Cytochrome c oxidase couples the reduction of dioxygen to proton pumping against an electrochemical gradient. The D-channel provides the principal uptake pathway for protons. A water chain is thought to mediate the relay of protons through the D-channel, but it is interrupted at N139 in all crystallographic structures. Here, free energy simulations are used to examine the proton uptake pathway in the wild type and in single-point mutants N139V and N139A, where reduction and pumping is compromised. A general approach for the calculation of water occupancy in protein cavities is presented and demonstrates that combining efficient sampling algorithms with long simulation times is required to achieve statistical convergence of equilibrium properties in the protein interior. The relative population of conformational and hydration states of the D-channel is characterized. Results shed light onto the role of N139 in the mechanism of proton uptake and clarify the physical basis for inactive phenotypes.

Numerical simulations of Mach shock reflections have shown that the Mach stem can bifurcate as a result of the slip line jetting forward. Numerical simulations were conducted in this study which determined that these bifurcations occur when the Mach number is high, the ramp angle is high, and specific heat ratio is low. It was clarified that the bifurcation is a result of a sufficiently large velocity difference across the slip line which drives the jet. This bifurcation phenomenon has also been observed after triple point collisions in detonation simulations. A triple point reflection was modelled as an inert shock reflecting off a wedge, and the accuracy of the model at early times after reflection indicates that bifurcations in detonations are a result of the shock reflection process. Further investigations revealed that bifurcations likely contribute to the irregular structure observed in certain detonations.

In the last few decades, an increasing number of physicists specialized in soft matter, including polymers, have turned their attention to biologically relevant materials. The properties of various molecules and fibres, such as DNA, RNA, proteins, and filaments of all sorts, are studied to better understand their behaviours and functions. Self-assembled biological membranes, or lipid bilayers, are also the focus of much attention as many life processes depend on these. Small lipid bilayers vesicles dubbed liposomes are also frequently used in the pharmaceutical and cosmetic industries. In this thesis, work is presented on both the elastic properties of polymers and the response of lipid bilayer vesicles to extrusion in narrow-channels. These two areas of research may seem disconnected but they both concern deformed soft materials. The thesis contains four articles: the first presenting a fundamental study of the entropic elasticity of circular chains; the second, a simple universal description of the effect of sequence on the elasticity of linear polymers such as DNA; the third, a model of the symmetric thermophoretic stretch of a nano-confined polymer; the fourth, a model that predicts the final sizes of vesicles obtained by pressure extrusion. These articles are preceded by an extensive introduction that covers all of the essential concepts and theories necessary to understand the work that has been done.

