Response Time Analysis of Slotted WiDOM in Noisy Wireless Channels

International Conference on Emerging Technologies and Factory Automation (ETFA 2015), Industrial Communication Technologies and Systems, Luxembourg, Luxembourg.

Communication strategy for Continente online store: improving the Ecommerce experience

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Deadlock avoidance with virtual channels

High Performance Computing is a rapidly evolving area of computer science which attends to solve complicated computational problems with the combination of computational nodes connected through high speed networks. This work concentrates on the networks problems that appear in such networks and specially focuses on the Deadlock problem that can decrease the efficiency of the communication or even destroy the balance and paralyze the network. Goal of this work is the Deadlock avoidance with the use of virtual channels, in the switches of the network where the problem appears. The deadlock avoidance assures that will not be loss of data inside network, having as result the increased latency of the served packets, due to the extra calculation that the switches have to make to apply the policy.

Participation of connexin-based channels in the control of vascular function

SUMMARYIntercellular communication is achieved at specialized regions of the plasma membrane by gap junctions. The proteins constituting the gap junctions are called connexins and are encoded by a family of genes highly conserved during evolution. In adult mouse, four connexins (Cxs) are known to be expressed in the vasculature: Cx37, Cx40, Cx43 and Cx45. Several recent studies have provided evidences that vascular connexins expression and blood pressure regulation are closely linked, suggesting a role for connexins in the control of blood pressure. However, the precise function that each vascular connexin plays under physiological and pathophysiological conditions is still not elucidated. In this context, this work was dedicated to evaluate the contribution of each of the four vascular connexins in the control of the vascular function and in the blood pressure regulation.In the present work, we first demonstrated that vascular connexins are differently regulated by hypertension in the mouse aorta. We also observed that endothelial connexins play a regulatory role on eNOS expression levels and function in the aorta, therefore in the control of vascular tone. Then, we demonstrated that Cx40 plays a pivotal role in the kidney by regulating the renal levels of COX-2 and nNOS, two key enzymes of the macula densa known to participate in the control of renin secreting cells. We also found that Cx43 forms the functional gap junction involved in intercellular Ca2+ wave propagation between vascular smooth muscle cells. Finally, we have started to generate transgenic mice expressing specifically Cx40 in the endothelium to investigate the involvement of Cx40 in the vasomotor tone, or in the renin secreting cells to evaluate the role of Cx40 in the control of renin secretion.In conclusion, this work has allowed us to identify new roles for connexins in the vasculature. Our results suggest that vascular connexins could be interesting targets for new therapies caring hypertension and vascular diseases.

Acid-sensing ion channels : modulation by serine-proteases and involvement in acid-induced action potential generation in hippocampal neurons

