1,032 research outputs found

    An Empirical Study on Collective Intelligence Algorithms for Video Games Problem-Solving

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    Computational intelligence (CI), such as evolutionary computation or swarm intelligence methods, is a set of bio-inspired algorithms that have been widely used to solve problems in areas like planning, scheduling or constraint satisfaction problems. Constrained satisfaction problems (CSP) have taken an important attention from the research community due to their applicability to real problems. Any CSP problem is usually modelled as a constrained graph where the edges represent a set of restrictions that must be verified by the variables (represented as nodes in the graph) which will define the solution of the problem. This paper studies the performance of two particular CI algorithms, ant colony optimization (ACO) and genetic algorithms (GA), when dealing with graph-constrained models in video games problems. As an application domain, the "Lemmings" video game has been selected, where a set of lemmings must reach the exit point of each level. In order to do that, each level is represented as a graph where the edges store the allowed movements inside the world. The goal of the algorithms is to assign the best skills in each position on a particular level, to guide the lemmings to reach the exit. The paper describes how the ACO and GA algorithms have been modelled and applied to the selected video game. Finally, a complete experimental comparison between both algorithms, based on the number of solutions found and the levels solved, is analysed to study the behaviour of those algorithms in the proposed domain

    Información climática asociada a estaciones productivas para el ajuste de modelos estadísticos de sistemas bovinos bajo condiciones extensivas

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    Artículo de investigación publicado en revista internacional indizada.El objeto de este estudio fue desarrollar una metodología para clasificar épocas de nacimiento (EN) y evaluar su impacto en indicadores productivos al compararlas con un método tradicional de clasificación. Con información meteorológica, se generó un índice de aridez para clasificar las EN. Las EN propuesta y tradicional se compararon, incluyéndolas como grupo contemporáneo (GC= hato, sexo, año y EN) a modelos de evaluación genética de caracteres de peso vivo. Fueron estimados los componentes de varianza y valores genéticos (DEP) con sus exactitudes. La clasifica- ción propuesta explicó mayor variabilidad que la clasificación tradicional (≥9,8%). Los parámetros genéticos mostraron cambios importantes, siendo los más evidentes en peso al destete. Los modelos fueron diferentes de acuerdo a la prueba de razón de verosimilitudes (P<0,01). Se observó una mejora de estructura en los GC. Para los dos caracteres evaluados las correlaciones entre los valores genéticos de los animales fueron diferentes, lo que indica cambio en la jerarquización. Este método de clasificación de EN puede ayudar a mejorar el ajuste de modelos estadísticos en condiciones en las que exista la información climática necesaria para su implementación.Los autores agradecen al Consejo Nacional de Cien- cia y Tecnología por el financiamiento del proyecto CB168207 y al Instituto Politécnico Nacional a través del proyecto SIP20150746

    Occult Follicular Thyroid Carcinoma presenting as Primary Breast Tumor with Sternal and Skull Metastasis

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    Introduction: Follicular thyroid carcinoma (FTC) that initially presented as breast tumor with no previous medical history of malignancy of thyroid gland is relatively rare and may cause diagnostic confusion.Presentation of case: We report a 59-year-old Mexican woman with no prior history of malignant thyroid neoplasm that presents with pain and swelling in the upper outer quadrant of the left breast with a year of evolution. Subsequently, subcutaneous tumor was identified in left parietal region. Clinically it was thought in primary breast tumor metastasis to skull. Furthermore, computerized tomography scan identified a tumor in the deep portion of the left breast, infiltrating the sternum that subsequently was confirmed a follicular carcinoma of the thyroid gland.Conclusion: Metastatic FTC may mimic a primary breast tumor. The combined use of clinical information, histopathology and immunohistochemistry were important to establishing a correct cancer diagnosis

    Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004-20: a national surveillance study

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    Background: Epidemiological studies are necessary to explore the effect of current pneumococcal conjugate vaccines (PCVs) against antibiotic resistance, including the rise of non-vaccine serotypes that are resistant to antibiotics. Hence, epidemiological changes in the antimicrobial pattern of Streptococcus pneumoniae before and during the first year of the COVID-19 pandemic were studied. Methods: In this national surveillance study, we characterised the antimicrobial susceptibility to a panel of antibiotics in 3017 pneumococcal clinical isolates with reduced susceptibility to penicillin during 2004-20 in Spain. This study covered the early and late PCV7 periods; the early, middle, and late PCV13 periods; and the first year of the COVID-19 pandemic, to evaluate the contribution of PCVs and the pandemic to the emergence of non-vaccine serotypes associated with antibiotic resistance. Findings: Serotypes included in PCV7 and PCV13 showed a decline after the introduction of PCVs in Spain. However, an increase in non-PCV13 serotypes (mainly 11A, 24F, and 23B) that were not susceptible to penicillin promptly appeared. A rise in the proportion of pneumococcal strains with reduced susceptibility to β-lactams and erythromycin was observed in 2020, coinciding with the emergence of SARS-CoV-2. Cefditoren was the β-lactam with the lowest minimum inhibitory concentration (MIC)50 or MIC90 values, and had the highest proportion of susceptible strains throughout 2004-20. Interpretation: The increase in non-PCV13 serotypes associated with antibiotic resistance is concerning, especially the increase of penicillin resistance linked to serotypes 11A and 24F. The future use of PCVs with an increasingly broad spectrum (such as PCV20, which includes serotype 11A) could reduce the impact of antibiotic resistance for non-PCV13 serotypes. The use of antibiotics to prevent co-infections in patients with COVID-19 might have affected the increased proportion of pneumococcal-resistant strains. Cefotaxime as a parenteral option, and cefditoren as an oral choice, were the antibiotics with the highest activity against non-PCV20 serotypes.This work was supported by the Spanish Ministry of Science and Innovation (grant PID2020–119298RB-I00), Meiji Pharma Spain (grant MVP 119/20), and internal funding from Instituto de Salud Carlos III.S

    Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract

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    The new generation of organoids derived from human pluripotent stem cells holds a promising strategy for modeling host-bacteria interaction studies. Organoids recapitulate the composition, diversity of cell types, and, to some extent, the functional features of the native organ. We generated lung bud organoids derived from human embryonic stem cells to study the interaction of Streptococcus pneumoniae (pneumococcus) with the alveolar epithelium. Invasive pneumococcal disease is an important health problem that may occur as a result of the spread of pneumococcus from the lower respiratory tract to sterile sites. We show here an efficient experimental approach to model the main events of the pneumococcal infection that occur in the human lung, exploring bacterial adherence to the epithelium and internalization and triggering an innate response that includes the interaction with surfactant and the expression of representative cytokines and chemokines. Thus, this model, based on human minilungs, can be used to study pneumococcal virulence factors and the pathogenesis of different serotypes, and it will allow therapeutic interventions in a reliable human context. Importance: Streptococcus pneumoniae is responsible for high morbidity and mortalities rates worldwide, affecting mainly children and adults older than 65 years. Pneumococcus is also the most common etiologic agent of bacterial pneumonia and nonepidemic meningitis, and it is a frequent cause of bacterial sepsis. Although the introduction of pneumococcal vaccines has decreased the burden of pneumococcal disease, the rise of antibiotic-resistant strains and nonvaccine types by serotype replacement is worrisome. To study the biology of pneumococcus and to establish a reliable human model for pneumococcal pathogenesis, we generated human minilungs from embryonic stem cells. The results show that these organoids can be used to model some events occurring during the interaction of pneumococcus with the lung, such as adherence, internalization, and the initial alveolar innate response. This model also represents a great alternative for studying virulence factors involved in pneumonia, drug screening, and other therapeutic interventions.This work was supported by grant PI19CIII/00003 from the ISCIII to A.Z. and grantsPID2020-119298RB-I00 and PID2020-114546RB-I00 from the Spanish Ministry of Scienceand Innovation (MICINN) to J.Y. and O.Z., respectively. M.P.D.L. and J.M.R.-C. received grantsupport from AESI (PI20CIII/0029), the Spanish Association Against Cancer (AECC,CGB14143035THOM), and CIBERONC (group CB16/12/00273). S.A.R. was granted apostdoctoral fellowship by the Fundacão de Amparo á pesquisa do Estado do SãoPaulo (reference FAPESP-BEBE 2020/09919-0).S

    Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations

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    Intestinal barrier dysfunction; Intestinal glycocalyx; Mucosal nerve fibresDisfunción de la barrera intestinal; Glicocálix intestinal; Fibras nerviosas de la mucosaDisfunció de la barrera intestinal; Glicocàlix intestinal; Fibres nervioses de la mucosaIrritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.This study was funded in part by Fondo Europeo de Desarrollo Regional (FEDER), Fondo de Investigación Sanitaria and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Economía y Competitividad: CP18/00116 (C.M.), PI19/01643 (B.L.); PI17/01443 (D.G.); PI15/00301 (C.A.-C.), PI17/0190 (J.S.), PI19/01643 & CPII16/00031, (M.V.); CIBEREHD CB06/04/0021 (F.A., C.A.-C., J.S., M.V.); Ministerio de Educación, Dirección General de Investigación: SAF 2016-76648-R (F.A.); Agència de Gestió d’Ajuts Universitaris i de Recerca, de la Generalitat de Catalunya: 2014 SGR 1285 (F.A.); Vall d’Hebron Institut de Recerca, Programa de becas predoctorales Amics de Vall d’Hebron: PRED-VHIR-2016-34 (C.P.-C.), PRED-VHIR-2014-018 (M.F.), the Swedish Research Council dnr 2019-00653 (J.-P.G.M.), and the European Union’s Horizon research and innovation programme 2020, grant no. 848228 (E.E., A.R.-U., B.L., C.A.-C., J.S.)

    Memoria del segundo simposium sobre historia, sociedad y cultura de México y América Latina

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    La presente obra reúne 20 ponencias de las 27 que se presentaron en el “Segundo simposium sobre historia, sociedad y cultura de México y América Latina”, realizado el 8 y 9 de noviembre de 2006, en el Centro de Investigación en Ciencias Sociales y Humanidades (CICSyH) de la Universidad Autónoma del Estado de México (UAEM), en Toluca, Estado de México

    Involvement of Raft Aggregates Enriched in Fas/CD95 Death-Inducing Signaling Complex in the Antileukemic Action of Edelfosine in Jurkat Cells

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    BACKGROUND: Recent evidence suggests that co-clustering of Fas/CD95 death receptor and lipid rafts plays a major role in death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: By a combination of genetic, biochemical, and ultrastructural approaches, we provide here compelling evidence for the involvement of lipid raft aggregates containing recruited Fas/CD95 death receptor, Fas-associated death domain-containing protein (FADD), and procaspase-8 in the induction of apoptosis in human T-cell leukemia Jurkat cells by the antitumor drug edelfosine, the prototype compound of a promising family of synthetic antitumor lipids named as synthetic alkyl-lysophospholipid analogues. Co-immunoprecipitation assays revealed that edelfosine induced the generation of the so-called death-inducing signaling complex (DISC), made up of Fas/CD95, FADD, and procaspase-8, in lipid rafts. Electron microscopy analyses allowed to visualize the formation of raft clusters and their co-localization with DISC components Fas/CD95, FADD, and procaspase-8 following edelfosine treatment of Jurkat cells. Silencing of Fas/CD95 by RNA interference, transfection with a FADD dominant-negative mutant that blocks Fas/CD95 signaling, and specific inhibition of caspase-8 prevented the apoptotic response triggered by edelfosine, hence demonstrating the functional role of DISC in drug-induced apoptosis. By using radioactive labeled edelfosine and a fluorescent analogue, we found that edelfosine accumulated in lipid rafts, forming edelfosine-rich membrane raft clusters in Jurkat leukemic T-cells. Disruption of these membrane raft domains abrogated drug uptake and drug-induced DISC assembly and apoptosis. Thus, edelfosine uptake into lipid rafts was critical for the onset of both co-aggregation of DISC in membrane rafts and subsequent apoptotic cell death. CONCLUSIONS/SIGNIFICANCE: This work shows the involvement of DISC clusters in lipid raft aggregates as a supramolecular and physical entity responsible for the induction of apoptosis in leukemic cells by the antitumor drug edelfosine. Our data set a novel framework and paradigm in leukemia therapy, as well as in death receptor-mediated apoptosis
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