Molecular mechanisms of hypertension-induced heart failure : Experimental studies with special emphasis on local renin-angiotensin system, cardiac metabolism and levosimendan

Hypertension is a major risk factor for stroke, ischaemic heart disease, and the development of heart failure. Hypertension-induced heart failure is usually preceded by the development of left ventricular hypertrophy (LVH), which represents an adaptive and compensatory response to the increased cardiac workload. Biomechanical stress and neurohumoral activation are the most important triggers of pathologic hypertrophy and the transition of cardiac hypertrophy to heart failure. Non-clinical and clinical studies have also revealed derangements of energy metabolism in hypertensive heart failure. The goal of this study was to investigate in experimental models the molecular mechanisms and signalling pathways involved in hypertension-induced heart failure with special emphasis on local renin-angiotensin-aldosterone system (RAAS), cardiac metabolism, and calcium sensitizers, a novel class of inotropic agents used currently in the treatment of acute decompensated heart failure. Two different animal models of hypertensive heart failure were used in the present study, i.e. hypertensive and salt-sensitive Dahl/Rapp rats on a high salt diet (a salt-sensitive model of hypertensive heart failure) and double transgenic rats (dTGR) harboring human renin and human angiotensinogen genes (a transgenic model of hypertensive heart failure with increased local RAAS activity). The influence of angiotensin II (Ang II) on cardiac substrate utilization and cardiac metabolomic profile was investigated by using gas chromatography coupled to time-of-flight mass spectrometry to detect 247 intermediary metabolites. It was found that Ang II could alter cardiac metabolomics both in normotensive and hypertensive rats in an Ang II receptor type 1 (AT1)-dependent manner. A distinct substrate use from fatty acid oxidation towards glycolysis was found in dTGR. Altered cardiac substrate utilization in dTGR was associated with mitochondrial dysfunction. Cardiac expression of the redox-sensitive metabolic sensor sirtuin1 (SIRT1) was increased in dTGR. Resveratrol supplementation prevented cardiovascular mortality and ameliorated Ang II-induced cardiac remodeling in dTGR via blood pressure-dependent pathways and mechanisms linked to increased mitochondrial biogenesis. Resveratrol dose-dependently increased SIRT1 activity in vitro. Oral levosimendan treatment was also found to improve survival and systolic function in dTGR via blood pressure-independent mechanisms, and ameliorate Ang II-induced coronary and cardiomyocyte damage. Finally, using Dahl/Rapp rats it was demonstrated that oral levosimendan as well as the AT1 receptor antagonist valsartan improved survival and prevented cardiac remodeling. The beneficial effects of levosimendan were associated with improved diastolic function without significantly improved systolic changes. These positive effects were potentiated when the drug combination was administered. In conclusion, the present study points to an important role for local RAAS in the pathophysiology of hypertension-induced heart failure as well as its involvement as a regulator of cardiac substrate utilization and mitochondrial function. Our findings suggest a therapeutic role for natural polyphenol resveratrol and calcium sensitizer, levosimendan, and the novel drug combination of valsartan and levosimendan, in prevention of hypertension-induced heart failure. The present study also provides a better understanding of the pathophysiology of hypertension-induced heart failure, and may help identify potential targets for novel therapeutic interventions.

Direct stability evaluation of power systems with detailed generator models using structure-preserving energy functions

Energy-based direct methods for transient stability analysis are potentially useful both as offline tools for planning purposes as well as for online security assessment. In this paper, a novel structure-preserving energy function (SPEF) is developed using the philosophy of structure-preserving model for the system and detailed generator model including flux decay, transient saliency, automatic voltage regulator (AVR), exciter and damper winding. A simpler and yet general expression for the SPEF is also derived which can simplify the computation of the energy function. The system equations and the energy function are derived using the centre-of-inertia (COI) formulation and the system loads are modelled as arbitrary functions of the respective bus voltages. Application of the proposed SPEF to transient stability evaluation of power systems is illustrated with numerical examples.

