Release of nociceptin-like substances from the dorsal horn of rat spinal cords in situ was measured by the immobilized-antibody microprobe technique. Spinal cords removed from anesthetized 4-6 week-old rats were superfused with oxygenated Krebs solution at room temperature (21 ± 1°C). Glass microelectrodes, coated with antibodies to nociceptin, were inserted into the dorsal horn of the lumbar spinal cord (1.9 mm lateral to the midline to a depth 2.5 mm below the surface of the cord) for 15 rain periods before, during and after electrical stimulation applied to the dorsal root entry zone of the same segment. There was a basal release of immunoreactive nociceptin- like substance (irNC) from the dorsal horns during the pre-stimulation period. A significant increase in irNC release was detected during the period of electrical stimulation and this increase was maintained for at least 15 min following the cessation of electrical stimulation. These results provide the first evidence on the release of irNC, albeit non-quantitative, from the in situ rat spinal cord dorsal horn and an enhanced release upon electrical stimulation.

In vitro and in situ experiments were conducted to evaluate the hypothesis that the nonclassical opioid peptide nociceptin acting on sympathetic preganglionic neurons (SPNs) inhibits spinal sympathetic outflow. First, whole cell patch recordings were made from antidromically identified SPNs from immature (12-16 day old) rat spinal cord slices. Nociceptin (0.1, 0.3, and 1 μM) concentration dependently suppressed the excitatory postsynaptic potentials (EPSPs) evoked by focal stimulation and hyperpolarized a population of SPNs; these effects were naloxone insensitive. L-Glutamate-induced depolarizations were not significantly changed by nociceptin. Results from this series of experiments indicate that nociceptin inhibits the activity of SPNs by either a presynaptic or postsynaptic site of action, whereby the peptide reduces, respectively, the amplitude of EPSPs or the excitability of SPNs. Second, intrathecal injection of nociceptin (3, 10, and 30 nmol) to urethan-anesthetized rats dose dependently reduced the mean arterial pressure and heart rate; these effects were not prevented by prior intravenous administration of naloxone (1 mg/kg). Physiological saline given intrathecally was without appreciable effects. These results, together with earlier observations of the detection of nociceptin-immunoreactive nerve fibers and nociceptin receptor immunoreactivity in the rat intermediolateral cell column, raise the possibility that the opioid peptide, which may be released endogenously, reduces spinal sympathetic outflow by depressing the activity of SPNs.

Nociceptin, also referred to as orphanin FQ, is believed to be the endogenous ligand for the ORL1. Nociceptin, when injected intracerebroventricularly to mice, produced hyperalgesia in behavioral tests. Recent studies have demonstrated the presence of ORL1 transcript in the spinal cord, and ORL1-like immunoreactivity has been localized to nerve fibers and somata throughout the spinal cord. Here, we report the localization of nociceptin-like immunoreactivity to fiber-like elements of the superficial layers of the rat dorsal horn by immunohistochemical techniques. Whole-cell recordings from substantia gelatinosa neurons in transverse lumbar spinal cord slices of 22-26-day-old rats showed that exogenous nociceptin at low concentrations (100-300 nM) depressed excitatory postsynaptic potentials evoked by stimulation of dorsal rootlets without causing an appreciable change of resting membrane potentials and glutamate- evoked depolarizations. At a concentration of 1 μM, nociceptin hyperpolarized substantia gelatinosa neurons and suppressed spike discharges. The hyperpolarizing and synaptic depressant action of nociceptin was not reversed by the known opioid receptor antagonist naloxone (1 μM). Our result provides evidence that nociceptin-like peptide is concentrated in nerve fibers of the rat dorsal horn and that it may serve as an inhibitory transmitter within the substantia gelatinosa.

