Understanding groundwater flow systems and how these control transport is an essential part in assessing the suitability of subsurface environments as hosts for storage of toxic waste. Therefore it is important to be able to integrate knowledge obtained from field characterisation of the subsurface with methods which can be used to evaluate and predict possible impact on surrounding environments.In this thesis I investigate the characteristics of flow and transport in discrete fracture networks by analysing Eulerian and Lagrangian descriptions within a stochastic framework. The analysis is conducted through numerical flow and transport simulations configured according to available field data, combined with independent theoretical analytic and semi-analytic methods which are able to reveal insight to relevant constitutive properties. It is shown that numerical simulations conducted with the discrete fracture network approach can be both conditioned and confirmed against field measurable quantities, and the developed theoretical methods are evaluated against results obtained from simulation. Thereby, a methodology which can provide links between field measurable quantities and tracer discharge is presented, developed and evaluated. It is shown to be robust with respect to underlying assumptions used for flow configurations.In particular, a specific sampling algorithm for obtaining a Lagrangian description of transport based on a Eulerian description of flow is proposed, evaluated and shown to be robust for the cases considered, providing accurate replications. Also a generalisation of both the advection-dispersion solution and the one-sided stable distribution is shown to be able to evaluate advective transport quantities, and combined with a Lagrangian retention model it is shown to be a fairly accurate and robust method for upscaling distributions, enabling predictions of transport in terms of tracer discharge. Evaluation of transport is also conducted against the advective-dispersion assumption, where results indicate advective transport is generally non-Fickian for the fracture networks and domain scales considered, but not necessarily anomalous. Additionally, the impact certain model assumptions have on tracer discharge are analysed. For example, transport is evaluated for assumptions regarding injection mode, fracture network heterogeneity, relationship between aperture and transmissivity, relationship between transmissivity and size, as well as scale and modelling dimension. In relation to hydraulic testing and flow analysis, a method for conditioning fracture transmissivity from field measurements of flow by simulation is developed and evaluated against homogenisation assumptions commonly used in field applications. Results indicate the homogenisation assumption generally fails for current interpretations of field data. / Miljökonsekvensbedömningar av toxiskt avfall i djupt bergförvar kräver engrundläggande förståelse av grundvattenströmning samt hur detta påverkartransportfenomet. Därför är det viktigt att kunna integrerafältundersökningsdata från berggrundsmätningar med metoder som kan användas föratt utvärdera och förutsäga potentiella konsekvenser på omgivningen.I denna avhandling undersöker jag flödes- och transportegenskaper i diskretaspricknätverk genom stokastisk analys av eulerska och lagrangeskafältbeskrivningar. Analysen sker genom en kombination av dels numeriska flödes-och transportsimuleringar som är konfigurerade enligt tillgänglig fältdata, samtdels med oberoende teoretiska analytiska och semi-analytiska metoder som gerdjupare insyn i relevanta konstitutiva egenskaper. Resultat visar att dennumeriska simuleringsmetoden för diskreta spricknätverk kan både konditionerastill fältdata och bestyrkas gentemot mätbara kvantiter. Detta är av betydelse dåde teoretiska metoderna i sin tur är främst evaluerade gentemotsimuleringsresultat. Därmed utvecklas en bestyrkt metodik som kansammanlänka och i viss mån omvandla fältdata till uppskattningar av mängdenspårämnen i ett utflöde. Resultat indikerar att denna metodik är robust avseendeflera antaganden som har används i simuleringskonfigurationen.En särskild urvalsalgoritm introduceras som kan erhålla en lagrangesktransportbeskrivning utifrån ett eulerskt strömningsfält. även denna utvärderasavseende vissa simuleringsantaganden och resultat tyder på att den är robust förde undersökta fallen. Vidare föreslås en viss generalisering av lösningen tillden advektiva-dispersionsekvationen samt av ensidigt stabila (one-sided stable)sannolikhetsfördelningar som metod för att prediktera advektiva kvantitetergenom upskalning av transportfördelningar i rummet. Denna modell kombineras meden tidigare utvecklad metod för transportretention för att uppskatta reaktivagenombrottsfördelningar. Således blir det möjligt att prediktera reaktivtransport d v s rumslig upskalning av genombrottstider för spårämnestransport.Metoden används också för att evaluera ett linärt dispersionsantagande, därresultat indikerar att även advektiv transport kan påvisa icke-linärt beteende.Transport i spricknätverk utvärderas bland annat för modellantaganden avseendeinjektionsmetod, heterogenitet i spricknätverk, konstitutiva relationer mellanapertur och transmissivitet samt mellan transmissivitet och spricklängd, ochmodelleringsskala samt dimension. Beträffande hydrauliska testmetoder ochflödesanalys introduceras en simuleringsmetod för att konditioneraspricktransmissivitet från flödesmätningar. Detta jämförs med etthomogeniseringsantaganden som inte sällan används i fältundersökningar för atttolka flödesmätningar till spricktransmissivitet, och resultat tyder på attdetta antagande kan betydligt undervärdera transmissivitet.

