Made available in DSpace on 2014-12-17T15:47:00Z (GMT). No. of bitstreams: 1 SilvioRFA_TESE.pdf: 5797455 bytes, checksum: 65da3be6db5be8c8185888e31c1f294c (MD5) Previous issue date: 2012-03-30 / It bet on the next generation of computers as architecture with multiple processors and/or multicore processors. In this sense there are challenges related to features interconnection, operating frequency, the area on chip, power dissipation, performance and programmability. The mechanism of interconnection and communication it was considered ideal for this type of architecture are the networks-on-chip, due its scalability, reusability and intrinsic parallelism. The networks-on-chip communication is accomplished by transmitting packets that carry data and instructions that represent requests and responses between the processing elements interconnected by the network. The transmission of packets is accomplished as in a pipeline between the routers in the network, from source to destination of the communication, even allowing simultaneous communications between pairs of different sources and destinations. From this fact, it is proposed to transform the entire infrastructure communication of network-on-chip, using the routing mechanisms, arbitration and storage, in a parallel processing system for high performance. In this proposal, the packages are formed by instructions and data that represent the applications, which are executed on routers as well as they are transmitted, using the pipeline and parallel communication transmissions. In contrast, traditional processors are not used, but only single cores that control the access to memory. An implementation of this idea is called IPNoSys (Integrated Processing NoC System), which has an own programming model and a routing algorithm that guarantees the execution of all instructions in the packets, preventing situations of deadlock, livelock and starvation. This architecture provides mechanisms for input and output, interruption and operating system support. As proof of concept was developed a programming environment and a simulator for this architecture in SystemC, which allows configuration of various parameters and to obtain several results to evaluate it / Aposta-se na pr?xima gera??o de computadores como sendo de arquitetura com m?ltiplos processadores e/ou processadores com v?rios n?cleos. Neste sentido h? desafios relacionados aos mecanismos de interconex?o, frequ?ncia de opera??o, ?rea ocupada em chip, pot?ncia dissipada, programabilidade e desempenho. O mecanismo de interconex?o e comunica??o considerado ideal para esse tipo de arquitetura s?o as redes em chip, pela escalabilidade, paralelismo intr?nseco e reusabilidade. A comunica??o nas redes em chip ? realizada atrav?s da transmiss?o de pacotes que carregam dados e instru??es que representam requisi??es e respostas entre os elementos processadores interligados pela rede. A transmiss?o desses pacotes acontece como em um pipeline entre os roteadores da rede, da origem at? o destino da comunica??o, permitindo inclusive comunica??es simult?neas entre pares de origem e destinos diferentes. Partindo desse fato, prop?ese transformar toda a infraestrutura de comunica??o de uma rede em chip, aproveitando os mecanismos de roteamento, arbitragem e memoriza??o em um sistema de processamento paralelo de alto desempenho. Nessa proposta os pacotes s?o formados por instru??es e dados que representam as aplica??es, os quais s?o executados nos roteadores enquanto s?o transmitidos, aproveitando o pipeline das transmiss?es e a comunica??o paralela. Em contrapartida, n?o s?o utilizados processadores tradicionais, mas apenas n?cleos simples que controlam o acesso a mem?ria. Uma implementa??o dessa ideia ? a arquitetura intitulada IPNoSys (Integrated Processing NoC System), que conta com um modelo de programa??o pr?prio e um algoritmo de roteamento que garante a execu??o de todas as instru??es presentes nos pacotes, prevenindo situa??es de deadlock, livelock e starvation. Essa arquitetura apresenta mecanismos de entrada e sa?da, interrup??o e suporte ao sistema operacional. Como prova de conceito foi desenvolvido um ambiente de programa??o e simula??o para esta arquitetura em SystemC, o qual permite a configura??o de v?rios par?metros da arquitetura e obten??o dos resultados para avalia??o da mesma

Made available in DSpace on 2014-12-17T15:47:45Z (GMT). No. of bitstreams: 1 SilvioRFA.pdf: 3522539 bytes, checksum: 0e7ac6eda46a29d5f5968d779986fb03 (MD5) Previous issue date: 2008-04-11 / The increase of capacity to integrate transistors permitted to develop completed systems, with several components, in single chip, they are called SoC (System-on-Chip). However, the interconnection subsystem cans influence the scalability of SoCs, like buses, or can be an ad hoc solution, like bus hierarchy. Thus, the ideal interconnection subsystem to SoCs is the Network-on-Chip (NoC). The NoCs permit to use simultaneous point-to-point channels between components and they can be reused in other projects. However, the NoCs can raise the complexity of project, the area in chip and the dissipated power. Thus, it is necessary or to modify the way how to use them or to change the development paradigm. Thus, a system based on NoC is proposed, where the applications are described through packages and performed