Modifications post-traductionnelles des canaux calciques cardiaques de type L : identification des résidus asparagine qui participent à la glycosylation de la sous-unité auxiliaire CaVα2δ1

Les canaux calciques de type L CaV1.2 sont principalement responsables de l’entrée des ions calcium pendant la phase plateau du potentiel d’action des cardiomyocytes ventriculaires. Cet influx calcique est requis pour initier la contraction du muscle cardiaque. Le canal CaV1.2 est un complexe oligomérique qui est composé de la sous-unité principale CaVα1 et des sous-unités auxiliaires CaVβ et CaVα2δ1. CaVβ joue un rôle déterminant dans l’adressage membranaire de la sous-unité CaVα1. CaVα2δ1 stabilise l’état ouvert du canal mais le mécanisme moléculaire responsable de cette modulation n’a pas été encore identifié. Nous avons récemment montré que cette modulation requiert une expression membranaire significative de CaVα2δ1 (Bourdin et al. 2015). CaVα2δ1 est une glycoprotéine qui possède 16 sites potentiels de glycosylation de type N. Nous avons donc évalué le rôle de la glycosylation de type-N dans l’adressage membranaire et la stabilité de CaVα2δ1. Nous avons d’abord confirmé que la protéine CaVα2δ1 recombinante, telle la protéine endogène, est significativement glycosylée puisque le traitement à la PNGase F se traduit par une diminution de 50 kDa de sa masse moléculaire, ce qui est compatible avec la présence de 16 sites Asn. Il s’est avéré par ailleurs que la mutation simultanée de 6/16 sites (6xNQ) est suffisante pour 1) réduire significativement la densité de surface de! CaVα2δ1 telle que mesurée par cytométrie en flux et par imagerie confocale 2) accélérer les cinétiques de dégradation telle qu’estimée après arrêt de la synthèse protéique et 3) diminuer la modulation fonctionnelle des courants générés par CaV1.2 telle qu’évaluée par la méthode du « patch-clamp ». Les effets les plus importants ont toutefois été obtenus avec les mutants N663Q, et les doubles mutants N348Q/N468Q, N348Q/N812Q, N468Q/N812Q. Ensemble, ces résultats montrent que Asn663 et à un moindre degré Asn348, Asn468 et Asn812 contribuent à la biogenèse et la stabilité de CaVα2δ1 et confirment que la glycosylation de type N de CaVα2δ1 est nécessaire à la fonction du canal calcique cardiaque de type L.

Automation of Chemical Spray Pyrolysis Unit and Fabrication of Sprayed CuInS2/In2S3 Solar Cell

Aim of the present work was to automate CSP process, to deposit and characterize CuInS2/In2S3 layers using this system and to fabricate devices using these films.An automated spray system for the deposition of compound semiconductor thin films was designed and developed so as to eliminate the manual labour involved in spraying and facilitate standardization of the method. The system was designed such that parameters like spray rate, movement of spray head, duration of spray, temperature of substrate, pressure of carrier gas and height of the spray head from the substrate could be varied. Using this system, binary, ternary as well as quaternary films could be successfully deposited.The second part of the work deal with deposition and characterization of CuInS2 and In2S3 layers respectively.In the case of CuInS2 absorbers, the effects of different preparation conditions and post deposition treatments on the optoelectronic, morphological and structural properties were investigated. It was observed that preparation conditions and post deposition treatments played crucial role in controlling the properties of the films. The studies in this direction were useful in understanding how the variation in spray parameters tailored the properties of the absorber layer. These results were subsequently made use of in device fabrication process.Effects of copper incorporation in In2S3 films were investigated to find how the diffusion of Cu from CuInS2 to In2S3 will affect the properties at the junction. It was noticed that there was a regular variation in the opto-electronic properties with increase in copper concentration.Devices were fabricated on ITO coated glass using CuInS2 as absorber and In2S3 as buffer layer with silver as the top electrode. Stable devices could be deposited over an area of 0.25 cm2, even though the efficiency obtained was not high. Using manual spray system, we could achieve devices of area 0.01 cm2 only. Thus automation helped in obtaining repeatable results over larger areas than those obtained while using the manual unit. Silver diffusion on the cells before coating the electrodes resulted in better collection of carriers.From this work it was seen CuInS2/In2S3 junction deposited through automated spray process has potential to achieve high efficiencies.