One of the most unforgiving processes in nature is that of Muller's ratchet, a seemingly irreversible accumulation of deleterious mutations that all organisms have to deal with or face extinction. The most obvious way to avoid fitness collapse is recombination, though asexual populations usually do not have the luxury of recombining freely.  With the aid of computational and mathematical models, we have studied other situations where this threat is averted and the organism can survive the ratchet. The results show that a ratchet where all mutations have the same deleterious fitness effect is very effectively stalled for large effects. However, if mutations are allowed to have a broad range of effects, the fitness-loss rate can be substantial even with the same mean effect as the one-type ratchet, but we have  identified parameter regions where even the broad-range effects are effectively stopped. The fitness-loss from a ratchet is very sensitive to the mutation rate and a mutation that increases the mutation rate (mutator) can easily start an otherwise stalled ratchet. Large effect mutators are heavily counter-selected, but smaller mutators can spread in the population. They can be stopped by reversals (antimutators), but even if the mutation rate is equilibrated in this way, there will be large fluctuations in mutation rate and even larger in the fitness-loss rate due to the feedback amplification in their coupling.    Another way of preventing the ratchet is by reversal of the deleterious mutations themselves through back-mutations or compensatory mutations. The rate required to stop the ratchet using only back-mutations before the fitness collapses is very large. A detailed comparison between the deleterious mutations in the ratchet and in a sexual population was made and the difference was found to be greatest for large populations with large genomes. There are obviously many ways to survive the ratchet, but even more ways to drive a species to extinction by enhancing and speeding up the ratchet. By modelling and testing the ratchet for numerous different situations, we show the effects of some of these threats and benefits.

L'étude de la dynamique des réseaux de réactions est un enjeu majeur de la biologie des systèmes. Cela peut-être réalisé de deux manières : soit de manière déterministe à l'aide d'équations différentielles, soit de manière probabiliste à l'aide de chaînes de Markov. Dans les deux cas, un problème majeur est celui de la détermination des lois cinétiques impliquées et l'inférence de paramètres cinétiques associés. Pour cette raison, l'étude directe de grands réseaux de réactions est impossible. Dans le cas de la modélisation déterministe, ce problème peut-être contourné à l'aide d'une analyse stationnaire du réseau. Une méthode connue est celle de l'analyse des flux à l'équilibre (FBA) qui permet d'obtenir des systèmes de contraintes à partir d'informations sur les pentes moyennes des trajectoires. Le but de cette thèse est d'introduire une méthode analogue dans le cas de la modélisation probabiliste. Les résultats de la thèse se divisent en trois parties. Tout d'abord on présente une analyse stationnaire de la modélisation probabiliste reposant sur une approximation de Bernoulli. Dans un deuxième temps, cette dynamique approximée nous permet d'établir des systèmes de contraintes à l'aide d'informations obtenues sur les moyennes, les variances et les co-variances des trajectoires du système. Enfin, on présente plusieurs applications à ces systèmes de contraintes telles que la possibilité de réfuter des réseaux de réactions à l'aide d'informations de variances ou de co-variances et la vérification formelle de propriétés logiques sur le régime stationnaire du système. / A major goal in systems biology is to inverstigate the dynamical behavior of reaction networks. There exists two main dynamical frameworks : the first one is the deterministic dynamics where the dynamics is described using odinary differential equations, the second one is probabilistic and relies on Markov chains. In both cases, one major issue is to determine the kinetic laws of the systems together with its kinetic parameters. As a consequence the direct study of large biological reaction networks is impossible. To deal with this issue, stationnary assumptions have been used. A widely used method is flux balance analysis, where systems of constraints are derived from information on the average slopes of the system trajectories. In this thesis, we construct a probabilistic analog of this stationnary analysis. The results are divided into three parts. First, we introduce a stationnary analysis of the probabilistic dynamics which relies on a Bernoulli approximation. Second, this approximated dynamics allows us to derive systems of constraints from information about the means, variances and co-variances of the system trajectories. Third, we present several applications of these systems of constraints such as the possibility to reject reaction networks using information from experimental variances and co-variances and the formal verification of logical properties concerning the stationnary regime of the system.

La production d'énergie renouvelable et la consommation d'électricité dépendent largement des conditions météorologiques : température, précipitations, vent, rayonnement solaire... Ainsi, pour réaliser des études d'impact sur l'équilibre offre-demande, on peut utiliser un générateur de temps, c'est-à-dire un modèle permettant de simuler rapidement de longues séries de variables météorologiques réalistes, au pas de temps journalier. L'une des approches possibles pour atteindre cet objectif utilise les modèles de Markov caché : l'évolution des variables à modéliser est supposée dépendre d'une variable latente que l'on peut interpréter comme un type de temps. En adoptant cette approche, nous proposons dans cette thèse un modèle permettant de simuler simultanément la température, la vitesse du vent et les précipitations, en tenant compte des non-stationnarités qui caractérisent les variables météorologiques. D'autre part, nous nous intéressons à certaines propriétés théoriques des modèles de Markov caché cyclo-stationnaires : nous donnons des conditions simples pour assurer leur identifiabilité et la consistance forte de l'estimateur du maximum de vraisemblance. On montre aussi cette propriété de l'EMV pour des modèles de Markov caché incluant des tendances de long terme sous forme polynomiale. / Renewable energy production and electricity consumption both depend heavily on weather: temperature, precipitations, wind, solar radiation... Thus, making impact studies on the supply/demand equilibrium may require a weather generator, that is a model capable of quickly simulating long, realistic times series of weather variables, at the daily time step. To this aim, one of the possible approaches is using hidden Markov models : we assume that the evolution of the weather variables are governed by a latent variable that can be interpreted as a weather type. Using this approach, we propose a model able to simulate simultaneously temperature, wind speed and precipitations, accounting for the specific non-stationarities of weather variables. Besides, we study some theoretical properties of cyclo-stationary hidden Markov models : we provide simple conditions of identifiability and we show the strong consistency of the maximum likelihood estimator. We also show this property of the MLE for hidden Markov models including long-term polynomial trends.

<p>As energy costs and energy used by server farms increase, so does the desire to implement energy-aware policies. Although under some cost functions, optimal policies for single as well as multiple server systems are known, large gaps in theoretical knowledge are present in the field. Specifically, there exists many widely used and non-trivial cost functions, where the corresponding optimal policy remains unknown. This work presents and leverages a model which allows for the exact analysis of these optimal policies with considerable generality, for on/off single server systems under a broad range of cost functions that are based on expected response time, energy usage and switching costs. Furthermore, from the results derived in the analysis, several applications and implications are presented and discussed. This includes the determination of routing probabilities to show a range of non-trivial optimal routing probabilities and server configurations when energy concerns are a factor.</p> / Master of Applied Science (MASc)

L’amélioration continue de la performance énergétique des bâtiments a été accompagnée par un développement d’outils numériques de plus en plus performants et précis. Alors que la prise en compte des phénomènes liés aux bâtiments, aux systèmes et à la météorologie est bien maîtrisée, le comportement des occupants est modélisé de manière très simplifiée par des scénarii répétitifs et des lois déterministes. L’impact des occupants sur les consommations énergétiques dans les bâtiments performants est pourtant majeur, comme en témoigne les écarts récurrents entre les résultats prédits et mesurés. Le travail de thèse propose, par l’intermédiaire d’une plateforme multi-agents et de modèles stochastiques, une mise à jour de la prise en compte de la présence des occupants et de leurs comportements sur la gestion des ouvrants, des dispositifs d’occultation, de l’éclairage et de la température de consigne de chauffage. Le champ d’application de la plateforme concerne les bâtiments de bureaux et de logements, pour des opérations neuves et de rénovation. Les modèles de comportement des occupants sont idéalement issus de campagnes de mesures in situ, d’études de laboratoire ou d’enquêtes sociologiques. La plateforme proposée est alors co-simulée avec le logiciel EnergyPlus, afin d’étudier l’influence des modèles sur les performances énergétiques. Dans la perspective de garantie de performance énergétique, ce travail contribue à la mise à jour et à la fiabilisation des outils de prédiction. / Continuous improvement of the building energy performance is associated with the development of increasingly efficient and accurate numerical tools. While the consideration of phenomena related to buildings, systems and weather is well mastered, occupants’ behaviours are modelled in a very simplified way by repetitive scenarios and deterministic laws. The impact of occupants on energy consumption in high-performance buildings is dominant, as evidenced by the recurring gaps between predicted and measured results. The thesis demonstrates, via a multi-agent platform and stochastic models, an update on the ability to model occupants’ presence, their behaviours on windows, occultation devices, artificial lighting and heating setpoint temperatures. The application of the platform applies to office and residential buildings, for new builds and refurbishments. Occupants’ behaviour models are ideally obtained from in situ surveys, laboratory studies or sociological works. The suggested platform is then co-simulated with the EnergyPlus software, to study the influence of the models on a buildings energy performance. In the perspective of energy performance guarantees, this work contributes to the updating and reliability of prediction tools.

[pt] Prospecção de petróleo usa um equipamento chamado coluna de perfuração para escavar o solo até o nível do reservatório. Este equipamento é uma longa coluna, sob rotação, composto por uma sequência de tubos de perfura ção e equipamentos auxiliares conectados. A dinâmica desta coluna é muito complexa, porque sob condições normais de operação, ela está sujeita à vibrações longitudinais, laterais e torcionais, que apresentam um acoplamento não-linear. Além disso, a estrutura está submetida a efeitos de atrito e choque devido a contatos mecânicos entre os pares broca/rocha e tubos de perfuração/parede do poço. Este trabalho apresenta um modelo mecânico-matemático para analisar uma coluna de perfuração em configuração horizontal. Este modelo usa uma teoria de viga com inércia de rotação, deformação cisalhante e acoplamento não-linear entre os três mecanismos de vibração. As equações do modelo são discretizadas utilizando o método dos elementos finitos. As incertezas dos parâmetros do modelo de interação broca-rocha são levandas em conta através de uma abordagem probabilística paramétrica, e as distribuições de probabilidades dos parâmetros aleatórios são construídas por meio do princípio da entropia máxima. Simulações numéricas são conduzidas de forma a caracterizar o comportamento dinâmico não-linear da estrutura, especialmente, da broca. Fenômenos dinâmicos inerentemente não-lineares, como stick-slip e bit-bounce, são observados nas simulações, bem como choques. Uma análise espectral mostra que, surpreendentemente, os fenômenos de stick-slip e bit-bounce são resultado do mecanismo de vibração lateral, e que os fenômenos de choque decorrem da vibração torcional. Visando aumentar a eficiência do processo de perfuração, um problema de otimização que tem como objetivo maximizar a taxa de penetração da coluna no solo, respeitando os seus limites estruturais, é proposto e resolvido. / [en] Oil prospecting uses an equipment called drillstring to drill the soil until the reservoir level. This equipment is a long column under rotation, composed by a sequence of connected drill-pipes and auxiliary equipment. The dynamics of this column is very complex because, under normal operational conditions, it is subjected to longitudinal, lateral, and torsional vibrations, which presents a nonlinear coupling. Also, this structure is subjected to friction and shocks effects due to the mechanical contacts between the pairs drill-bit/soil and drill-pipes/borehole. This work presents a mechanical-mathematical model to analyze a drillstring in horizontal configuration. This model uses a beam theory which accounts rotatory inertia, shear deformation, and the nonlinear coupling between three mechanisms of vibration. The model equations are discretized using the finite element method. The uncertainties in bit-rock interaction model parameters are taken into account through a parametric probabilistic approach, and the random parameters probability distributions are constructed by means of maximum entropy principle. Numerical simulations are conducted in order to characterize the nonlinear dynamic behavior of the structure, specially, the drill-bit. Dynamical phenomena inherently nonlinear, such as slick-slip and bit-bounce, are observed in the simulations, as well as shocks. A spectral analysis shows, surprisingly, that slick-slip and bit-bounce phenomena result from the lateral vibration mechanism, and that shock phenomena comes from the torsional vibration. Seeking to increase the efficiency of the drilling process, an optimization problem that aims to maximize the rate of penetration of the column into the soil, respecting its structural limits, is proposed and solved. / [fr] La prospection de pétrole utilise un équipement appelé tube de forage pour forer le sol jusqu au niveau du réservoir. Cet équipement est une longue colonne rotative, composée d une série de tiges de forage interconnectées et d équipements auxiliaires. La dynamique de cette colonne est très complexe car dans des conditions opérationnelles normales, elle est soumise à des vibrations longitudinales, latérales et de torsion, qui présentent un couplage non linéaire. En outre, cette structure est soumise à des effets de frottement et à des chocs dûs aux contacts mécaniques entre les paires tête de forage/sol et tube de forage/sol. Ce travail présente un modèle mécaniquemathématique pour analyser un tube de forage en configuration horizontale. Ce modèle utilise la théorie des poutres qui utilise l inertie de rotation, la déformation de cisaillement et le couplage non linéaire entre les trois mécanismes de vibration. Les équations du modèle sont discrétisées par la méthode des éléments finis. Les incertitudes des paramètres du modèle d interaction tête de forage/sol sont prises en compte par l approche probabiliste paramétrique, et les distributions de probabilité des paramètres aléatoires sont construites par le principe du maximum d entropie. Des simulations numériques sont réalisées afin de caractériser le comportement dynamique non lináaire de la structure, et en particulier, de l outil de forage. Des phénom ènes dynamiques non linéaires par nature, comme le slick-slip et le bit- bounce, sont observés dans les simulations, ainsi que les chocs. Une analyse spectrale montre étonnamment que les phénomènes slick-slip et bit-bounce résultent du mécanisme de vibration latérale, et ce phénomène de choc vient de la vibration de torsion. Cherchant à améliorer l efficacité de l opération de forage, un problème d optimisation, qui cherche à maximiser la vitesse de pénétration de la colonne dans le sol, sur ses limites structurelles, est proposé et résolu.

Cette thèse explore l’utilisation des réseaux Bayésiens (RB) afin de répondre à des problématiques de dégradation en grandes dimensions concernant des infrastructures du génie civil. Alors que les approches traditionnelles basées l’évolution physique déterministe de détérioration sont déficientes pour des problèmes à grande échelle, les gestionnaires d’ouvrages ont développé une connaissance de modèles nécessitant la gestion de l’incertain. L’utilisation de la dépendance probabiliste se révèle être une approche adéquate dans ce contexte tandis que la possibilité de modéliser l’incertain est une composante attrayante. Le concept de dépendance au sein des RB s’exprime principalement de deux façons. D’une part, les probabilités conditionnelles classiques s’appuyant le théorème de Bayes et d’autre part, une classe de RB faisant l’usage de copules et corrélation de rang comme mesures de dépendance. Nous présentons à la fois des contributions théoriques et pratiques dans le cadre de ces deux classes de RB ; les RB dynamiques discrets et les RB non paramétriques, respectivement. Des problématiques concernant la paramétrisation de chacune des classes sont également abordées. Dans un contexte théorique, nous montrons que les RBNP permet de caractériser n’importe quel processus de Markov. / This thesis explores high-dimensional deterioration-related problems using Bayesian networks (BN). Asset managers become more and more familiar on how to reason with uncertainty as traditional physics-based models fail to fully encompass the dynamics of large-scale degradation issues. Probabilistic dependence is able to achieve this while the ability to incorporate randomness is enticing.In fact, dependence in BN is mainly expressed in two ways. On the one hand, classic conditional probabilities that lean on thewell-known Bayes rule and, on the other hand, a more recent classof BN featuring copulae and rank correlation as dependence metrics. Both theoretical and practical contributions are presented for the two classes of BN referred to as discrete dynamic andnon-parametric BN, respectively. Issues related to the parametrization for each class of BN are addressed. For the discrete dynamic class, we extend the current framework by incorporating an additional dimension. We observed that this dimension allows to have more control on the deterioration mechanism through the main endogenous governing variables impacting it. For the non-parametric class, we demonstrate its remarkable capacity to handle a high-dimension crack growth issue for a steel bridge. We further show that this type of BN can characterize any Markov process.

