CFD simulation of a novel anaerobic-anoxic reactor for biological nutrient removal: model construction, validation and hydrodynamic analysis based on OpenFOAM®

AnoxAn is a novel multi-environment reactor for biological nutrient removal (BNR) from wastewater. Although its biological efficacy has been demonstrated on a pilot scale, hydrodynamics is observed to significantly affect the performance of AnoxAn. To study its complex hydraulic behaviour, a model based on Computational Fluid Dynamics 3D (CFD) is constructed using the OpenFOAM® open source toolbox and validated by experimental tests of Residence Time Distribution (RTD). Reactor elements represent a key factor in the modelling process. In this sense, the impeller of the anoxic zone is modelled as a flat disk, and the baffle after the anoxic zone as a porous media. According to CFD model simulations, stagnant, short-circuit zones and mixing quality are established and quantified. Finally, the influence on the hydrodynamics of reactor elements is also evaluated. The results of this detailed hydrodynamic analysis will form the basis for the design and optimization of scalable AnoxAn configurations.Peer ReviewedPostprint (author's final draft

Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas

Esta publicación detalla los experimentos realizados para la clonación de un ADNc que codifica una nueva metaloproteasa de matriz extracelular a partir de una biblioteca de ADNc procedente de un carcinoma mamario. Este trabajo es de gran interés en la investigación del cáncer, ya que describe la identificación de una nueva colagenasa en los carcinomas mamarios proponiendo un posible papel en el proceso tumoral. Hay evidencia de que las metaloproteasas participan en el proceso de degradación proteolítica de los diferentes componentes de la membrana basal, favoreciendo así la invasión tumoral y las metástasis. El ADNc de la colagenasa-3 se expresó en un sistema de virus vaccinia, y la proteína recombinante fue capaz de degradar los colágenos fibrilares, lo que apoya la hipótesis de que el ADNc aislado codifica para una colagenasa auténtica. El análisis por Northern blot del ARN de tejidos normales y patológicos demostró la existencia de tres especies diferentes de ARNm en los tumores de mama, que parecen ser el resultado de la utilización de distintos sitios de poliadenilación presentes en la región 3'-no codificante del gen. Por el contrario, no se detectó ARNm de la colalagenasa-3 por Northern blot ni por PCR en otros tejidos humanos como mama normal, fibroadenomas mamarios, hígado, placenta, ovario, útero, próstata y glándula parótida. Sobre la base del aumento de la expresión de la colagenasa-3 en los carcinomas de mama y la ausencia de expresión detectable en los tejidos normales, se propone un posible papel de esta metaloproteinasa en el proceso tumoral

Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP

The transcriptional regulator YAP orchestrates many cellular functions, including tissue homeostasis, organ growth control, and tumorigenesis. Mechanical stimuli are a key input to YAP activity, but the mechanisms controlling this regulation remain largely uncharacterized. We show that CAV1 positively modulates the YAP mechanoresponse to substrate stiffness through actin-cytoskeleton-dependent and Hippo-kinase-independent mechanisms. RHO activity is necessary, but not sufficient, for CAV1-dependent mechanoregulation of YAP activity. Systematic quantitative interactomic studies and image-based small interfering RNA (siRNA) screens provide evidence that this actin-dependent regulation is determined by YAP interaction with the 14-3-3 protein YWHAH. Constitutive YAP activation rescued phenotypes associated with CAV1 loss, including defective extracellular matrix (ECM) remodeling. CAV1-mediated control of YAP activity was validated in vivo in a model of pancreatitis-driven acinar-to-ductal metaplasia. We propose that this CAV1-YAP mechanotransduction system controls a significant share of cell programs linked to these two pivotal regulators, with potentially broad physiological and pathological implications. Moreno-Vicente et al. report that CAV1, a key component of PM mechanosensing caveolae, mediates adaptation to ECM rigidity by modulating YAP activity through the control of actin dynamics and phosphorylation-dependent interaction of YAP with the 14-3-3-domain protein YWHAH. Cav1-dependent YAP regulation drives two pathophysiological processes: ECM remodeling and pancreatic ADM. © 2018 The Author

