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Les transitions de phase près d'un point critique - dites du second ordre - sont un sujet toujours d'actualité en raison des nombreux phénomènes critiques intéressants tels que la force de Casimir critique, les problèmes de confinements ou les phénomènes hors d'équilibre suivant une trempe au point critique. Cette thèse vise à étudier expérimentalement certains phénomènes engendrés près d'un point critique. La thèse est divisée en deux axes : le premier consiste à développer plusieurs systèmes expérimentaux qui permettront de mesurer essentiellement la viscosité, par l'intermédiaire des fluctuations thermiques à l'échelle micrométrique. Le deuxième axe consiste à trouver et caractériser des mélanges binaires présentant une transition de phase du second ordre dans lesquelles on souhaite faire des mesures. Les enjeux de ces systèmes expérimentaux sont d'avoir une régulation en température précise, une sonde de mesure sensible aux fluctuations thermiques et/ou à des forces de l'ordre du pN, et un échantillon fiable et reproductible présentant un point critique accessible expérimentalement. Nous avons ainsi monté à partir d'un microscope à force atomique (AFM) déjà présent au laboratoire, un système de mesure de viscosité à sonde AFM fibrée. Malgré sa faible efficacité en terme de sonde de mesure métrologique, nous avons pu décrire et développer un modèle de couplage de modes de vibration permettant de comprendre la mécanique de microleviers AFM fibrés. J'ai également développé au laboratoire la mesure de microscopie dynamique différentielle qui permet de faire des mesures à sondes multiples contrairement au premier montage. J'ai discuté de la précision de la mesure dans le cadre de notre objectif d'étude des fluctuations critiques. En ce qui concerne l'échantillon de mesure, nous avons étudié plusieurs mélanges binaires que nous avons caractérisés par des méthodes classiques de turbidité et diffusion statique de la lumière. Cette caractérisation nous a permis de connaître les mélanges binaires pour les utiliser dans un troisième système de mesure : billes micrométriques piégées dans des pinces optiques déjà monté au laboratoire. Nous y avons rajouté un système de régulation thermique fait maison pour être exploité avec les contraintes de la pince optique. Ces tests ont fait apparaître un phénomène inattendu d'oscillations de transition de phase induites par laser. Nous avons développé un modèle pour les décrire. Enfin, des expériences préliminaires - toujours avec les pinces optiques dans les mélanges binaires - nous ont permis d'observer qualitativement des effets de l'approche au point critique par des mesures de viscosité et d'interaction type force de Casimir critique. / Phase transitions near a critical point, or second order phase transitions, are still a recent object of studies because of the large amount of interesting critical phenomena as the critical Casimir force, confinements problems or out of equilibrium phenomena following a quench at the critical point. This thesis experimentally studies phenomena near a critical point. This manuscript is divided in two parts : the first one consists in building several experimental set-up which measure viscosity through thermal fluctuation at micrometric scale. The second part consists in finding and characterize binary mixtures which show a second order phase transition. Preliminary results have been done in these samples. One of the principal points of these experimental set-up are a well regulated temperature, a probe sensitive to thermal fluctuation and/or pN forces and a reproducible binary mixture which presents a critical point easy to reach experimentally. We mounted from an Atomic Force Microscope (AFM) already built in the laboratory, a hanging-fiber probe to measure viscosity of liquids. Despite its weak efficiency as a metrologic probe, we described and developed a mode coupling model which let us understand mechanics of hanging-fiber probes. I also developed in the lab the dynamic differential microscopy technique (DDM) which do measurements with several probes. I discussed about the measure precision with in mind the aim of studying critical fluctuations. For the choice of the sample, we studied several binary mixtures. We characterized them by classical methods as turbidity measurements and static light scattering. These characterizations let us learn about binary mixtures in order to use them in a third experimental set-up : beads trapped in an optical tweezers already built in the lab. We added to it a home-made thermal regulation which can be used with the constraints of optical tweezers. These tests showed an unexpected phenomenon of oscillating phase transition induce by laser. We developed a model to describe it. At last, preliminary experiments with optical tweezers in binary mixtures showed qualitative effects of an approach near a critical point on the viscosity and on interactions between beads as critical Casimir force.