Reinforcement Learning Approaches to Power System Scheduling

One major component of power system operation is generation scheduling. The objective of the work is to develop efficient control strategies to the power scheduling problems through Reinforcement Learning approaches. The three important active power scheduling problems are Unit Commitment, Economic Dispatch and Automatic Generation Control. Numerical solution methods proposed for solution of power scheduling are insufficient in handling large and complex systems. Soft Computing methods like Simulated Annealing, Evolutionary Programming etc., are efficient in handling complex cost functions, but find limitation in handling stochastic data existing in a practical system. Also the learning steps are to be repeated for each load demand which increases the computation time.Reinforcement Learning (RL) is a method of learning through interactions with environment. The main advantage of this approach is it does not require a precise mathematical formulation. It can learn either by interacting with the environment or interacting with a simulation model. Several optimization and control problems have been solved through Reinforcement Learning approach. The application of Reinforcement Learning in the field of Power system has been a few. The objective is to introduce and extend Reinforcement Learning approaches for the active power scheduling problems in an implementable manner. The main objectives can be enumerated as:(i) Evolve Reinforcement Learning based solutions to the Unit Commitment Problem.(ii) Find suitable solution strategies through Reinforcement Learning approach for Economic Dispatch. (iii) Extend the Reinforcement Learning solution to Automatic Generation Control with a different perspective. (iv) Check the suitability of the scheduling solutions to one of the existing power systems.First part of the thesis is concerned with the Reinforcement Learning approach to Unit Commitment problem. Unit Commitment Problem is formulated as a multi stage decision process. Q learning solution is developed to obtain the optimwn commitment schedule. Method of state aggregation is used to formulate an efficient solution considering the minimwn up time I down time constraints. The performance of the algorithms are evaluated for different systems and compared with other stochastic methods like Genetic Algorithm.Second stage of the work is concerned with solving Economic Dispatch problem. A simple and straight forward decision making strategy is first proposed in the Learning Automata algorithm. Then to solve the scheduling task of systems with large number of generating units, the problem is formulated as a multi stage decision making task. The solution obtained is extended in order to incorporate the transmission losses in the system. To make the Reinforcement Learning solution more efficient and to handle continuous state space, a fimction approximation strategy is proposed. The performance of the developed algorithms are tested for several standard test cases. Proposed method is compared with other recent methods like Partition Approach Algorithm, Simulated Annealing etc.As the final step of implementing the active power control loops in power system, Automatic Generation Control is also taken into consideration.Reinforcement Learning has already been applied to solve Automatic Generation Control loop. The RL solution is extended to take up the approach of common frequency for all the interconnected areas, more similar to practical systems. Performance of the RL controller is also compared with that of the conventional integral controller.In order to prove the suitability of the proposed methods to practical systems, second plant ofNeyveli Thennal Power Station (NTPS IT) is taken for case study. The perfonnance of the Reinforcement Learning solution is found to be better than the other existing methods, which provide the promising step towards RL based control schemes for practical power industry.Reinforcement Learning is applied to solve the scheduling problems in the power industry and found to give satisfactory perfonnance. Proposed solution provides a scope for getting more profit as the economic schedule is obtained instantaneously. Since Reinforcement Learning method can take the stochastic cost data obtained time to time from a plant, it gives an implementable method. As a further step, with suitable methods to interface with on line data, economic scheduling can be achieved instantaneously in a generation control center. Also power scheduling of systems with different sources such as hydro, thermal etc. can be looked into and Reinforcement Learning solutions can be achieved.