Propuesta de adaptación del sistema de producción de serie a régimen a la fase de escalada de producción de un nuevo modelo en el sector de automoción

La industrialización de la producción de un nuevo modelo en el sector de la automoción es un proceso que conlleva grandes inversiones en medios productivos, los cuales deben de estar preparados para producir en el momento del inicio de la fabricación en serie del mencionado nuevo modelo (SOP Start of production). A partir de este momento el alcanzar la producción de régimen según la curva planificada (curva de escalada) es el objetivo principal de toda la organización. A lo largo de la historia se repiten lanzamientos que no consiguen alcanzar los objetivos de volumen de producción, plazos de entrega, calidad del producto y en definitiva los costes planificados. Este suceso ha sido ampliamente estudiado, pero es en los últimos 10 años cuando más interés ha suscitado impulsado por la reducción de los ciclos de vida de los productos y en consecuencia el creciente aumento de los lanzamientos de nuevos modelos. A través de metodologías cuantitativas y cualitativas, esta tesis contribuye a paliar este problema presentando dos propuestas complementarias. La primera de ellas ha resultado de la aplicación de la metodología “Action Research” realizada en una importante empresa fabricante de automóviles de la que se concluyó la necesidad de la creación y organización de equipos de mejora específicos para el lanzamiento. Al comparar las condiciones de contorno de la fábrica durante las fases de escalada y serie se aprecian diferencias importantes tanto en material en flujo (WIP) como en la frecuencia y gravedad de los problemas aparecidos diariamente de tal forma que finalmente esta tesis reconoce a la época de escalada como un estadio diferenciado del ciclo de vida del modelo debiendo ser aplicado un sistema de producción (PS) diferenciado al habitual de la producción en serie. El hecho de que el estudio “Action Research” ha sido realizado en una única fábrica de un solo modelo, limita los resultados a esa tipología de fábrica, no por ello dejando de ser interesantes. La segunda propuesta está relacionada con la posibilidad de definir unos almacenes intermedios óptimos para la época de la escalada diferentes a los establecidos para la producción a régimen. En este segundo caso la metodología elegida ha sido la simulación discreta. A pesar de las limitaciones del estudio, los resultados presentados serán de gran interés tanto para profesionales del sector de la automoción y de otros sectores que tengan que incrementar los lanzamientos de nuevos productos, así como para académicos. Desde el punto de vista académico la tesis trata el problema de lanzamientos de nuevos modelos analizando de una forma global la aplicación del sistema de producción como posible causa de la aparición de los problemas durante esta fase. Desde el punto de vista práctico, el contenido de esta tesis puede ayudar a entender algunos de los factores que explican por qué los objetivos de calidad y producción no son obtenidos durante esta fase. En resumen, esta tesis presenta un enfoque innovador para entender y manejar la problemática de los lanzamientos de los nuevos modelos bajo el prisma de la aplicación del sistema de producción (PS). Dado que los resultados de la tesis están contrastados en una fábrica de un solo modelo queda abierta la investigación futura en el caso de fábricas de más de un modelo.The industrialization of the production of a new model in the automotive sector is a process that entails large investments in production means, which must be prepared to produce at the time of the start of serial production of the aforementioned new model (SOP Start of production). From this moment on, reaching the summit-production according to the planned curve (ramp-up curve) is the main objective of the entire organization. Throughout history, launches have been repeated that fail to achieve the objectives of production volume, delivery times, product quality and, ultimately, planned costs. This event has been widely studied, but it is in the last 10 years when it has aroused the most interest, driven by the reduction of the life cycles of the products and consequently the increasing in the launches of new models. Through quantitative and qualitative methodologies, this thesis contributes to alleviating this problem by presenting two complementary proposals. The first of these has resulted from the application of the “Action Research” methodology carried out in a major automobile manufacturer company, which concluded the need for the creation and organization of specific improvement teams for the launch. When comparing the contour conditions of the factory during the ramp-up and series phases, important differences are appreciated. Both in material in flow (WIP) and in the frequency and severity of the problems that appear daily in such a way that finally this thesis recognizes the ramp-up phase as a differentiated stage of the life cycle of the model. A production system (PS) differentiated from the usual one of series production must be applied. The fact that the “Action Research” study has been carried out in a single factory with a single model, limits the results to that type of factory, but is nonetheless uninteresting. The second proposal is related to the possibility of defining optimal intermediate buffers for the ramp-up phase, different from those established for regime production. In this second case, the methodology chosen has been the discrete simulation. Despite the limitations of the study, the results presented will be of great interest both to professionals in the automotive sector and from other sectors who have to increase the launches of new products, as well as for academics. From an academic point of view, the thesis deals with the problem of launching new models, analyzing in a global way the application of the production system as a possible cause of the appearance of problems during this phase. From a practical point of view, the content of this thesis can help to understand some of the factors that explain why the quality and production objectives are not obtained during this phase. In summary, this thesis presents an innovative approach to understand and handle the problem of new model launches from the point of view of the application of the production system (PS). Given that the results of the thesis are contrasted in a factory with a single model, future research is open in the case of factories with more than one model