The number of devices and internet traffic for applications connected to the internet increases continuously. Devices provide increasing support for multi-homing and can utilize different access networks for end-to-end communication. The simultaneous use of multiple access networks can increase end-to-end performance by aggregating capacities from multiple disjoint networks by exploiting multipath communication. However, at this current point in time, multipath compatible transport layer protocols or multipath support at lower layers of the network stack have not seen widespread adaptation. Tunneled transport layer access bundling is an approach that allows for all types of single-path resources to exploit multipath communication by tunneling data over a Virtual Private Network (VPN) with transparent entry points on the User Equipment (UE) and on the internet. Commonly, such adaptation utilizes a single queue to buffer incoming packets which pose problems with fair multiplexing between concurrent application flows while being susceptible to bufferbloat. We designed and implemented extensions to Pluganized QUIC (PQUIC) which enables Flow Queuing Controlled Delay (FQ-CoDel) as a queueing discipline in tunneled transport layer access bundling to investigate if it is possible to achieve fair multiplexing between application flows while mitigating bufferbloat at the transport layer. An evaluation in the network emulator, mininet, shows that FQ-CoDel can add mechanisms for an instant, constant, and fair access to the VPN while significantly lowering the end-to-end latency for tunneled application flows. Furthermore, the results indicate that packet schedulers, such as Lowest-RTT-First (LowRTT) that adapt to current network characteristics, upholds the performance over heterogeneous networks while keeping the benefits of FQ-CoDel.

No description available.

Au cours de cette thèse, nous avons étudié des modèles de partitions aléatoires issus de la théorie des représentations des groupes symétriques et des groupes de Chevalley finis classiques, en particulier les groupes GL(n,Fq). Nous avons démontré des résultats de concentration gaussienne pour :- les q-mesures de Plancherel (de type A), qui correspondent à l'action de GL(n,Fq) sur la variété des drapeaux complets de (Fq)^n, et sont liées à la théorie des représentations des algèbres d'Hecke des groupes symétriques.- l'analogue en type B du modèle précédent, correspondant à l'action de Sp(2n,Fq) sur la variété des drapeaux totalement isotropes complets dans (Fq)^2n.- les mesures de Schur-Weyl, qui correspondent aux actions commutantes de GL(N,C) et Sn sur l'espace des n-tenseurs d'un espace vectoriel de dimension N.- et les mesures de Gelfand, qui correspondent à la représentation du groupe symétrique qui est la somme directe sans multiplicité de toutes les représentations irréductibles de Sn.Dans chaque cas, nous avons établi une loi des grands nombres et un théorème central limite tout à fait semblable à la loi des grands nombres de Logan-Shepp-Kerov-Vershik (1977) et au théorème central limite de Kerov (1993) pour les mesures de Plancherel des groupes symétriques.Nos résultats peuvent presque tous être traduits en termes de combinatoire des mots, et d'autre part, les techniques employées sont inspirées des techniques de la théorie des matrices aléatoires. Ainsi, on a calculé pour chaque modèle l'espérance de fonctions polynomiales sur les partitions, qui jouent un rôle tout à fait analogue aux polynômes traciaux en théorie des matrices aléatoires. L'outil principal des preuves est ainsi une algèbre d'observables de diagrammes de Young, qu'on peut aussi interpréter comme algèbre de permutations partielles. Nous avons tenté de généraliser cette construction au cas d'autres groupes et algèbres, et nous avons construit une telle généralisation dans le cas des algèbres d'Hecke des groupes symétriques. Ces constructions rentrent dans le cadre très abstrait des fibrés de semi-groupes par des semi-treillis ; dans le même contexte, on peut formaliser des problèmes combinatoires sur les permutations, par exemple le problème du calcul des nombres de Hurwitz / During this thesis, we have studied models of random partitions stemming from the representation theory of the symmetric groups and the classical finite Chevalley groups, in particular the groups GL(n,Fq). We have shown results of gaussian concentration in the case of:- q-Plancherel measures (of type A), that correspond to the action of GL(n,Fq) on the variety of complete flags of (Fq)^n, and are related to the representation theory of the Hecke algebras of the symmetric groups.