“Reconstruction of Gene Regulatory Network from Expression Profile of Plasma RNA Data of Colorectal Cancer Patients using Soft Computing Techniques”

Microarray data analysis is one of data mining tool which is used to extract meaningful information hidden in biological data. One of the major focuses on microarray data analysis is the reconstruction of gene regulatory network that may be used to provide a broader understanding on the functioning of complex cellular systems. Since cancer is a genetic disease arising from the abnormal gene function, the identification of cancerous genes and the regulatory pathways they control will provide a better platform for understanding the tumor formation and development. The major focus of this thesis is to understand the regulation of genes responsible for the development of cancer, particularly colorectal cancer by analyzing the microarray expression data. In this thesis, four computational algorithms namely fuzzy logic algorithm, modified genetic algorithm, dynamic neural fuzzy network and Takagi Sugeno Kang-type recurrent neural fuzzy network are used to extract cancer specific gene regulatory network from plasma RNA dataset of colorectal cancer patients. Plasma RNA is highly attractive for cancer analysis since it requires a collection of small amount of blood and it can be obtained at any time in repetitive fashion allowing the analysis of disease progression and treatment response.

Cooperative Caching Framework for Mobile Cloud Computing

Due to the advancement in mobile devices and wireless networks mobile cloud computing, which combines mobile computing and cloud computing has gained momentum since 2009. The characteristics of mobile devices and wireless network makes the implementation of mobile cloud computing more complicated than for fixed clouds. This section lists some of the major issues in Mobile Cloud Computing. One of the key issues in mobile cloud computing is the end to end delay in servicing a request. Data caching is one of the techniques widely used in wired and wireless networks to improve data access efficiency. In this paper we explore the possibility of a cooperative caching approach to enhance data access efficiency in mobile cloud computing. The proposed approach is based on cloudlets, one of the architecture designed for mobile cloud computing.

Computing median and antimedian sets in median graphs

The median (antimedian) set of a profile π = (u1, . . . , uk) of vertices of a graphG is the set of vertices x that minimize (maximize) the remoteness i d(x,ui ). Two algorithms for median graphs G of complexity O(nidim(G)) are designed, where n is the order and idim(G) the isometric dimension of G. The first algorithm computes median sets of profiles and will be in practice often faster than the other algorithm which in addition computes antimedian sets and remoteness functions and works in all partial cubes

Reinforcement Learning Solution for Unit Commitment Problem Considering Minimum Start Up and Shut Down Times

Unit Commitment Problem (UCP) in power system refers to the problem of determining the on/ off status of generating units that minimize the operating cost during a given time horizon. Since various system and generation constraints are to be satisfied while finding the optimum schedule, UCP turns to be a constrained optimization problem in power system scheduling. Numerical solutions developed are limited for small systems and heuristic methodologies find difficulty in handling stochastic cost functions associated with practical systems. This paper models Unit Commitment as a multi stage decision making task and an efficient Reinforcement Learning solution is formulated considering minimum up time /down time constraints. The correctness and efficiency of the developed solutions are verified for standard test systems

Soft Computing Approach for Optimization of siRNA Efficiency Prediction for Post-transcriptional Gene Silencing