SUMMARY Acid-sensing ion channels (ASICs) are non-voltage gated sodium channels. They are activated by rapid extracellular acidification and generate an inactivating inward current. Four ASIC genes have been cloned: ASIC1, 2, 3 and 4, with variants a and b for ASIC1and AS1C2. ASICs are expressed in neurons of the central (CNS) and peripheral nervous system (PNS). In the CNS, ASICs have a role in learning, memory, as well as in neuronal death in ischemia. In the PNS, ASICs are involved in the perception of acid-induced pain, as well as in mechanoperception. In one part of my thesis project, we addressed the question of the mechanism of regulation of ASIC1 a by the serine protease trypsin at the molecular level. Trypsin modifies the function of ASIC1 a but not of ASIC1b. In order to identify the channel region responsible for this effect, we created chimeras between ASIC1 a and 1b. Subsequently, to identify the exact trypsin target(s), we mutated predicted trypsin sites in the region identified by the chimera. In the second part of a project, we investigated the role of ASICs at the cellular level, in neuronal signaling. Using the whole-cell patch clamp in hippocampal neuronal culture, we studied the potential involvement of ASICs in action potential (AP) generation. In the first part of the thesis work, we showed that trypsin modifies ASIC1a function: it shifts the pH activation and the steady-state inactivation curve towards more acidic values and accelerates the time course of the channel recovery from inactivation. We also showed that trypsin cleaves ASIC1a and that the functional effect and a channel cleavage correlate. In the inactivated state, channels cannot be modified by trypsin. Cleavage occurs in a channel region that is also important for inactivation of all ASICs; a part of this region is critical for the inhibition of ASIC1 a by the spider toxin Psalmotoxin1. In the second part of the thesis work, we showed that ASIC activity can modulate AP generation. ASIC activity by itself can induce trains of APs. In situations in which this activity by itself is not sufficient to induce APs, it can contribute to AP generation. During high neuronal activity, ASIC activity can block already existing trains of APs. In conclusion, depending on the activity of neuron in a particular moment, ASICs can differently modulate AP generation; they can induce, facilitate or inhibit APs. We also showed that trypsin changes the capability of ASICs to modulate AP generation by shifting the pH dependence to more acidic values, which adapts channel gating to pH conditions which may occur in pathological conditions such as ischemia. Our finding that trypsin modifies ASIC1 a function identifies a novel pharmacological tool, and proposes a mechanism of ASIC1a regulation that may have a physiological importance. The identification of the exact site of trypsin action gives insight to the molecular mechanisms of ASIC regulation. This work proposes a role in modulation of AP generation for ASICs in the CNS. RESUME Les canaux ASIC sont les canaux ioniques activés par l'acidification rapide extracellulaire. Activés, ils génèrent un courant entrant qui inactive en présence de stimulus acide. Quatre gènes ASIC ont été clonés, ASIC1, 2, 3 et 4, avec les variants a et b pour ASIC1 et 2. Les ASICs sont exprimés dans les neurones du système nerveux central (SNC) et périphérique (SNP). Dans le SNC, les ASIC ont un rôle dans le mémoire, apprentissage et la mort neuronale dans t'ischémie. Dans le SNP, ils ont un rôle dans la perception de la douleur et méchanosensation. Dans une partie de mon projet de thèse, nous avons étudié les mécanismes de la régulation d'ASIC1a par la sérine-protéase trypsine au niveau moléculaire. La trypsine modifie la fonction d'ASIC1a et pas ASIC1b. Nous avons créé les chimères entre ASIC1 a et 1 b, afin d'identifier la région du canal responsable pour l'effet. Pour identifier le(s) site(s) exactes de l'action de la trypsine, nous avons muté les sites potentiels de la trypsine dans la région identifiée par les chimères. Dans la deuxième partie du projet, nous avons étudié le rôle des ASICs au niveau cellulaire. En utilisant la technique du patch clamp dans les cultures des neurones de l'hippocampe, nous avons étudié l'implication des ASICs dans la génération des potentiels d'action (PA). Nous avons montré que la trypsine agit sur le canal ASIC1a ; elle décale l'activation et « steady-state » inactivation vers les valeurs plus acides, et elle raccourcit le temps du « recovery » du canal. La trypsine coupe ASIC1a sur le résidu K145 et l'effet fonctionnel et la coupure corrèlent. Nous avons identifié la région du canal responsable pour l'inactivation de tous les ASICs ; une partie de cette région est responsable pour ['inhibition d'ASIC1 a par la Psalmotoxinel . Nous avons montré que les ASICs peuvent moduler la génération des PAs. L'activité des ASICs peut induire les trains des PAs. Quand l'activité des ASICs n'est pas suffisante pour induire le PA, elle peut contribuer à sa génération. Pendant l'activité neuronale forte, l'activité des ASICs peut bloquer les trains des PAs qui existent déjà. En conclusion, dépendant de l'activité neuronale, les ASICs peuvent moduler la génération des PAs différemment ; ils peuvent induire, faciliter ou inhiber les PAs. La trypsine change la capacité des ASICs de moduler les PAs. Après l'action de la trypsine, les ASICs peuvent moduler la génération des PAs dans les conditions légèrement acides, suivies par les fluctuations du pH acide, qui peuvent exister dans l'ischémie. Le fait que la trypsine agit sur ASIC1a définit l'outil pharmacologique et propose le mécanisme de la régulation d'ASICI a qui pourrait avoir l'importance physiologique. L'identification du site de l'action de la trypsine éclaircit les mécanismes moléculaires de la régulation des ASICs. Cette étude propose un rôle des ASICs dans la modulation de la génération des PAs. Résumé pour le public large Les neurones sont les cellules de système nerveux dont la fonction est la signalisation. Comme toutes les autres cellules, les neurones ont une membrane qui sépare l'intérieur du milieu extérieur. Cette membrane est imperméable pour des particules chargées (ions). Dans cette membrane existent les protéines spécifiques, « canaux », qui permettent le transport des ions d'un côté de la membrane à l'autre, comme réponse aux stimuli différents. Ce transport des ions à travers la membrane génère un courant, qu'on peut mesurer. Ce courant est la base de la communication entre les neurones, ou, ce qu'on appelle la signalisation neuronale. Quand ce courant est suffisamment grand, il permet la génération du potentiel d'action, qui est le message principal de communication neuronale. Les canaux ASIC (acid-sensing ion channel), que nous étudions dans le laboratoire, sont activés par les acides. Les acides sont relâchés dans beaucoup de situations dans le système nerveux. Les ASIC ont été découverts récemment (en 1996), et nous ne connaissons pas encore très bien toutes les fonctions de ces canaux. Nous savons qu'ils ont un rôle dans le mémoire, apprentissage, la sensation de la douleur et l'infarctus cérébral. Dans la première partie de ce projet de thèse, nous avons voulu mieux comprendre comment fonctionnent ces canaux. Pour faire ça, nous avons étudié la régulation des ASICs par une protéine, trypsine, qui coupe le canal ASIC. Nous avons étudié ou exactement la trypsine coupe le canal et quels effets ça produit sur la fonction du canal. Dans la deuxième partie du projet de thèse, nous avons voulu mieux connaître comment le canal fonctionne au niveau de la cellule, comment il interagit avec les autres canaux et si il a un rôle dans la génération des potentiels d'action. Nous avons pu montrer que la trypsine change la fonction du canal, ce qui lui permet de fonctionner différemment. Nous avons aussi déterminé ou exactement ta trypsine coupe le canal. Au niveau de la cellule, nous avons montré que les ASIC peuvent moduler la génération des potentiels d'action, étant, dépendant de l'activité du neurone, soit activateurs, soit inhibiteurs. La trypsine est une molécule qui peut être libérée dans le système nerveux pendant certaines conditions, comme l'infarctus cérébral. A cause de ça, les connaissances que la trypsine agit sur le anal ASIC pourraient être important physiologiquement. La connaissance de l'endroit exacte ou la trypsine coupe le canal nous aide à mieux comprendre la relation structure-fonction du canal. La modulation de la génération des potentiels d'actions par les ASIC indique que ces canaux peuvent avoir un rôle important dans la signalisation neuronale.

