Exact and numerical solutions for diffusio-reaction equations with convection term

Esta dissertação estuda essencialmente dois problemas: (A) uma classe de equações unidimensionais de reacção-difusão-convecção em meios não uniformes (dependentes do espaço), e (B) um problema elíptico não-linear e paramétrico ligado a fenómenos de capilaridade. A Análise de Perturbação Singular e a dinâmica de Hamilton-Jacobi são utilizadas na obtenção de expressões assimptóticas para a solução (com comportamento de frente) e para a sua velocidade de propagação. Os seguintes três métodos de decomposição, Adomian Decomposition Method (ADM), Decomposition Method based on Infinite Products (DIP), e New Iterative Method (NIM), são apresentados e brevemente comparados. Adicionalmente, condições suficientes para a convergência da solução em série, obtida pelo ADM, e uma aplicação a um problema da Telecomunicações por Fibras Ópticas, envolvendo EDOs não-lineares designadas equações de Raman, são discutidas. Um ponto de vista mais abrangente que unifica os métodos de decomposição referidos é também apresentado. Para subclasses desta EDP são obtidas soluções numa forma explícita, para diferentes tipos de dados e usando uma variante do método de simetrias de Bluman-Cole. Usando Teoria de Pontos Críticos (o teorema usualmente designado mountain pass) e técnicas de truncatura, prova-se a existência de duas soluções não triviais (uma positiva e uma negativa) para o problema elíptico não-linear e paramétrico (B). A existência de uma terceira solução não trivial é demonstrada usando Grupos Críticos e Teoria de Morse.

Developmental switch in the kinase dependency of long-term potentiation depends on expression of GluA4 subunit-containing AMPA receptors

The AMPA-receptor subunit GluA4 is expressed transiently in CA1 pyramidal neurons at the time synaptic connectivity is forming, but its physiological significance is unknown. Here we show that GluA4 expression is sufficient to alter the signaling requirements of long-term potentiation (LTP) and can fully explain the switch in the LTP kinase dependency from PKA to Ca2(+)/calmodulin-dependent protein kinase II during synapse maturation. At immature synapses, activation of PKA leads to a robust potentiation of AMPA-receptor function via the mobilization of GluA4. Analysis of GluA4-deficient mice indicates that this mechanism is critical for neonatal PKA-dependent LTP. Furthermore, lentiviral expression of GluA4 in CA1 neurons conferred a PKA-dependent synaptic potentiation and LTP regardless of the developmental stage. Thus, GluA4 defines the signaling requirements for LTP and silent synapse activation during a critical period of synapse development.

A short-term risk management tool applied to OMEL electricity market using particle swarm optimization

Short-term risk management is highly dependent on long-term contractual decisions previously established; risk aversion factor of the agent and short-term price forecast accuracy. Trying to give answers to that problem, this paper provides a different approach for short-term risk management on electricity markets. Based on long-term contractual decisions and making use of a price range forecast method developed by the authors, the short-term risk management tool presented here has as main concern to find the optimal spot market strategies that a producer should have for a specific day in function of his risk aversion factor, with the objective to maximize the profits and simultaneously to practice the hedge against price market volatility. Due to the complexity of the optimization problem, the authors make use of Particle Swarm Optimization (PSO) to find the optimal solution. Results from realistic data, namely from OMEL electricity market, are presented and discussed in detail.

Short-term Wind Speed Forecasting using Support Vector Machines

Wind speed forecasting has been becoming an important field of research to support the electricity industry mainly due to the increasing use of distributed energy sources, largely based on renewable sources. This type of electricity generation is highly dependent on the weather conditions variability, particularly the variability of the wind speed. Therefore, accurate wind power forecasting models are required to the operation and planning of wind plants and power systems. A Support Vector Machines (SVM) model for short-term wind speed is proposed and its performance is evaluated and compared with several artificial neural network (ANN) based approaches. A case study based on a real database regarding 3 years for predicting wind speed at 5 minutes intervals is presented.

Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response.

RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). METHODS: Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e., decrease in HAM-D21 total score). The model demonstrated that the interaction of CSF S-CIT concentrations and clinical improvement was the most powerful predictor of AUC cortisol responsiveness. CONCLUSION: The present study shows that decreased AUC cortisol was highly associated with S-CIT concentrations in plasma and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations rather than the R/S-CIT dose should be considered as an indicator of the selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis responsiveness as measured by AUC cortisol response.

Treatment-dependent loss of polyfunctional CD8+ T-cell responses in HIV-infected kidney transplant recipients is associated with herpesvirus reactivation.

Antiretroviral-therapy has dramatically changed the course of HIV infection and HIV-infected (HIV(+)) individuals are becoming more frequently eligible for solid-organ transplantation. However, only scarce data are available on how immunosuppressive (IS) strategies relate to transplantation outcome and immune function. We determined the impact of transplantation and immune-depleting treatment on CD4+ T-cell counts, HIV-, EBV-, and Cytomegalovirus (CMV)-viral loads and virus-specific T-cell immunity in a 1-year prospective cohort of 27 HIV(+) kidney transplant recipients. While the results show an increasing breadth and magnitude of the herpesvirus-specific cytotoxic T-cell (CTL) response over-time, they also revealed a significant depletion of polyfunctional virus-specific CTL in individuals receiving thymoglobulin as a lymphocyte-depleting treatment. The disappearance of polyfunctional CTL was accompanied by virologic EBV-reactivation events, directly linking the absence of specific polyfunctional CTL to viral reactivation. The data provide first insights into the immune-reserve in HIV+ infected transplant recipients and highlight new immunological effects of thymoglobulin treatment. Long-term studies will be needed to assess the clinical risk associated with thymoglobulin treatment, in particular with regards to EBV-associated lymphoproliferative diseases.

Developing a numerical inverse-theory-based extraction of orientation-dependent relaxation rates from partially- relaxed spectra

Second-rank tensor interactions, such as quadrupolar interactions between the spin- 1 deuterium nuclei and the electric field gradients created by chemical bonds, are affected by rapid random molecular motions that modulate the orientation of the molecule with respect to the external magnetic field. In biological and model membrane systems, where a distribution of dynamically averaged anisotropies (quadrupolar splittings, chemical shift anisotropies, etc.) is present and where, in addition, various parts of the sample may undergo a partial magnetic alignment, the numerical analysis of the resulting Nuclear Magnetic Resonance (NMR) spectra is a mathematically ill-posed problem. However, numerical methods (de-Pakeing, Tikhonov regularization) exist that allow for a simultaneous determination of both the anisotropy and orientational distributions. An additional complication arises when relaxation is taken into account. This work presents a method of obtaining the orientation dependence of the relaxation rates that can be used for the analysis of the molecular motions on a broad range of time scales. An arbitrary set of exponential decay rates is described by a three-term truncated Legendre polynomial expansion in the orientation dependence, as appropriate for a second-rank tensor interaction, and a linear approximation to the individual decay rates is made. Thus a severe numerical instability caused by the presence of noise in the experimental data is avoided. At the same time, enough flexibility in the inversion algorithm is retained to achieve a meaningful mapping from raw experimental data to a set of intermediate, model-free

Mechanisms of long-term modulation of synaptic transmission in crayfish

Please consult the paper edition of this thesis to read. It is available on the 5th Floor of the Library at Call Number: Z 9999 B56 M68 2007

The role of retinoic acid in long-term memory formation and synaptic plasticity in the mollusc Lymnaea stagnalis

The active metabolite of vitamin A, retinoic acid (RA), is involved in memory formation and hippocampal plasticity in vertebrates. A similar role for retinoid signaling in learning and memory formation has not previously been examined in an invertebrate species. However, the conservation of retinoid signaling between vertebrates and invertebrates is supported by the presence of retinoid signaling machinery in invertebrates. For example, in the mollusc Lymnaea stagnalis the metabolic enzymes and retinoid receptors have been cloned from the CNS. In this study I demonstrated that impairing retinoid signaling in Lymnaea by either inhibiting RALDH activity or using retinoid receptor antagonists, prevented the formation of long-term memory (LTM). However, learning and intermediate-term memory were not affected. An additional finding was that exposure to constant darkness (due to the light-sensitive nature of RA) itself enhanced memory formation. This memory-promoting effect of darkness was sufficient to overcome the inhibitory effects of RALDH inhibition, but not that of a retinoid receptor antagonist, suggesting that environmental light conditions may influence retinoid signaling. Since RA also influences synaptic plasticity underlying hippocampal-dependent memory formation, I also examined whether RA would act in a trophic manner to influence synapse formation and/or synaptic transmission between invertebrate neurons. However, I found no evidence to support an effect of RA on post-tetanic potentiation of a chemical synapse. Retinoic acid did, however, reduce transmission at electrical synapses in a cell-specific manner. Overall, these studies provide the first evidence for a role of RA in the formation of implicit long-term memories in an invertebrate species and suggest that the role of retinoid signaling in memory formation has an ancient origin.

Some Implications of the Zero Lower Bound on Interest Rates for the Term Structure and Monetary Policy

In an economy where cash can be stored costlessly (in nominal terms), the nominal interest rate is bounded below by zero. This paper derives the implications of this nonnegativity constraint for the term structure and shows that it induces a nonlinear and convex relation between short- and long-term interest rates. As a result, the long-term rate responds asymmetrically to changes in the short-term rate, and by less than predicted by a benchmark linear model. In particular, a decrease in the short-term rate leads to a decrease in the long-term rate that is smaller in magnitude than the increase in the long-term rate associated with an increase in the short-term rate of the same size. Up to the extent that monetary policy acts by affecting long-term rates through the term structure, its power is considerably reduced at low interest rates. The empirical predictions of the model are examined using data from Japan.

Neural substrates and functional connectivity associated with sleep-dependent and independent consolidation of new motor skills

La mémoire n’est pas un processus unitaire et est souvent divisée en deux catégories majeures: la mémoire déclarative (pour les faits) et procédurale (pour les habitudes et habiletés motrices). Pour perdurer, une trace mnésique doit passer par la consolidation, un processus par lequel elle devient plus robuste et moins susceptible à l’interférence. Le sommeil est connu comme jouant un rôle clé pour permettre le processus de consolidation, particulièrement pour la mémoire déclarative. Depuis plusieurs années cependant, son rôle est aussi reconnu pour la mémoire procédurale. Il est par contre intéressant de noter que ce ne sont pas tous les types de mémoire procédurale qui requiert le sommeil afin d’être consolidée. Entre autres, le sommeil semble nécessaire pour consolider un apprentissage de séquences motrices (s’apparentant à l’apprentissage du piano), mais pas un apprentissage d’adaptation visuomotrice (tel qu’apprendre à rouler à bicyclette). Parallèlement, l’apprentissage à long terme de ces deux types d’habiletés semble également sous-tendu par des circuits neuronaux distincts; c’est-à-dire un réseau cortico-striatal et cortico-cérébelleux respectivement. Toutefois, l’implication de ces réseaux dans le processus de consolidation comme tel demeure incertain. Le but de cette thèse est donc de mieux comprendre le rôle du sommeil, en contrôlant pour le simple passage du temps, dans la consolidation de ces deux types d’apprentissage, à l’aide de l’imagerie par résonnance magnétique fonctionnelle et d’analyses de connectivité cérébrale. Nos résultats comportementaux supportent l’idée que seul l’apprentissage séquentiel requiert le sommeil pour déclencher le processus de consolidation. Nous suggérons de plus que le putamen est fortement associé à ce processus. En revanche, les performances d’un apprentissage visuomoteur s’améliorent indépendamment du sommeil et sont de plus corrélées à une plus grande activation du cervelet. Finalement, en explorant l’effet du sommeil sur la connectivité cérébrale, nos résultats démontrent qu’en fait, un système cortico-striatal semble être plus intégré suite à la consolidation. C’est-à-dire que l’interaction au sein des régions du système est plus forte lorsque la consolidation a eu lieu, après une nuit de sommeil. En opposition, le simple passage du temps semble nuire à l’intégration de ce réseau cortico-striatal. En somme, nous avons pu élargir les connaissances quant au rôle du sommeil pour la mémoire procédurale, notamment en démontrant que ce ne sont pas tous les types d’apprentissages qui requièrent le sommeil pour amorcer le processus de consolidation. D’ailleurs, nous avons également démontré que cette dissociation de l’effet du sommeil est également reflétée par l’implication de deux réseaux cérébraux distincts. À savoir, un réseau cortico-striatal et un réseau cortico-cérébelleux pour la consolidation respective de l’apprentissage de séquence et d’adaptation visuomotrice. Enfin, nous suggérons que la consolidation durant le sommeil permet de protéger et favoriser une meilleure cohésion au sein du réseau cortico-striatal associé à notre tâche; un phénomène qui, s’il est retrouvé avec d’autres types d’apprentissage, pourrait être considéré comme un nouveau marqueur de la consolidation.

Relating Dependent Terms in Information Retrieval

Les moteurs de recherche font partie de notre vie quotidienne. Actuellement, plus d’un tiers de la population mondiale utilise l’Internet. Les moteurs de recherche leur permettent de trouver rapidement les informations ou les produits qu'ils veulent. La recherche d'information (IR) est le fondement de moteurs de recherche modernes. Les approches traditionnelles de recherche d'information supposent que les termes d'indexation sont indépendants. Pourtant, les termes qui apparaissent dans le même contexte sont souvent dépendants. L’absence de la prise en compte de ces dépendances est une des causes de l’introduction de bruit dans le résultat (résultat non pertinents). Certaines études ont proposé d’intégrer certains types de dépendance, tels que la proximité, la cooccurrence, la contiguïté et de la dépendance grammaticale. Dans la plupart des cas, les modèles de dépendance sont construits séparément et ensuite combinés avec le modèle traditionnel de mots avec une importance constante. Par conséquent, ils ne peuvent pas capturer correctement la dépendance variable et la force de dépendance. Par exemple, la dépendance entre les mots adjacents "Black Friday" est plus importante que celle entre les mots "road constructions". Dans cette thèse, nous étudions différentes approches pour capturer les relations des termes et de leurs forces de dépendance. Nous avons proposé des méthodes suivantes: ─ Nous réexaminons l'approche de combinaison en utilisant différentes unités d'indexation pour la RI monolingue en chinois et la RI translinguistique entre anglais et chinois. En plus d’utiliser des mots, nous étudions la possibilité d'utiliser bi-gramme et uni-gramme comme unité de traduction pour le chinois. Plusieurs modèles de traduction sont construits pour traduire des mots anglais en uni-grammes, bi-grammes et mots chinois avec un corpus parallèle. Une requête en anglais est ensuite traduite de plusieurs façons, et un score classement est produit avec chaque traduction. Le score final de classement combine tous ces types de traduction. Nous considérons la dépendance entre les termes en utilisant la théorie d’évidence de Dempster-Shafer. Une occurrence d'un fragment de texte (de plusieurs mots) dans un document est considérée comme représentant l'ensemble de tous les termes constituants. La probabilité est assignée à un tel ensemble de termes plutôt qu’a chaque terme individuel. Au moment d’évaluation de requête, cette probabilité est redistribuée aux termes de la requête si ces derniers sont différents. Cette approche nous permet d'intégrer les relations de dépendance entre les termes. Nous proposons un modèle discriminant pour intégrer les différentes types de dépendance selon leur force et leur utilité pour la RI. Notamment, nous considérons la dépendance de contiguïté et de cooccurrence à de différentes distances, c’est-à-dire les bi-grammes et les paires de termes dans une fenêtre de 2, 4, 8 et 16 mots. Le poids d’un bi-gramme ou d’une paire de termes dépendants est déterminé selon un ensemble des caractères, en utilisant la régression SVM. Toutes les méthodes proposées sont évaluées sur plusieurs collections en anglais et/ou chinois, et les résultats expérimentaux montrent que ces méthodes produisent des améliorations substantielles sur l'état de l'art.

Crosstalk with insulin and dependence on PI3K/Akt/mTOR rather than MAPK pathways in upregulation of basal growth following long-term oestrogen deprivation in three human breast cancer cell lines

Background: MCF-7, T-47-D, ZR-75-1 human breast cancer cell lines are dependent on oestrogen for growth but can adapt to grow during long-term oestrogen deprivation. This serves as a model for identification of therapeutic targets in endocrine-resistant breast cancer. Methods: An overlooked complication of this model is that it involves more than non-addition of oestrogen, and inadequate attention has been given to separating molecular events associated with each of the culture manipulations. Results: Insulin and oestradiol were shown to protect MCF-7 cells against upregulation of basal growth, demonstrating a crosstalk in the growth adaptation process. Increased phosphorylation of p44/42MAPK and c-Raf reflected removal of insulin from the medium and proliferation of all three cell lines was inhibited to a lesser extent by PD98059 and U0126 following long-term oestrogen/insulin withdrawal, demonstrating a reduced dependence on the MAPK pathway. By contrast, long-term oestrogen/insulin deprivation did not alter levels of phosphorylated Akt and did not alter the dose-response of growth inhibition with LY294002 in any of the three cell lines. The IGF1R inhibitor picropodophyllin inhibited growth of all MCF-7 cells but only in the long-term oestrogen/insulin-deprived cells was this paralleled by reduction in phosphorylated p70S6K, a downstream target of mTOR. Long-term oestrogen/insulin-deprived MCF-7 cells had higher levels of phosphorylated p70S6K and developed increased sensitivity to growth inhibition by rapamycin. Conclusions: The greater sensitivity to growth inhibition by rapamycin in all three cell lines following long-term oestrogen/insulin deprivation suggests rapamycin-based therapies might be more effective in breast cancers with acquired oestrogen resistance. Keywords Akt, breast cancer cells, endocrine resistance, insulin, MAPK, MCF-7 cells, mTOR, oestrogen, oestrogen-deprived, PI3K, picropodophyllin, rapamycin, T-47-D cells, ZR-75-1 cells

Social networks: evolving graphs with memory dependent edges

The plethora, and mass take up, of digital communication tech- nologies has resulted in a wealth of interest in social network data collection and analysis in recent years. Within many such networks the interactions are transient: thus those networks evolve over time. In this paper we introduce a class of models for such networks using evolving graphs with memory dependent edges, which may appear and disappear according to their recent history. We consider time discrete and time continuous variants of the model. We consider the long term asymptotic behaviour as a function of parameters controlling the memory dependence. In particular we show that such networks may continue evolving forever, or else may quench and become static (containing immortal and/or extinct edges). This depends on the ex- istence or otherwise of certain infinite products and series involving age dependent model parameters. To test these ideas we show how model parameters may be calibrated based on limited samples of time dependent data, and we apply these concepts to three real networks: summary data on mobile phone use from a developing region; online social-business network data from China; and disaggregated mobile phone communications data from a reality mining experiment in the US. In each case we show that there is evidence for memory dependent dynamics, such as that embodied within the class of models proposed here.

The long-term stability of a possible aqueous ammonium sulfate ocean inside Titan

We model the thermal evolution of a subsurface ocean of aqueous ammonium sulfate inside Titan using a parameterized convection scheme. The cooling and crystallization of such an ocean depends on its heat flux balance, and is governed by the pressure-dependent melting temperatures at the top and bottom of the ocean. Using recent observations and previous experimental data, we present a nominal model which predicts the thickness of the ocean throughout the evolution of Titan; after 4.5 Ga we expect an aqueous ammonium sulfate ocean 56 km thick, overlain by a thick (176 km) heterogeneous crust of methane clathrate, ice I and ammonium sulfate. Underplating of the crust by ice I will give rise to compositional diapirs that are capable of rising through the crust and providing a mechanism for cryovolcanism at the surface. We have conducted a parameter space survey to account for possible variations in the nominal model, and find that for a wide range of plausible conditions, an ocean of aqueous ammonium sulfate can survive to the present day, which is consistent with the recent observations of Titan's spin state from Cassini radar data [Lorenz, R.D., Stiles, B.W., Kirk, R.L., Allison, M.D., del Marmo, P.P., Iess, L., Lunine, J.I., Ostro, S.J., Hensley, S., 2008. Science 319, 1649–1651].