- the analogue in type B of the aforementioned model, that corresponds to the action of Sp(2n,Fq) on the variety of complete totally isotropic flags in (Fq)^2n.- Schur-Weyl measures, that correspond to the two commuting actions of GL(N,C) and Sn on the space of n-tensors of a vector space of dimension N.- Gelfand measures, that correspond to the representation of the symmetric group which is the multiplicity-free direct sum of all irreducible representations of Sn.In each case, we have established a law of large numbers and a central limit theorem similar to the law of large numbers of Logan-Shepp-Kerov-Vershik (1977) and to Kerov's central limit theorem (1993) for the Plancherel measures of the symmetric groups. Almost all our results can be restated in terms of combinatorics of words, and besides, the tools of the proofs are inspired by the usual techniques of random matrix theory. Hence, we have computed for each model the expectation of polynomial functions on partitions, that play a role similar to the tracial polynomials in random matrix theory. The principal tool of the proofs is therefore an algebra of observables of diagrams, that can also be interpreted as an algebra of partial permutations. We have tried to generalize this construction to the case of other groups and algebras, and we have constructed such a generalization in the case of the Hecke algebras of the symmetric groups. These constructions belong to the abstract setting of semilattice bundles over semigroups; in the same setting, one can formalize combinatorial problems on permutations, for instance the problem of computing the Hurwitz numbers

No description available.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2015-12-14T22:12:12Z No. of bitstreams: 1 DiegoAlexandreDaCunhaFernandes_DISSERT.pdf: 2456718 bytes, checksum: 24278166db119fb91c70503ebcefc8dd (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2015-12-18T21:13:23Z (GMT) No. of bitstreams: 1 DiegoAlexandreDaCunhaFernandes_DISSERT.pdf: 2456718 bytes, checksum: 24278166db119fb91c70503ebcefc8dd (MD5) / Made available in DSpace on 2015-12-18T21:13:23Z (GMT). No. of bitstreams: 1 DiegoAlexandreDaCunhaFernandes_DISSERT.pdf: 2456718 bytes, checksum: 24278166db119fb91c70503ebcefc8dd (MD5) Previous issue date: 2014-09-22 / O transtorno bipolar ? uma psicopatologia cr?nica que atinge de 1 ? 4% da popula??o mundial. Esse transtorno do humor ? caracterizado por altera??es c?clicas do humor, nas quais o indiv?duo alterna entre os estados de depress?o e mania. A mania ? descrita na literatura, como um estado de exacerba??o anormal do humor, em que o sujeito apresenta um comportamento expansivo, euf?rico, por?m com aumento da irritabilidade, intensa agita??o psicomotora e um sentimento de invencibilidade inconsequente, que contribui para a exposi??o ? comportamentos de risco. O tratamento dessa psicopatologia ? complexo e n?o apresenta efic?cia em todos os casos, al?m de possuir muitos efeitos colaterais. Nesse aspecto, o sistema da Nociceptina/Orfanina FQ (N/OFQ) pode ser estudado como um poss?vel alvo terap?utico para o tratamento do transtorno bipolar, devido ao seu papel modulat?rio sobre os sistemas monoamin?rgicos e sua participa??o na modula??o do humor. Este trabalho visa investigar o efeito de ligantes do receptor NOP em um modelo animal de mania induzida por metilfenidato. Para isso foi avaliada a atividade motora espont?nea, em um campo aberto, de camundongos tratados com metilfenidato (10 mg/kg, sc, 15 min). O valproato de s?dio (300 mg/kg, ip, 30 min), f?rmaco utilizado no tratamento cl?nico da mania, foi capaz de prevenir a hiperlocomo??o causada pelo metilfenidato. O tratamento agudo com o antagonista do receptor NOP, UFP-101 (1-10 nmol, icv, 5 min), n?o afetou per se a locomo??o espont?nea dos camundongos, mas foi capaz de atenuar a hiperlocomo??o induzida por metilfenidato. Por sua vez, o tratamento agudo com N/OFQ (0,1 e 1 nmol, icv, 5 min) n?o alterou significativamente a dist?ncia percorrida, mas quando testada na dose de 1 ?mol, a N/OFQ foi capaz de reverter discretamente os efeitos hiperlocomotores promovidos pelo metilfenidato. Em conclus?o, tanto a administra??o de N/OFQ quanto de UFP produzem a??es do tipo antiman?acas. Al?m disso, estes dados sugerem que o sistema da N/OFQ efetua uma modula??o complexa sobre o movimento volunt?rio e, consequentemente, sobre a neurotransmiss?o dopamin?rgica. / Bipolar disorder is a chronic psychopathology that reaches from 1 to 4% of the world population. This mood disorder is characterized by cyclical