Digital inmigrants and digital natives expectation collection in the Andalusian Public Health System Virtual Library: communication with our users

The Andalusian Public Health System Virtual Library (Biblioteca Virtual del Sistema Sanitario Público de Andalucía, BV-SSPA) provides access to health information resources and services to healthcare professionals through its Website. This virtual environment demands higher users’ knowledge in order to satisfy of the need of information of our users, as digital natives as digital immigrants, improving at the same time the communication with all of them. 1. To collect clients' views and expectations according to their nature of digital natives and immigrants. 2. To know our online reputation. A Collecting User Expectation Questionnaire will be built, taking into account the segmentation of the BV-SSPA users’ professional groups of the Andalusian Public Health System. A pilot test will be run to check the survey dimensions and items about practices, attitudes and knowledge of our users. Two Quality Function Deployment (QFD) matrices will enable the BV-SSPA services to be targeted to our digital natives or digital immigrants, according to their nature, finding the best way to satisfy their information needs. We provide feedback on BV-SSPA: users can have the opportunity to post feedback about the site via the 'Contact us' section and comment about their experience. And Web 2.0 is a shop window, providing the opportunity to show the comments; and through time, our online reputation will be built, but the BV-SSPA must manage its own personal branding. Web 2.0 tools are a driver of improvement, because they provide a key source of insight into people's attitudes. Besides, the BV-SSPA digital identity will be analyzed through indicators like major search engine referrals breakdown, top referring sites (non search engines), or top search engine referral phrases, among others. Definition of digital native and digital immigrant profiles of the BV-SSPA, and their difference, will be explained by their expectations. The design of the two QFD matrices will illustrate in just one graph the requirements of both groups for tackling digital abilities and inequalities. The BV-SSPA could deliver information and services through alternative channels. On the other hand, we are developing a strategy to identify, to measure and to manage a digital identity through communication with the user and to find out our online reputation. With the use of different tools from quantitative and qualitative methodology, and the opportunities offered by Web 2.0 tools, the BV-SSPA will know the expectations of their users as a first step to satisfy their necessities. Personalization is pivotal to the success of the Site, delivering tailored content to individuals based on their recorded preferences. The valuable user research can be used during new product development and redesign. Besides positive interaction let us build trust, show authenticity, and foster loyalty: we improve with effort, communication and show.

Interplay of spectral efficiency, power and doppler spectrum for reference-signal-assisted wireless communication

Expressions relating spectral efficiency, power, and Doppler spectrum, are derived for Rayleigh-faded wireless channels with Gaussian signal transmission. No side information on the state of the channel is assumed at the receiver. Rather, periodic reference signals are postulated in accordance with the functioning of most wireless systems. The analysis relies on a well-established lower bound, generally tight and asymptotically exact at low SNR. In contrast with most previous studies, which relied on block-fading channel models, a continuous-fading model is adopted. This embeds the Doppler spectrum directly in the derived expressions, imbuing them with practical significance. Closed-form relationships are obtained for the popular Clarke-Jakes spectrum and informative expansions, valid for arbitrary spectra, are found for the low- and high-power regimes. While the paper focuses on scalar channels, the extension to multiantenna settings is also discussed.

High-SNR power offset in multiantenna communication

The analysis of the multiantenna capacity in the high-SNR regime has hitherto focused on the high-SNR slope (or maximum multiplexing gain), which quantifies the multiplicative increase as function of the number of antennas. This traditional characterization is unable to assess the impact of prominent channel features since, for a majority of channels, the slope equals the minimum of the number of transmit and receive antennas. Furthermore, a characterization based solely on the slope captures only the scaling but it has no notion of the power required for a certain capacity. This paper advocates a more refined characterization whereby, as function of SNRjdB, the high-SNR capacity is expanded as an affine function where the impact of channel features such as antenna correlation, unfaded components, etc, resides in the zero-order term or power offset. The power offset, for which we find insightful closed-form expressions, is shown to play a chief role for SNR levels of practical interest.

Spectral efficiency in reference-signal-assisted low-power wireless communication

Expressions relating spectral efficiency, power and Doppler spectrum are derived for low-power Rayleighfaded wireless channels with proper complex signaling. Noside information on the state of the channel is assumed at the receiver. Rather, periodic reference signals are postulated inaccordance with the functioning of most wireless systems. In contrast with most previous studies, which relied on block-fading channel models, a continuous-fading model is adopted. This embeds the Doppler spectrum directly in thederived expressions thereby imbuing them with practical significance.

