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Borutzky W.,Bonn-Rhein-Sieg University of Applied Sciences
Proceedings of the Institution of Mechanical Engineers. Part I: Journal of Systems and Control Engineering | Year: 2012

A bond graph representation of switching devices known for a long time has been a modulated transformer with a modulus b(t) ∈ {0, 1} ∀ t≥0 in conjunction with a resistor R : Ron accounting for the ON-resistance of a switch considered non-ideal. Besides other representations, this simple model has been used in bond graphs for simulation of the dynamic behaviour of hybrid systems. A previous article of the author has proposed to use the transformer-resistor pair in bond graphs for fault diagnosis in hybrid systems. Advantages are a unique bond graph for all system modes, the application of the unmodified standard Sequential Causality Assignment Procedure, fixed computational causalities and the derivation of analytical redundancy relations incorporating 'Boolean' transformer moduli so that they hold for all system modes. Switches temporarily connect and disconnect model parts. As a result, some independent storage elements may temporarily become dependent, so that the number of state variables is not time-invariant. This article addresses this problem in the context of modelling and simulation of fault scenarios in hybrid systems. In order to keep time-invariant preferred integral causality at storage ports, residual sinks previously introduced by the author are used. When two storage elements become dependent at a switching time instance ts, a residual sink is activated. It enforces that the outputs of two dependent storage elements become immediately equal by imposing the conjugate3 power variable of appropriate value on their inputs. The approach is illustrated by the bond graph modelling and simulation of some fault scenarios in a standard three-phase switched power inverter supplying power into an RL-load in a delta configuration. A well-developed approach to model-based fault detection and isolation is to evaluate the residual of analytical redundancy relations. In this article, analytical redundancy relation residuals have been computed numerically by coupling a bond graph of the faulty system to one of the non-faulty systems by means of residual sinks. The presented approach is not confined to power electronic systems but can be used for hybrid systems in other domains as well. In further work, the RL-load may be replaced by a bond graph model of an alternating current motor in order to study the effect of switch failures in the power inverter on to the dynamic behaviour of the motor. © 2012 IMechE. Source

Borutzky W.,Bonn-Rhein-Sieg University of Applied Sciences
Proceedings of the Institution of Mechanical Engineers. Part I: Journal of Systems and Control Engineering | Year: 2012

For the case when the abstraction of instantaneous state transitions is adopted, this paper proposes to start fault detection and isolation in an engineering system from a single time-invariant causality bond graph representation of a hybrid model. To that end, the paper picks up on a long-known proposal to model switching devices by a transformer modulated by a Boolean variable and a resistor in fixed conductance causality accounting for its ON resistance. Bond graph representations of hybrid system models developed in this way have been used so far mainly for the purpose of simulation. The paper shows that they can well constitute an approach to the bond-graph-based quantitative fault detection and isolation of hybrid models. Advantages are that the standard sequential causality assignment procedure can be a used without modification. A single set of analytical redundancy relations valid for all physically feasible system modes can be (automatically) derived from the bond graph. Stiff model equations due to small values of the ON resistance in the switch model may be avoided by symbolic reformulation of equations and letting the ON resistance of some switches tend to zero, turning them into ideal switches.First, for two examples considered in the literature, it is shown that the approach proposed in this paper can produce the same analytical redundancy relations as were obtained from a hybrid bond graph with controlled junctions and the use of a sequential causality assignment procedure especially for fault detection and isolation purpose. Moreover, the usefulness of the proposed approach is illustrated in two case studies by its application to standard switching circuits extensively used in power electronic systems and by simulation of some fault scenarios. The approach, however, is not confined to the fault detection and isolation of such systems. Analytically validated simulation results obtained by means of the program Scilab give confidence in the approach. © IMechE 2012. Source

Volk C.,Bonn-Rhein-Sieg University of Applied Sciences
Wiley Interdisciplinary Reviews: Membrane Transport and Signaling | Year: 2014

The SLC22 protein family includes more than 30 different proteins that operate as transporters for organic cations (OCTs), organic cations and zwitterions (OCTNs) or organic anions (OATs). These transporters play a pivotal role in the secretion of organic ions in kidney and liver. Furthermore, they contribute to the homeostasis of organic ions in several other tissues such as brain, placenta, intestine, and lung. Substrates include not only endogenous compounds such as monoamine neurotransmitters, choline, carnitine, α-ketoglutarate, urate, or steroid hormones, but also a broad spectrum of therapeutic drugs. Therefore, they control the bioavailability of many drugs and are responsible for several side effects or drug-drug interactions. SLC22 proteins are polyspecific transporters as they are able to transport structurally different compounds. All SLC22 proteins share a common membrane topology with 12 α-helical transmembrane domains. Mutational analyses and homology modeling of the steric structure of the proteins led to the conclusion that they possess a large cleft that is accessible from the aqueous phase. Located within this cleft is an inner cavity containing different interaction sites for different substrates. During the transport cycle the transporter undergoes conformational changes including an outward-open conformation, a transient occluded state and an inward-open conformation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Kennedy D.,Apoptosis Research Center | Jager R.,Bonn-Rhein-Sieg University of Applied Sciences | Mosser D.D.,University of Guelph | Samali A.,Apoptosis Research Center
IUBMB Life | Year: 2014

Thermotolerance, the acquired resistance of cells to stress, is a well-established phenomenon. Studies of the key mediators of this response, the heat shock proteins (HSPs), have led to the discovery of the important roles played by these proteins in the regulation of apoptotic cell death. Apoptosis is critical for normal tissue homeostasis and is involved in diverse processes including development and immune clearance. Apoptosis is tightly regulated by both proapoptotic and antiapoptotic factors, and dysregulation of apoptosis plays a significant role in the pathophysiology of many diseases. In the recent years, HSPs have been identified as key determinants of cell survival, which can modulate apoptosis by directly interacting with components of the apoptotic machinery. Therefore, manipulation of the HSPs could represent a viable strategy for the treatment of diseases. Here, we review the current knowledge with regard to the mechanisms of HSP-mediated regulation of apoptosis. © 2014 International Union of Biochemistry and Molecular Biology. Source

Connolly P.F.,National University of Ireland | Jager R.,Bonn-Rhein-Sieg University of Applied Sciences | Fearnhead H.O.,National University of Ireland
Frontiers in Physiology | Year: 2014

It has become increasingly clear that caspases, far from being merely cell death effectors, have a much wider range of functions within the cell. These functions are as diverse as signal transduction and cytoskeletal remodeling, and caspases are now known to have an essential role in cell proliferation, migration, and differentiation. There is also evidence that apoptotic cells themselves can direct the behavior of nearby cells through the caspase-dependent secretion of paracrine signaling factors. In some processes, including the differentiation of skeletal muscle myoblasts, both caspase activation in differentiating cells as well as signaling from apoptotic cells has been reported. Here, we review the non-apoptotic outcomes of caspase activity in a range of different model systems and attempt to integrate this knowledge. © 2014 Connolly, Jäger and Fearnhead. Source

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