Tranilast increases vasodilator response to acetylcholine in rat mesenteric resistance arteries through increased EDHF participation

Background and Purpose: Tranilast, in addition to its capacity to inhibit mast cell degranulation, has other biological effects, including inhibition of reactive oxygen species, cytokines, leukotrienes and prostaglandin release. In the current study, we analyzed whether tranilast could alter endothelial function in rat mesenteric resistance arteries (MRA). Experimental Approach: Acetylcholine-induced relaxation was analyzed in MRA (untreated and 1-hour tranilast treatment) from 6 month-old Wistar rats. To assess the possible participation of endothelial nitric oxide or prostanoids, acetylcholineinduced relaxation was analyzed in the presence of L-NAME or indomethacin. The participation of endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced response was analyzed by preincubation with TRAM-34 plus apamin or by precontraction with a high K+ solution. Nitric oxide (NO) and superoxide anion levels were measured, as well as vasomotor responses to NO donor DEA-NO and to large conductance calcium-activated potassium channel opener NS1619. Key Results: Acetylcholine-induced relaxation was greater in tranilast-incubated MRA. Acetylcholine-induced vasodilation was decreased by L-NAME in a similar manner in both experimental groups. Indomethacin did not modify vasodilation. Preincubation with a high K+ solution or TRAM-34 plus apamin reduced the vasodilation to ACh more markedly in tranilastincubated segments. NO and superoxide anion production, and vasodilator responses to DEA-NO or NS1619 remained unmodified in the presence of tranilast. Conclusions and Implications: Tranilast increased the endothelium-dependent relaxation to acetylcholine in rat MRA. This effect is independent of the nitric oxide and cyclooxygenase pathways but involves EDHF, and is mediated by an increased role of small conductance calcium-activated K+ channelsThis study was supported by Ministerio de Ciencia e Innovación (SAF 2009-10374), Ministerio de Economía y Competitividad (SAF 2012-38530), and Fundación Mapfre. F.E. Xavier is recipient of research fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brazil

Maternal hyperleptinemia is associated with male offspring’s altered vascular function and structure in mice

Children of mothers with gestational diabetes have greater risk of developing hypertension but little is known about the mechanisms by which this occurs. The objective of this study was to test the hypothesis that high maternal concentrations of leptin during pregnancy, which are present in mothers with gestational diabetes and/or obesity, alter blood pressure, vascular structure and vascular function in offspring. Wildtype (WT) offspring of hyperleptinemic, normoglycemic, Lepr db/+ dams were compared to genotype matched offspring of WT-control dams. Vascular function was assessed in male offspring at 6, and at 31 weeks of age after half the offspring had been fed a high fat, high sucrose diet (HFD) for 6 weeks. Blood pressure was increased by HFD but not affected by maternal hyperleptinemia. On a standard diet, offspring of hyperleptinemic dams had outwardly remodeled mesenteric arteries and an enhanced vasodilatory response to insulin. In offspring of WT but not Leprdb/+ dams, HFD induced vessel hypertrophy and enhanced vasodilatory responses to acetylcholine, while HFD reduced insulin responsiveness in offspring of hyperleptinemic dams. Offspring of hyperleptinemic dams had stiffer arteries regardless of diet. Therefore, while maternal hyperleptinemia was largely beneficial to offspring vascular health under astandard diet, it had detrimental effects in offspring fed HFD. These results suggest that circulating maternal leptin concentrations may interact with other factors in the pre- and post-natal environments to contribute to altered vascular function in offspring of diabetic pregnancie

Implementation and demonstration of a building simulation based testbed for assessment of data centre multi-domain control strategies

The traditional data centre (DC) infrastructure is being\u3cbr/\u3esignificantly extended by modern information technology\u3cbr/\u3e(IT) trends on one side, and lasting calling for DC\u3cbr/\u3esustainability on the other. A holistic DC management\u3cbr/\u3ewill be necessary to coordinate different DC processes\u3cbr/\u3eand to dock the DC environment into modern cities and\u3cbr/\u3edistrict infrastructure. A development of such a complex\u3cbr/\u3emanagement requires comprehensive testing possibilities.\u3cbr/\u3eThe testing is hardly possible on the real DC infrastructure\u3cbr/\u3edue to the mission critical nature. Building energy\u3cbr/\u3emodelling methods offer a suitable platform for the\u3cbr/\u3edevelopment of a safe and reliable testing environment.\u3cbr/\u3eThis paper deals with new application of Building Energy\u3cbr/\u3eSimulation (BES) method and introduces a workflow for\u3cbr/\u3evirtual closed-loop testing of enhanced multi-domain\u3cbr/\u3eoperation for data centres\u3cbr/\u3

Simulation-based assessment of thermal aware computation of a bespoke data centre