Asymptotic capacity of static multiuser channels with an unknown number of users

We examine a multiple-access communication system in which multiuser detection is performed without knowledge of the number of active interferers. Using a statistical-physics approach, we compute the single-user channel capacity and spectral efficiency in the large-system limit.

The psychostimulant modafinil enhances gap junctional communication in cortical astrocytes.

Sleep-wake cycle is characterized by changes in neuronal network activity. However, for the last decade there is increasing evidence that neuroglial interaction may play a role in the modulation of sleep homeostasis and that astrocytes have a critical impact in this process. Interestingly, astrocytes are organized into communicating networks based on their high expression of connexins, which are the molecular constituents of gap junction channels. Thus, neuroglial interactions should also be considered as the result of the interplay between neuronal and astroglial networks. Here, we investigate the effect of modafinil, a wakefulness-promoting agent, on astrocyte gap junctional communication. We report that in the cortex modafinil injection increases the expression of mRNA and protein of connexin 30 but not those of connexin 43, the other major astroglial connexin. These increases are correlated with an enhancement of intercellular dye coupling in cortical astrocytes, which is abolished when neuronal activity is silenced by tetrodotoxin. Moreover, gamma-hydroxybutyric acid, which at a millimolar concentration induces sleep, has an opposite effect on astroglial gap junctions in an activity-independent manner. These results support the proposition that astroglia may play an important role in complex physiological brain functions, such as sleep regulation, and that neuroglial networking interaction is modified during sleep-wake cycle. This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'.

Involvement of gap junctional intercellular communication in the pathophysiology of inflammation

SUMMARY Inflammation has evolved as a mechanism to defend the body against invading microorganisms and to respond to injury. It requires the coordinated response of a large number of cell types from the whole organism in a time- and space-dependent fashion. This coordination involves several cell-cell communication mechanisms. Exchange of humoral mediators such as cytokines is a major one. Moreover, direct contact between cells happens and plays a primordial role, for example when macrophages present antigens to lymphocytes. Contact between endothelial cells and leucocytes occurs when the latter cross the blood vessel barrier and transmigrate to the inflammatory site. A particular way by which cells communicate with each other in the course of inflammation, which at this time starts to gain attention, is the intercellular communication mediated by gap junctions. Gap junctions are channels providing a direct pathway (i.e. without transit through the extracellular space) for the diffusion of small molecules between adjacent cells. This process is known as gap junctional intercellular communication (GJIC). The general aim of this thesis was to study a possible involvement of GJIC in the pathophysiology of inflammation. A first part of the work was dedicated to study the implication of GJIC in the modification of vascular endothelial function by inflammation. In a second part, we were interested in the possible role of GJIC in the transmigration of neutrophil polymorphonuclear leucocytes through the endothelium. The main positive finding of this work is that acute inflammation preferentially modulates the expression of connexin 40 (Cx40), a gap junction protein specifically expressed in vascular endothelium. The modulation could be towards overexpression (aortic endothelium of septic rats) or towards downregulation (acutely inflamed mouse lung). We put a lot of efforts in search of possible functions of these modulations, in two directions: a potential protective role of Cx40 increased expression against sepsis-induced endothelial dysfunction, and a facilitating role of Cx40 decreased expression in neutrophil transmigration. To pursue both directions, it seemed logical to study the impact of Cx40 deletion using knock-out mice. Concerning the potential protective role of Cx40 overexpression we encountered a roadblock as we observed, in the aorta, a Cx40 downregulation in wild type mouse whereas Cx40 was upregulated in the rat. Regarding the second direction and using an in vivo approach, we observed that pulmonary neutrophil transmigration was not affected by the genetic deletion of Cx40. In spite of their negative nature, these results are the very first ones regarding the potential implication of GJIC concerning leucocyte transmigration in vivo. Because this process involves such tight cell-cell physical contacts, the hypothesis for a role of GJIC remains attractive.