DNA polymorphism and local variation in base-pair orientation: a theoretical rationale

Basepair stacking calculations have been carried out to understand the conformational polymorphism of DNA and its sequence dependence. The recently developed self-consistent parameter set, which is specially suitable for describing irregular DNA structures, has been used to describe the geometry of a basepair doublet. While for basepairs without any propeller, the favourable stacking patterns do not appear to have very strong features, much more noticeable sequence dependent stacking patterns emerge once a propeller is applied to the basepairs. The absolute minima for most sequences occurs for a doublet geometry close to the B-DNA fibre models. Hence in the B-DNA region, no strong sequence dependent features are found, but the range of doublet geometries observed in the crystal structures generally lie within the low energy contours, obtained from stacking energy calculations. The doublet geometry corresponding to the A-DNA fibre model is not energetically favourable for the purine-pyrimidine sequences, which prefer small roll angle values when the slide has a large negative value as in A-DNA. However positive roll with large negative slide is allowed for GG, GA, AG and the pyrimidine-purine steps. This is consistent with the observed geometries of various steps in A-DNA crystals. Thus the general features of the basepair doublets predicted from these theoretical studies agree very well with the results from crystal structure analysis. However, since most sequences show an overall preference for B-type doublet geometry, the B --> A transition for random sequence DNA cannot be explained on the basis of basepair stacking interactions.

Local systems, global impacts : Using life cycle assessment to analyse the potential and constraints of industrial symbioses

Human activities extract and displace different substances and materials from the earth s crust, thus causing various environmental problems, such as climate change, acidification and eutrophication. As problems have become more complicated, more holistic measures that consider the origins and sources of pollutants have been called for. Industrial ecology is a field of science that forms a comprehensive framework for studying the interactions between the modern technological society and the environment. Industrial ecology considers humans and their technologies to be part of the natural environment, not separate from it. Industrial operations form natural systems that must also function as such within the constraints set by the biosphere. Industrial symbiosis (IS) is a central concept of industrial ecology. Industrial symbiosis studies look at the physical flows of materials and energy in local industrial systems. In an ideal IS, waste material and energy are exchanged by the actors of the system, thereby reducing the consumption of virgin material and energy inputs and the generation of waste and emissions. Companies are seen as part of the chains of suppliers and consumers that resemble those of natural ecosystems. The aim of this study was to analyse the environmental performance of an industrial symbiosis based on pulp and paper production, taking into account life cycle impacts as well. Life Cycle Assessment (LCA) is a tool for quantitatively and systematically evaluating the environmental aspects of a product, technology or service throughout its whole life cycle. Moreover, the Natural Step Sustainability Principles formed a conceptual framework for assessing the environmental performance of the case study symbiosis (Paper I). The environmental performance of the case study symbiosis was compared to four counterfactual reference scenarios in which the actors of the symbiosis operated on their own. The research methods used were process-based life cycle assessment (LCA) (Papers II and III) and hybrid LCA, which combines both process and input-output LCA (Paper IV). The results showed that the environmental impacts caused by the extraction and processing of the materials and the energy used by the symbiosis were considerable. If only the direct emissions and resource use of the symbiosis had been considered, less than half of the total environmental impacts of the system would have been taken into account. When the results were compared with the counterfactual reference scenarios, the net environmental impacts of the symbiosis were smaller than those of the reference scenarios. The reduction in environmental impacts was mainly due to changes in the way energy was produced. However, the results are sensitive to the way the reference scenarios are defined. LCA is a useful tool for assessing the overall environmental performance of industrial symbioses. It is recommended that in addition to the direct effects, the upstream impacts should be taken into account as well when assessing the environmental performance of industrial symbioses. Industrial symbiosis should be seen as part of the process of improving the environmental performance of a system. In some cases, it may be more efficient, from an environmental point of view, to focus on supply chain management instead.  

An experimental study on acoustic emission energy as a quantitative measure of size independent specific fracture energy of concrete beams

Notched three point bend specimens (TPB) were tested under crack mouth opening displacement (CMOD) control at a rate of 0.0004 mm/s and during the fracture process acoustic emissions (AE) were simultaneously monitored. It was observed that AE energy could be related to fracture energy. An experimental study was done to understand the behavior of AE energy with parameters of concrete like its strength and size. In this study, AE energy was used as a quantitative measure of size independent specific fracture energy of concrete beams and the concepts of boundary effect and local fracture energy were used to obtain size independent AE energy from which size independent fracture energy was obtained. (C) 2010 Elsevier Ltd. All rights reserved.