in each router between source and destination, without traditional processors. To perform applications, independent of number of instructions and of the NoC dimensions, it was developed the spiral complement algorithm, which finds other destination until all instructions has been performed. Therefore, the objective is to study the viability of development that system, denominated IPNoSys system. In this study, it was developed a tool in SystemC, using accurate cycle, to simulate the system that performs applications, which was implemented in a package description language, also developed to this study. Through the simulation tool, several result were obtained that could be used to evaluate the system performance. The methodology used to describe the application corresponds to transform the high level application in data-flow graph that become one or more packages. This methodology was used in three applications: a counter, DCT-2D and float add. The counter was used to evaluate a deadlock solution and to perform parallel application. The DCT was used to compare to STORM platform. Finally, the float add aimed to evaluate the efficiency of the software routine to perform a unimplemented hardware instruction. The results from simulation confirm the viability of development of IPNoSys system. They showed that is possible to perform application described in packages, sequentially or parallelly, without interruptions caused by deadlock, and also showed that the execution time of IPNoSys is more efficient than the STORM platform / O aumento na capacidade de integra??o de transistores permitiu o desenvolvimento de sistemas completos, com in?meros componentes, dentro de um ?nico chip, s?o os chamados SoCs (System-on-Chip). No entanto, o subsistema de interconex?o utilizado pode limitar a escalabilidade dos SoCs, como os barramentos, ou ser uma solu??o ad hoc, como a hierarquia de barramentos. Desse modo, a solu??o ideal para interconex?o no SoCs s?o as redes em chip ou NoCs (Network-on-Chip). As NoCs permitem m?ltiplas conex?o ponto-a-ponto entre os componente e podem ser reusadas em projetos diversos. Entretanto, o uso de NoCs pode representar o aumento na complexidade do projeto do sistema, da ?rea em chip e/ou pot?ncia dissipada. Dessa forma, ? necess?rio ampliar o horizonte de utiliza??o dos sistemas ou quebrar o paradigma do seu desenvolvimento. Assim, ? proposto um sistema baseado em uma NoC, onde as aplica??es s?o descritas em forma de pacotes e executadas de roteador em roteador durante o percurso entre origem e destino dos pacotes, sem a necessidade do uso de processadores convencionais. Para permitir a execu??o de aplica??es, independente do n?mero de instru??es e das dimens?es da rede, foi desenvolvido o algoritmo spiral complement, que permite re-rotear pacotes at? que todas as instru??es contidas nele sejam executadas. Portanto, o objetivo desse trabalho foi estudar a viabilidade do desenvolvimento de tal sistema, denominado sistema IPNoSys. Nesse estudo, foi desenvolvida em SystemC, com precis?o de ciclo, uma ferramenta para simula??o do sistema, a qual permite executar aplica??es implementadas na linguagem de descri??o de pacotes, tamb?m desenvolvida para esse fim. Atrav?s da ferramenta podem ser obtidos diversos resultados que permitem avaliar o funcionamento e desempenho do sistema. A metodologia empregada para descri??o das aplica??es corresponde, a priori, em obter o grafo de fluxo de dados da aplica??o em alto n?vel, e desse grafo descrev?-la em um ou mais pacotes. Utilizando essa metodologia, foram realizados tr?s estudos de casos: contador, DCT-2D e adi??o de ponto flutuante. O contador foi usado para avaliar a capacidade do sistema em tratar situa??es de deadlock e executar aplica??es em paralelo. A DCT-2D foi utilizada para realizar compara??es com a plataforma STORM. E, finalmente, a adi??o de ponto flutuante teve como objetivo ser usada como rotina de tratamento de uma instru??o n?o implementada em hardware. Os resultados de simula??o apontam favoravelmente com rela??o ? viabilidade do desenvolvimento do sistema IPNoSys. Mostrando que ? poss?vel executar aplica??es em forma de pacotes, inclusive paralelamente, sem interrup??es provocadas por eventuais deadlocks, e ainda indicam maior efici?ncia do sistema IPNoSys a respeito do tempo de execu??o comparada a plataforma STORM

There is a growing consensus that life-threatening cardiac arrhythmias like ven- tricular tachycardia (VT) or ventricular fibrillation (VF) arise because of the formation of spiral waves of electrical activation in cardiac tissue; unbroken spiral waves are associated with VT and broken ones with VF. Several experimental studies have shown that in homogeneities in cardiac tissue can have dramatic effects on such spiral waves. In this thesis we focus on spiral-wave dynamics in mathematical models of human ventricular tissue which contain (a) conduction in homogeneities, (b) ionic in- homogeneities, (c) fibroblasts, (d) Purkinje fibers. We also study the effect of a periodic deformation of the simulation domain on spiral wave-dynamics. Chapter 2 contains our study of “Spiral-Wave Dynamics and Its Control in the Presence of In homogeneities in Two Mathematical Models for Human Cardiac Tissue”; this chapter follows closely parts of a paper we have published [1]. Chapter 3 contains