Establecer una cota global a las emisiones de gases de efecto invernadero ha sido imposibilitado por la complejidad que conlleva demostrar los efectos de la contribución humana al efecto invernadero. Para alcanzar un desarrollo sostenible es necesario, primero limitar y en lo posible eliminar las emisiones de dichos gases a la atmosfera. En este contexto, la adsorción de gases se ha establecido como una de las alternativas más efectivas a mediano plazo para la reducción de emisiones de gases de efecto invernadero. Por lo tanto, en esta tesis, el objetivo principal es estudiar a nivel molecular la adsorción de gases de efecto invernadero y comprender mejor la interacción entre las distintas variables que afectan el proceso de captura. En la primera parte de esta tesis se estudió, la separación de una mezcla de hexafluoruro de azufre (SF6) y nitrógeno (N2). El SF6 se emite en pequeñas cantidades, sin embargo por ser un potente gas de efecto invernadero con un tiempo de vida extremadamente alto se requiere un control estricto de sus emisiones. En este trabajo se estudió, empleando modelos simples, el efecto del tamaño de poro, la presión y la composición de la mezcla en la separación selectiva del SF6. Posteriormente, se realizaron simulaciones con modelos realistas de dos carbonos réplicas de zeolitas y se encontró que la selectividad predicha para el SF6 en dichos materiales es superior a la de los materiales previamente reportados en la literatura. En la segunda parte del trabajo se estudió el uso de estos materiales de carbono para la captura de dióxido de carbono (CO2) a temperatura ambiente, y se encontró que su capacidad de captura de CO2 a altas presiones es comparable a la de los mejores adsorbentes de CO2 reportados. Para comprender mejor la captura en los carbonos réplicas de zeolitas, se emplearon simulaciones moleculares para obtener información acerca de su compleja estructura interna y predecir las interacciones del CO2 con el interior de estos materiales. En la parte final de esta tesis se estudiaron materiales híbridos organo-inorgánicos, en particular, adsorbentes de sílica funcionalizados con grupos amino. Se desarrolló una nueva metodología de simulación para la generación de materiales de sílica funcionalizados con cadenas orgánicas y el cálculo de sus propiedades de adsorción. La metodología se evaluó empleando modelos de sílica gel y MCM-41 funcionalizados con diferentes cadenas orgánicas, comparando los resultados de las simulaciones de las isotermas de adsorción y la densidad de funcionalización con datos experimentales. Simultáneamente, se desarrolló un nuevo método que permite calcular adicionalmente a la fisisorción la quimisorción del CO2 en las aminas empleando simulaciones moleculares. En resumen, esta tesis de doctorado resalta diferentes posibilidades para la captura y separación de gases de efecto invernadero y proporciona nuevas herramientas de simulación para evaluar y optimizar sistemas de captura de gases. Esta tesis se enmarca dentro de la ciencia de materiales y muestra como la investigación básica en este campo puede ser usada como una herramienta para evaluar y optimizar procesos industriales. / The establishment of a global limit on the emissions of greenhouse gases has been hindered by the complexity to prove the effects of manmade greenhouse gases on a global scale. In order to achieve a sustainable development it is important to limit, and when possible eliminate, emissions of industrial greenhouse gases to the atmosphere. In this context, adsorption has been established as one of the best cost-effective means of reducing emissions of greenhouse gases in the short-term. Thus, in this thesis, the main objective is to study at a molecular level the adsorption of greenhouse gases and to obtain a better insight into the capture processes for their future optimization. Molecular simulations are used in order to find the optimal diameter for the separation of sulfur hexafluoride (SF6) from nitrogen (N2); this mixture is commonly used in electrical applications. SF6 is typically emitted in small quantities, but because it is a potent greenhouse gas and possesses extremely long lifetimes, there is a pressing need for a strict control of its emissions. The effect of pore size, pressure, and mixture compositions on the selective adsorption of SF6 was investigated using simple models. Subsequently, simulations using two atomistic models of zeolite templated carbons were performed. The separation selectivities compared favorably to the materials previously reported for the separation of this mixture. Moreover, the potential use of these two templated carbon materials to capture carbon dioxide (CO2) at room temperature is reported. Their high-pressure CO2 adsorption isotherms are among the highest carbon capture capacity for carbonaceous materials and are comparable to the best CO2 adsorbing materials. In addition, the simulated adsorption isotherms were used to obtain new insights into the adsorption process of the templated carbons. In the final part of the thesis hybrid organic-inorganic adsorbents were studied. For CO2 capture, solid adsorbents are functionalized with amino groups that largely increase their adsorption capabilities. However, the underlying mechanism of the adsorption process in the functionalized materials is not fully understood, limiting the possibility of designing optimal adsorbent materials for different applications. The adsorption of CO2 in aminefunctionalized silica materials was studied using Monte Carlo molecular simulations. A simulation methodology for the design of functionalized silica materials was proposed. The methodology was evaluated using models of silica gel and MCM-41 functionalized with different organic groups, comparing the resulting adsorption isotherms and grafting density to available experimental data. Furthermore, a new scheme that allows accounting for the chemisorbed CO2 on the adsorption isotherms is presented In summary, this PhD thesis highlights different possibilities for the capture and separation of greenhouse gases and provides new tools for evaluating and optimizing capture systems. Finally, this dissertation shows the use of basic research in Materials Science as an established tool for evaluating and optimizing thermodynamics of engineering processes.