The discounted cash flow model and relative valuation models are ever-increasingly prevalent in today’s investment-heavy environment. In other words, theoretically inferior models are used in practice. It is this paradox that has lead us to compare the discounted cash flow model (DCFM), discounted dividend model (DDM), residual income-based model (RIVM) and the abnormal earnings growth model (AEGM) and their relative accuracy to observed stockprices. Adding to previous research, we investigate their performance in relation to the OMX30 index. What is more, we test how the performance of each model is affected by an extension of the forecast horizon. The study finds that AEGM outperforms the other models, both before and after extending the horizon. Our analysis was conducted by looking at accuracy, spread and the inherent speculative nature of each model. Taking all this into account, RIVM outperforms the other models. In this sense, one can question the rationale behind investor’s decision to primarily use the discounted cash flow model in equity valuation.

Made available in DSpace on 2016-06-02T19:03:57Z (GMT). No. of bitstreams: 1 DissNDHV.pdf: 2131970 bytes, checksum: c7f6510e36c70fc8b4fd05d431744457 (MD5) Previous issue date: 2006-05-26 / Financiadora de Estudos e Projetos / In Large Scale Collaborative Virtual Environments LSCVEs, extensive synthetic 3D environments are shared among a large number of users that collaborate towards the same objective. As all users in these environments need immediate answer for their actions and these actions must be sent to all participating users, the application success depends not only on a strong graphic processing but also in the capacity of the network to deliver information in time. Data distribution management algorithms in conformity with the High Level Architecture / Run Time Infrastructure (HLA/RTI) pattern for parallel and distributed simulations have been used to reduce latency and to limit and control the data amount exchanged during simulations. The data distribution of LSCVEs is generally made by one of these communication models: client/server or Peer-to-peer. Differently of the client/server where the server can be a bottleneck of the network, in Peer-to-peer solutions the tasks are distributed and consequently applications are scalable, i.e., support a crescent client number. Motivated by these largely studied and commonly used technologies, a fault tolerant and low latency solution was searched, addressing the strict requirements of large scale collaborative virtual environments simulations. This was made in conformity with the HLA pattern, which users, using their own computer connected at Gnutella network, can participate in simulation sessions without the limitations found in kits that support distributed simulations like the RTI-Kit existent. For this reason an architecture was proposed with data distribution management in conformity with the HLA/RTI and that use the Gnutella Peer-to-peer communication model to make available and to share these environments over Mobile Ad-Hoc Networks (MANETs). Towards this propose simulations were made comparing the RTI-Kit developed by Georgia Tech with one speed objects and the RTI-Kit Adapted with varied speed objects in a cluster. The evaluation of the total time of the federation execution, the total number of the multicast messages generated and the total number of messages exchanged by the grid originated graphics that show up considerable increasing in the time and the number of messages exchanged by the grid mainly. In the same way the fault tolerant technique was evaluated. / Em Ambientes Virtuais Colaborativos de Larga Escala (AVCs-LE), ambientes 3D sintéticos extensos são compartilhados entre um número muito grande de usuários que colaboram entre si para atingir um objetivo comum. Nesses ambientes, os usuários precisam ter uma resposta imediata às suas ações, e estas devem ser refletidas nos ambientes de todos os usuários participantes. Assim, o sucesso da aplicação depende não