our study of “Spiral-wave dynamics in a Mathematical Model of Human Ventricular Tissue with Myocytes and Fibroblasts”; this chapter follows closely a paper that we have submitted for publication. Chapter 4 contains our study of “Spiral-wave Dynamics in Ionically Realistic Mathematical Models for Human Ventricular Tis- sue: The Effects of Periodic Deformation”; this chapter follows closely a paper that we have submitted for publication. Chapter 5 contains our study of “Spiral-wave dynamics in a Mathematical Model of Human Ventricular Tissue with Myocytes and Purkinje fibers”; this chapter follows closely a paper that we will submit for publication soon. In chapter 2, we study systematically the AP morphology in a state-of-the-art mathematical model of human ventricular tissue due to ten-Tusscher, Noble, Noble, and Panfilov (the TNNP04 model); we also look at the contribution of individual ionic currents to the AP by partially or completely blocking ion channels associated with the ionic currents. We then carry out systematic studies of plane- wave and circular-wave dynamics in the TNNP04 model for cardiac tissue model. We present a detailed and systematic study of spiral-wave turbulence and spa- tiotemporal chaos in two mathematical models for human cardiac tissue due to (a) ten-Tusscher and Panfilov (the TP06 model) and (b) ten-Tusscher, Noble, Noble, and Panfilov (the TNNP04 model). In particular, we use extensive numerical simulations to elucidate the interaction of spiral waves in these models with conduction and ionic in homogeneities. Our central qualitative result is that, in all these models, the dynamics of such spiral waves depends very sensitively on such in homogeneities. A major goal here is to develop low amplitude defibrillation schemes for the elimination of VT and VF, especially in the presence of in homogeneities that occur commonly in cardiac tissue. Therefore, we study a control scheme that has been suggested for the control of spiral turbulence, via low-amplitude current pulses, in such mathematical models for cardiac tissue; our investigations here are designed to examine the efficacy of such control scheme in the presence of in homogeneities in biophysical realistic models. We find that a scheme that uses control pulses on a spatially extended mesh is more successful in the elimination of spiral turbulence than other control schemes. We discuss the theoretical and experimental implications of our study that have a direct bearing on defibrillation, the control of life-threatening cardiac arrhythmias such as ventricular fibrillation. In chapter 3, we study the role of cardiac fibroblasts in ventricular tissue; we use the TNNP04 model for the myocyte cell, and the fibroblasts are modelled as passive cells. Cardiac fibroblasts, when coupled functionally with myocytes, can modulate their electrophysiological properties at both cellular and tissue levels. Therefore, it is important to study the effects of such fibroblasts when they are coupled with myocytes. Chapter 3 contains our detailed and systematic study of spiral-wave dynamics in the presence of fibroblasts in both homogeneous and inhomogeneous domains of the TNNP04 model for cardiac tissue. We carry out extensive numerical studies of such modulation of electrophysiological properties in mathematical models for (a) single myocyte fibroblast (MF) units and (b) two-dimensional (2D) arrays of such units; our models build on earlier ones and allow for no, one-way, or two-way MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP) morphology on parameters such as Ef , the fibroblast resting membrane potential, the fibroblast conductance Gf , and the MF gap-junctional coupling Ggap. Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various ranges for parameters such as Ggap, Gf , and Ef , and (c) intercellular couplings that can be no, one-way, and two-way connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity CV decreases as a function of Ggap, for no and one-way couplings; however, for two-sided coupling, CV decreases initially and then increases as a function of Ggap, and, eventually, we observe that conduction failure occurs for low values of Ggap. In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling Ggap or Ef . Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models for cardiac tissue, in our MF model both with and without heterogeneities. In chapter 4, we carry out a detailed, systematic study of spiral-wave dynamics in the presence of periodic deformation (PD) in two state-of-the-art mathematical models of human ventricular tissue, namely, the TNNP04 model and the TP06 model. To the best of our knowledge, our work is the first, systematic study of the dynamics of spiral waves of electrical activation and their transitions, in the presence of PD, in such biophysically realistic mathematical models of cardiac tissue. In our studies, we use three types of initial conditions whose time evolutions lead to the following states in the absence of PD: (a) a single rotating spiral (RS), (b) a spiral-turbulence (ST) state, with a single meandering spiral, and (c) an ST state with multiple broken spirals for both these models. We then show that the imposition of PD in these three cases leads to a rich variety of spatiotemporal pat- terns in the transmembrane potential including states