ACID-SENSING ION CHANNELS: functional and molecular characterization in putative nociceptors, and modulation by nerve injury and serine protease

Résumé Les canaux ioniques ASICs (acid-sensing ion channels) appartiennent à la famille des canaux ENaC/Degenerin. Pour l'instant, quatre gènes (1 à 4) ont été clonés dont certains présentent des variants d'épissage. Leur activation par une acidification rapide du milieu extracellulaire génère un courant entrant transitoire essentiellement sodique accompagné pour certains types d'ASICs d'une phase soutenue. Les ASICs sont exprimés dans le système nerveux, central (SNC) et périphérique (SNP). On leur attribue un rôle dans l'apprentissage, la mémoire et l'ischémie cérébrale au niveau central ainsi que dans la nociception (douleur aiguë et inflammatoire) et la méchanotransduction au niveau périphérique. Toutefois, les données sont parfois contradictoires. Certaines études suggèrent qu'ils sont des senseurs primordiaux impliqués dans la détection de l'acidification et la douleur. D'autres études suggèrent plutôt qu'ils ont un rôle modulateur inhibiteur dans la douleur. De plus, le fait que leur activation génère majoritairement un courant transitoire alors que les fibres nerveuses impliquées dans la douleur répondent à un stimulus nocif avec une adaptation lente suggère que leurs propriétés doivent être modulés par des molécules endogènes. Dans une première partie de ma thèse, nous avons abordé la question de l'expression fonctionnelle des ASICs dans les neurones sensoriels primaires afférents du rat adulte pour clarifier le rôle des ASICs dans les neurones sensoriels. Nous avons caractérisé leurs propriétés biophysiques et pharmacologiques par la technique du patch-clamp en configuration « whole-cell ». Nous avons pu démontrer que près de 60% des neurones sensoriels de petit diamètre expriment des courants ASICs. Nous avons mis en évidence trois types de courant ASIC dans ces neurones. Les types 1 et 3 ont des propriétés compatibles avec un rôle de senseur du pH alors que le type 2 est majoritairement activé par des pH inférieurs à pH6. Le type 1 est médié par des homomers de la sous-unité ASIC1 a qui sont perméables aux Ca2+. Nous avons étudié leur co-expression avec des marqueurs des nocicepteurs ainsi que la possibilité d'induire une activité neuronale suite à une acidification qui soit dépendante des ASICs. Le but était d'associer un type de courant ASIC avec une fonction potentielle dans les neurones sensoriels. Une majorité des neurones exprimant les courants ASIC co-expriment des marqueurs des nocicepteurs. Toutefois, une plus grande proportion des neurones exprimant le type 1 n'est pas associée à la nociception par rapport aux types 2 et 3. Nous avons montré qu'il est possible d'induire des potentiels d'actions suite à une acidification. La probabilité d'induction est proportionnelle à la densité des courants ASIC et à l'acidité de la stimulation. Puis, nous avons utilisé cette classification comme un outil pour appréhender les potentielles modulations fonctionnelles des ASICs dans un model de neuropathie (spared nerve injury). Cette approche fut complétée par des expériences de «quantitative RT-PCR ». En situation de neuropathie, les courants ASIC sont dramatiquement changés au niveau de leur expression fonctionnelle et transcriptionnelle dans les neurones lésés ainsi que non-lésés. Dans une deuxième partie de ma thèse, suite au test de différentes substances sécrétées lors de l'inflammation et l'ischémie sur les propriétés des ASICs, nous avons caractérisé en détail la modulation des propriétés des courants ASICs notamment ASIC1 par les sérines protéases dans des systèmes d'expression recombinants ainsi que dans des neurones d'hippocampe. Nous avons montré que l'exposition aux sérine-protéases décale la dépendance au pH de l'activation ainsi que la « steady-state inactivation »des ASICs -1a et -1b vers des valeurs plus acidiques. Ainsi, l'exposition aux serine protéases conduit à une diminution du courant quand l'acidification a lieu à partir d'un pH7.4 et conduit à une augmentation du courant quand l'acidification alleu à partir d'un pH7. Nous avons aussi montré que cette régulation a lieu des les neurones d'hippocampe. Nos résultats dans les neurones sensoriels suggèrent que certains courants ASICs sont impliqués dans la transduction de l'acidification et de la douleur ainsi que dans une des phases du processus conduisant à la neuropathie. Une partie des courants de type 1 perméables au Ca 2+ peuvent être impliqués dans la neurosécrétion. La modulation par les sérines protéases pourrait expliquer qu'en situation d'acidose les canaux ASICs soient toujours activables. Résumé grand publique Les neurones sont les principales cellules du système nerveux. Le système nerveux est formé par le système nerveux central - principalement le cerveau, le cervelet et la moelle épinière - et le système nerveux périphérique -principalement les nerfs et les neurones sensoriels. Grâce à leur nombreux "bras" (les neurites), les neurones sont connectés entre eux, formant un véritable réseau de communication qui s'étend dans tout le corps. L'information se propage sous forme d'un phénomène électrique, l'influx nerveux (ou potentiels d'actions). A la base des phénomènes électriques dans les neurones il y a ce que l'on appelle les canaux ioniques. Un canal ionique est une sorte de tunnel qui traverse l'enveloppe qui entoure les cellules (la membrane) et par lequel passent les ions. La plupart de ces canaux sont normalement fermés et nécessitent d'être activés pour