101 research outputs found

    Evaluación de las condiciones de mezcla y su influencia sobre el cloro residual entanques de compensación de un sistema de distribución de agua potable

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    We performed a real scale evaluation of mixing conditions and its influence on water quality in a compensation tank of drinking-water distribution system located in the city of Cali, Colombia. The hydrodynamic study with continuous injection of tracer, and temperature and free chlorine measurements for identifying the mixing regime in the tank’s interior, residence time, thermal stratification, and chlorine variations in the stored water showed the typical characteristics of a compensation tank. We concluded that water recirculation, inadequate water exchange, low moment fluxes associated with low velocity flows, and punctual thermal stratification could lead to high water age, high residence times in the tank, inadequate mixing, and important loss of free residual chlorine. The methodology developed is suitable for evaluation and optimization of compensation tanks of drinking water distribution systems.Realizamos una evaluación a escala real de las condiciones de mezcla y su influencia en la calidad del agua en un tanque de compensación del sistema de distribución de agua potable ubicado en la ciudad de Cali, Colombia. El estudio hidrodinámico con inyección continua de marcador y mediciones de temperatura y cloro libre para identificar el régimen de mezcla en el interior del tanque, el tiempo de residencia, la estratificación térmica y las variaciones de cloro en el agua almacenada mostraron las características típicas de un tanque de compensación. Llegamos a la conclusión de que la recirculación de agua, el intercambio de agua inadecuado, los flujos de momento bajos asociados con los flujos de baja velocidad y la estratificación térmica puntual podrían conducir a una alta edad del agua, tiempos de residencia elevados en el tanque, mezcla inadecuada y pérdida importante de cloro residual libre. La metodología desarrollada es adecuada para la evaluación y optimización de tanques de compensación de sistemas de distribución de agua potable

    Woody encroachment and soil carbon stocks in subalpine areas in the Central Spanish Pyrenees

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    Woody encroachment has been an ongoing process in the subalpine belt of Mediterranean mountains, after land abandonment, the disappearance of the transhumant system and the decrease of the livestock number. The main objectives of this study were: (i) to identify land use/land cover (LULC) changes from 1956 to 2015, and (ii) to investigate the effects of LULC changes in physical and chemical soil properties and soil organic carbon (SOC) and nitrogen (N) stocks. It is hypothesized that woody encroachment in the subalpine belt may lead to significant changes in soil properties, and will generate an increase in the SOC stocks. A land use gradient was identified in the subalpine belt of the Central Spanish Pyrenees: (i) subalpine grasslands, (ii) shrublands, (iii) young forests, and (iv) old forests. Mineral soil samples were collected every 10 cm, down to 40 cm, at three points per each LULC and a total of 48 samples were analyzed. The results showed that (i) woody encroachment has occurred from 1956 to 2015 due to the expansion of coniferous forests and shrublands (at the expense of grasslands), (ii) land cover and soil depth had significant effects on soil properties (except for pH), being larger in the uppermost 0–10 cm depth, (iii) SOC and N contents and stocks were higher in the grassland sites, and (iv) the woody encroachment process initially produced a decrease in the SOC stocks (shrublands), but no differences were observed considering the complete soil profile between grasslands and young and old forests. Further studies, describing SOC stabilization and quantifying above-ground carbon (shrub and tree biomass) are required

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

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    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

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    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

    Miositis viral con rabdomiólisis secundaria: un caso confirmado y revisión de la literatura

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    Rhabdomyolysis is a severe syndrome that can produce acute renal failure and even death. Causative mechanisms of rhabdomyolysis include various viruses, among which are the Coxsackie viruses. We report the case of a 36-year-old woman who had rhabdomyolysis due to Coxsackie A9 virus, with severe muscle involvement, though with no important kidney damage. She recovered with intravenous hydration and alkalinization of the urine.La rabdomiólisis es un síndrome grave que puede producir insuficiencia renal aguda e incluso la muerte. Los mecanismos causantes de rabdomiólisis incluyen varios virus, entre los que se encuentran los virus Coxsackie. Presentamos el caso de una mujer de 36 años de edad que tenía rabdomiólisis debido a Coxsackie A9, con afectación muscular grave, aunque sin daño renal importante. Se recuperó con la hidratación intravenosa y la alcalinización de la orina

