Este trabalho apresenta uma variação do problema de roteamento de veículos que permite o uso de veículos com múltiplos compartimentos. A necessidade de veículos com múltiplos compartimentos surge com frequência em aplicações práticas quando uma série de produtos, que possuem diferentes qualidades ou tipo, precisam ser transportados mas não podem ser misturados. Este problema é chamado na literatura de roteamento de veículos com múltiplos compartimentos (PRVMC). Nós propomos uma heurística busca tabu implementada em uma busca local iterada para resolver este problema. Experimentos foram feitos para avaliar a performance da busca tabu iterada e os resultados obtidos foram comparados com os resultados disponíveis na literatura. O algoritimo proposto é capaz de encontrar soluções melhores e em menos tempo de processamento que as heurísticas existentes. / We study a variant of the vehicle routing problem that allows vehicles with multiple compartments. The need for multiple compartments frequently arises in practical applications when there are several products of different quality or type, that must be kept or handled separately. The resulting problem is called the multi-compartment vehicle routing problem (MCVRP). We propose a tabu search heuristic and embed it into an iterated local search to solve the MCVRP. In several experiments we analyze the performance of the iterated tabu search and compare it with results from the literature. We find that it consistently produces solutions that are better than existing heuristic algorithms.

Noise-like activity (NLA) refers to spontaneous subthreshold fluctuations in membrane potential. In this thesis, we examine the role that synaptic channel fluctuations play in contributing to NLA by comparing a detailed biophysical model to experimental data from whole-intact hippocampal interneurons. To represent the contribution from synaptic channel fluctuations, we switch the synapses in the model from traditional to Markovian formalisms and demonstrate statistically relevant increases the standard deviation; power-law scaling exponent; and power spectral density in the 5-100 Hz and 1-5 kHz ranges. However, while synaptic channel fluctuations have a definite effect, we found that they were significantly more subtle than the synaptic response to network activity. This indicates that synaptic channel fluctuations do indeed play a significant role in subthreshold noise, but, overall, synaptic NLA is dominated by the synaptic response to presynaptic network activity.

Noise-like activity (NLA) refers to spontaneous subthreshold fluctuations in membrane potential. In this thesis, we examine the role that synaptic channel fluctuations play in contributing to NLA by comparing a detailed biophysical model to experimental data from whole-intact hippocampal interneurons. To represent the contribution from synaptic channel fluctuations, we switch the synapses in the model from traditional to Markovian formalisms and demonstrate statistically relevant increases the standard deviation; power-law scaling exponent; and power spectral density in the 5-100 Hz and 1-5 kHz ranges. However, while synaptic channel fluctuations have a definite effect, we found that they were significantly more subtle than the synaptic response to network activity. This indicates that synaptic channel fluctuations do indeed play a significant role in subthreshold noise, but, overall, synaptic NLA is dominated by the synaptic response to presynaptic network activity.

Stochastic compartment models are widely used in modeling processes for biological populations. The residence time has been especially useful in describing the system dynamics in the models. The direct calculation of the distribution for the residence time of stochastic multi-compartment models is very complicated even with a relatively simple model and often impossible to calculate directly. This dissertation presents an analytical method to obtain the moment generating function for stochastic multi-compartment models and describe the distribution of the residence times, especially systems with nonexponential lifetime distributions. A common method for obtaining moments of the residence time is using the coefficient matrix, however it has a limitation in obtaining high order moments and moments for combined compartments in a system. In this dissertation, we first derive the bivariate moment generating function of the residence time distribution for stochastic two-compartment models with general lifetimes. It provides any order of moments and also enables us to approximate the density of the residence time using the saddlepoint approximation. The approximation method is applied to various situations including the approximation of the bivariate distribution of residence times in two-compartment models or approximations based on the truncated moment generating function. Special attention is given to the distribution of the residence time for multi-compartment semi-Markov models. The cofactor rule and the analytic approach to the two-compartment model facilitate the derivation of the moment generating function. The properties from the embedded Markov chain are also used to extend the application of the approach. This approach provides a complete specification of the residence time distribution based on the moment generating function and thus provides an easier calculation of high-order moments than the approach using the coefficient matrix. Applications to drug kinetics demonstrate the simplicity and usefulness of this approach.