with (a) an RS state with n-cycle temporal evolution (here n is a positive integer), (b) rotating-spiral states with quasiperiodic (QP) temporal evolution, (c) a state with a single meandering spiral MS, which displays spatiotemporal chaos, (d) an ST state, with multiple bro- ken spirals, and (e) a quiescent state in which all spirals are absorbed (SA). For all three initial conditions, precisely which one of the states is obtained depends on the amplitudes and the frequencies of the PD in the x and y directions. We also suggest specific experiments that can test the results of our simulations. We also study, in the presence of PD, the efficacy of a low-amplitude control scheme that has been suggested, hitherto only without PD, for the control of spiral-wave turbulence, via low-amplitude current pulses applied on a square mesh, in mathematical models for cardiac tissue. We also develop line-mesh and rectangular-mesh variants of this control scheme. We find that square- and line-mesh-based, low-amplitude control schemes suppress spiral-wave turbulence in both the TP06 and TNNP04 models in the absence of PD; however, we show that the line-based scheme works with PD only if the PD is applied along one spatial direction. We then demonstrate that a minor modification of our line-based control scheme can suppress spiral-wave turbulence: in particular, we introduce a rectangular-mesh-based control scheme, in which we add a few control lines perpendicular to the parallel lines of the line- based control scheme; this rectangular-mesh scheme is a significant improvement over the square-mesh scheme because it uses fewer control lines than the one based on a square mesh. In chapter 5, we have carried out detailed numerical studies of (a) a single unit of an endocardial cell and Purkinje cell (EP) composite and (b) a two-dimensional bilayer, which contains such EP composites at each site. We have considered bio- physically realistic ionic models for human endocardial cells (Ecells) and Purkinje cells (Pcells) to model EP composites. Our study has been designed to elucidate the sensitive dependence, on parameters and initial conditions, of (a) the dynamics of EP composites and (b) the spatiotemporal evolution of spiral waves of electrical activation in EP-bilayer domains. We examine this dependence on myocyte parameters by using the three different parameter sets P1, P2, and P3; to elucidate the initial-condition dependence we vary the time at which we apply the S2 pulse in our S1-S2 protocol; we also investigate the dependence of the spatiotemporal dynamics of our system on the EP coupling Dgap, and on the number of Purkinje- ventricular junctions (PVJs), which are measured here by the ratio R, the ratio of the total number of sites to the number of PVJs in our simulation domain. Our studies on EP composites show that the frequency of autorhythmic activity of a P cell depends on the diffusive gap-junctional conductance Dgap. We perform a set of simulations to understand the source-sink relation between the E and P cells in an EP composite; such a source-sink relation is an important determinant of wave dynamics at the tissue level. Furthermore, we have studied the restitution properties of an isolated E cell and a composite EP unit to uncover this effect on wave dynamics in 2D, bilayers of EP composites. Autorhythmicity is an important property of Purkinje cell; it helps to carry electrical signals rapidly from bundle of His to the endocardium. Our investigation of an EP composite shows that the cycle length (CL) of autorhythmic activity decreases, compared to that of an uncoupled Purkinje cell. Furthermore, we find that the APD increases for an EP composite, compared to that of an uncoupled P cell. In our second set of simulations for an EP-composite unit, we have obtained the AP behaviors and the amount of flux that flows from the E to the P cell during the course of the AP. The direction of flow of this flux is an important quantity that identifies which one of these cells act as a source or a sink in this EP composite. We have found that the P cell in an EP composite acts as a stimulation-current source for the E cell in the depolarization phase of the AP, when the stimulus is applied to both cells or to the P cell only. However, the P cell behaves both as a source and a sink when the stimulus is applied to the E cell only. In our third set of simulations for an EP composite unit, we have calculated the restitution of the APD; this plays an important role in deciding the stability of spiral waves in mathematical models for cardiac tissue. Our simulation shows that, for the EP composite with high coupling (Dgap = Dmm~10), the APDR slope decreases, relative to its value for an isolated E cell, for parameter sets P1 and P2, and first increases (for 50 ≤ DI ≤ 100 ms) and then decreases for the parameter set P3 ; however, for low coupling (Dgap = Dmm~100), the variation of the AP D as function of DI, for an EP composite, shows biphasic behavior for all these three parameter sets. We found that the above dynamics in EP cable type domains, with EP composites, depends sensitively on R. We hope our in silico studies of spiral-wave dynamics in a variety of state-of-the- art ionic models for ventricular tissue will stimulate more experimental studies that examine such dynamics.

The physical explanation for the existence of the galactic warp is one of the major research areas in Astronomy. People have proposed various theories but nobody has yet given a convincing explanation. Most of the spiral galaxies are observed to be warped which reveals that the galactic warp is a stable characteristic. In the theory of kinematic bending wave, warp is considered as a wave that is propagated through the galactic disk with a speed called pattern speed. If the pattern initially had straight line of nodes, according to bending wave theory, the warp would tend to wind up rapidly in the gravitational field of galactic disk. But still we observe warped galaxies in the sky. In the literature, it has been claimed that the winding problem of galactic warp may be solved by incorporating the effect of gravitational field of the dark matter halo in which the galactic disk is embedded. Recently some works on the dynamics of galactic disk claim that the shape of the dark matter halo is pro late spheroid. In this thesis, the effect of the gravitational field of a prolate spheroidal dark matter halo with varying eccentricity to the galactic warp is calculated and discussed. Chapter1 gives the general introduction of the topics discussed in the following chapters. The structure of the spiral galaxy, their classifications, and the disk dynamics are discussed in the first few sections. One of the revolutionary concepts that emerged in the previous century was the existence of the dark matter. Presently tracing the mass distribution and the constituent particles of dark matter is one of the major research areas in theoretical and experimental physics. In this thesis, the effect of a particular type of mass distribution in dark matter halo on the warp is discussed in detail. In the next few sections, the following topics are discussed namely; how the concept of dark matter came into astrophysics, how to measure the total mass inside a given radius and what are the different distributions used for various purposes. A new theory called Modified Newtonian Mechanism was also proposed in the previous century as an alternative to the dark matter concept which is also discussed briefly. Kinematic bending wave theory and the winding problem of the galactic warp is also discussed in detail. In the last section a relation between the pattern speed of the warp and the shape of the dark matter halo is obtained. The calculation of the potential of a prolate spheroidal mass distribution with varying eccentricity is not done in any literature as we know. The calculation of the potential and the patten speed of prolate spheroidal mass distributions and of the galactic disk are described in chapter 2. The calculations of oblate spheroidal mass distribution are also discussed in this chapter but that is out of main theme. In chapter 3 we apply the equations obtained in the Chapter 2 to one simple toy model and to the Galaxy. The rotation curve and the pattern speed of a warp in the gravitational field of prolate spheroidal mass distribution of varying eccentricity are described. Usually the Milky Way disk is treated as an in infinitesimally thin disk but for our calculations the three dimensional but thin disk is used. The usually people use some approximation to calculate the potential due to galactic infinitesimal thin disk. The difference of the work from earlier works done by different people(with the approximation mentioned in above line) is also discussed in this Chapter. Chapter 4 discusses the summary of the entire work.

Les surdités neurosensorielles sont classiquement décrites par une élévation des seuils auditifs généralement corrélée à une dégénérescence des cellules ciliées externes (CCE). Toutefois, des travaux récents sur des modèles animaux ont montré qu’un audiogramme normal pouvait être associé à des atteintes auditives périphériques. Ce travail de thèse a contribué à mieux caractériser chez des modèles murins, ces déficiences supraliminaires cachées liées d’une part, à des altérations des CCE et d’autre part, à la dégénérescence de certaines fibres nerveuses auditives. Dans la première partie de cette thèse, l’évolution des profils auditifs de souris présentant une dégénérescence accélérée des CCE, les souris de souche CD1-RjOrl : SWISS, a été caractérisée. Dans cette étude longitudinale, menée au cours du premier mois postnatal, une progressivité de la déficience auditive a été montrée. Toutefois, une discordance surprenante a été mise en évidence entre des seuils auditifs proches des valeurs normales à haute fréquence combinés à des produits de distorsions acoustiques (PDA) absents. Les courbes d’accord de masquage montrent un décalage des pointes vers les basses fréquences. Ces données indiquent que les CCE de la base ne sont plus fonctionnelles et que la perception des hautes fréquences est perturbée. Les observations en microscopie électronique à balayage ont révélé une conformation anormale de la touffe stéréociliaire des CCE au niveau de la base de la cochlée. Ces données témoignent d’une désorganisation de la tonotopie cochléaire. Dans la deuxième partie de cette thèse, l’effet de l’oxaliplatine sur la fonction auditive et sur la morphologie cochléaire a été décrit chez des souris adultes de souche CBA/J. L’oxaliplatine, un sel de platine utilisé en chimiothérapie, a de nombreux effets secondaires parmi lesquels l’apparition d’une neuropathie périphérique. À la suite d’un traitement avec cette drogue, les souris ne présentent pas d’élévation des seuils auditifs et pas d’altération de la fonction des CCE. Cependant, l’étude histologique révèle une dégénérescence surprenante des fibres auditives du ganglion spiral. Avec des tests électrophysiologiques supplémentaires, une diminution de l’amplitude du potentiel d’action composite a été mise en évidence. Le réflexe du système efférent olivocochléaire médian, évalué par un test de suppression controlatéral, semble également être diminué par