Non-Marcus energy gap dependence of electron transfer rate in contact ion pairs. Novel interplay between relaxation and reaction in solution

Electron transfer reactions between donor-acceptor pairs in solution and in organized media exhibit diverse behaviour. Recent experiments have indicated an interesting breakdown of the Marcus parabolic energy gap dependence in the normal regime for back electron transfer from contact ion pairs. A novel explanation of this breakdown has recently been proposed (M. Tachiya and S. Murata, J. Am. Chem. Sec., 116(1994) 2434) which attributes the breakdown to the interplay between the relaxation in the reactant well and the reaction. A particularly interesting aspect of the model is that it envisages the electron transfer in the normal regime to take place from a completely non-equilibrium condition. In this article a time dependent solution of the model is presented for the first time, after generalizing it to include a realistic initial population distribution. The decay of the contact ion pair population is completely non-exponential. This can be used to check the validity of the Tachiya-Murata model. The dynamics of electron transfer from the solvent separated ion pair, which seem to obey the Marcus relation, is exponential.

Time scales for transitions between free-energy minima of a dense hard-sphere system

Time scales associated with activated transitions between glassy metastable states of a free-energy functional appropriate for a dense hard-sphere system are calculated by using a new Monte Carlo method for the local density variables. In particular, we calculate the time the system, initially placed in a shallow glassy minimum of the free-energy, spends in the neighborhood of this minimum before making a transition to the basin of attraction of another free-energy minimum. This time scale is found to increase as the average density is increased. We find a crossover density near which this time scale increases very sharply and becomes longer than the longest times accessible in our simulation. This time scale does not show any evidence of increasing with sample size

Decentralized Sustainable Energy Planning of Tumkur District, India

Present work shows the feasibility of decentralized energy options for the Tumkur district in India. Decentralized energy planning (DEP) involves scaling down energy planning to subnational or regional scales. The important aspect of the energy planning at decentralized level would be to prepare an area-based DEP to meet energy needs and development of alternate energy sources at least-cost to the economy and environment. The geographical coverage and scale reflects the level at which the analysis takes place, which is an important factor in determining the structure of models. In the present work, DEP modeling under different scenarios has been carried out for Tumkur district of India for the year 2020. DEP model is suitably scaled for obtaining the optimal mix of energy resources and technologies using a computer-based goal programming technique. The rural areas of the Tumkur district have different energy needs. Results show that electricity needs can be met by biomass gasifier technology, using biomass feedstock produced by allocating only 12% of the wasteland in the district at 8 t/ha/yr of biomass productivity. Surplus electricity can be produced by adopting the option of biomass power generation from energy plantations. The surplus electricity generated can be supplied to the grid. The sustainable development scenario is a least cost scenario apart from promoting self-reliance, local employment, and environmental benefits. (C) 2010 American Institute of Chemical Engineers Environ Prog, 30: 248-258, 2011

Statistical thermodynamics of lattice models in zeolites: Implications of local versus global mean field interactions

The statistical thermodynamics of adsorption in caged zeolites is developed by treating the zeolite as an ensemble of M identical cages or subsystems. Within each cage adsorption is assumed to occur onto a lattice of n identical sites. Expressions for the average occupancy per cage are obtained by minimizing the Helmholtz free energy in the canonical ensemble subject to the constraints of constant M and constant number of adsorbates N. Adsorbate-adsorbate interactions in the Brag-Williams or mean field approximation are treated in two ways. The local mean field approximation (LMFA) is based on the local cage occupancy and the global mean field approximation (GMFA) is based on the average coverage of the ensemble. The GMFA is shown to be equivalent in formulation to treating the zeolite as a collection of interacting single site subsystems. In contrast, the treatment in the LMFA retains the description of the zeolite as an ensemble of identical cages, whose thermodynamic properties are conveniently derived in the grand canonical ensemble. For a z coordinated lattice within the zeolite cage, with epsilon(aa) as the adsorbate-adsorbate interaction parameter, the comparisons for different values of epsilon(aa)(*)=epsilon(aa)z/2kT, and number of sites per cage, n, illustrate that for -1 0. We compare the isotherms predicted with the LMFA with previous GMFA predictions [K. G. Ayappa, C. R. Kamala, and T. A. Abinandanan, J. Chem. Phys. 110, 8714 (1999)] (which incorporates both the site volume reduction and a coverage-dependent epsilon(aa)) for xenon and methane in zeolite NaA. In all cases the predicted isotherms are very similar, with the exception of a small steplike feature present in the LMFA for xenon at higher coverages. (C) 1999 American Institute of Physics. [S0021-9606(99)70333-8].