mood changes, in which an individual alternates between states of depression and mania. Mania is described in the literature as an abnormal state of exacerbation of humor, in which the subject presents an expansive, euphoric behavior, but with increased irritability, psychomotor agitation and a feeling of invincibility, which will contribute to risks exposure. The treatment of this psychopathology is complex and it is not effective in all cases, and it evokes many side effects. In this respect, the system of Nociceptin/Orphanin FQ (N/OFQ) can be studied as a possible therapeutic target for the treatment of bipolar disorder, due to its modulatory role on monoaminergic systems and on mood. This study aims to investigate the effect of NOP receptor ligands in an animal model of mania induced by methylphenidate. To this aim, locomotor activity was assessed in an open field, in mice treated with methylphenidate (10 mg/kg, sc, 15 min). Valproate (300 mg / kg, ip, 30 min), standard treatment of mania, prevented methylphenidate-induced hyperlocomotion. The acute treatment with the antagonist of NOP receptor UFP-101 (1-10 nmol, icv, 5 min) per se did not affect the spontaneous locomotion of mice, but it was able of attenuating hyperlocomotion induced by methylphenidate. The acute treatment with N/OFQ (1 and 0.1 nmol, icv, 5 min) did not alter the distance moved, but when tested at a dose of 1 ?mol, N/OFQ slightly reduced methylphenidate-induced hiperlocomotion. In conclusion, the administration of UFP-101 and N/OFQ produced antimanic-like actions. Furthermore, these data suggest that the system of N/OFQ performs a complex modulation of voluntary movement, and consequently on dopaminergic neurotransmission.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-22T22:44:30Z No. of bitstreams: 1 LisianeDeSantanaSouza_DISSERT.pdf: 745201 bytes, checksum: 806e3c4a0c61a452eb082563d4b09ac0 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-02-25T22:35:00Z (GMT) No. of bitstreams: 1 LisianeDeSantanaSouza_DISSERT.pdf: 745201 bytes, checksum: 806e3c4a0c61a452eb082563d4b09ac0 (MD5) / Made available in DSpace on 2016-02-25T22:35:00Z (GMT). No. of bitstreams: 1 LisianeDeSantanaSouza_DISSERT.pdf: 745201 bytes, checksum: 806e3c4a0c61a452eb082563d4b09ac0 (MD5) Previous issue date: 2015-03-13 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / O transtorno bipolar ? caracterizado pela disfun??o do humor, alternando entre epis?dios de mania/hipomania e depress?o, e sua fisiopatologia exata ainda continua indeterminada. A farmacoterapia do transtorno bipolar baseia-se na preven??o dos epis?dios de mania e depress?o atrav?s do uso de estabilizadores do humor. A nociceptina/orfanina FQ (N/OFQ) ? um heptadecapept?deo end?geno e agonista do receptor NOP, um receptor acoplado ? prote?na G do tipo inibit?ria. A N/OFQ e seu receptor desempenham uma s?rie de pap?is funcionais no organismo, e, entre eles, est? a modula??o de processos emocionais. Sabe-se que h? altera??o na concentra??o plasm?tica de N/OFQ em pacientes na fase depressiva e man?aca do transtorno bipolar e, por isso, presume-se que esse sistema teria algum papel na etiologia deste transtorno. Com rela??o ? mania, os modelos animais utilizados na pesquisa tendem a focar em apenas um aspecto do quadro man?aco, como a hiperatividade ou agressividade. Nos anos 60, foi proposto o teste do hole board, aparato provido de furos onde prioritariamente se mede nos animais um comportamento conhecido como ?imers?o de cabe?a? (head-dipping). Altos n?veis de head-dippings podem ser indicativos de neofilia, enquanto baixos n?veis poderiam ser reflexo de um comportamento do tipo ansioso. Como o aumento do comportamento explorat?rio e direcionado a objetivos s?o sintomas caracter?sticos dos quadros man?acos, este teste poderia oferecer subs?dios para a pesquisa deste transtorno. Deste modo, o presente trabalho foi dividido em 3 etapas e visa apresentar (1) a indu??o de um estado similar ao de mania promovido pela administra??o de ouaba?na, um inibidor da enzima Na+ /K+ -ATPase, em camundongos no campo aberto; (2) a padroniza??o do hole board como um teste para mensura??o de comportamentos do tipo man?acos; e (3) a investiga??o do efeito da N/OFQ na preven??o destes comportamentos no hole board. Para o desenvolvimento deste estudo, foram usados camundongos Swiss machos que participaram de apenas uma das etapas descritas acima e receberam um ou mais dos seguintes tratamentos, de acordo com a etapa: (1) ouaba?na, nas doses de 10-6 , 10-5 , 10-4 , 10-3 ou 10-2 M, intracerebroventricular (icv); (2) valproato de s?dio 300 