le traitement. Les souris traitées avec de l’oxaliplatine constituent donc un modèle animal précieux de surdité cachée, qui demande à être mieux caractérisé. Les résultats de ces études confirment l’insuffisance de l’audiogramme pour détecter des altérations subtiles de la cochlée et montrent la nécessité d’améliorer le diagnostic de ces déficiences supraliminaires. Ainsi, les atteintes cachées des CCE peuvent être détectées par l’absence de PDA associée à des potentiels évoqués auditifs normaux et les neuropathies par des PDA présents associés à des potentiels évoqués auditifs anormaux. La combinaison de ces différents tests fonctionnels et électrophysiologiques permettrait une meilleure prise en charge des patients et une amélioration de leur qualité de vie. / Sensorineural hearing loss are classically described by auditory thresholds elevation usually correlated with outer hair cells (OHC) degeneration. However, recent work on animal models has shown that normal audiogram can be associated with peripheral hearing impairments. This thesis contributed to better characterize, in mouse models, these hidden supraliminal deficiencies related on the one hand, with OHC alterations and on the other, to auditory nerve fibers degeneration. In the first part of this thesis, the auditory profiles evolution of mice exhibiting an OHC accelerated degeneration, the CD1-RjOrl: SWISS strain mice, was characterized. In this longitudinal study, conducted in the first postnatal month, a progressivity of the hearing impairment has been observed. However, a surprising discrepancy was found between high frequency hearing thresholds close to normal values associated with missing distortion product otoacoustic emission (DPOAE). The masking tuning curves dips are shifted toward low frequencies. Those data indicate that basal OHC are no longer functional and the perception of high frequencies is disrupted. Observations in scanning electron microscopy revealed an abnormal conformation of the OHC stereocilia bundles at the cochlea base. These results represent an evidence of a disorganized cochlear tonotopy. In the second part of this thesis, the effect of oxaliplatin on the auditory function and on the cochlear morphology was described in adult CBA/J strain mice. Oxaliplatin, a platinum salt used in chemotherapy, has many side effects including development of peripheral neuropathy. Following one treatment with this drug, mice did not present any hearing threshold elevation or OHC function impairment. However, the histological study reveals a surprising degeneration of the spiral ganglion cells. With additional electrophysiological tests, a decrease in the compound action potential amplitude has been demonstrated. The median olivocochlear efferent system reflex, evaluated by a contralateral suppression test, also seems to be diminished by the treatment. The mice treated with oxaliplatin, therefore constitute a precious animal model of hidden deafness, which needs to be better characterized. The results of these studies confirm the audiogram insufficiency to detect subtle cochlea alterations and reveal the need to improve supraliminal deficiencies diagnosis. Thus, hidden OHC impairments can be detected by the absence of DPOAE associated with normal auditory evoked potentials and neuropathies by the presence of DPOAE associated with abnormal auditory evoked potentials. The combination of these functional and electrophysiological tests would allow better management of patients and an improvement in their quality of life.Keywords: hidden hearing loss, CD1 mice, outer hair cells, masking tuning curves, tonotopy, oxaliplatine, spiral

Abstract  Erik Samuelsson: A View Towards the Sea – Towards a Changed Understanding of the Culture and Social Life of the Middle Neolithic in Eastern Central Sweden.  The objective of this essay is to undertake an investigation and critical review of the Neolithic cultural groups as defined by contemporary archaeologists. This will be achieved through the analysis of empirical material derived from the Neolithic site of Tibble, located in the Björklinge parish of Uppland, Sweden. The primary aim is to develop a more comprehensive understanding and interpretation of not only the specific site but also the cultural and social aspects of the Neolithic period as a whole. Key questions addressed in this study include the impact of material studies on the overall interpretation of Neolithic culture and social life, as well as the potential for attaining a more holistic understanding of a time and place through an analytical approach that oscillates between detailed analysis and broader contextual perspectives. The primary sources utilized in this research consist of material artifacts, reports, and relevant literature pertaining to the Middle Neolithic settlement at Tibble, Björklinge parish, Uppland, Sweden. The theoretical framework employed in this study, as well as the chosen methodology, is rooted in the hermeneutic spiral. Previous investigations into the Stone Age have been largely characterized by the classification of cultural groups, with limited consideration given to the criticism of the concept of culture itself. Consequently, substantial changes in the interpretation of the Neolithic period and its inhabitants have not been extensively pursued. In this essay, the integration of hermeneutics and interdisciplinary approaches is demonstrated as a valuable means to foster a transformative understanding of both specific sites and broader chronological periods. By doing so, it becomes possible to harness the knowledge embedded in material studies.It is important to note that this essay does not aspire to provide an ultimate solution to the perceived problem but rather represents an initial step towards a new direction of inquiry. This process is not necessarily confined to a singular location or region but can be applied to the interpretative work concerning other Neolithic sites as well.