Post-transcriptional gene silencing by RNA interference is mediated by small interfering RNA called siRNA. This gene silencing mechanism can be exploited therapeutically to a wide variety of disease-associated targets, especially in AIDS, neurodegenerative diseases, cholesterol and cancer on mice with the hope of extending these approaches to treat humans. Over the recent past, a significant amount of work has been undertaken to understand the gene silencing mediated by exogenous siRNA. The design of efficient exogenous siRNA sequences is challenging because of many issues related to siRNA. While designing efficient siRNA, target mRNAs must be selected such that their corresponding siRNAs are likely to be efficient against that target and unlikely to accidentally silence other transcripts due to sequence similarity. So before doing gene silencing by siRNAs, it is essential to analyze their off-target effects in addition to their inhibition efficiency against a particular target. Hence designing exogenous siRNA with good knock-down efficiency and target specificity is an area of concern to be addressed. Some methods have been developed already by considering both inhibition efficiency and off-target possibility of siRNA against agene. Out of these methods, only a few have achieved good inhibition efficiency, specificity and sensitivity. The main focus of this thesis is to develop computational methods to optimize the efficiency of siRNA in terms of “inhibition capacity and off-target possibility” against target mRNAs with improved efficacy, which may be useful in the area of gene silencing and drug design for tumor development. This study aims to investigate the currently available siRNA prediction approaches and to devise a better computational approach to tackle the problem of siRNA efficacy by inhibition capacity and off-target possibility. The strength and limitations of the available approaches are investigated and taken into consideration for making improved solution. Thus the approaches proposed in this study extend some of the good scoring previous state of the art techniques by incorporating machine learning and statistical approaches and thermodynamic features like whole stacking energy to improve the prediction accuracy, inhibition efficiency, sensitivity and specificity. Here, we propose one Support Vector Machine (SVM) model, and two Artificial Neural Network (ANN) models for siRNA efficiency prediction. In SVM model, the classification property is used to classify whether the siRNA is efficient or inefficient in silencing a target gene. The first ANNmodel, named siRNA Designer, is used for optimizing the inhibition efficiency of siRNA against target genes. The second ANN model, named Optimized siRNA Designer, OpsiD, produces efficient siRNAs with high inhibition efficiency to degrade target genes with improved sensitivity-specificity, and identifies the off-target knockdown possibility of siRNA against non-target genes. The models are trained and tested against a large data set of siRNA sequences. The validations are conducted using Pearson Correlation Coefficient, Mathews Correlation Coefficient, Receiver Operating Characteristic analysis, Accuracy of prediction, Sensitivity and Specificity. It is found that the approach, OpsiD, is capable of predicting the inhibition capacity of siRNA against a target mRNA with improved results over the state of the art techniques. Also we are able to understand the influence of whole stacking energy on efficiency of siRNA. The model is further improved by including the ability to identify the “off-target possibility” of predicted siRNA on non-target genes. Thus the proposed model, OpsiD, can predict optimized siRNA by considering both “inhibition efficiency on target genes and off-target possibility on non-target genes”, with improved inhibition efficiency, specificity and sensitivity. Since we have taken efforts to optimize the siRNA efficacy in terms of “inhibition efficiency and offtarget possibility”, we hope that the risk of “off-target effect” while doing gene silencing in various bioinformatics fields can be overcome to a great extent. These findings may provide new insights into cancer diagnosis, prognosis and therapy by gene silencing. The approach may be found useful for designing exogenous siRNA for therapeutic applications and gene silencing techniques in different areas of bioinformatics.

Rezentralisierung: Server-Based Computing in der Praxis einer Universitätsbibliothek

Der Beitrag beschreibt die Ein- und Durchführung einer Server-basierten Computerinfrastruktur in einer Universitätsbibliothek. Beschrieben wird das so genannte MetaFrame-DV-Konzept der Universitätsbibliothek Kassel, das das dortige Informationsmanagement in den letzten vier Jahren initiiert, konzipiert und umgesetzt hat. Hierbei werden nunmehr nicht mehr nur Applikationsserver z.B. für das CD-Angebot eingesetzt, sondern sämtliche ca. 200 Mitarbeiter- und Funktionsarbeitsplätze über eine Citrix MetaFrame-Installation serverseitig betreut. Besonderes Augenmerk gilt in diesem Beitrag der Konfiguration, der praktischen Administration und den täglichen Arbeitsbedingungen an den Bibliotheksmitarbeiterarbeitsplätzen.

Computing Generators of Free Modules over Orders in Group Algebras

Let E be a number field and G be a finite group. Let A be any O_E-order of full rank in the group algebra E[G] and X be a (left) A-lattice. We give a necessary and sufficient condition for X to be free of given rank d over A. In the case that the Wedderburn decomposition E[G] \cong \oplus_xM_x is explicitly computable and each M_x is in fact a matrix ring over a field, this leads to an algorithm that either gives elements \alpha_1,...,\alpha_d \in X such that X = A\alpha_1 \oplus ... \oplusA\alpha_d or determines that no such elements exist. Let L/K be a finite Galois extension of number fields with Galois group G such that E is a subfield of K and put d = [K : E]. The algorithm can be applied to certain Galois modules that arise naturally in this situation. For example, one can take X to be O_L, the ring of algebraic integers of L, and A to be the associated order A(E[G];O_L) \subseteq E[G]. The application of the algorithm to this special situation is implemented in Magma under certain extra hypotheses when K = E = \IQ.