mg/kg, intraperitoneal (ip); (3) valproato de s?dio 400 mg/kg, ip; (4) diazepam 1 mg/kg, ip; (5) metilfenidato 10 mg/kg, ip; e (6) N/OFQ nas doses de 0,1 ou 1 nmol, icv. Os resultados sugerem que o hole board ? um teste que pode ser usado para a avalia??o de quadros man?acos, atrav?s da an?lise de v?rios comportamentos do animal. Entretanto, n?o foi poss?vel padronizar o modelo da disfun??o da enzima Na+ /K+ -ATPase induzido pela administra??o de ouaba?na usando camundongos como sujeitos experimentais. Ainda, os dados sugerem que a N/OFQ, nas doses testadas, n?o ? eficaz na preven??o de um quadro de mania. Tomados em conjunto, os resultados apontam para uma nova abordagem na pesquisa da mania, atrav?s do uso do hole board. Entretanto, mais estudos precisam ser feitos a fim de comprovar o envolvimento do sistema da nociceptina/orfanina FQ na ocorr?ncia do transtorno bipolar. / Bipolar disorder is characterized by mood impairment, alternating between mania/hypomania and depression, and its exact pathophysiology is already unknown. The treatment of bipolar disorder is based on prevention of the manic and depressive episodes using mood stabilizers. Nociceptin/orfanin FQ (N/OFQ) is an endogenous heptadecapeptide which binds as an agonist to NOP receptor, which is a G-coupled inhibitory receptor. N/OFQ and its receptor modulate a lot of functions in the organism, including emotional processes. It is known that the plasmatic concentration of N/OFQ is altered in patients in both phases depressive and manic of bipolar disorder and it is assumed that this system has a role on the etiology of this disorder. Concerning mania, the animal models used in research tend to focus in an unique aspect of the manic behavior, as hyperactivity or agressivity. In the 60?s, the hole board test was proposed, and it consists of an apparatus with holes where a behavior known as head-dippings is measured. High levels of head-dippings are suggestive of neophilia, while low levels can be characteristic of an anxious-like behavior. As the increase of exploratory and goal-directed behavior are characteristics of manic behavior, this test could help in mania research. Thus, this work was organized in 3 steps and aims to: (1) investigate the induction of a manic-like state promoted by ouabain, a Na+/K+-ATPase inhibitor, in the mouse open field test; (2) set up the hole board as a test to measure manic-like behaviors; and (3) investigate the N/OFQ effects in prevention of this kind of behavior on hole board. Male Swiss mice were used in this study, and they take part of only one of the described steps. Depending on the step performed, mice received one or more of the following treatments: (1) ouabain 10-6 , 10-5 , 10-4 , 10-3 or 10-2 M, intracerebroventricular (icv); (2) sodium valproate 300 mg/kg, intraperitoneal (ip); (3) sodium valproate 400 mg/kg, ip; (4) diazepam 1 mg/kg, ip; (5) methylphenidate 10 mg/kg, ip; and (6) N/OFQ 0,1 or 1 nmol, icv. The results suggest that hole board can be used to evaluate a manic state, through analysis of different animal behaviors. However, it was not possible to standard the model of Na+ /K+ -ATPase dysfunction through ouabain administration in mice. Moreover, the data suggest that N/OFQ, at the doses tested, has not affected the methylphenidate-induced mania-like behavior. Taken together, the results point to a new approach of manic research, through the hole board using. However, more studies are necessary in order to verify the role of N/OFQ system on bipolar disorder.

1. Whole-cell patch recordings were made from antidromically identified sympathetic preganglionic neurons (SPN) of immature rat spinal cord slices. Bath application of nociceptin (0.1-1 μmol/L) suppressed excitatory postsynaptic potentials (EPSP) and hyperpolarized a population of SPN; these effects were naloxone (1 μmol/L) insensitive. 2. Nociceptin suppressed the amplitude of EPSP without causing a concomitant change in glutamate-induced depolarizations, suggesting a presynaptic inhibitory action. 3. Analysis of current-voltage relationships showed that nociceptin hyperpolarized SPN by increasing an inwardly rectifying K+ current. 4. Intrathecal injection of nociceptin (3, 10 and 30 nmol) to urethane-anaesthetized rats dose-dependently reduced the mean arterial pressure and heart rate; these effects were not prevented by prior intravenous injection of naloxone (1 mg/kg). 5. Results from our in vitro and in vivo experiments suggest that nociceptin suppresses spinal sympathetic outflow either by attenuating excitatory synaptic responses or hyperpolarizing SPN.