Los surfactantes son moléculas anfifílicas, con una cabeza solvofílica y una cola solvofóbica. Cuando la concentración de surfactante en solución es suficientemente alta, las moléculas se agregan entre ellas para proteger las partes solvofóbicas del contacto con el medio. Tales agregados pueden tener forma y tamaño muy diferentes, dependiendo del surfactante y de las condiciones del sistema. La auto-organización de los surfactantes (self-assembly), debida a un compromiso energético y entrópico de su estructura molecular, es la clave que permite observar cristales líquidos muy ordenados. En presencia de un precursor inorgánico y dependiendo de las interacciones que este precursor establece con el surfactante, se puede observar la formación del material híbrido. Los materiales híbridos constituyen un paso intermedio fundamental para la síntesis de los materiales mesoporosos ordenados, los cuales se obtienen eliminando la matriz orgánica (surfactante) del substrato inorgánico. El presente estudio tiene como principal objetivo estudiar bajo cuales condiciones los sistemas formados por un surfactante, un precursor inorgánico y un solvente, se auto-organizan para dar lugar a estructuras híbridas muy ordenadas. En particular nos proponemos individuar cuales son las características más importantes que los precursores inorgánicos deberían tener para poder observar la formación de materiales mesoporosos ordenados.Simulaciones Monte Carlo en el colectivo canónico han sido utilizadas para analizar la agregación de los surfactantes en estructuras complejas, como micelas, cilindros organizados en forma hexagonal, o laminas, a partir de configuraciones totalmente desordenadas. Con particular interés hemos analizado el rango de condiciones que llevan a la formación de las estructuras cilíndricas, y estas mismas estructuras han sido comparadas en función de algunas importantes características morfológicas, como el tamaño de poro, el grosor de las paredes, la presencia y accesibilidad de los grupos funcionales en los poros. El modelo usado representa las moléculas de surfactante y de precursor inorgánico como cadenas de segmentos en una red tridimensional que discretiza el espacio en sitios de volumen unitario. Este modelo no entra en el detalle de las características físicas y químicas de las moléculas, pero permite reproducir su agregación en estructuras complejas en un tiempo de cálculo muy razonable. La separación de fase ha sido también evaluada recorriendo a una teoría de campo medio, la quasi-chemical theory, que, aunque no pueda predecir la formación de estructuras ordenadas, ha sido muy útil para confirmar los resultados de las simulaciones, sobretodo cuando no se observa formación de fases ordenadas. El estudio de surfactantes distintos, uno modelado por una cadena lineal y otro con una cabeza ramificada, nos ha permitido evaluar algunas diferencias estructurales de los materiales obtenidos. La ramificación de la cabeza, que merecería un estudio más profundo del que hemos descrito en este trabajo, ha evidenciado unas interesantes consecuencias en el tamaño de los poros. Este mismo surfactante con cabeza ramificada ha sido elegido para la síntesis de agregados cilíndricos utilizados como templates en la formación, agregación, y condensación de una capa de sílica modelada a través de un modelo atomístico. En particular, hemos aislado uno de los cilindros presentes en los cristales líquidos de estructura hexagonal, y a su alrededor hemos simulado la formación de una capa de sílica utilizando un modelo atomístico. De esta forma, hemos obtenido un poro típico de una estructura mesoporosa más realista, sin necesidad de asumir una forma mas o menos cilíndrica del template, por ser este generado de la auto-agregación del surfactante. / Surfactants are amphiphilic molecules with a solvophilic head and a solvophobic tail. When the surfactant concentration in a given solution is high enough, the molecules aggregate between them to shield the solvophobic part from the contact with the solvent. Such aggregates can show very different sizes and shapes, according to the surfactant and the conditions of the system. The surfactants self-assembly, being due to an energetic and entropic compromise of their molecular structure, is fundamental to observe the formation of very ordered liquid crystals. In the presence of an inorganic precursor and depending on the interactions established between such a precursor and the surfactant, it is possible to synthesize a hybrid material. Hybrid materials are the key step for the formation of periodic ordered mesoporous materials, which can be obtained by eliminating the organic soft matter (the surfactants) from the inorganic framework. Periodic ordered mesoporous materials represent an important family of porous materials as they find a large number of applications in several industrial fields, such as separations, catalysis, sensors, etc. In the last decade, the range of potential applications has increased with the possibility of functionalizing the pore walls by incorporating organic groups during the synthesis, or with post-synthesis treatments.In this work, we are interested in studying the formation of ordered materials when hybrid organic-inorganic precursors are used. Lattice Monte Carlo simulations in the NVT ensemble have been used to study the equilibrium phase behavior and the synthesis of self-assembling ordered mesoporous materials formed by an organic template with amphiphilic properties and an inorganic precursor in a model solvent. Three classes of inorganic precursors have been modeled: terminal (R-Si-(OEt)3) and bridging ((EtO)3-Si-R-Si-(OEt)3)) organosilica precursors (OSPs), along with pure silica precursors (Si-(OEt)4). Each class has been studied by analyzing its solubility in the solvent and the solvophobicity of the inorganic group. At high surfactant concentrations, periodic ordered structures, such as hexagonally-ordered cylinders or lamellas, can be obtained depending on the OSPs used. In particular, ordered structures were obtained in a wider range of conditions when bridging hydrophilic OSPs have been used, because a higher surfactant concentration was reached in the phase where the material was formed. Terminal and bridging OSPs produced ordered structures only when the organic group is solvophilic. In this case, a partial solubility between the precursor and the solvent or a lower temperature favored the formation of ordered phases.With particular interest, we have analyzed the range of conditions leaving to the formation of cylindrical structures, which have been evaluated according to the pore size distribution, the pore wall thickness, the distribution and the accessibility of the functional organic groups around the pores. The phase behavior has been also evaluated by applying the quasi-chemical theory, which cannot predict the formation of ordered structures, but was very useful to confirm the results of simulations, especially when no ordered structures were observed.The study of the phase and aggregation behavior of two different surfactants, one modeled by a linear chain of head segments and the other modeled by a branched-head, permitted us to evaluate some structural differences of the materials obtained.