Integración de impactos ecológicos causados por plantas exóticas invasoras: propuesta metodológica

Tanto en España como en Europa existen demasiadas plantas exóticas invasoras para poder afrontar la gestión de todas ellas, por lo que es necesario priorizar las más nocivas. Sin embargo, ello requiere disponer de medidas cuantitativas, sistemáticas y comparables de su impacto. La información disponible es desigual en cuanto a los criterios y variables para medir impactos y por tanto difícil de integrar. Proponemos el siguiente método para integrar medidas de impactos procedentes de distintos estudios: 1) Búsqueda de casos de estudio, 2) cálculo de tamaños del efecto; 3) clasificación de los casos por nivel de organización, 4) integración de los tamaños del efecto para cada especie y nivel de impacto con técnicas de meta-análisis, y 5) estima de un índice de fiabilidad (basado en el número de casos) y otro de consistencia (basado en la heterogeneidad entre casos). Aplicamos este método para estimar los impactos en España de tres árboles invasores (Ailanthus altissima, Robinia pseudoacacia y Ulmus pumila). Encontramos 50 casos para A. altissima, 39 para R. pseudoacacia y 15 para U. pumila. Los impactos en el nivel de ecosistema (fertilidad) fueron los más estudiados, mientras que los de comunidad e individuo están menos documentados. Robinia pseudoacacia tiende a incrementar la fertilidad, mientras que A. altissima no altera esta propiedad. La metodología propuesta tiene la ventaja de permitir estimar el impacto con datos de estudios diversos, pero su aplicación está limitada por la disponibilidad de casos de estudio

Reduced circulating sTWEAK levels are associated with metabolic syndrome in elderly individuals at high cardiovascular risk

BACKGROUND: The circulating soluble TNF-like weak inducer of apoptosis (sTWEAK) is a cytokine that modulates inflammatory and atherogenic reactions related to cardiometabolic risk. We investigated the association between sTWEAK levels and metabolic syndrome (MetS) and its components in older subjects at high cardiovascular risk. METHODS: Cross-sectional analysis of 452 non-diabetic individuals (men and women aged 55-80 years) at high cardiovascular risk. MetS was defined by AHA/NHLBI and IDF criteria. Logistic regression analyses were used to estimate odds ratios (ORs) for MetS and its components by tertiles of serum sTWEAK concentrations measured by ELISA. RESULTS: sTWEAK concentrations were lower in subjects with MetS than in those without. In gender- and age-adjusted analyses, subjects in the lowest sTWEAK tertile had higher ORs for overall MetS [1.71 (95% CI, 1.07-2.72)] and its components abdominal obesity [2.01 (1.15-3.52)], hyperglycemia [1.94 (1.20-3.11)], and hypertriglyceridemia [1.73 (1.05-2.82)] than those in the upper tertile. These associations persisted after controlling for family history of diabetes and premature coronary heart disease, lifestyle, kidney function and other MetS components. sTWEAK concentrations decreased as the number of MetS components increased. Individuals in the lowest vs the upper sTWEAK tertile had an increased risk of disclosing greater number of MetS features. Adjusted ORs for individuals with 2 vs ≤1, 3 vs ≤1, and ≥4 vs ≤ 1 MetS components were 2.60 (1.09-6.22), 2.83 (1.16-6.87) and 6.39 (2.42-16.85), respectively. CONCLUSION: In older subjects at high cardiovascular risk, reduced sTWEAK levels are associated with MetS: abdominal obesity, hypertriglyceridemia and hyperglycemia are the main contributors to this association

Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus

Post-transplant complications.-- et al.Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P<0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.Peer Reviewe

Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis

BACKGROUND: Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis). OBJECTIVES: This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress. METHODS: Patients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm2/m2) were assessed pre-aortic valve replacement (AVR) by echocardiography (AS severity, diastology), cardiovascular magnetic resonance (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T), and the 6-min walk test. CMR was used to measure the extracellular volume fraction (ECV), thereby deriving matrix volume (LV mass × ECV) and cell volume (LV mass × [1 - ECV]). Biopsy excluded occult bystander disease. Assessment was repeated at 1 year post-AVR. RESULTS: At 1 year post-AVR in 116 pacemaker-free survivors (age 70 ± 10 years; 54% male), mean valve gradient had improved (48 ± 16 mm Hg to 12 ± 6 mm Hg; p < 0.001), and indexed LV mass had regressed by 19% (88 ± 26 g/m2to 71 ± 19 g/m2; p < 0.001). Focal fibrosis by CMR late gadolinium enhancement did not change, but ECV increased (28.2 ± 2.9% to 29.9 ± 4.0%; p < 0.001): this was the result of a 16% reduction in matrix volume (25 ± 9 ml/m2to 21 ± 7 ml/m2; p < 0.001) but a proportionally greater 22% reduction in cell volume (64 ± 18 ml/m2to 50 ± 13 ml/m2; p < 0.001). These changes were accompanied by improvement in diastolic function, N-terminal pro-B-type natriuretic peptide, 6-min walk test results, and New York Heart Association functional class. CONCLUSIONS: Post-AVR, focal fibrosis does not resolve, but diffuse fibrosis and myocardial cellular hypertrophy regress. Regression is accompanied by structural and functional improvements suggesting that human diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic target. (Regression of Myocardial Fibrosis After Aortic Valve Replacement; NCT02174471)

Variation in assignment of the COPD patients into a GOLD group according to symptoms severity

Introduction: The Global Organization of Lung Disease (GOLD) classifies patients with chronic obstructive pulmonary disease (COPD) taking into account the symptoms. The modified Medical Research Council’s dyspnea scale (mMRC) and the COPD assessment test (CAT) are used to assess these symptoms. In this study, we analyze the concordance of GOLD classification using mMRC and CAT. Patients and Methods: This is an observational study of a cohort of 169 patients with COPD, who were classified following the GOLD 2017 recommendations, using both mMRC and CAT. A concordance analysis was applied, and a ROC curve was generated to identify the CAT score that best concorded with the mMRC scale. Results: The concordance for the GOLD groups classified by CAT and mMRC was moderate (kappa 0.492). For mMRC score of 1 and 2, a CAT score of =9 and =16 showed the maximum value of the Youden index, respectively. By reclassifying the patients with the new cut-off points obtained, the best concordance was obtained between the cut-off point for CAT of 16 and for mMRC of 2, followed by CAT of 9 and mMRC of 1. Conclusion: Because of the deficient concordance between CAT and mMRC, we propose the use of new cut-off points in future updates of the GOLD strategy