Sublevel caving (SLC) is a mass mining method relying on the flowability of the blasted material. The ore is blasted in slices against caved material which is mainly waste rock. The result of the confined blast is greatly influenced by the interaction between the blasted material and the caved material. During blasting both materials change characteristics; the blasted material increases its porosity and compressibility due to breakage and swelling while the caved material is compacted and decreases in porosity and compressibility. The understanding of the mechanisms involved in this process is of significant importance. The behavior of the caved material (confining material) was studied in laboratory under dynamic loading. A new apparatus was developed to conduct impact tests to simulate blasting conditions. The tested material was a blend of crushed waste rock from drift development in the Kiirunavaara mine with maximum particle size 32 mm. The material was tested for two conditions, i.e. dry and wet (pendular state), and with different impact velocities (low (5 m/s), medium (8 m/s) and high (10-12 m/s)). During the impact tests, two types of measurements were taken; dynamic measurements based on the recordings from the installed accelerometers on the machine and static measurements pre- and post-impact. Additionally, the angle of repose, the impact duration, and the fragmentation was measured. In addition to the laboratory tests, small-scale blasting tests were carried out to investigate the burden behavior in confined conditions. The blasted specimen was a cuboid magnetic mortar block and the confining material was crushed concrete with maximum particle size 16 mm. The blocks were instrumented with custom-made incremental displacement sensor. After the analysis of the results from the above experimental work, two confined pillar tests (test #1 and test #2) were carried out at the Kiirunavaara mine. The preparation work for the pillar tests involved the development of instrumentation and installation techniques. The experimental configuration contained two blastholes and measurement holes in between the blastholes drilled from the neighboring drift. Test #1 mainly focused on the evaluation of the instrumentation and techniques while test #2 was focused on the interaction between the blasted burden and the confining material. The confining material in test #1 was a blend of ore and waste material from drift development at the Kiirunavaara mine. The characteristics of the material were unknown. Test #2 was split into two parts, the confining material in the first part was the same as in the laboratory impact tests and the second part of the pillar was confined by caved masses. The instrumentation was installed in the burden of the pillars and was equipped with accelerometers and displacement sensor. Additional instrumentation was also installed in the confining material. The burden in the small-scale blasting tests reached maximum velocity 29 m/s and maximum displacement 12.6 mm. In pillar tests, the burden movement was in the range of 0.9 to 1.1 m. In both pillar tests, burden erosion material was observed in the gap between the intact and the blasted burden. This material was finer compared to the blasted burden. The origin of this material was from the vicinity of the blastholes. The results of the laboratory tests showed that the wet material exhibited larger compaction zone than that of the dry material. The wet material showed apparent cohesion close to the impact surface of the tested material. A similar observation was made in test #2 where an agglomeration of the confining material, as a result of apparent cohesion, was observed on the surface of the blasted burden. The displacement data from the instrumentation in the burden and inside the confining material showed that the compaction zone follows an inverse exponential behavior. After the blast steeper angles of repose were measured indicating higher frictional forces between the particles. Moreover, the evidence of apparent cohesion and a larger angle of repose indicated the introduction of tensile strength in the material. The mass of the confining material was compressed elastically and plastically during the blast. After the blast, the material recovered its elastic deformation and pushed the blasted burden backward as observed in the small-scale blasting tests and the pillar tests. At this stage, the burden erosion material was compacted. Hence, there were 3 materials, i.e. burden erosion material, burden and confining material, which were compacted with different compaction rates. This condition promotes interlocking of the particles in the materials. If this behavior is correlated with a production SLC ring, then it indicates disturbances in flowability of the blasted material.

Genetic algorithms are modern algorithms intended to solve optimization problems. Inspiration originates in evolutionary principles in nature. Parallelization of genetic algorithms provides not only faster processing but also new and better solutions. Parallel genetic algorithms are also closer to real nature than their sequential counterparts. This paper describes the most used models of parallelization of genetic algorithms. Moreover, it provides the design and implementation in programming language Python. Finally, the implementation is verified in several test cases.