Este trabalho apresenta uma variação do problema de roteamento de veículos que permite o uso de veículos com múltiplos compartimentos. A necessidade de veículos com múltiplos compartimentos surge com frequência em aplicações práticas quando uma série de produtos, que possuem diferentes qualidades ou tipo, precisam ser transportados mas não podem ser misturados. Este problema é chamado na literatura de roteamento de veículos com múltiplos compartimentos (PRVMC). Nós propomos uma heurística busca tabu implementada em uma busca local iterada para resolver este problema. Experimentos foram feitos para avaliar a performance da busca tabu iterada e os resultados obtidos foram comparados com os resultados disponíveis na literatura. O algoritimo proposto é capaz de encontrar soluções melhores e em menos tempo de processamento que as heurísticas existentes. / We study a variant of the vehicle routing problem that allows vehicles with multiple compartments. The need for multiple compartments frequently arises in practical applications when there are several products of different quality or type, that must be kept or handled separately. The resulting problem is called the multi-compartment vehicle routing problem (MCVRP). We propose a tabu search heuristic and embed it into an iterated local search to solve the MCVRP. In several experiments we analyze the performance of the iterated tabu search and compare it with results from the literature. We find that it consistently produces solutions that are better than existing heuristic algorithms.

Este trabalho apresenta uma variação do problema de roteamento de veículos que permite o uso de veículos com múltiplos compartimentos. A necessidade de veículos com múltiplos compartimentos surge com frequência em aplicações práticas quando uma série de produtos, que possuem diferentes qualidades ou tipo, precisam ser transportados mas não podem ser misturados. Este problema é chamado na literatura de roteamento de veículos com múltiplos compartimentos (PRVMC). Nós propomos uma heurística busca tabu implementada em uma busca local iterada para resolver este problema. Experimentos foram feitos para avaliar a performance da busca tabu iterada e os resultados obtidos foram comparados com os resultados disponíveis na literatura. O algoritimo proposto é capaz de encontrar soluções melhores e em menos tempo de processamento que as heurísticas existentes. / We study a variant of the vehicle routing problem that allows vehicles with multiple compartments. The need for multiple compartments frequently arises in practical applications when there are several products of different quality or type, that must be kept or handled separately. The resulting problem is called the multi-compartment vehicle routing problem (MCVRP). We propose a tabu search heuristic and embed it into an iterated local search to solve the MCVRP. In several experiments we analyze the performance of the iterated tabu search and compare it with results from the literature. We find that it consistently produces solutions that are better than existing heuristic algorithms.

L'imagerie pondérée en diffusion est un type d'acquisition IRM spécifique basé sur la direction de diffusion des molécules d'eau dans le cerveau. Cela permet, au moyen de plusieurs acquisitions, de modéliser la microstructure du cerveau, comme la matière blanche qui à une taille très inférieur à la résolution du voxel. L'obtention d'un grand nombre d'images nécessite, pour un usage clinique, des techniques d'acquisition ultra rapide tel que l'imagerie parallèle. Malheureusement, ces images sont entachées de large distorsions. Nous proposons une méthode de recalage par blocs basée sur l'acquisition d'images avec des directions de phase d'encodage opposées. Cette technique spécialement conçue pour des images écho planaires, mais qui peut être générique, corrige les images de façon robuste tout en fournissant un champs de déformation. Cette transformation est applicable à une série entière d'image de diffusion à partir d'une seule image b 0 renversée, ce qui permet de faire de la correction de distorsion avec un temps d'acquisition supplémentaire minimal. Cet algorithme de recalage, qui a été validé à la fois sur des données synthétiques et cliniques, est disponible avec notre programme de traitement d'images Anima. A partir de ces images de diffusion, nous sommes capable de construire des modèles de diffusion multi-compartiment qui représentent la microstructure complexe du cerveau. Pour pouvoir produire des analyses statistiques sur ces modèles, nous devons être capable de faire du recalage, du moyennage, ou encore de créer un atlas d'images. Nous proposons une méthode générale pour interpoler des modèles multi-compartiment comme un problème de simplification basé sur le partitionnement spectral. Cette technique qui est adaptable pour n'importe quel modèle, a été validé à la fois sur des données synthétiques et réelles. Ensuite à partir d'une base de données recalée, nous faisons des analyses statistiques en extrayant des paramètres au niveau du voxel. Une tractographie, spécifiquement conçue pour les modèles multi-compartiment, est aussi utilisée pour faire des analyses en suivant les fibres de matière blanche. Ces outils sont conçus et appliqués à des données réelles pour contribuer à la recherche de biomarqueurs pour les pathologies cérébrales. / Diffusion weighted imaging (DWI) is a specific type of MRI acquisition based on the direction of diffusion of the brain water molecule. Its allow, through several acquisitions, to model brain microstructure, as white matter, which are significantly smaller than the voxel-resolution. To acquire a large number of images in a clinical use, very-fast acquisition technique are required as single-shot imaging, however these acquisitions suffer local large distortions. We propose a Block-Matching registration method based on a the acquisition of images with opposite phase-encoding directions (PED). This technique specially designs for Echo-Planar Images (EPI), but which could be generic, robustly correct images and provide a deformation field. This field is applicable to an entire DWI series from only one reversed b 0 allowing distortion correction with a minimal time acquisition cost. This registration algorithm has been validated both on a phantom data set and on in-vivo data and is available in our source medical image processing toolbox Anima. From these diffusion images, we are able to construct multi-compartments models (MCM) which could represented complex brain microstructure. We need to do registration, average, create atlas on these MCM to be able to make studies and produce statistic analysis. We propose a general method to interpolate MCM as a simplification problem based on spectral clustering. This technique, which is adaptable for any MCM, has been validated for both synthetic and real data. Then, from a registered dataset, we made analysis at a voxel-level doing statistic on MCM parameters. Specifically design tractography can also be perform to make analysis, following tracks, based on individual compartment. All these tools are designed and used on real data and contribute to the search of biomakers for brain diseases.