s'ouvrire et générer un influx nerveux. Les canaux ASICs sont activés par l'acidification et sont exprimés dans tout le système nerveux. Cette acidification a lieu notamment lors d'une attaque cérébrale (ischémie cérébrale) ou lors de l'inflammation. Les expériences sur les animaux ont montré que les canaux ASICs avaient entre autre un rôle dans la mort des neurones lors d'une attaque cérébrale et dans la douleur inflammatoire. Lors de ma thèse je me suis intéressé au rôle des ASICs dans la douleur et à l'influence des substances produites pendant l'inflammation sur leur activation par l'acidification. J'ai ainsi pu montrer chez le rat que la majorité des neurones sensoriels impliqués dans la douleur ont des canaux ASICs et que l'activation de ces canaux induit des potentiels d'action. Nous avons opéré des rats pour qu'ils présentent les symptômes d'une maladie chronique appelée neuropathie. La neuropathie se caractérise par une plus grande sensibilité à la douleur. Les rats neuropathiques présentent des changements de leurs canaux ASICs suggérant que ces canaux ont une peut-être un rôle dans la genèse ou les symptômes de cette maladie. J'ai aussi montré in vitro qu'un type d'enryme produit lors de l'inflammation et l'ischémie change les propriétés des ASICs. Ces résultats confirment un rôle des ASICs dans la douleur suggérant notamment un rôle jusque là encore non étudié dans la douleur neuropathique. De plus, ces résultats mettent en évidence une régulation des ASICs qui pourrait être importante si elle se confirmait in vivo de part les différents rôles des ASICs. Abstract Acid-sensing ion channels (ASICs) are members of the ENaC/Degenerin superfamily of ion channels. Their activation by a rapid extracellular acidification generates a transient and for some ASIC types also a sustained current mainly mediated by Na+. ASICs are expressed in the central (CNS) and in the peripheral (PNS) nervous system. In the CNS, ASICs have a putative role in learning, memory and in neuronal death after cerebral ischemia. In the PNS, ASICs have a putative role in nociception (acute and inflammatory pain) and in mechanotransduction. However, studies on ASIC function are somewhat controversial. Some studies suggest a crucial role of ASICs in transduction of acidification and in pain whereas other studies suggest rather a modulatory inhibitory role of ASICs in pain. Moreover, the basic property of ASICs, that they are activated only transiently is irreconcilable with the well-known property of nociception that the firing of nociceptive fibers demonstrated very little adaptation. Endogenous molecules may exist that can modulate ASIC properties. In a first part of my thesis, we addressed the question of the functional expression of ASICs in adult rat dorsal root ganglion (DRG) neurons. Our goal was to elucidate ASIC roles in DRG neurons. We characterized biophysical and pharmacological properties of ASIC currents using the patch-clamp technique in the whole-cell configuration. We observed that around 60% of small-diameter sensory neurons express ASICs currents. We described in these neurons three ASIC current types. Types 1 and 3 have properties compatible with a role of pH-sensor whereas type 2 is mainly activated by pH lower than pH6. Type 1 is mediated by ASIC1a homomultimers which are permeable to Ca 2+. We studied ASIC co-expression with nociceptor markers. The goal was to associate an ASIC current type with a potential function in sensory neurons. Most neurons expressing ASIC currents co-expressed nociceptor markers. However, a higher proportion of the neurons expressing type 1 was not associated with nociception compared to type 2 and -3. We completed this approach with current-clamp measurements of acidification-induced action potentials (APs). We showed that activation of ASICs in small-diameter neurons can induce APs. The probability of AP induction is positively correlated with the ASIC current density and the acidity of stimulation. Then, we used this classification as a tool to characterize the potential functional modulation of ASICs in the spared nerve injury model of neuropathy. This approach was completed by quantitative RT-PCR experiments. ASICs current expression was dramatically changed at the functional and transcriptional level in injured and non-injured small-diameter DRG neurons. In a second part of my thesis, following an initial screening of the effect of various substances secreted during inflammation and ischemia on ASIC current properties, we characterized in detail the modulation of ASICs, in particular of ASIC1 by serine proteases in a recombinant expression system as well as in hippocampal neurons. We showed that protease exposure shifts the pH dependence of ASIC1 activation and steady-state inactivation to more acidic pH. As a consequence, protease exposure leads to a decrease in the current response if ASIC1 is activated by a pH drop from pH 7.4. If, however, acidification occurs from a basal pH of 7, protease-exposed ASIC1a shows higher activity than untreated ASIC1a. We provided evidence that this bi-directional regulation of ASIC1a function also occurs in hippocampal neurons. Our results in DRG neurons suggest that some ASIC currents are involved in the transduction of peripheral acidification and pain. Furthermore, ASICs may participate to the processes leading to neuropathy. Some Ca 2+-permeable type 1 currents may be involved in neurosecretion. ASIC modulation by serine proteases may be physiologically relevant, allowing ASIC activation under sustained slightly acidic conditions.