Protein-protein interaction dominates all major biology processes in living cells. Recent studies suggestthat the surface expression and activity of G protein-coupled receptors (GPCRs), which are the largestfamily of receptors in human cells, can be modulated by receptor activity–modifying proteins (RAMPs). Computational tools are essential to complement experimental approaches for the understanding ofmolecular activity of living cells and molecular dynamics simulations are well suited to providemolecular details of proteins function and structure. The classical atom-level molecular modeling ofbiological systems is limited to small systems and short time scales. Therefore, its application iscomplicated for systems such as protein-protein interaction in cell-surface membrane. For this reason, coarse-grained (CG) models have become widely used and they represent an importantstep in the study of large biomolecular systems. CG models are computationally more effective becausethey simplify the complexity of the protein structure allowing simulations to have longer timescales. The aim of this degree project was to determine if the applications of coarse-grained molecularsimulations were suitable for the understanding of the dynamics and structural basis of the GPCRRAMP interactions in a membrane environment. Results indicate that the study of protein-proteininteractions using CG needs further improvement with a more accurate parameterization that will allowthe study of complex systems.

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Les protéines amyloïdes sont retrouvées sous forme de fibres dans de nombreuses maladies neurodégénératives. En tentant d’élucider le mécanisme de fibrillation, les chercheurs ont découvert que cette réaction se fait par un phénomène de nucléation passant par des oligomères. Il semblerait que ces espèces soient la principale cause de la toxicité observée dans les cellules des patients atteints d’amyloïdose. C’est pourquoi un intérêt particulier est donc porté aux premières étapes d’oligomérisation. Dans ce mémoire, nous nous intéressons à une séquence d’acide aminé fortement hydrophobe de l’α-synucléine appelée composante non β -amyloïde (Non-Amyloid β Component ou NAC). Cette dernière est retrouvée sous forme de fibres dans les corps et les neurites de Lewy des patients atteints de la maladie de Parkinson. De plus, elle constitue une composante minoritaire des fibres impliquées dans la maladie d’Alzheimer. Nous avons observé les changements structuraux qui ont lieu pour le monomère, le dimère et le trimère de la séquence NAC de l’α-synucléine. Nous nous sommes aussi intéressés aux conséquences structurelles observées dans des oligomères hétérogènes qui impliqueraient, Aβ1−40. Pour cela nous utilisons des dynamiques moléculaires, d’échange de répliques couplées au potentiel gros-grain, OPEP. Nous constatons une disparition des hélices α au profit des feuillets β , ainsi que le polymorphisme caractéristique des fibres amyloïdes. Certaines régions se sont démarquées par leurs capacités à former des feuillets β . La disparition de ces régions lorsque NAC est combinée à Aβ laisse entrevoir l’importance de l’emplacement des résidus hydrophobes dans des structures susceptibles de former des fibres amyloïdes. / Amyloid proteins are found in fiber form in many neurodegenerative diseases. In attempting to elucidate the mechanism of fibrillation, researchers have found that fibril formation occurs by a nucleation mechanisms involving oligomers. It seems, in particular, that the latter species are responsible for the toxicity observed in the cells of patients suffering from amyloidosis. That is why special interest is focused in the early stages of oligomerization. In this this work, we focus on a highly hydrophobic amino acid sequence of the α-synuclein called Non-Amyloid β Component (NAC). The NAC is recovered in the form of fibers in the body and Lewy neurites in patients with Parkin- son’s disease. Moreover, it is a minority component of the fibers involved in Alzheimer’s disease. In particular, we observe the structural changes taking place for the monomer, dimer and trimer of the NAC region of α-synuclein. We are also interested in the structural consequences observed in heterogeneous oligomers which involve Aβ1−40. We use Hamiltonian and temperature replica exchange molecular dynamics (HT-REMD) simulations combined with the coarse-grained OPEP potential. We observe a loss of α-helices in favor of β -strands and the characteristic polymorphism of amyloid fibers. We also find that some regions are distinguished by their ability to form β -strands. The disappearance of these regions when combined Aβ with NAC suggests the importance of the location of hydrophobic residues in amyloid fibers structures.

