Effects of water inlet configuration in a service reservoir applying CFD modelling

This study investigated the state of a service reservoir of a drinking water distribution network. Numerical simulation was applied to establish its flow pattern, mixing conditions, and free residual chlorine decay. The influence of the change in the water inlet configuration on these characteristics was evaluated. Four scenarios were established with different water level and flow rate as the differences between the first three scenarios. The fourth scenario was evaluated to assess the influence of the inlet configuration, momentum flow and water level on hydrodynamic conditions within the service reservoir. The distribution of four nozzles of 152.4 mm diameter was identified as a viable measure to preserve the water quality in this type of hydraulic structures

Influencia del tipo de alabe en el desempeño hidrodinamico de una turbina tipo darrieus

The study of vertical axis turbines has gained great interest in recent years for its great potential. Computational fluid dynamics (CFD) is an alternative analysis tool that is being used for the understanding of the problem. This paper presents and discusses the results of the computational parametric study of the airfoil of the blades in a turbine Darrieus type H. We assessed the influence of two parameters: thickness and curvature on the hydrodynamic performance estimated by CFD. We designed a factorial experiment 32 in which each factor had 3 levels, thickness (6, 12 and 15) and symmetry / asymmetry (00XX, 24XX and 44XX). The 9 final simulations were performed in the commercial software Fluent, while the mesh was parameterized in the commercial software Gridgen. The hydrodynamic performance of the turbine was evaluated by analyzing three nondimensional coefficients: Coefficient of moment (Cm), tangential force coefficient (Ct) and radial force coefficient (Cn). Numerical results show a strong influence of the thickness on Cm and Ct, while the asymmetry of the profile influences on Cn, which can be relevant from the point of view of design fatigue of the turbine.El estudio de turbinas de eje vertical ha cobrado gran interés en los últimos años debido a su gran potencial. Herramientas de análisis alternativas a la experimentación, como la dinámica de fluidos computacional (CFD), están siendo utilizadas para el entendimiento del problema. Este artículo muestra y discute los resultados del estudio computacional paramétrico del perfil alar de los alabes en una turbina Darrieus tipo H. Se evaluó la influencia de dos parámetros del perfil: espesor y curvatura en el desempeño hidrodinámico, estimado por medio de CFD. Se diseñó un experimento factorial 32 en el cual cada factor tiene tres niveles: espesor (6, 12 y 15) y simetría/asimetría (00XX, 24XX y 44XX). Las nueve simulaciones finales fueron realizadas en el software comercial Fluent, mientras que la malla fue parametrizada en el software comercial Gridgen. El desempeño hidrodinámico de la turbina se evaluó mediante el análisis de tres coeficientes adimensionales: coeficiente de momento (Cm), coeficiente de fuerza tangencial (Ct) y coeficiente de fuerza radial (Cn). Los resultados numéricos muestran una gran influencia del espesor del perfil en Cm y Ct, mientras que la asimetría del perfil tiene influencia en Cn, la cual puede ser relevante desde el punto de vista de diseño a fatiga de la turbina

Application of Drought Management Guidelines in Spain

The Spanish case study presents the drought planning process carried in the Tagus Basin. The presentation is structured in four parts: organizational, methodological, operational and public review components. The organizational component presents the framework and specific legislations and the organizations and institutions in Spain that work on drought preparedness and mitigation. The methodological component presents the analytical techniques used for drought risk analysis and management. The operational component describes the proposed structure for the drought management plan and presents the specific actions that are contemplated in it. The process review component identifies stakeholders that are involved in the decision making process and presents their views on the process

Tumor-derived pericytes driven by egfr mutations govern the vascular and immune microenvironment of gliomas

The extraordinary plasticity of glioma cells allows them to contribute to different cellular compartments in tumor vessels, reinforcing the vascular architecture. It was recently revealed that targeting glioma-derived pericytes, which represent a big percentage of the mural cell population in aggressive tumors, increases the permeability of the vessels and improves the efficiency of chemotherapy. However, the molecular determinants of this transdifferentiation process have not been elucidated. Here we show that mutations in EGFR stimulate the capacity of glioma cells to function as pericytes in a BMX- (bone marrow and X-linked) and SOX9-dependent manner. Subsequent activation of platelet-derived growth factor receptor beta in the vessel walls of EGFR-mutant gliomas stabilized the vasculature and facilitated the recruitment of immune cells. These changes in the tumor microenvironment conferred a growth advantage to the tumors but also rendered them sensitive to pericyte-targeting molecules such as ibrutinib or sunitinib. In the absence of EGFR mutations, high-grade gliomas were enriched in blood vessels, but showed a highly disrupted blood–brain barrier due to the decreased BMX/SOX9 activation and pericyte coverage, which led to poor oxygenation, necrosis, and hypoxia. Overall, these findings identify EGFR mutations as key regulators of the glioma-to-pericyte transdifferentiation, highlighting the intricate relationship between the tumor cells and their vascular and immune milieu. Our results lay the foundations for a vascular-dependent stratification of gliomas and suggest different therapeutic vulnerabilities determined by the genetic status of EGFR.This work was supported by FONDECYT grant (1140697 to V. Palma), CONICYT Fellowship (to B.S. Casas), by Ministerio de Economía y Competitividad and FEDER funds (PI13/01258 to A. Hernandez-Laín; PI17/01621 to J.M. Sepulveda-S anchez; and PI16/01580 and DTS18/00181 to A. Matheu), by Young Employment Initiative (Comunidad de Madrid) to M. Garranzo-Asensio, by “Asociacion Espanola contra ~ el Cancer” (AECC) grants (INVES192GARG to R. Gargini; GCTRA16015SEDA to J.M. Sepulveda-S anchez); and by Ministerio de Ciencia, Innovacion y Universidades and FEDER funds (RTI2018-093596 to P. Sanchez-Gomez).Peer reviewe

Performance measures for upper gastrointestinal endoscopy:A European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative

N/

Structural Basis for the Aminoacid Composition of Proteins from Halophilic Archea

In order to survive in highly saline environments, proteins from halophilic archea have evolved with biased amino acid compositions that have the capacity to reduce contacts with the solvent

Heterozygous CAPN3 missense variants causing autosomal-dominant calpainopathy in seven unrelated families

[Aims] Recessive variants in CAPN3 gene are the cause of the commonest form of autosomal recessive limb girdle muscle dystrophy. However, two distinct in-frame deletions in CAPN3 (NM_000070.3:c.643_663del21 and c.598_621del15) and more recently, Gly445Arg and Arg572Pro substitutions have been linked to autosomal dominant (AD) forms of calpainopathy. We report 21 affected individuals from seven unrelated families presenting with an autosomal dominant form of muscular dystrophy associated with five different heterozygous missense variants in CAPN.[Methods] We have used massively parallel gene sequencing (MPS) to determine the genetic basis of a dominant form of limb girdle muscular dystrophy in affected individuals from seven unrelated families.[Results] The c.700G> A, [p.(Gly234Arg)], c.1327T> C [p.(Ser443Pro], c.1333G> A [p.(Gly445Arg)], c.1661A> C [p.(Tyr554Ser)] and c.1706T> C [p.(Phe569Ser)] CAPN3 variants were identified. Affected individuals presented in young adulthood with progressive proximal and axial weakness, waddling walking and scapular winging or with isolated hyperCKaemia. Muscle imaging showed fatty replacement of paraspinal muscles, variable degrees of involvement of the gluteal muscles, and the posterior compartment of the thigh and minor changes at the mid-leg level. Muscle biopsies revealed mild myopathic changes. Western blot analysis revealed a clear reduction in calpain 3 in skeletal muscle relative to controls. Protein modelling of these variants on the predicted structure of calpain 3 revealed that all variants are located in proximity to the calmodulin-binding site and are predicted to interfere with proteolytic activation.[Conclusions] We expand the genotypic spectrum of CAPN3-associated muscular dystrophy due to autosomal dominant missense variants.This study was funded in part by Instituto de Salud Carlos III through the project PI14/00738 to M. O. (co-funded by European Regional Development Fund. ERDF, a way to build Europe). We thank CERCA Programme / Generalitat de Catalunya for institutional support NGL (APP1117510) and GR (APP1122952) are supported by the Australian National Health and Medical Research Council (NHMRC). This work is also funded by an NHMRC Project Grant (APP1080587).Peer reviewe

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis

We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere