Isogeometric analysis for fluid shear stress in cancer cells

Este trabalho foi financiado pelo Concurso Anual para Projetos de Investigação, Desenvolvimento, Inovação e Criação Artística (IDI&CA) 2018 do Instituto Politécnico de Lisboa. Código de referência IPL/2018/IGACFC_ISELThe microenvironment of the tumor is a key factor regulating tumor cell invasion and metastasis. The effects of physical factors in tumorigenesis is unclear. Shear stress, induced by liquid flow, plays a key role in proliferation, apoptosis, invasion, and metastasis of tumor cells. The mathematical models have the potential to elucidate the metastatic behavior of the cells’ membrane exposed to these microenvironment forces. Due to the shape configuration of the cancer cells, Non-uniform Rational B-splines (NURBS) lines are very adequate to define its geometric model. The Isogeometric Analysis allows a simplified transition of exact CAD models into the analysis avoiding the geometrical discontinuities of the traditional Galerkin traditional techniques. In this work, we use an isogeometric analysis to model the fluid-generated forces that tumor cells are exposed to in the vascular and tumor microenvironments, in the metastatic process. Using information provided by experimental tests in vitro, we present a suite of numerical experiments which indicate, for standard configurations, the metastatic behavior of cells exposed to such forces. The focus of this paper is strictly on geometrical sensitivities to the shear stress’ exhibition for the cell membrane, this being its innovation.info:eu-repo/semantics/publishedVersio

Evaluación del efecto protector del aceite esencial ocotea sp. frente a los efectos citogenéticos del cadmio sobre raices de allium cepa

El aceite esencial de Ocotea sp. fue obtenido de una planta que hace parte de la gran biodiversidad que posee Colombia y que no es muy conocida, pero es ampliamente utilizado por la medicina folklórica con diferentes fines terapéuticos. En estudios previos este aceite esencial ha mostrado alta actividad antioxidante. Además ejerce un efecto protector sobre la disminución en el tamaño y el peso de las raíces de Allium cepa expuestas a soluciones de nitrato de cadmio a 200μM. Tambien, el aceite esencial de Ocotea sp. puede reversar la acción anti-mitogénica de este metal, considerado altamente toxico

PI3Kγ/δ and NOTCH1 Cross-Regulate Pathways That Define the T-cell Acute Lymphoblastic Leukemia Disease Signature

PI3K/AKT and NOTCH1 signaling pathways are frequently dysregulated in T-cell acute lymphoblastic leukemias (T-ALL). Although we have shown that the combined activities of the class I PI3K isoforms p110γ and p110δ play a major role in the development and progression of PTEN-null T-ALL, it has yet to be determined whether their contribution to leukemogenic programing is unique from that associated with NOTCH1 activation. Using an Lmo2-driven mouse model of T-ALL in which both the PI3K/AKT and NOTCH1 pathways are aberrantly upregulated, we now demonstrate that the combined activities of PI3Kγ/δ have both overlapping and distinct roles from NOTCH1 in generating T-ALL disease signature and in promoting tumor cell growth. Treatment of diseased animals with either a dual PI3Kγ/δ or a γ-secretase inhibitor reduced tumor burden, prolonged survival, and induced proapoptotic pathways. Consistent with their similar biological effects, both inhibitors downregulated genes involved in cMYC-dependent metabolism in gene set enrichment analyses. Furthermore, overexpression of cMYC in mice or T-ALL cell lines conferred resistance to both inhibitors, suggesting a point of pathway convergence. Of note, interrogation of transcriptional regulators and analysis of mitochondrial function showed that PI3Kγ/δ activity played a greater role in supporting the disease signature and critical bioenergetic pathways. Results provide insight into the interrelationship between T-ALL oncogenic networks and the therapeutic efficacy of dual PI3Kγ/δ inhibition in the context of NOTCH1 and cMYC signaling

Reference percentiles of frame index in girls and boys (4-14 years old): a cross-sectional anthropometric study in three Argentine provinces

El ancho bicondíleo humeral en relación con la talla se reconoce como un adecuado índice de la robustez esquelética (IRE). El objetivo del presente trabajo es estimar y describir valores percentilares de referencia del índice de robustez esquelética de niñas y niños de 4 a 14 años, residentes en tres provincias argentinas. La muestra incluyó 7883 escolares (3913 varones y 3970 mujeres) de las provincias de Buenos Aires, Chubut y Mendoza. Las mediciones antropométricas del ancho bicondíleo humeral (mm) y la talla (cm) se realizaron entre los años 2014 y 2018 siguiendo protocolos estandarizados. A partir de estas variables se estimó el IRE [(ancho bicondíleo humeral/talla)*100] y se calcularon los percentiles por edad y sexo usando el método LMS. Los valores del IRE fueron mayores a la edad de 4 años, en tanto que luego de esa edad los valores percentilares mostraron un comportamiento descendente, hasta alcanzar, a los 14 años, el menor valor. La comparación entre sexos indicó valores mayores en varones que en mujeres en todas las edades y en las diferentes curvas percentilares. Los valores tabulados y graficados del IRE pueden considerarse una referencia local y ser empleados en estudios epidemiológicos y antropológicos que requieran inferir la contextura ósea de niñas y niños y en el monitoreo de la obesidad oculta en individuos con índice de masa corporal normal.Elbow breadth relative to height is recognized as an adequate index of skeletal robustness (frame index -FI). The objective of this paper is to estimate and describe reference percentile values of frame index in girls and boys, aged 4 to 14 years, from three Argentine provinces. The sample included 7883 schoolchildren (3913 males and 3970 females) from the provinces of Buenos Aires, Chubut and Mendoza. Anthropometric measurements of elbow breadth (mm) and height (cm) were made between 2014 and 2018 following standardized protocols. From these variables, FI [(elbow breadth / height)*100] was estimated and the percentiles by age and sex were calculated using the LMS method. FI values were higher at the age of 4 years, while after that age the percentile values showed a downward behavior, until reaching the lowest value at age 14. The comparison between sexes indicated higher values in males than in females at all ages and in the different percentile curves. The tabulated and graphed values of FI can be considered a local reference and used in epidemiological and anthropological studies for inferring bone structure of girls and boys, and in the monitoring of hidden obesity in individuals with normal body mass index.Fil: Torres, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropológicas; ArgentinaFil: Navazo, Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; ArgentinaFil: Garraza, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; ArgentinaFil: Dahinten, Silvia Lucrecia V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; ArgentinaFil: Quintero, Fabian Anibal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; ArgentinaFil: Luna, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; ArgentinaFil: Bergel Sanchís, Maria Laura. Universidad Nacional de Lanús. Departamento de Salud Comunitaria; ArgentinaFil: Luis, María Antonia. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; ArgentinaFil: Cesani Rossi, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; Argentin

Extended composite index of anthropometric failure in Argentinean preschool and school children

Objective:The Composite Index of Anthropometric Failure (CIAF) can only be applied to children under 5 years of age and does not contemplate obesity. The aim of this study was to propose an Extended CIAF (ECIAF) that combines the characterization of malnutrition due to undernutrition and excess weight, and apply it in six Argentine provinces.Design:ECIAF excludes children not in anthropometric failure (group A) and was calculated from a percentage of children included in malnutrition categories B: wasting only; C: wasting and underweight; D: wasting, stunting and underweight; E: stunting and underweight; F: stunting only; Y: underweight only; G: only weight excess; and H: stunting and weight excess.Setting:Cross-sectional study conducted in Buenos Aires, Catamarca, Chubut, Jujuy, Mendoza and Misiones (Argentina).Participants:10 879 children of both sexes aged between 3 and 13·99.Results:ECIAF in preschool children (3 to 4·99 years) was 15·1 %. The highest prevalence was registered in Mendoza (16·7 %) and the lowest in Misiones (12·0 %). In school children (5 to 13·99 years) ECIAF was 28·6 %. Mendoza also recorded the highest rate (30·7 %), while Catamarca and Chubut had the lowest values (27·0 %). In the whole sample, about 25 % of the malnutrition was caused by undernutrition and 75 % by excess weight.Conclusions:The ECIAF summarizes anthropometric failure by both deficiency and excess weight and it highlights that a quarter of the malnutrition in the Argentine population was caused by undernutrition, although there are differences between Provinces (P < 0·05). ECIAF estimates are higher than those of CIAF or under-nutrition.Fil: Bejarano, Ignacio Felipe. Universidad Nacional de Jujuy. Instituto de Biología de la Altura; ArgentinaFil: Oyhenart, Evelia Edith. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Torres, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Cesani Rossi, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; ArgentinaFil: Garraza, Mariela. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Navazo, Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; ArgentinaFil: Zonta, Maria Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Estudios Parasitológicos y de Vectores. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitológicos y de Vectores; ArgentinaFil: Luis, María Antonia. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; ArgentinaFil: Quintero, Fabian Anibal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Ontogenia y Adaptación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Dipierri, Jose Edgardo. Universidad Nacional de Jujuy. Instituto de Biología de la Altura; ArgentinaFil: Alfaro, E.. Universidad Nacional de Jujuy. Instituto de Biología de la Altura; ArgentinaFil: Román, Estela María. Universidad Nacional de Jujuy. Instituto de Biología de la Altura; ArgentinaFil: Carrillo, Rafael Angel. Universidad Nacional de Jujuy. Instituto de Biología de la Altura; ArgentinaFil: Dahinten, Silvia Lucrecia V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Lomaglio, Delia Beatriz. Universidad Nacional de Catamarca; ArgentinaFil: Menecier, Natalia. Universidad Nacional de Catamarca; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marrodán, María Dolores. Universidad Complutense de Madrid; Españ

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts