Seven empirical equations were developed for the prediction of seal strength for medical device trays. A new methodology was developed and used for identifying burst and peel locations and comparing burst pressure and peel force. Multiple linear regression was used to fit 76 models, selecting the best models based on the Akaike Information Criterion (AIC) and adjusted R2 (R2 adj) value of each model. The selected models have R2 adj and prediction R2 (R2 pred) values of .83 to .94. Factors investigated for the peel force response were sealing pressure (3 levels), dwell time (3 levels), sealing temperature (3 levels), and adhesive. Additional factors investigated for the burst pressure response were restraining plate gap, and tray volume, height, length-to-width ratio and area. Polyethylene terephthalate-glycol (PETG) trays with Tyvek 1073B lids and two popular water-based adhesives were used. Trays were selected to yield three levels of area and three levels of length-to-width ratio, defining nine package configurations. Packages for burst testing were sealed under a fractional factorial design with 27 treatments. Packages for peel testing were sealed under a 17-point face-centered central composite design. Packages were tested using peel testing following the ASTM F88-07 standard and restrained burst testing with three gap distances following the ASTM F2054-00 standard. All possible subsets of the factors were evaluated, with the best models selected based on AIC value. Equations were developed to predict peak and average peel force based on sealing process parameters (R2 pred =.94 and .92), burst pressure based on tray and sealing parameters and gap (R2 pred =.94), and four peel force responses based on burst pressure and gap (R2 pred =.83 to .86). Models were validated through cross-validation, using the prediction error sum of squares (PRESS) statistic. The R2 pred was calculated to estimate the predictive ability of each model.

Η οπτική μεταγωγή καταιγισμών (Optical Burst Switching – OBS) συνδυάζει τα πλεονεκτήματα της οπτικής μεταγωγής κυκλώματος και της οπτικής μεταγωγής πακέτου. Οι βασικές ιδέες που κυριαρχούν σε ένα σύστημα OBS είναι η συναρμολόγηση των πακέτων σε καταιγισμούς οι οποίοι δρομολογούνται με ξεχωριστά πακέτα ελέγχου και ο διαχωρισμός της μεταγωγής και της μετάδοσης του πακέτου ελέγχου και του αντίστοιχου καταιγισμού. Κατά την τεχνική συναρμολόγησης υπερπακέτων, πολλά πακέτα συναθροίζονται σε ένα υπερπακέτο στην είσοδο του δικτύου. Κάθε ακραίος κόμβος διατηρεί μια ξεχωριστή ουρά ανάλογα με την ποιότητα των υπηρεσιών που είναι επιθυμητή. Σε αυτή την ουρά συγκεντρώνονται τα πακέτα που καταλήγουν στον ίδιο προορισμό και ανήκουν επίσης στην ίδια κλάση προτεραιότητας μέχρι να σχηματιστεί ο καταιγισμός. Το πακέτο ελέγχου που ονομάζεται και Burst Header packet (BHP), μεταδίδεται νωρίτερα σε σχέση με το αντίστοιχο υπερπακέτο, κατά ένα συγκεκριμένο χρονικό διάστημα. Το BHP υφίσταται επεξεργασία σε κάθε κόμβο του δικτύου κορμού προκειμένου να δεσμεύσει πόρους και να εγκαταστήσει ένα μονοπάτι, ενώ το αντίστοιχο υπερπακέτο μεταδίδεται μέσω του δικτύου χωρίς να χρειάζεται η μετατροπή του από οπτική σε ηλεκτρονική μορφή και πάλι σε οπτική. Στη βιβλιογραφία έχουν προταθεί διάφοροι μηχανισμοί συναρμολόγησης υπερπακέτων εκρηκτικής ροής όπως οι BSMIN, TMAX και TAVE, στους οποίους ένα υπερπακέτο εκρηκτικής ροής σχηματίζεται και είναι έτοιμο να αποσταλεί στο δίκτυο όταν ικανοποιηθεί κάποιο κριτήριο που έχει καθοριστεί και διαφέρει για κάθε έναν από τους αλγορίθμους αυτούς. Στη συγκεκριμένη εργασία προτείνουμε τρόπους για τη γρήγορη δέσμευση της χωρητικότητας (Fast Reservation – FR schemes) οι οποίοι μπορούν να συνδυαστούν με τους αλγορίθμους συναρμολόγησης υπερπακέτων εκρηκτικής ροής BSMIN, TMAX και TAVE. Οι μέθοδοι αυτές χρησιμοποιούν ένα ή δύο γραμμικά φίλτρα προκειμένου να προβλέψουν το μέγεθος του υπερπακέτου ή/και το χρόνο που απαιτείται μέχρι να ολοκληρωθεί η συναρμολόγηση των πακέτων σε ένα υπερπακέτο. Σε αντίθεση με τα τυπικά πρωτόκολλα σηματοδοσίας που χρησιμοποιούνται στα OBS δίκτυα, στην εργασία μας το πακέτο ελέγχου BHP στέλνεται στο δίκτυο κορμού για να δεσμεύσει τους απαραίτητους πόρους, χωρίς να έχει προηγουμένως ολοκληρωθεί η δημιουργία του υπερπακέτου. Με βάση τις τιμές που έχουν εκτιμηθεί από τα φίλτρα και χωρίς οι αντίστοιχες πραγματικές τιμές να είναι ακόμα γνωστές, το BHP στέλνεται για να δεσμεύσει το απαιτούμενο εύρος ζώνης σε κάθε κόμβο του δικτύου κορμού και για το χρονικό διάστημα που το burst θα περάσει από αυτόν τον κόμβο. Η πρόβλεψη του μεγέθους του burst είναι απαραίτητη ώστε να δεσμευτούν οι κατάλληλοι πόροι στο δίκτυο κορμού για τη διάρκεια της μετάδοσης του burst, ενώ η πρόβλεψη της διάρκειας συναρμολόγησης χρειάζεται προκειμένου η δέσμευση των πόρων αυτών να ξεκινήσει τη σωστή χρονική στιγμή. Στόχος μας είναι να μειώσουμε την καθυστέρηση μετάδοσης από άκρο – σε – άκρο ενός υπερπακέτου, μειώνοντας όσο είναι δυνατό το χρόνο που μεσολαβεί από τη μετάδοση του BHP μέχρι τη μετάδοση του burst και ταυτόχρονα να χρησιμοποιήσουμε αποδοτικά το εύρος ζώνης δεσμεύοντας το για το ελάχιστο δυνατό χρονικό διάστημα. Η εφαρμογή της πρόβλεψης της κίνησης στην είσοδο του δικτύου έχει εξεταστεί σε ένα μεγάλο αριθμό εργασιών. Συγκεκριμένα, έχει μελετηθεί η χρήση ενός γραμμικού φίλτρου πρόβλεψης σε συνδυασμό με τον αλγόριθμο TMAX ώστε να μειωθεί ο χρόνος που μεσολαβεί από τη μετάδοση του BHP μέχρι τη μετάδοση του burst. Τα αποτελέσματα της δικής μας εργασίας δείχνουν ότι η μέθοδος της πρόβλεψης μπορεί να χρησιμοποιηθεί επίσης και σε συνδυασμό με τους αλγορίθμους BSMIN και TAVE, οδηγώντας στη μείωση της καθυστέρησης μετάδοσης από άκρο – σε – άκρο ενός υπερπακέτου. Στη συνέχεια της εργασίας περιγράφουμε τη μέθοδο που προτείνουμε καθώς και τα αποτελέσματα από την πειραματική εφαρμογή της. Τέλος, σχολιάζουμε και παρουσιάζουμε τα συμπεράσματά μας και αναφέρουμε πιθανά θέματα προς μελέτη. / We propose and evaluate fast reservation (FR) protocols for Optical Burst Switched (OBS) networks. The proposed reservation schemes aim at reducing the end-to-end delay of a data burst, by sending the Burst Header Packet (BHP) in the core network before the burst assembly is completed at the ingress node. We use linear prediction filters to estimate the expected length of the burst and the time needed for the burstification process to complete. A BHP packet carrying these estimates is sent before burst completion, in order to reserve bandwidth at each intermediate node for the time interval the burst is expected to pass from that node. Reducing the total time needed for a packet to be transported over an OBS network is important, especially for real-time applications. Reserving bandwidth only for the time interval it is actual going to be used by a burst is important for network utilization efficiency. In the simulations conducted we evaluate the proposed extensions and prove their usefulness.

O mecanismo de rock burst envolve ruptura violenta e instantânea do maciço rochoso ao redor de uma escavação subterrânea, com liberação de grandes quantidades de energia. Neste trabalho, será apresentado uma abordagem baseada na teoria da elasticidade, a partir da qual a importância dos parâmetros elásticos serão avaliados no processo de acúmulo de energia elástica (W). Foram utilizados métodos analíticos e numéricos e equações que definem W a partir da matriz de tensões \'sigma\', da matriz de deformação \'épsilon\', e dos parâmetros elásticos E (módulo de Young, ou módulo de elasticidade) e \'nü\' (coeficiente de Poisson). A influência dos parâmetros E e \'nü\' na quantificação de W foi testada usando uma gama de valores, baseada em valores médios para as rochas cristalinas apresentados na literatura. Variações nos valores de E induzem mudanças consideráveis nos valores de W. Quanto menor E , maior W. Baixos valores de E definem maciços rochosos que sofrem maiores deformações sob um determinado regime de tensões, assim resultado em maior trabalho exercido pelo maciço e, consequentemente, mais energia elástica (W). Isto é, para um determinado estado de tensões, maciços mais deformáveis (com baixos valores de E ) têm a capacidade de acumular mais energia elástica que maciços pouco deformáveis. No entanto, considerando também a mecânica de ruptura, maciços menos resistentes rompem sob condições menos extremas de tensões, enquanto maciços mais resistentes necessitam de tensões muito elevadas para sofrerem ruptura. Portanto, maciços mais resistentes acumulam mais energia elástica que maciços menos resistentes. Embora o coeficiente \'nü\' seja apontado por alguns autores como maior responsável pelo acúmulo de W, este fato não foi observado neste trabalho, e o valor de W não é consideravelmente afetado por variações de \'nü\" , um resultado direto das equações utilizadas. No entanto, uma tendência \"anômala\" foi observada: fixado o valor de E, valores de \'nü\' medianos (próximo a 0,25) induzem maiores valores de W no limite da escavação, e conforme se afasta do limite para o sentido do interior do maciço, valores cada vez menores de passam a induzir os maiores valores de W. A teoria da elasticidade, por si só, não é capaz de explicar os fenômenos complexos que causam os processos de rock burst. Para uma compreensão completa do problema, é necessário também o estudo de mecânica de fraturas, mecânica de danos no maciço, dissipação de energia ao longo de fraturas, etc. / The mechanism or rock burst involves sudden and violent fracturing of the rock mass around the opening, with high amounts of energy released. This work demonstrates an approach based on the theory of elasticty and the role of elastic parameters in the process of storing elastic strain energy (W). Analytical and numerical methods were used. The main equations define W based on the stress matrix \'sigma\', the strain matrix \'épsilon\' and the elastic parameters E (Young\'s modulus) and \'nü\' (Poisson\'s ratio). The influence of E and \'nü\' was tested using minimum, average and maximum values, based on the values for crystalline hard rocks from the literature. Variations in values of E induce significant changes to the values of W. The lower E the higher W. Low values of E define rock masses which suffer greater displacements under a given stress condition, leading to higher values of W. This leads to the conclusion that, for a given stress state, soft rocks (lower values of E ) have the ability to store more elastic strain energy than stiff rocks. However, if fracture mechanics is also considered, strong rock masses have the ability to endure more stress than weaker rocks before failing, leading to higher amounts of elastic energy stored. Although Poisson\'s ratio (\'nü\') is considered by some authors as a fundamental piece in energy storage, such conclusion was not observed in this work, and values of W are not considerably affected by variations of \'nü\', a direct result of the application of the equations of theory of elasticity. However, an interesting trend was observed: for a given value of E , moderate values of \'ü\' (around 0,25) induce higher values of W at the edge of the excavation. In the rock mass interior, lower values of induce higher values of W. An analysis purely based on the theory of elasticity is not enough to explain the complex phenomena which occur around an excavation that induce violent failure and rock bursting. For a deeper understanding of the problem, it is also necessary the study of complementary theories, such as fracture mechanics, damage mechanics, energy dissipation during fracturing, and so on.

We present multi-wavelength observations and modeling of the exceptionally bright long gamma-ray burst GRB 160625B. The optical and X-ray data are well fit by synchrotron emission from a collimated blastwave with an opening angle of theta(j) approximate to 3 degrees.6 and kinetic energy of E-K approximate to 2 x 10(51) erg, propagating into a low-density (n approximate to 5 x 10(-5) cm(-3)) medium with a uniform profile. The forward shock is sub-dominant in the radio band; instead, the radio emission is dominated by two additional components. The first component is consistent with emission from a reverse shock, indicating an initial Lorentz factor of Gamma(0) greater than or similar to 100 and an ejecta magnetization of R-B approximate to 1-100. The second component exhibits peculiar spectral and temporal evolution and is most likely the result of scattering of the radio emission by the turbulent Milky Way interstellar medium (ISM). Such scattering is expected in any sufficiently compact extragalactic source and has been seen in GRBs before, but the large amplitude and long duration of the variability seen here are qualitatively more similar to extreme scattering events previously observed in quasars, rather than normal interstellar scintillation effects. High-cadence, broadband radio observations of future GRBs are needed to fully characterize such effects, which can sensitively probe the properties of the ISM and must be taken into account before variability intrinsic to the GRB can be interpreted correctly.

Claritromicina e clofazimina são utilizadas no tratamento da hanseníase e em infecções causadas pelo complexo Mycobacterium avium, comuns em portadores do HIV. Devido à escassez de dados sobre a toxicidade de esquemas terapêuticos que associam estes fármacos, este estudo teve por objetivo avaliar os efeitos adversos desta terapia, em ratos machos Wistar, por meio da determinação de parâmetros hematológicos, hemostáticos e bioquímicos e correlação destes parâmetros com a dose e concentração plasmática dos medicamentos, em regime de doses únicas e múltiplas. Para tanto foram realizados: a) contagem global e específica de leucócitos (método manual) e ensaios de fagocitose e burst oxidativo de neutrófilos (citometria de fluxo); b) contagem de plaquetas (método manual), tempo de protrombina, tempo de tromboplastina parcial ativada, níveis plasmáticos dos fatores VII e X (método automatizado); c) níveis séricos de gama-glutamiltransferase (método cinéticocolorimétrico) e bilirrubinas total e direta (método colorimétrico); d) concentrações plasmáticas dos fármacos (Cromatografia Líquida de Alta Eficiência). Não houve diferenças entre as concentrações plasmáticas dos fármacos administrados em monoterapia ou politerapia. Entretanto, tanto clofazimina como claritromicina tiveram redução das concentrações plasmáticas em regime de doses múltiplas, quando comparadas à dose única. Houve aumento do número de leucócitos (dose múltipla) e de células polimorfonucleares (doses única e múltipla) nos grupos tratados com claritromicina em monoterapia ou associada à clofazimina, e redução das células mononucleares, em doses única e múltipla, nos mesmos grupos. Os fármacos parecem inverter a proporção entre células mono e polimorfonucleares. Observou-se aumento do burst oxidativo nos animais tratados com os fármacos tanto em monoterapia como em regime de politerapia. Entretanto, não houve diferença entre os tratamentos com os fármacos em relação ao controle DMSO, em dose única. Em doses múltiplas, os tratamentos com clofazimina e claritromicina em monoterapia ou politerapia estimularam o aumento do burst oxidativo (p < 0,0001) em relação ao controle DMSO. Não foram verificadas diferenças na fagocitose entre os grupos tratados e controle, tanto em dose única como em doses múltiplas. Tempo de protrombina e tempo de tromboplastina parcial ativada não foram alterados com o uso dos fármacos. Os fatores VII e X da coagulação tiveram aumento de suas atividades quando os ratos foram tratados em regime de dose múltipla com claritromicina, em regime de mono e politerapia. Houve perda de cerca de 8 % do peso de ratos tratados com clofazimina e 18 % daqueles tratados com claritromicina ou com a associação dos dois fármacos, no esquema de doses múltiplas, entretanto não houve diferença entre os grupos quando foram avaliados os níveis de gama-glutamiltransferase e bilirrubinas total e direta. Concluindo, clofazimina e claritromicina provocam alterações hematológicas, hemostáticas e bioquímicas e os resultados de concentração plasmática são valiosos para avaliação de efeitos adversos em estudos comparativos de monoterapia e politerapia entre os medicamentos. / Clarithromycin and clofazimine have been used to treat leprosy and infections caused by Mycobacterium avium complex in HIV patients. Because there are few data about the toxicity of treatment regimens involving these drugs, this study aimed to evaluate the adverse effects of this therapy in male Wistar rats through the determination of hematological, haemostatic and biochemical parameters and correlate them with the dose and plasma concentrations of drugs, under a single and multiple dose regimen. Evaluation was performed as follows: a) Global and specific count of leukocytes (manual method), phagocytosis and oxidative burst of neutrophils assays (flow cytometry), b) platelet count (manual method), prothrombin time, activated partial thromboplastin time, plasma levels of factors VII and X (automated method), c) Gamma-glutamyltransferase (kinetic-colorimetric method) and total and direct bilirubin serum levels (colorimetric method), d) plasma concentrations of drugs (High-Performance Liquid Chromatography). There were no differences between plasma concentrations of the drugs administered in monotherapy or polytherapy. However, the concentrations of both clofazimine and clarithromycin have decreased in plasma in multiple dose regimen compared to single dose. There was an increase in the number of leukocytes (multiple dose) and polymorphonuclear cells (single and multiple doses) in the groups treated with clarithromycin in monotherapy or in association with clofazimine, and a decrease in the number of mononuclear cells in single and multiple doses, in the same groups. Both drugs seemed to reverse the proportion between mononuclear and polymorphonuclear cells. The oxidative burst was observed in animals treated with drugs in polytherapy or in monotherapy, however there was no difference between the treatment with drugs and the control with DMSO in single dose. In multiple doses, treatment with clofazimine and clarithromycin in monotherapy or polytherapy stimulated the increase of oxidative burst (p <0.0001) compared to control. There were no differences in phagocytosis between the treated and control groups in single and multiple doses. Prothrombin time and activated partial thromboplastin time have not changed with the use drugs. In contrast, the activities of factors VII and X of coagulation have increased when rats were treated with multiple doses regimes with clarithromycin alone or in association with clofazimine. There was weight loss of 8% in rats treated with clofazimine and 18% in those treated with clarithromycin or with association of the drugs in the multiple doses regimen. However, there was no difference between the groups when gammaglutamyltransferase and total and direct bilirubin levels were analyzed. Therefore, clofazimine and clarithromycin induce hematological, hemostatic and biochemical changes and the results of plasma concentration is valuable for assessing adverse effects in comparative studies of monotherapy and polytherapy of these drugs.

No description available.

The neurotransmitter dopamine (DA) represents a neural substrate for positive motivation as its spatiotemporal distribution across the brain is responsible for goaldirected behavior and learning reward associations. The critical determinant of DA release throughout the brain is the firing pattern of DA-producing neurons. Synchronized bursts of spikes can be triggered by sensory stimuli in these neurons, evoking phasic release of DA in target brain areas to drive reward-based reinforcement learning and behavior. These bursts are generated by NMDA-type glutamate receptors (NMDARs). This dissertation reports a novel form of long-term potentiation (LTP) of NMDARmediated excitatory transmission at DA neurons as a putative cellular substrate for changes in DA neuron firing during reward learning. Patch-clamp electrophysiological recording from DA neurons in acute brain slices from young adult rats demonstrated that synaptic NMDARs exhibit LTP in an associative manner, requiring coordinated pre- and postsynaptic burst firing. Ca2+ signals produced by postsynaptic burst firing needed to be amplified by preceding metabotropic neurotransmitter inputs to effectively drive plasticity. Activation of NMDARs themselves was also necessary. These two coincidence detectors governed the timingdependence of NMDAR plasticity in a manner analogous to the timing rule for cuereward learning paradigms in behaving animals. Further mechanistic study revealed that PKA, but not PKC, activity gated LTP induction by regulating the magnitude of Ca2+ signal amplification via the inositol 1,4,5-triphospate (IP3) receptor and release of Ca2+ from intracellular stores. Plasticity of NMDARs was input specific and appeared to be expressed postsynaptically, but was not associated with a change in NMDAR subunit stoichiometry. LTP of NDMARs was DA-independent, and was specific for NMDARs: the same induction protocol produced long-term depression of AMPA receptors. NMDARs that had undergone LTP could be depotentiated in a spike-conditional manner, consistent with active unlearning. Finally, repeated, in vivo amphetamine experience dramatically increased facilitation of spike-evoked Ca2+ signals, which in turn drove enhanced plasticity. NMDAR plasticity thus represents a potential neural substrate for conditioned DA neuron burst responses to environmental stimuli acquired during reward-based learning as well a novel therapeutic target for intervention-based therapy of addictive disorders. / text

The presented thesis investigates the identification of burst locations in water distribution systems (WDS) by analysis of field and simulation experimental data. This required the development of a new hybrid method of burst detection and sizing, and also a burst location identification algorithm. Generally, existing practice relies on a combination of some simple procedure and experience of the involved staff and cannot be easily automated. The practical methods are based on direct manifestation of burst on the surface or on systematically surveying suspected areas e.g. by using listening sticks, such methods are very time consuming. The proposed burst location algorithm is based on comparing data by means of statistical analysis of field data with results of water network simulation. An extended network hydraulic simulator is used to model pressure dependent leakage terms. The presence of a burst changes the flow pattern and also pressure at network nodes which may be used to estimate the burst size and its location. The influence of such random factors as demand flows and background leakage on the process of burst detection is also considered. The field data is from a generalised fixed area and variable area (FAVOR) test where inlet pressure is being stepped up and down and the following variables are measured: inlet flow, inlet pressure (head) and pressure at a number of selected sensitive nodes. The method has three stages and uses two different models, one is inlet flow model (IFM) to represent the total inlet flow and another is the extended hydraulic model to simulate different burst locations. Initially the presence of a potential burst is investigated. If this is confirmed precise values of the demand, background leakage flow and burst flow in IFM are subsequently estimated. They are used to identify the burst site at the third stage of the method. The method can be easily adapted for practical use. It requires data from experiments carried out at night between 1am and 5am and involves placing typically about 20 temporary loggers to collect the measurements during this period. It also requires the availability of a hydraulic model which normally is in the possession of a water company. The program has been implemented in the Matlab package and is easy to use. The current methodology is tuned to identify a single burst but can be generalised to identify locations of multiple bursts.

L'intégration sensori motrice (ISM) est le processus par lequel les afférences sensitives sont intégrées par le système nerveux central et utilisées pour assister l'exécution des programmes moteurs. Plusieurs données suggèrent que celle-ci est anormale dans la maladie de Parkinson et serait impliquée dans la pathophysiologie de l'akinésie. En effet, la discrimination cutanée, l'acuité tactile spatiale, la kinesthésie ont été décrites déficientes dans cette maladie. Sa sensibilité aux traitements dopaminergiques est controversée. L'objectif de notre travail a été de tacher de mettre en évidence cette ISM anormale dans la maladie de Parkinson grâce à 2 techniques neurophysiologiques. Il s'agissait pour la 1e de la synchronisation liée à l'évènement des rythmes bêta (SLE bêta) qui permet d'étudier la désactivation corticale à la fin d'un mouvement actif mais aussi l'intégration corticale des afférences somesthésiques notamment lors des mouvements passifs et de la stimulation électrique des nerfs périphériques. La 2nde était l'étude de la modulation de l'excitabilité du cortex moteur primaire (évalué par la stimulation magnétique transcrânienne (TMS)) par des afférences somesthésiques générées par la stimulation électrique du nerf médian. Le but était de mettre en évidence des anomalies dans la modulation de l'excitabilité du cortex moteur primaire dans les intervalles inhibiteurs courts et longs (SAI et LAI) et/ou facilitateur (AIF). L'effet des traitements dopaminergiques a été évalué dans les deux cas par un enregistrement des patients après un sevrage thérapeutique. De nombreux protocoles de stimulation magnétique transcrânienne répétitive du cortex moteur que ce soit à basse ou haute fréquence, ont montré une efficacité sur l'akinésie. Il semblerait que les séances à fréquence plus rapides soient plus efficaces. Nous avons testé une nouvelle technique excitatrice à haute fréquence dite theta burst intermittente (ITBS) en regard du cortex moteur primaire chez des patients parkinsoniens et évalué l'effet sur l'akinésie. Nous avons par ailleurs étudié l'effet de cette stimulation sur l'ISM évaluée en conditionnant la TMS par une stimulation électrique du nerf médian. Notre 1e partie de l'étude a mis en évidence un effondrement de la SLE bêta dans la maladie de Parkinson après un mouvement actif, passif et une stimulation électrique du nerf médian. La levodopa a amélioré seulement la SLE bêta lors du mouvement actif. Nous avons pu ainsi confirmer l'atteinte de la SLE bêta active dans la maladie de Parkinson en lien avec un déficit de désactivation corticale en fin de mouvement mais aussi mettre en évidence une atteinte de la SLE bêta sensitive témoin d'un déficit du traitement cortical des afférences proprioceptives. La SLE bêta active a été améliorée par la levodopa alors que la SLE sensitive n'a pas été modifiée ce qui montre la dopa sensibilité de la désactivation corticale et le caractère non dopa sensible de l'ISM. Notre 2e partie n'a pas mis en évidence de différence significative dans la modulation de l'excitabilité du cortex moteur primaire par la stimulation électrique du nerf médian entre des patients parkinsoniens en début de maladie ni à un stade plus avancé par rapport à des témoins appariés par l'âge. En revanche la prise de levodopa a été associée à une aggravation de la LAI ce qui suggère aussi l'absence d'amélioration de l'ISM dans la maladie de Parkinson voire son aggravation par le traitement dopaminergique. Nous avons par contre montré que la modulation de l'excitabilité du cortex moteur primaire déclinait avec le vieillissement normal pour ce qui concerne les intervalles longs inhibiteurs (LAI) et facilitateurs (AIF) grâce à une comparaison d'une population de sujets contrôles jeunes et âgés sains. La session unique d'ITBS appliquée sur le cortex moteur primaire des patients parkinsoniens a permis d'améliorer transitoirement l'akinésie et la rigidité du membre supérieur controlatéral. Cette amélioration a été mise en évidence surtout chez les patients sous leur traitement habituel par levodopa mais aussi de manière moins nette chez les patients de novo ou ayant été sevré de leur traitement dopaminergique usuel. Nous avons par ailleurs observé une nette amélioration de l'AIF chez les patients sous levodopa uniquement ce qui suggère que l'ITBS du cortex moteur permettrait d'améliorer l'akinésie chez les patients parkinsoniens sous levodopa par une amélioration de l'ISM.

The Radio Ice Cherenkov Experiment(RICE) located at the South Pole, is designed to detect the coherent broad-band radio Cherenkov radiation emitted when a high energy (10¹⁵ to 10¹⁸ eV) neutrino interacts with a nucleon in the ice. Observations have identified that Gamma Ray Bursts(GRBs) are possible sites for high energy neutrino production. We consider here GRBs which occurred in the years 2001 to 2005 inclusive during the operational times of RICE. Using GRB photon spectral data, we calculate the neutrino spectra predicted for these GRBs and the subsequent event number expected in RICE. We re-analyze RICE data in small time windows surrounding the GRB burst start times using a refined method involving by eye analysis of this reduced data set and find no neutrino events in the data set. Using the effective volume of RICE appropriate for each GRB we calculate neutrino flux limits for the GRBs. Although the flux limits are several orders of magnitude weaker than the expected flux, the RICE GRB neutrino limits are the only limits in the PeV to EeV energy range.