No description available.

Fixed-collision correlated sampling for Monte Carlo (MC) simulations is a method which can be used in order to shorten the simulation time for brachytherapy treatment planning in a 3D patient geometry. The increased efficiency compared to conventional MC simulation is measured by efficiency gain. However, a previous study showed that, in some cases, PDFs (probability density functions) of estimates of the efficiency gain, simulated using resampling and other MC methods, were multimodal with values below 1. This means that the method was less effective than conventional sampling for these cases. The aims of this thesis were to trace the causes of the multimodal distributions and to propose techniques to mitigate the problem caused by photons with high statistical weights.Two simulation environments were used for the study case, a homogeneous and a heterogeneous environment. The homogenous environment consisted of a water sphere with the radius 100mm. For the heterogeneous environment a cylindrical block of tungsten alloy (diameter 15 mm, height 2.5 mm) was placed in the water sphere. The sphere was divided into an array of cubic voxels of size 2.5 mm x 2.5 mm x 2.5 mm for dose calculations. A photon source was positioned in the middle of the water sphere and emitted photons with the energy 400 keV.It was found that the low values and multimodal PDFs for the efficiency gain estimates originated from photons depositing high values of energy in some voxels in the heterogeneous environment. The high energy deposits were due to extremely high statistical weights of photons interacting repeatedly in the highly attenuating tungsten cylinder. When photon histories contributing to the rare events of high energy deposits (outliers) were removed, the PDFs became uni-modal and efficiency gain increased. However, removing outliers will cause results to be biased calling for other techniques to handle the problem with high statistical weights.One way to resolve the problem in the current implementation of the fixed-collision correlated sampling scheme in PTRAN (the MC code used) could be to split photons with high statistical weights into several photons with the same sum weight as the initial photon. The splitting of photons will result in more time consuming simulations in areas with high attenuation coefficients, which may not be the areas of interest. This could be resolved by using Russian roulette, eliminating some of the photons with high statistical weight in such areas.Fixed-collision correlated sampling for Monte Carlo (MC) simulations is a method which can be used in order to shorten the simulation time for brachytherapy treatment planning in a 3D patient geometry. The increased efficiency compared to conventional MC simulation is measured by efficiency gain. However, a previous study showed that, in some cases, PDFs (probability density functions) of estimates of the efficiency gain, simulated using resampling and other MC methods, were multimodal with values below 1. This means that the method was less effective than conventional sampling for these cases. The aims of this thesis were to trace the causes of the multimodal distributions and to propose techniques to mitigate the problem caused by photons with high statistical weights.Two simulation environments were used for the study case, a homogeneous and a heterogeneous environment. The homogenous environment consisted of a water sphere with the radius 100mm. For the heterogeneous environment a cylindrical block of tungsten alloy (diameter 15 mm, height 2.5 mm) was placed in the water sphere. The sphere was divided into an array of cubic voxels of size 2.5 mm x 2.5 mm x 2.5 mm for dose calculations. A photon source was positioned in the middle of the water sphere and emitted photons with the energy 400 keV.It was found that the low values and multimodal PDFs for the efficiency gain estimates originated from photons depositing high values of energy in some voxels in the heterogeneous environment. The high energy deposits were due to extremely high statistical weights of photons interacting repeatedly in the highly attenuating tungsten cylinder. When photon histories contributing to the rare events of high energy deposits (outliers) were removed, the PDFs became uni-modal and efficiency gain increased. However, removing outliers will cause results to be biased calling for other techniques to handle the problem with high statistical weights.One way to resolve the problem in the current implementation of the fixed-collision correlated sampling scheme in PTRAN (the MC code used) could be to split photons with high statistical weights into several photons with the same sum weight as the initial photon. The splitting of photons will result in more time consuming simulations in areas with high attenuation coefficients, which may not be the areas of interest. This could be resolved by using Russian roulette, eliminating some of the photons with high statistical weight in such areas.