Neuronal networks produce reliable functional output throughout the lifespan of an animal despite ceaseless molecular turnover and a constantly changing environment. The cellular and molecular mechanisms underlying the ability of these networks to maintain functional stability remain poorly understood. Central pattern generating circuits produce a stable, predictable rhythm, making them ideal candidates for studying mechanisms of activity maintenance. By identifying and characterizing the regulators of activity in small neuronal circuits, we not only obtain a clearer understanding of how neural activity is generated, but also arm ourselves with knowledge that may eventually be used to improve medical care for patients whose normal nervous system activity has been disrupted through trauma or disease. We utilize the pattern-generating pyloric circuit in the crustacean stomatogastric nervous system to investigate the general scientific question: How are specific aspects of rhythmic activity regulated in a small neuronal network? The first aim of this thesis poses this question in the context of a single neuron. We used a single-compartment model neuron database to investigate whether co-regulation of ionic conductances supports the maintenance of spike phase in rhythmically bursting “pacemaker” neurons. The second aim of the project extends the question to a network context. Through a combination of computational and electrophysiology studies, we investigated how the intrinsic membrane conductances of the pacemaker neuron influence its response to synaptic input within the framework of the Phase Resetting Curve (PRC). The third aim of the project further extends the question to a systems-level context. We examined how ambient temperatures affect the stability of the pyloric rhythm in the intact, behaving animal. The results of this work have furthered our understanding of the principles underlying the long-term stability of neuronal network function.

Indiana University-Purdue University Indianapolis (IUPUI) / A crucial task in computer vision and biomedical image applications is to represent images in a numerically compact form for understanding, evaluating and/or mining their content. The fundamental step of this task is the segmentation of images into regions, given some homogeneity criteria, prior appearance and/or shape information criteria. Specifically, segmentation of cells in microscopic images is the first step in analyzing many biomedical applications. This thesis is a part of the project entitled "Construction and profiling of biodegradable cardiac patches for the co-delivery of bFGF and G-CSF growth factors" funded by National Institutes of Health (NIH). We present a method that simultaneously segments the population of cells while partitioning the cell regions into cytoplasm and nucleus in order to evaluate the spatial coordination on the image plane, density and orientation of cells. Having static microscopic images, with no edge information of a cytoplasm boundary and no time sequence constraints, traditional cell segmentation methods would not perform well. The proposed method combines deformable models with a probabilistic framework in a simple graphical model such that it would capture the shape, structure and appearance of a cell. The process aims at the simultaneous cell partitioning into nucleus and cytoplasm. We considered the relative topology of the two distinct cell compartments to derive a better segmentation and compensate for the lack of edge information. The framework is applied to static fluorescent microscopy, where the cultured cells are stained with calcein AM.

Numerous prediction models of SARS-CoV-2 pandemic were proposed in the past. Unknown parameters of these models are often estimated based on observational data. However, lag in case-reporting, changing testing policy or incompleteness of data lead to biased estimates. Moreover, parametrization is time-dependent due to changing age-structures, emerging virus variants, non-pharmaceutical interventions, and vaccination programs. To cover these aspects, we propose a principled approach to parametrize a SIR-type epidemiologic model by embedding it as a hidden layer into an input-output non-linear dynamical system (IO-NLDS). Observable data are coupled to hidden states of the model by appropriate data models considering possible biases of the data. This includes data issues such as known delays or biases in reporting. We estimate model parameters including their time-dependence by a Bayesian knowledge synthesis process considering parameter ranges derived from external studies as prior information. We applied this approach on a specific SIR-type model and data of Germany and Saxony demonstrating good prediction performances. Our approach can estimate and compare the relative effectiveness of non-pharmaceutical interventions and provide scenarios of the future course of the epidemic under specified conditions. It can be translated to other data sets, i.e., other countries and other SIR-type models.