal development and after their activation with LPS by using the quail retina as model. iNOS expression was analyzed by iNOS immunolabeling, western-blot, and RT-PCR. NO production was determined by using DAR-4M AM, a reliable fluorescent indicator of subcellular NO production by iNOS. Embryonic, postnatal, and adult in situ quail retinas were used to analyze the pattern of iNOS expression in microglial cells during normal development. iNOS expression and NO production in LPS-treated microglial cells were investigated by an in vitro approach based on organotypic cultures of E8 retinas, in which microglial cell behavior is similar to that of the in situ retina, as previously demonstrated in our laboratory. We show here that amoeboid microglia in the quail retina express iNOS during normal development. This expression is stronger in microglial cells migrating tangentially in the vitreal part of the retina and is downregulated, albeit maintained, when microglia differentiate and become ramified. LPS treatment of retina explants also induces changes in the morphology of amoeboid microglia compatible with their activation, increasing their lysosomal compartment and upregulating iNOS expression with a concomitant production of NO. Taken together, our findings demonstrate that immature microglial cells express iNOS during normal development, suggesting a certain degree of activation. Furthermore, LPS treatment induces overactivation of amoeboid microglia, resulting in a significant iNOS upregulation.This work was supported by grants from Ministerio de Economía y Competitividad, Spain (BFU2010-19981) and Junta de Andalucía, Spain (P07-CVI-03008)

Microglia and Microglia-Like Cells: Similar but Different

We want to thank all people for fighting in the front line of the COVID-19 pandemic, during which most parts of this article was written. We also acknowledge the task of the reviewers who contributed to improve the quality of this article.Microglia are the tissue-resident macrophages of the central nervous parenchyma. In mammals, microglia are thought to originate from yolk sac precursors and posteriorly maintained through the entire life of the organism. However, the contribution of microglial cells from other sources should also be considered. In addition to “true” or “bonafide” microglia, which are of embryonic origin, the so-called “microglia-like cells” are hematopoietic cells of bone marrow origin that can engraft the mature brain mainly under pathological conditions. These cells implement great parts of the microglial immune phenotype, but they do not completely adopt the “true microglia” features. Because of their pronounced similarity, true microglia and microglia-like cells are usually considered together as one population. In this review, we discuss the origin and development of these two distinct cell types and their differences. We will also review the factors determining the appearance and presence of microglia-like cells, which can vary among species. This knowledge might contribute to the development of therapeutic strategies aiming at microglial cells for the treatment of diseases in which they are involved, for example neurodegenerative disorders like Alzheimer’s and Parkinson’s diseases.University of Granada, Spain, and FEDER-Junta de Andalucía, Spain (grant number A1-CTS-324- UGR18

His452Tyr polymorphism in the human 5-HT2A receptor affects clozapine-induced signaling networks revealed by quantitative phosphoproteomics

Antipsychotic drugs remain the current standard for schizophrenia treatment. Although they directly recognize the orthosteric binding site of numerous monoaminergic G protein-coupled receptors (GPCRs), these drugs, and particularly second-generation antipsychotics such as clozapine, all have in common a very high affinity for the serotonin 5-HT receptor (5-HTR). Using classical pharmacology and targeted signaling pathway assays, previous findings suggest that clozapine and other atypical antipsychotics behave principally as 5-HTR neutral antagonists and/or inverse agonists. However, more recent findings showed that antipsychotics may also behave as pathway-specific agonists. Reversible phosphorylation is a common element in multiple signaling networks. Combining a quantitative phosphoproteomic method with signaling network analysis, we tested the effect of clozapine treatment on the overall level of protein phosphorylation and signal transduction cascades in vitro in mammalian cell lines induced to express either the human 5-HTR or the H452Y variant of the gene encoding the 5-HTR receptor. This naturally occurring variation within the 5-HTR gene was selected because it has been repeatedly associated with schizophrenia patients who do not respond to clozapine treatment. Our data show that short time exposure (5 or 10 min) to clozapine (10 M) led to phosphorylation of numerous signaling components of pathways involved in processes such as endocytosis, ErbB signaling, insulin signaling or estrogen signaling. Cells induced to express the H452Y variant showed a different basal phosphoproteome, with increases in the phosphorylation of mTOR signaling components as a translationally relevant example. However, the effect of clozapine on the functional landscape of the phosphoproteome was significantly reduced in cells expressing the 5-HTR-H452Y construct. Together, these findings suggest that clozapine behaves as an agonist inducing phosphorylation of numerous pathways downstream of the 5-HTR, and that the single nucleotide polymorphism encoding 5-HTR-H452Y affects these clozapine-induced phosphorylation-dependent signaling networks

Ozone Therapy for Tumor Oxygenation: a Pilot Study

Tumor hypoxia is an adverse factor for chemotherapy and radiotherapy. Ozone therapy is a non-conventional form of medicine that has been used successfully in the treatment of ischemic disorders. This prospective study was designed to assess the effect of ozone therapy on tumor oxygenation. Eighteen subjects were recruited for the study. Systemic ozone therapy was administered by autohemotransfusion on three alternate days over one week. Tumor oxygenation levels were measured using polarographic needle probes before and after the first and the third ozone therapy session. Overall, no statistically significant change was observed in the tumor oxygenation in the 18 patients. However, a significant decrease was observed in hypoxic values ≤10 and ≤5 mmHg of pO(2). When individually assessed, a significant and inverse non-linear correlation was observed between increase in oxygenation and the initial tumor pO(2) values at each measuring time-point, thus indicating that the more poorly-oxygenated tumors benefited most (rho = −0.725; P = 0.001). Additionally, the effect of ozone therapy was found to be lower in patients with higher hemoglobin concentrations (rho = −0.531; P < 0.034). Despite being administered over a very short period, ozone therapy improved oxygenation in the most hypoxic tumors. Ozone therapy as adjuvant in chemo-radiotherapy warrants further research