Les propriétés mécaniques des polymères et des copolymères à blocs ont été étudiées par simulation de type dynamique moléculaire (modèle billes-ressorts). Les échantillons polymères ont été générés par la méthode de « radical like polymerisation ». Ces échantillons ont été soumis à des essais de traction uniaxiaux et triaxiaux dans le but d’étudier leurs réponses mécaniques. Dans la première partie de ce travail on a comparé deux méthodes de traction : « méthode de traction homogène» et la traction « pilotée par les bords » de l’échantillon. Les résultats montrent que les deux méthodes sont équivalentes à faible vitesse de traction. Le changement de distance entre enchevêtrement dans un polymère modèle sous traction est analysé, les résultats montrent que le désenchevêtrèrent des chaines est plus prononcé lorsque la déformation de l’échantillon est uniaxiale du fait de la relaxation latérale de l’échantillon. La nucléation des cavités dans les polymères amorphes soumis à une déformation triaxial a été également étudiée. On a trouvé que les cavités se forment dans des zones qui sont caractérisées par un faible module d’incompressibilité élastique. Ces zones sont identifiables dès le début de la déformation à une température très basse (T~0K). La seconde partie de ce travail se concentre sur la simulation de la réponse mécanique des copolymères à blocs. L’influence de l’architecture moléculaire sur le comportement mécanique de l’échantillon a été analysée. Les résultats montrent que le comportement mécanique des échantillons est piloté par le taux des chaines liantes qui assurent la transmission des contraintes entre les phases. Le flambement des lamelles dans les copolymères à blocs a été également étudié, l’influence de la taille de l’échantillon et de la vitesse de déformation sur la réponse mécanique de l’échantillon a été explorée. Les résultats montrent un changement de mode du flambement selon la vitesse de déformation imposée. Un nouveau modèle qui prend en compte le facteur cinétique du flambement est proposé pour décrire la compétition entre les modes. / We use molecular dynamics simulation of a coarse grained model to investigate the mechanical properties of homogenous polymers and lamellar block copolymers. Polymer samples have been generated using “radical like polymerisation” method. These samples were submitted to uniaxial and triaxial tensile tests in order to study their mechanical responses. First we compare two tensile test methods: the “homogenous deformation method” and the “boundary driven deformation method”. We find that the two methods lead to similar results at low strain rate. The change of the entanglement network in polymer sample undergoing a tensile deformation was investigated. We have found that the sample exhibits an increase of its entanglement length in uniaxial deformation test compared to triaxial deformation one. Our finding was interpreted by the pronounced chain disentanglement observed in the uniaxial deformation test due to the lateral relaxation of the sample. The cavity nucleation in amorphous polymers has been also studied. We have found that the cavities nucleate preferentially in zones that exhibit a low elastic bulk modulus. These zones can be identified from the initial undeformed state of the sample at low temperature (T~0K). The second part of the work focused in the simulation of the mechanical response of block copolymers. The influence of chain architecture on the mechanical properties was investigated: our finding reveals an important role of the bridging molecules (cilia chains and knotted loop chains) on the stress transmission between phases at high strain. The initiation of plasticity in copolymer samples was also studied. The role of the buckling has been found to be determinant in the mechanical response of the sample The dependence of the buckling instability with the sample size and the deformation rate was investigated. We have found that the fundamental (first) mode of buckling develops at relatively low strain rate whereas at high strain rate the buckling of the sample occurs with the second or higher mode of buckling. A new model that takes into account the buckling kinetic was developed to describe this competition between the buckling modes.

Nous proposons un algorithme basé sur une approche orientée d'ensemble de système dynamique pour extraire une organisation grossière de l'espace d'état de cerveau sur la base des signaux de l'EEG. Nous l'utilisons pour comparer l'organisation de l'espace d'état des données simulées à grande échelle avec la dynamique cérébrale réelle au repos chez des sujets sains et pathologiques (SEP). / We propose an algorithme based on set oriented approach of dynamical system to extract a coarse grained organization of brain state space on the basis of EEG signals. We use it for comparing the organization of the state space of large scale simulation of brain dynamics with actual brain dynamics of resting activity in healthy and SEP subjects.