The role of Data Centres (DCs) as global electricity consumers is growing rapidly due to the exponential increase of computational demand that modern times require. Control strategies that minimize energy consumption while guaranteeing optimal operation conditions in DC are essential to achieve sustainable and energy efficient DCs. Unfortunately, the development and testing of novel control strategies are often slowed down, if not discarded. This is generally due to the lack of access caused by safety and economic reasons. Alternatively, simulation experiments represent a “safe” virtual environment to test novel control strategies, accelerating the process for their implementation in physical DCs. The virtual DC testbed, originated in the GENiC project, supports the development and dynamic testing of control and energy management algorithms. This paper introduces its features and describes its functionality through a simulation-based assessment of thermal aware computation strategy. For this, the virtual DC will be based on a bespoke DC located in Cork (Ireland). This DC has 30 kW capacity, 40 m2 floor area and its layout follows a hot aisle - cold aisle arrangement without containment. The performance the IT Workload allocation under different scenarios and their influence both on the whitespace environment and overall DC performance are evaluated and quantified. Finally, the benefits of a coordinated operation between the thermal and the IT workload managements are discussed

Modelica for design of building and district energy systems:IEA EBC Annex60: Research projects demonstrating the benefits/utilization of Modelica

Under the umbrella of the International Energy Agency's Energy in Buildings and Community Programme (IEA EBC), a team of 41 institutes from 16 countries started collaborating in 2012 on the development and demonstration of new generation computational tools for building and community energy systems. The IEA EBC Annex 60 is based on the Modelica language and the Functional Mockup Interface (FMI) standards and is planned to end in 2017. This article briefly introduces the Annex 60 structure and objectives and presents some contributing projects carried out by the Computational Building Performance Simulation (CBPS) research group from Eindhoven University of Technology (TU/e) in the validation and demonstration sub-task related to the design of building and district energy systems

Comparison of two simulation methods for the technical feasibility of a district heating system using waste heat from a copper plant with thermal storage

Prior studies have noted that modelling and simulation approaches provide useful assistance in designing new generation district heating systems to deal with the increasing complexity of technologies. The available models and tools cover wide varieties in terms of technologies, model complexities, etc. In order to identify the applicability of different modelling methods for certain cases, the present study compared an energy planning tool with a dynamic simulation method for a district heating system using waste heat from a copper plant with thermal storage. The results showed the two methods predicted similar usage of heating energy from sources and demand for the case with short-term thermal storage, especially in cold months. However, large discrepancies were observed when including long-term thermal storage

Model-based assessment of retrofit strategies for the extension of a small district heating system

This contribution aims to investigate the viability of a district heating system (DHS) on the long-term, by studying a method to extend an existing DHS with new buildings while keeping the same generation and distribution facilities. The study is conducted by simulating the DHS. The models are developed in Modelica.\u3cbr/\u3eSimulation results show that extending a DHS is possible under scenarios. Retrofitting the envelope of some buildings and applying a centralised control over every customer’s thermostat both give satisfying results. On the other hand, decentralised storage manages to improve indoor comfort but slightly increases the energy demand. Centralised storage proves to be very dependent on its\u3cbr/\u3esizing and control strategy, and only provides poor results when non-optimal

A Modelica based computational model for evaluating a renewable district heating system

District heating (DH) systems are considered a viable method for mitigating long-term climate change effects, through reduction of CO2 emissions, their high conversion efficiencies and their ability to be integrated with renewable energy sources (RES). The current evolution towards sustainable DH, e.g. integration of RES, results in increased complexity and diversity during the early-design phase. In the early-design phase of DH systems a feasibility study is conducted to assess if the economic and environmental factors of the project meet the given requirements. This assessment is generally conducted with traditional district heating computational models (DHCM), utilizing a simulation language which limits the evaluation of sustainable DH systems in terms of flexibility and comprehensibility. The need for an alternative language capable of effectively modeling DH systems with integrated RES led to the use of Modelica, which offers improved flexibility, reusability as well as hierarchical and multi-domain modeling. This paper presents a case study, for the evaluation of a new DHCM analyzing its modeling capabilities and system performance, of an educational campus formed by eight institutional buildings connected to a centralized power plant, holding among others a biomass gasifier and a gas boiler. For an optimum utilization of the biomass gasifier, two power plant configurations are assessed: a biomass gasifier system with and without thermal energy storage (TES). The system performance evaluation indicates a significant increase in the utilization of the biomass gasifier with 8.2% (353 hours) compared to results obtained from the traditional DHCM. This deviation is due to a more accurate consideration of the DH thermal capacity and the space heating demand. Furthermore, the models in this DHCM enable assessments of the impact of building retrofits or climate change scenarios. Thus, the increased modeling capabilities and system performance demonstrate that this new DHCM is suitable and beneficial for early-design feasibility studies of innovative RES integrated DH systems