apenas de processamento gráfico poderoso, mas também, da capacidade da rede na entrega das informações a tempo. Algoritmos de gerenciamento de distribuição de dados, em conformidade com o padrão High Level Architecture / Run Time Infrastructure (HLA/RTI) para simulações paralelas e distribuídas, vêm sendo utilizados na redução da latência e como limitantes e controladores do volume de dados trocados durante simulações. A distribuição de dados de AVCs-LE é realizada normalmente por um destes modelos de comunicação: cliente/servidor ou Peer-to-peer. Diferentemente do modelo cliente/servidor no qual a figura do servidor pode caracterizar um gargalo na rede, nas soluções Peer-to-peer as atividades estão distribuídas e conseqüentemente, suas aplicações são escaláveis, ou seja, suportam uma quantidade crescente de usuários. Motivados por essas tecnologias amplamente estudadas e comumente utilizadas, procurou-se criar uma solução tolerante a falhas e de baixa latência, dentro dos requisitos de simulações de ambientes virtuais colaborativos de larga escala. Isso foi feito em conformidade com o padrão HLA, em que usuários, utilizando seu próprio computador conectado a uma rede Gnutella, possam participar de sessões de simulações sem as limitações encontradas em kits de suporte à simulação distribuída, como o Kit RTI existente. Em razão disso, foi proposta uma arquitetura com gerenciamento de distribuição de dados em conformidade com o HLA, padrão comumente utilizado em simulações paralelas e distribuídas e que utiliza o modelo de comunicação Peer-to-peer da rede Gnutella para disponibilização e compartilhamento de tais ambientes, sobre redes móveis Ad-Hoc (Mobile Ad-Hoc Networks - MANETs). Para tanto, realizaram-se simulações comparativas entre o Kit RTI desenvolvido pela Georgia Tech, com objetos de apenas uma velocidade, contra o Kit RTI Adaptado, com objetos de velocidade variada, em um cluster. A avaliação do tempo total de execução da federação, o número total de mensagens multicast geradas e o número total de mensagens trocadas pela grade deu origem a gráficos que mostraram aumentos consideráveis, principalmente, no tempo e no número de mensagens trocadas pela grade. Da mesma forma, foi avaliada a técnica proposta, tolerante a falhas.

Deer Vehicle Collisions (DVCs) are a global problem that is not only resulting in seriousinjuries to humans but also results in loss of human and deer lives. Deer are more active and less attentive during the mating and hunting seasons. Roadside deer activity such as feeding and strolling along the roadside has a significant correlation with DVCs. To mitigate DVCs, several strategies were used that include vegetation management, fences, underpasses and overpasses, population reduction, warning signs and animal detection systems (ADS). These strategies vary in their efficacy. These strategies may help to reduce DVCs. However, they are not always easily feasible due to false alarms, high cost, unsuitable terrain, land ownership, and other factors. Thus, DVCs are increasing due to the increase in number of vehicles and the absence of intelligent highway safety and alert systems. Detecting deer in real-time on our roads is a challenging problem. Thus, this research work proposed a deer detection and movement DDM technique to automate DVCs mitigation system. The DDM combines computer vision, artificial intelligent methods with deep learning techniques. DDM includes two main deep learning algorithms 1)onestage deep learning algorithm based on Yolov5 that generates a detection model(DM) to detect deer and 2) deep learning algorithm developed by python toolkit DeepLabCut to generate movement model(MM) for detecting the movement of the deer. The proposed method can detect deer with 99.7% precision and succeeds to ascertain if the deer is moving or static with an inference speed of 0.29s. The proposed method can detect deer with 99.7% precision and using DeepLabCut toolkit on the detected deer we can ascertain if the deer is moving or static with an inference speed of 0.29s.

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Eukaryotic organisms rely on the coordinated beating of motile cilia for a multitude of fundamental reasons. In smaller organisms, such as Paramecium and the single cell alga Chlamydomonas reinhardtii, it is a matter of propulsion, to swim towards a higher concentration of nutrients or away from damaging environments. Larger organisms use instead the coordinated motion of cilia to push fluid along an epithelium: examples common to mammals are the circulation of cerebrospinal fluid in the brain, the transport of ovules in the fallopian tubes, and breaking the left/right symmetry in the embryo. Another notable example, and one that is central to this thesis, is mucociliary clearance in human airways: A carpet of motile cilia helps keeping the cell surface free from pathogens and foreign particles by constantly evacuating from lungs, bronchi, and trachea a barrier of mucus. The question of how motile cilia interact with one another to beat in a coordinated fashion is an open and pressing one, with immediate implications for the medical community. In order for the fluid propulsion to be effective, the motion of cilia needs to be phase-locked across significant distances, in the form of travelling waves (``metachronal waves''). It is still not known how this long-range coordination emerges from local rules, as there is no central node regulating the coordination among cilia. In the first part of this thesis I will focus on studying the coordination in carpets of cilia with a top-down approach, by proposing, implementing, and applying a new method of analysing microscope videos of ciliated epithelia. Chapter 1 provides the reader with an introduction on motile cilia and flagella, treating their structure and motion and reporting the different open questions currently tackled by the scientific community, with particular interest in the coordination mechanisms of cilia and the mucociliary clearance apparatus. Chapter 2 introduces Differential Dynamic Microscopy (DDM), a powerful and versatile image analysis tool that bridges the gap between spectroscopy and microscopy by allowing to perform scattering experiments on a microscope. The most interesting aspects of DDM for this work are that it can be applied to microscope videos where it is not possible to resolve individual objects in the field of view, and it requires no user input. These two characteristics make DDM a perfect candidate for analysing several hundred microscope videos of weakly scattering filaments such as cilia. In Chapter 3 I will present how it is possible to employ DDM to extract a wealth of often-overlooked information from videos of ciliated epithelia: DDM can successfully probe the ciliary beat frequency (CBF) in a sample, measure the direction of beating of the cilia, and detect metachronal waves and read their direction and wavelength. In vitro ciliated epithelia however often do not show perfect coordination or alignment among cilia. For the analysis of these samples, where the metachronal coordination might not be evident, we developed a new approach, called multiscale DDM (multiDDM), to measure a coordination length scale, a characteristic length of the system over which the coordination between cilia is lost. The new technique of multiDDM is employed in Chapter 4 to study how the coordination among cilia changes as a response to changes in the rheology of the mucous layer. In particular, we show that cilia beating under a thick, gel-like mucus layer show a larger coordination length scale, as if the mucus acted as an elastic raft effectively coupling cilia over long distances. This is corroborated by the coordination length scale being larger in samples from patients affected by Cystic Fibrosis than in healthy samples, and much shorter when the mucus layer is washed and cilia therefore beat in a near-Newtonian fluid. We then show how it is possible to employ multiDDM to measure the effectiveness of drugs in recovering, in CF samples, a coordination length scale typical of a healthy phenotype. In the second part I will focus instead on the single cilium scale, showing how we can attempt to link the beating pattern of cilia to numerical simulations studying synchronisation in a model system. In particular in Chapter 5 I will describe our approach to quantitatively describe the beating pattern of single cilia obtained from human airway cells of either healthy individuals or patients affected by Primary Ciliary Dyskinesia. Our description of the beating pattern, and the selection of a few meaningful, summary parameters, are then shown to be accurate enough to discriminate between different mutations within Primary Ciliary Dyskinesia. In Chapter 6 instead I report the results obtained by coarse-graining the ciliary beat pattern into a model system consisting of two ``rotors''. The rotors are simulated colloidal particles driven along closed trajectories while leaving their phase free. In my study, the trajectories followed by the rotors are analytical fits of experimental trajectories of the centre of drag of real cilia. The rotors, that are coupled only via hydrodynamics interactions, are seen to phase-lock, and the shape of the trajectory they are driven along is seen to influence the steady state of the system.