Enhanced MDIR receiver for space-time dispersive channels

A particular property of the matched desiredimpulse response receiver is introduced in this paper, namely,the fact that full exploitation of the diversity is obtained withmultiple beamformers when the channel is spatially and timelydispersive. This particularity makes the receiver specially suitablefor mobile and underwater communications. The new structureprovides better performance than conventional and weightedVRAKE receivers, and a diversity gain with no needs of additionalradio frequency equipment. The baseband hardware neededfor this new receiver may be obtained through reconfigurabilityof the RAKE architectures available at the base station. Theproposed receiver is tested through simulations assuming UTRAfrequency-division-duplexing mode.

Joint array combining and MLSE for single-user receivers in multipath Gaussian multiuser channels

The well-known structure of an array combiner along with a maximum likelihood sequence estimator (MLSE) receiveris the basis for the derivation of a space-time processor presentinggood properties in terms of co-channel and intersymbol interferencerejection. The use of spatial diversity at the receiver front-endtogether with a scalar MLSE implies a joint design of the spatialcombiner and the impulse response for the sequence detector. Thisis faced using the MMSE criterion under the constraint that thedesired user signal power is not cancelled, yielding an impulse responsefor the sequence detector that is matched to the channel andcombiner response. The procedure maximizes the signal-to-noiseratio at the input of the detector and exhibits excellent performancein realistic multipath channels.