Hybrid Power System Modelling - Simulation and Energy Management Unit Development

Weltweit leben mehr als 2 Milliarden Menschen in ländlichen Gebieten. Als Konzept für die elektrische Energieversorgung solcher Gebiete kommen dezentrale elektrische Energieversorgungseinheiten zum Einsatz, die lokal verfügbare erneuerbare Ressourcen nutzen. Stand der Technik bilden Einheiten, die auf PV-Diesel-Batterie System basieren. Die verwendeten Versorgungsskonzepte in Hybridsystemen sind durch den Einsatz von Batterien als Energiespeicher meist wenig zuverlässig und teuer. Diese Energiespeicher sind sehr aufwendig zu überwachen und schwerig zu entsorgen. Den Schwerpunkt dieser Arbeit bildet die Entwicklung eines neuen Hybridsystems mit einem Wasserreservoir als Energiespeicher. Dieses Konzept eignet sich für Bergregionen in Entwicklungsländern wie Nepal, wo z.B. neben der solaren Strahlung kleine Flüsse in großer Anzahl vorhanden sind. Das Hybridsystem verfügt über einen Synchrongenerator, der die Netzgrößen Frequenz und Spannung vorgibt und zusätzlich unterstützen PV und Windkraftanlage die Versorgung. Die Wasserkraftanlage soll den Anteil der erneuerbaren Energienutzung erhöhen. Die Erweiterung des Systems um ein Dieselaggregat soll die Zuverlässigkeit der Versorgung erhöhen. Das Hybridsystem inkl. der Batterien wird modelliert und simuliert. Anschließend werden die Simulations- und Messergebnisse verglichen, um eine Validierung des Modells zu erreichen. Die Regelungsstruktur ist aufgrund der hohen Anzahl an Systemen und Parametern sehr komplex. Sie wird mit dem Simulationstool Matlab/Simulink nachgebildet. Das Verhalten des Gesamtsystems wird unter verschiedene Lasten und unterschiedlichen meteorologischen Gegebenheiten untersucht. Ein weiterer Schwerpunkt dieser Arbeit ist die Entwicklung einer modularen Energiemanagementeinheit, die auf Basis der erneuerbaren Energieversorgung aufgebaut wird. Dabei stellt die Netzfrequenz eine wichtige Eingangsgröße für die Regelung dar. Sie gibt über die Wirkleistungsstatik die Leistungsänderung im Netz wider. Über diese Angabe und die meteorologischen Daten kann eine optimale wirtschaftliche Aufteilung der Energieversorgung berechnet und eine zuverlässige Versorgung gewährleistet werden. Abschließend wurde die entwickelte Energiemanagementeinheit hardwaretechnisch aufgebaut, sowie Sensoren, Anzeige- und Eingabeeinheit in die Hardware integriert. Die Algorithmen werden in einer höheren Programmiersprache umgesetzt. Die Simulationen unter verschiedenen meteorologischen und netztechnischen Gegebenheiten mit dem entwickelten Model eines Hybridsystems für die elektrische Energieversorgung haben gezeigt, dass das verwendete Konzept mit einem Wasserreservoir als Energiespeicher ökologisch und ökonomisch eine geeignete Lösung für Entwicklungsländer sein kann. Die hardwaretechnische Umsetzung des entwickelten Modells einer Energiemanagementeinheit hat seine sichere Funktion bei der praktischen Anwendung in einem Hybridsystem bestätigen können.