La construction du cerveau et de ses connexions pendant le développement reste une question ouverte dans la communauté scientifique. Des efforts fructueux ont été faits pour élucider les mécanismes de la croissance axonale, tels que la guidance axonale et les molécules de guidage. Cependant, des preuves récentes suggèrent que d'autres acteurs seraient impliqués dans la croissance des neurones in vivo. Notamment, les axones se développent dans des environnements mécaniquement contraints. Ainsi, pour bien comprendre ce processus dynamique, il faut prendre en compte les mécanismes collectifs et les interactions mécaniques au sein des populations axonales. Néanmoins, les techniques pour mesurer directement cela à partir de cerveaux vivants sont aujourd'hui insuffisantes ou lourdes à mettre en œuvre. Cette thèse résulte d'une collaboration multidisciplinaire, pour faire la lumière sur le développement axonal in vivo et les morphologies complexes des axones adultes. Notre travail a été inspiré et validé à partir d'images d'axones y individuels chez la drosophile, de type sauvage et modifiés génétiquement, que nous avons segmentés et normalisés. Nous avons d'abord proposé un cadre mathématique pour l'étude morphologique et la classification des groupes axonaux. A partir de cette analyse, nous avons émis l'hypothèse que la croissance axonale dérive d'un processus stochastique et que la variabilité et la complexité des arbres axonaux résultent de sa nature intrinsèque, ainsi que des stratégies d'élongation développées pour surmonter les contraintes mécaniques du cerveau en développement. Nous avons conçu un modèle mathématique de la croissance d'un axone isolé fondé sur des chaînes de Markov gaussiennes avec deux paramètres, représentant la rigidité axonale et l'attraction du champ cible. Nous avons estimé les paramètres de ce modèle à partir de données réelles et simulé la croissance des axones à l'échelle de populations et avec des contraintes spatiales pour tester notre hypothèse. Nous avons abordé des thèmes de mathématiques appliquées ainsi que de la biologie, et dévoilé des effets inexplorés de la croissance collective sur le développement axonal in vivo. / How the brain wires up during development remains an open question in the scientific community across disciplines. Fruitful efforts have been made to elucidate the mechanisms of axonal growth, such as pathfinding and guiding molecules. However, recent evidence suggests other actors to be involved in neuron growth in vivo. Notably, axons develop in populations and embedded in mechanically constrained environments. Thus, to fully understand this dynamic process, one must take into account collective mechanisms and mechanical interactions within the axonal populations. However, techniques to directly measure this from living brains are today lacking or heavy to implement. This thesis emerges from a multidisciplinary collaboration, to shed light on axonal development in vivo and how adult complex axonal morphologies are attained. Our work is inspired and validated from images of single wild type and mutated Drosophila y axons, which we have segmented and normalized. We first proposed a mathematical framework for the morphological study and classification of axonal groups. From this analysis we hypothesized that axon growth derives from a stochastic process, and that the variability and complexity of axonal trees result from its intrinsic nature, as well as from elongation strategies developed to overcome the mechanical constraints of the developing brain. We designed a mathematical model of single axon growth based on Gaussian Markov Chains with two parameters, accounting for axon rigidity and attraction to the target field. We estimated the model parameters from data, and simulated the growing axons embedded in spatially constraint populations to test our hypothesis. We dealt with themes from applied mathematics as well as from biology, and unveiled unexplored effects of collective growth on axonal development in vivo.

The stochastic behavior of voltage-gated ion channels causes fluctuations of conductances and voltages across neuronal membranes, contributing to the neuronal noise which is ubiquitous in the nervous system. While this phenomenon can be observed also on other parts of the neuron, here we concentrated on the axon and the way the channel noise influences axonal input-output characteristics. This was analysed by working with our newly created computational compartmental model, programmed in Matlab environment, built up using the Hodgkin-Huxley mathematical formalism and channel noise implemented via extended Markov Chain Monte Carlo method. The model was thoroughly verified to simulate plausibly a mammalian axon of CA3 neuron. Based on our simulations, we confirmed quantitatively the findings that the channel noise is the most prominent on membranes with smaller number of Na+ and K+ channels and that it majorly increases the variability of travel times of action potentials (APs) along axons, decreasing thereby the temporal precision of APs. The simulations analysing the effect of axonal demyelination and axonal diameter correlated well with other finding referred in Literature. We further focused on spike pattern and how is its propagation influenced by inter-spike intervals (ISI). We found, that APs fired...