In geothermal reservoirs and unconventional gas reservoirs with very low matrix permeability, fractures are the main routes of fluid flow and heat transport, so the fracture permeability change is important. In fact, reservoir development under this circumstance relies on generation and stimulation of a fracture network. This thesis presents numerical simulation of the response of a fractured rock to injection and extraction considering the role of poro-thermoelasticity and joint deformation. Fluid flow and heat transport in the fracture are treated using a finite difference method while the fracture and rock matrix deformation are determined using the displacement discontinuity method (DDM). The fractures response to fluid injection and extraction is affected both by the induced stresses as well as by the initial far-field stress. The latter is accounted for using the non-equilibrium condition, i.e., relaxing the assumption that the rock joints are in equilibrium with the in-situ stress state. The fully coupled DDM simulation has been used to carry out several case studies to model the fracture response under different injection/extractions, in-situ stresses, joint geometries and properties, for both equilibrium and non-equilibrium conditions. The following observations are made: i) Fluid injection increases the pressure causing the joint to open. For non-isothermal injection, cooling increases the fracture aperture drastically by inducing tensile stresses. Higher fracture aperture means higher conductivity. ii) In a single fracture under constant anisotropic in-situ stress (non-equilibrium condition), permanent shear slip is encountered on all fracture segments when the shear strength is overcome by shear stress in response to fluid injection. With cooling operation, the fracture segments in the vicinity of the injection point are opened due to cooling-induced tensile stress and injection pressure, and all the fracture segments experience slip. iii) Fluid pressure in fractures increases in response to compression. The fluid compressibility and joint stiffness play a role. iv) When there are injection and extraction in fractured reservoirs, the cooler fluid flows through the fracture channels from the injection point to extraction well extracting heat from the warmer reservoir matrix. As the matrix cools, the resulting thermal stress increases the fracture apertures and thus increases the fracture conductivity. v) Injection decreases the amount of effective stress due to pressure increase in fracture and matrix near a well. In contrast, extraction increases the amount of effective stress due to pressure drop in fracture and matrix.

DNA methylation is an important epigenetic mark spanning all of life's kingdoms. In humans, DNA methylation has been associated with a wide range of age-related pathologies, including type II diabetes and cancer. More recently, in humans, changes in DNA methylation at specific positions in the genome have been found to be predictive of chronological age. Interestingly, DNA methylation age is also predictive of health status and time-to-death. A better understanding of what these DNA methylation changes represent and whether they might be causative in the ageing process will be important to ascertain. However, at present there is no animal model system with which this process can be studied at a mechanistic level. Furthermore, it is becoming increasingly apparent that many disease states that increase in prevalence with age are not caused by all cells within the individual, but are often the result of changes to a subset of cells. This underscores the importance of studying these processes at the single cell level. The recent advances in single cell sequencing approaches now mean that we can study multiple layers of biology within the same single cell, such as the epigenome and the transcriptome (scM&T-Seq). Unfortunately, we are still only able to probe these important aspects of single cell biology in a static sense. This is a major limitation in the study of ageing because ageing and age-related disease processes are inherently dynamic. As such, it is incumbent upon us to develop approaches to assay single cell biology in a dynamic manner. 
In this thesis, I describe an epigenetic age predictor in the mouse. This predictor is tissue-independent and can accurately predict age (with an error of 3.33 weeks) and can record deviations in biological age upon interventions including ovariectomy and high fat diet both of which are known to reduce lifespan. Next, I describe the analysis of a homogeneous population of muscle satellite cells (MuSCs) that I have interrogated at the single cell level, using single cell combined transcriptome and methylome sequencing (scM&T-seq). I found that with age there was increased global transcriptional variability and increased feature-specific methylome variability. These findings explain the loss of functionality of these cells with age. Lastly, I describe two imaging approaches to study DNA methylation dynamically in single cells. Using these methods, I demonstrate that it is possible to accurately determine methylation status across a wide spectrum of global methylation levels and that by using such approaches novel information about dynamic methylation processes can be obtained. These methods represent the first to study DNA methylation dynamically.

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