In this thesis I investigate the dynamics and stellar populations of a sample of 28 edge-on early-type (S0--Sb) disk galaxies, 22 of which host a boxy or peanut-shaped bulge. I begin by constructing mass models of the galaxies based on their observed photometry and stellar kinematics. Subject to cosmologically motivated assumptions about the shape of dark haloes, I measure in a purely dynamical way their stellar and dark masses. I make a preliminary comparison between the dynamically determined stellar masses and those predicted by stellar population models. I then compare the Tully-Fisher (luminosity--velocity) relations of the spirals and S0s in the sample. I show that S0s are systematically fainter at a given rotational velocity, but the amount by which they are fainter is less than expected by models in which they are the products of truncation of star formation in spirals. This raises the possibility that S0s are smaller or more concentrated than spirals of the same mass. I then study the vertical structure of the boxy and peanut-shaped bulges of a subset of the sample. Among this sample of five galaxies, I find one example in which the stellar populations show no evidence that the bulge and the disk formed in different processes, and in which the bulge is in perfectly cylindrical rotation, i.e. its line-of-sight velocity does not change with height above the disk. This galaxy is probably a pure disk galaxy. However, even with this small sample, I also show that cylindrical rotation and homogeneous stellar populations are not ubiquitous properties of boxy and peanut-shaped bulges. Finally I analyse central and radial trends in the stellar populations of the bulges of full sample of 28 galaxies. I find that, at a given velocity dispersion, the central stellar populations of these barred early-type disk galaxies are identical to those of elliptical galaxies, which suggests that secular evolution does not dominate the centre of these galaxies. However, the radial metallicity gradients are shallower than those of ellipticals. This is qualitatively consistent with chemodynamical models of bar formation, in which radial inflow and outflow smears out pre-existing gradients.

The survival and sustainable development of construction contractors depends on their own capacity as well as their ability to cope with the ever changing environment. Hong Kong was once a large construction market by the world standards; but in the period 1998 to 2007 has suffered from long term market shrinkage. This shrinkage in the work load available in the market has demanded that Hong Kong contractors change their business strategy and consider expanding their construction business to the international marketplace. From surveys and studies of Hong Kong contractors, it is noted that traditionally the majority of contractors organizations were not active in participating in the international construction markets. The prime reasons were that the Hong Kong domestic market was large enough to sustain the contractors and that Hong Kong construction professionals are reluctant to work overseas. However due to the continuous shrinkage of the market, Hong Kong contractors were being forced to consider expanding their construction business to the overseas markets in order to survive. This thesis reviews existing theories and previous studies in overseas con-struction business development. It analyzes surveys of Hong Kong con-struction contractors and conducts a scientific study of a Hong Kong based contractor organization which expanded its construction business to overseas markets. This study was conducted through an integrated action research methodology. Based on the problems, impacts, difficulties and success this organization faced during its practical experience in the overseas business expansion, this thesis explores and recommends a structured approach for Hong Kong contractors to re-define and develop their business overseas. The focus of study is the pre-contract award stage of business development. It focuses on the entry modes, strategic planning, risk management and tender management of the organization. The author also presents various models for use in attaining width and depth of understanding of overseas knowledge. These include preliminary entry selection model, dynamic management, and a spiral model (a learning & knowledge based business development model), for use in the management of international construction business development at the pre-contract stage. The groundwork laid down in this thesis will form the basis for further studies and the development of theories / models. It is the expectation of the author that other contractors in Hong Kong and other nation s contractors may make use of this research as assistance to their overseas business development. The ultimate aim of the author has been to change the goal of contractors from being companies able to compete with international contractors in their domestic market to contractors that are able to compete in the international market place.