Probing the Allosteric Mechanism in Pyrrolysyl-tRNA Synthetase Using Energy-Weighted Network Formalism

Pyrrolysyl-tRNA synthetase (PyIRS) is an atypical enzyme responsible for charging tRNA(Pyl) with pyrrolysine, despite lacking precise tRNA anticodon recognition. This dimeric protein exhibits allosteric regulation of function, like any other tRNA synthetases. In this study we examine the paths of allosteric communication at the atomic level, through energy-weighted networks of Desulfitobacterium hafniense PyIRS (DhPyIRS) and its complexes with tRNA(Pyl) and activated pyrrolysine. We performed molecular dynamics simulations of the structures of these complexes to obtain an ensemble conformation-population perspective. Weighted graph parameters relevant to identifying key players and ties in the context of social networks such as edge/node betweenness, closeness index, and the concept of funneling are explored in identifying key residues and interactions leading to shortest paths of communication in the structure networks of DhPylRS. Further, the changes in the status of important residues and connections and the costs of communication due to ligand induced perturbations are evaluated. The optimal, suboptimal, and preexisting paths are also investigated. Many of these parameters have exhibited an enhanced asymmetry between the two subunits of the dimeric protein, especially in the pretransfer complex, leading us to conclude that encoding of function goes beyond the sequence/structure of proteins. The local and global perturbations mediated by appropriate ligands and their influence on the equilibrium ensemble of conformations also have a significant role to play in the functioning of proteins. Taking a comprehensive view of these observations, we propose that the origin of many functional aspects (allostery rand half-sites reactivity in the case of DhPyIRS) lies in subtle rearrangements of interactions and dynamics at a global level.

Experimental investigation of link between growth and decay of fiber Bragg gratings

We report here an experimental investigation for establishing and quantifying a link between the growth and decay characteristics of fiber Bragg gratings. One of the key aspects of our work is the determination of the defect energy distribution from the grating characteristics measured during their fabrication. We observe a strong correlation between the growth-based defect energy distribution and that obtained through accelerated aging experiments, paving the way for predicting the decay characteristics of fiber Bragg gratings from their growth data. Such a prediction is significant in simplifying the postfabrication steps required to enhance the thermal stability of fiber Bragg gratings. (c) 2011 Optical Society of America

WEPA: Wind energy potential assessment-spatial decision support system

Spatial Decision Support System (SDSS) assist in strategic decision-making activities considering spatial and temporal variables, which help in Regional planning. WEPA is a SDSS designed for assessment of wind potential spatially. A wind energy system transforms the kinetic energy of the wind into mechanical or electrical energy that can be harnessed for practical use. Wind energy can diversify the economies of rural communities, adding to the tax base and providing new types of income. Wind turbines can add a new source of property value in rural areas that have a hard time attracting new industry. Wind speed is extremely important parameter for assessing the amount of energy a wind turbine can convert to electricity: The energy content of the wind varies with the cube (the third power) of the average wind speed. Estimation of the wind power potential for a site is the most important requirement for selecting a site for the installation of a wind electric generator and evaluating projects in economic terms. It is based on data of the wind frequency distribution at the site, which are collected from a meteorological mast consisting of wind anemometer and a wind vane and spatial parameters (like area available for setting up wind farm, landscape, etc.). The wind resource is governed by the climatology of the region concerned and has large variability with reference to space (spatial expanse) and time (season) at any fixed location. Hence the need to conduct wind resource surveys and spatial analysis constitute vital components in programs for exploiting wind energy. SDSS for assessing wind potential of a region / location is designed with user friendly GUI’s (Graphic User Interface) using VB as front end with MS Access database (backend). Validation and pilot testing of WEPA SDSS has been done with the data collected for 45 locations in Karnataka based on primary data at selected locations and data collected from the meteorological observatories of the India Meteorological Department (IMD). Wind energy and its characteristics have been analysed for these locations to generate user-friendly reports and spatial maps. Energy Pattern Factor (EPF) and Power Densities are computed for sites with hourly wind data. With the knowledge of EPF and mean wind speed, mean power density is computed for the locations with only monthly data. Wind energy conversion systems would be most effective in these locations during May to August. The analyses show that coastal and dry arid zones in Karnataka have good wind potential, which if exploited would help local industries, coconut and areca plantations, and agriculture. Pre-monsoon availability of wind energy would help in irrigating these orchards, making wind energy a desirable alternative.