    Autophagic flux blockage by accumulation of weakly basic tenovins leads to elimination of B-Raf mutant tumour cells that survive vemurafenib

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    This work was supported by five grants to Sonia Laín: Vetenskapsrådet (VR) 521-2014-3341, Cancerfonden (Swedish Cancer Society) 150393, CAN 2014/702, Association for International Cancer Research (AICR) 130086, Barncancerfonden (Swedish Childhood Cancer Foundation) TJ-2014-0038, Barncancerfonden (Swedish Childhood Cancer Foundation) PR-2014-0038; two grants to Ravi Bhatia: Leukemia and Lymphoma Society (LLS) 6137-14 and NIH R01 CA95684; one grant to David P Lane: Vetenskapsrådet (VR) 538-2013-8807; one grant to Marcus J G W Ladds: Karolinska Institute KID Doctoral Student Funding; one grant to Gergana Popova: Karolinska Institutet KID Doctoral Student Funding; two grants to Nicholas J Westwood: Cancer Research UK C21383 and Cancer Research UK A6950; two grants to Gerald McInerney: Vetenskapsrådet (VR) 621-2014-4718 and Cancerfonden (Swedish Cancer Society) 150393, CAN 2015/751; and four grants to Emmet McCormack: Kreftforeningen 182735, Kreftforeningen 732200, Halse Vest 911884, Halse Vest 911789.Tenovin-6 is the most studied member of a family of small molecules with antitumour activity in vivo. Previously, it has been determined that part of the effects of tenovin-6 associate with its ability to inhibit SirT1 and activate p53. However, tenovin-6 has also been shown to modulate autophagic flux. Here we show that blockage of autophagic flux occurs in a variety of cell lines in response to certain tenovins, that autophagy blockage occurs regardless of the effect of tenovins on SirT1 or p53, and that this blockage is dependent on the aliphatic tertiary amine side chain of these molecules. Additionally, we evaluate the contribution of this tertiary amine to the elimination of proliferating melanoma cells in culture. We also demonstrate that the presence of the tertiary amine is sufficient to lead to death of tumour cells arrested in G1 phase following vemurafenib treatment. We conclude that blockage of autophagic flux by tenovins is necessary to eliminate melanoma cells that survive B-Raf inhibition and achieve total tumour cell kill and that autophagy blockage can be achieved at a lower concentration than by chloroquine. This observation is of great relevance as relapse and resistance are frequently observed in cancer patients treated with B-Raf inhibitors.Publisher PDFPeer reviewe

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

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    [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 DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

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    ML, CD, IvL, GP, TM, SD, MS, APF, CT, DL, MAH, KL and SL: project grants from the Swedish Research Council, the Swedish Cancer Society and the Swedish Childhood Cancer Foundation. MHi and JC: Cancer Research UK (C8/A6613). MC, EP and WE: Wellcome Trust (073915). MN and BV: projects MEYS-NPS-LO1413 and GACR P206/12/G151. EMC, MP, MMS, ZF and PG: Norwegian Cancer Society (182735, 732200) and Helse Vest (911884, 911789). RB and SC: NIH (R01 CA95684), the Leukemia and Lymphoma Society and the Waxman Foundation. NW, AH, Ad’H: Cancer Research UK (C21383/A6950) and Engineering and Physical Sciences Research Council Doctoral Training Program. JL and YZ: Cancer Research UK (C240/A15751). MH and BW: SARomics Biostructures ABUY, KF: DDDP SciLife, Sweden. LJ, MHa, RS and A-LG: CBCS, Sweden. VP: SciLife fellowship. AT: Breast Cancer Research Scotland.The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.Publisher PDFPeer reviewe
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