Asymptotically Zero Energy Computing Using Split-Level Charge Recovery Logic

The dynamic power requirement of CMOS circuits is rapidly becoming a major concern in the design of personal information systems and large computers. In this work we present a number of new CMOS logic families, Charge Recovery Logic (CRL) as well as the much improved Split-Level Charge Recovery Logic (SCRL), within which the transfer of charge between the nodes occurs quasistatically. Operating quasistatically, these logic families have an energy dissipation that drops linearly with operating frequency, i.e., their power consumption drops quadratically with operating frequency as opposed to the linear drop of conventional CMOS. The circuit techniques in these new families rely on constructing an explicitly reversible pipelined logic gate, where the information necessary to recover the energy used to compute a value is provided by computing its logical inverse. Information necessary to uncompute the inverse is available from the subsequent inverse logic stage. We demonstrate the low energy operation of SCRL by presenting the results from the testing of the first fully quasistatic 8 x 8 multiplier chip (SCRL-1) employing SCRL circuit techniques.

Reconfigurable Architectures for General-Purpose Computing

General-purpose computing devices allow us to (1) customize computation after fabrication and (2) conserve area by reusing expensive active circuitry for different functions in time. We define RP-space, a restricted domain of the general-purpose architectural space focussed on reconfigurable computing architectures. Two dominant features differentiate reconfigurable from special-purpose architectures and account for most of the area overhead associated with RP devices: (1) instructions which tell the device how to behave, and (2) flexible interconnect which supports task dependent dataflow between operations. We can characterize RP-space by the allocation and structure of these resources and compare the efficiencies of architectural points across broad application characteristics. Conventional FPGAs fall at one extreme end of this space and their efficiency ranges over two orders of magnitude across the space of application characteristics. Understanding RP-space and its consequences allows us to pick the best architecture for a task and to search for more robust design points in the space. Our DPGA, a fine- grained computing device which adds small, on-chip instruction memories to FPGAs is one such design point. For typical logic applications and finite- state machines, a DPGA can implement tasks in one-third the area of a traditional FPGA. TSFPGA, a variant of the DPGA which focuses on heavily time-switched interconnect, achieves circuit densities close to the DPGA, while reducing typical physical mapping times from hours to seconds. Rigid, fabrication-time organization of instruction resources significantly narrows the range of efficiency for conventional architectures. To avoid this performance brittleness, we developed MATRIX, the first architecture to defer the binding of instruction resources until run-time, allowing the application to organize resources according to its needs. Our focus MATRIX design point is based on an array of 8-bit ALU and register-file building blocks interconnected via a byte-wide network. With today's silicon, a single chip MATRIX array can deliver over 10 Gop/s (8-bit ops). On sample image processing tasks, we show that MATRIX yields 10-20x the computational density of conventional processors. Understanding the cost structure of RP-space helps us identify these intermediate architectural points and may provide useful insight more broadly in guiding our continual search for robust and efficient general-purpose computing structures.

New Architectural Models for Visibly Controllable Computing: The Relevance of Dynamic Object Oriented Architectures and Plan Based Computing Models

Traditionally, we've focussed on the question of how to make a system easy to code the first time, or perhaps on how to ease the system's continued evolution. But if we look at life cycle costs, then we must conclude that the important question is how to make a system easy to operate. To do this we need to make it easy for the operators to see what's going on and to then manipulate the system so that it does what it is supposed to. This is a radically different criterion for success. What makes a computer system visible and controllable? This is a difficult question, but it's clear that today's modern operating systems with nearly 50 million source lines of code are neither. Strikingly, the MIT Lisp Machine and its commercial successors provided almost the same functionality as today's mainstream sytsems, but with only 1 Million lines of code. This paper is a retrospective examination of the features of the Lisp Machine hardware and software system. Our key claim is that by building the Object Abstraction into the lowest tiers of the system, great synergy and clarity were obtained. It is our hope that this is a lesson that can impact tomorrow's designs. We also speculate on how the spirit of the Lisp Machine could be extended to include a comprehensive access control model and how new layers of abstraction could further enrich this model.