Internet applications have been extended to various aspects of everyday life and offer services of high reliability and security. In the Academia, Internet applications offer useful tools for the remote creation of simulation models and real-time conduction of control experiments. The aim of this study was the design of a reliable, safe and secure software system for real time operation of a remote aero gas turbine, with the use of standard Internet technology at very low cost. The gas turbine used in this application was an AMT Netherlands Olympus micro gas turbine. The project presented three prototypes: operation from an adjacent computer station, operation within the Local Area Netwok (LAN) of Cranfield University and finally, remotely through the Internet. The gas turbine is a safety critical component, thus the project was driven by risk assessment at all the stages of the software process, which adhered to the Spiral Model. Elements of safety critical systems design were applied, with risk assessment present in every round of the software process. For the implementation, various software tools were used, with the majority to be open source API’s. LabVIEW with compatible hardware from National Instruments was used to interface the gas turbine with an adjacent computer work station. The main interaction has been established between the computer and the ECU of the engine, with additional instrumentation installed, wherever required. The Internet user interface web page implements AJAX technology in order to facilitate asynchronous update of the individual fields that present the indications of the operating gas turbine. The parameters of the gas turbine were acquired with high accuracy, with most attention given to the most critical indications, exhaust gas temperature (EGT) and rotational speed (RPM). These are provided to a designed real-time monitoring application, which automatically triggers actions when necessary. The acceptance validation was accomplished with a formal validation method – Model Checking. The final web application was inspired by the RESTful architecture and allows the user to operate the remote gas turbine through a standard browser, without requiring any additional downloading or local data processing. The web application was designed with provisions for generic applications. It can be configured to function with multiple different gas turbines and also integrated with external performance simulation or diagnostics Internet platforms. Also, an analytical proposal is presented, to integrate this application with the TURBOMATCH WebEngine web application, for gas turbine performance simulation, developed by Cranfield University.

Bakgrund:Spiral är en högeffektiv preventivmedelsmetod och har tidigare enbart rekommenderats till kvinnor som fött barn. Dessa riktlinjer har förändrats och spiral är ett förstahandsalternativ till unga kvinnor. Barnmorskor ger trots det varierande information kring spiral till unga kvinnor. Syfte: Att belysa barnmorskors uppfattning av spiral som preventivmedelsmetod till unga kvinnor.Metod:Fenomenografisk forskningsmetod med induktiv ansats användes i studien. Sju barnmorskor intervjuades med semistrukturerade frågor i Västra Götaland.Resultat: Resultatet presenteras i tre beskrivningskategorier och fem uppfattningar: rätt information är av betydelse; unga kvinnors sexuella erfarenhet är av betydelse; Omgivningens kunskap varierar.Konklusion:Resultatet visar att individanpassad information är av stor vikt och att unga kvinnor ska få möjlighet till ett informerat val. Barnmorskor uppfattar att spiral är en effektiv preventivmedelsmetod till unga kvinnor som har debuterat sexuellt. Till de kvinnor som inte haft penetrerande samlag, rekommenderas en annan preventivmedelsmetod. Hur information om spiral ges är viktigt för följsamheten i användningen. De unga kvinnorna bör ha en realistisk bild av spiral och det är betydelsefullt att barnmorskor informerar om både för- och nackdelar. Genom att barnmorskorna är uppdaterade och inhämtar ny forskning kan rätt kunskap kring spiral förmedlas. / Background: Intrauterine device is an effective contraceptive method and was earlier only recommended for women who have had given birth. These guidelines have changed, and intrauterine device is a first choice for young women. Still midwives give various information about intrauterine device to young women.   Purpose: To illustrate midwives’ perceptions of intrauterine device to young women.Method: Phenomenographical research with an inductive approach was used in the study. 7 midwives were interviewed with semi-structured questions in western Sweden. Result: The midwives’ perceptions of intrauterine device as a contraceptive method to young women are presented in three descriptive categories and five perceptions: Rightinformation is of meaning; Young women’s sexual experience are of relevance; The environment’s knowledge varies.Conclusion: Midwives perception is that intrauterine deviceis an effective contraceptive method for young women who have had their sexual debut. For the young women who haven’t lost their virginity other contraceptive methods are preferred. How the information about intrauterine device is given is important for adherence among young women. The young women should have a realistic imageof the intrauterine device and there for it’s important that the midwives provide both advantages and disadvantages when they give information.If Midwives are updated and stays ahead with research they can provide a better knowledge of the intrauterine device.