Energy-Efficient Decentralized Routing with Localized Cooperation Suitable for Fast Fading

Wireless networks transmit information from a source to a destination via multiple hops in order to save energy and, thus, increase the lifetime of battery-operated nodes. The energy savings can be especially significant in cooperative transmission schemes, where several nodes cooperate during one hop to forward the information to the next node along a route to the destination. Finding the best multi-hop transmission policy in such a network which determines nodes that are involved in each hop, is a very important problem, but also a very difficult one especially when the physical wireless channel behavior is to be accounted for and exploited. We model the above optimization problem for randomly fading channels as a decentralized control problem – the channel observations available at each node define the information structure, while the control policy is defined by the power and phase of the signal transmitted by each node.In particular, we consider the problem of computing an energy-optimal cooperative transmission scheme in a wireless network for two different channel fading models: (i) slow fading channels, where the channel gains of the links remain the same for a large number of transmissions, and (ii) fast fading channels,where the channel gains of the links change quickly from one transmission to another. For slow fading, we consider a factored class of policies (corresponding to local cooperation between nodes), and show that the computation of an optimal policy in this class is equivalent to a shortest path computation on an induced graph, whose edge costs can be computed in a decentralized manner using only locally available channel state information(CSI). For fast fading, both CSI acquisition and data transmission consume energy. Hence, we need to jointly optimize over both these; we cast this optimization problem as a large stochastic optimization problem. We then jointly optimize over a set of CSI functions of the local channel states, and a corresponding factored class of control policies corresponding to local cooperation between nodes with a local outage constraint. The resulting optimal scheme in this class can again be computed efficiently in a decentralized manner. We demonstrate significant energy savings for both slow and fast fading channels through numerical simulations of randomly distributed networks.

Reactive interdiffusion: deviation from local equilibrium in the Fe-NiTiO3 couple

Deviation from local equilibrium between Fe–Ni alloy and (Fe,Ni)TiO3 solid solution in the reaction–diffusion zone of the Fe–NiTiO3 couple at 1273 K is evaluated by comparing the measured compositions in the zone with experimentally determined equilibrium tie-lines. The deviation is quantified by computing the Gibbs energy change for the reaction, Fe + NiTiO3 → FeTiO3 + Ni, from measured compositions in the zone and activity data available in the literature. Except near the extremities of the zone, the computed Gibbs energy change is constant, 8.2 kJ mol−1 higher than the standard Gibbs energy change for the reaction.

Characterization of the dynamics of glass-forming liquids from the properties of the potential energy landscape

We develop a framework for understanding the difference between strong and fragile behavior in the dynamics of glass-forming liquids from the properties of the potential energy landscape. Our approach is based on a master equation description of the activated jump dynamics among the local minima of the potential energy (the so-called inherent structures) that characterize the potential energy landscape of the system. We study the dynamics of a small atomic cluster using this description as well as molecular dynamics simulations and demonstrate the usefulness of our approach for this system. Many of the remarkable features of the complex dynamics of glassy systems emerge from the activated dynamics in the potential energy landscape of the atomic cluster. The dynamics of the system exhibits typical characteristics of a strong supercooled liquid when the system is allowed to explore the full configuration space. This behavior arises because the dynamics is dominated by a few lowest-lying minima of the potential energy and the potential energy barriers between these minima. When the system is constrained to explore only a limited region of the potential energy landscape that excludes the basins of attraction of a few lowest-lying minima, the dynamics is found to exhibit the characteristics of a fragile liquid.