Moral contractarianism, as demonstrated in the work of David Gauthier, is an attempt to derive moral principles from the non-moral premises of rational choice. However, this contractarian enterprise runs aground because it is unable to show that agents would commit to norms in a fairly realistic world where knowledge is limited in space and time, where random shocks are likely, and where agents can be arbitrarily differentiated from one another. In a world like this, agents will find that the most "rational" strategy is to behave "non-rationally," imitating the behavior of others in their vicinity and preserving a limited sort of ignorance.

Recently it has been suggested that the use of neuromechanical simulations could be used to further our understanding of the neural control mechanisms involved in the control of animal locomotion. The models used to carry out these neuromechanical simulations typically consist of a representation of the neural control systems involved in walking and a representation of the mechanical locomotor apparatus. These separate models are then integrated to produce motion of the locomotor apparatus based on signals that are generated by the neural control models. Typically in past neuromechanical simulations of human walking the parameters of the neural control model have been specifically chosen to produce a walking pattern that resembles the normal human walking pattern as closely as possible. Relatively few of these studies have systematically tested the effect of manipulating the control parameters on the walking pattern that is produced by the locomotor apparatus. The goal of this thesis was to develop models of the locomotor control system and the human locomotor apparatus and systematically manipulate several parameters of the neural control system and determine what effects these parameters would have on the walking pattern of the mechanical model. Specifically neural control models were created of the Central Pattern Generator (CPG), feedback mechanisms from muscle spindles and contact sensors that detect when the foot was contact with the ground. Two models of the human locomotor apparatus were used to evaluate the outputs of the neural control systems; the first was a rod pendulum, which represented a swinging lower-limb, while the second was a 5-segment biped model, which included contact dynamics with the ground and a support system model to maintain balance. The first study of this thesis tested the ability of a CPG model to control the frequency and amplitude of the pendulum model of the lower-limb, with a strictly feedforward control mechanism. It was found that the frequency of the pendulum’s motion was directly linked (or entrained) to the frequency of the CPG’s output. It was also found that the amplitude of the pendulum’s motion was affected by the frequency of the CPG’s output, with the greatest amplitude of motion occurring when the frequency of the CPG matched the pendulum’s natural frequency. The effects of altering several other parameters of the pendulum model, such as the initial angle, the magnitude of the applied viscous damping or the moment arms of the muscles, were also analyzed. The second study again used the pendulum model, and added feedback to the neural control model, via output from simulated muscle spindles. The output from these spindle models was used to trigger a simulated stretch reflex. It was found that the addition of feedback led to sensory entrainment of the CPG output to the natural frequency of the pendulum. The effects of altering the muscle spindle’s sensitivity to length and velocity changes were also examined. The ability of this type of feedback system to respond to mechanical perturbations was also analyzed. The third and fourth studies used a biped model of the musculoskeletal system to assess the effects of altering the parameters of the neural control systems that were developed in the first two studies. In the third study, the neural control system consisted only of feedforward control from the CPG model. It was found that the walking speed of the biped model could be controlled by altering the frequency of the CPG’s output. It was also observed that variability of the walking pattern was decreased when there was a moderate level of inhibition between the CPGs of the left and right hip joints. The final study added feedback from muscle receptors and from contact sensors with the ground. It was found that the most important source of feedback was from the contact sensors to the extensor centres of the CPG. This feedback increased the level of extensor activity and produced significantly faster walking speeds when compared to other types of feedback. This thesis was successful in testing the effects of several control parameters of the neural control system on the movement of mechanical systems. Particularly important findings included the importance of connectivity between the CPGs of the left and right hip joints and positive feedback regarding the loading of the limb for establishing an appropriate forward walking speed. It is hoped that the models developed in this thesis can form the basis of future neuromechanical models and that the simulations carried out in this thesis help provide a better understanding of the interactions between neural and mechanical systems during the control of locomotion.

Hot microelectrodes are very small electrodes (usually 1 100 µm in diameter), which have a surface temperature much higher than the temperature in the bulk solution. In this work, the heating is achieved by applying an alternating potential of very high frequency (100 MHz 2 GHz) and of high amplitude (up to 2.8 Vrms) to the microelectrode. As a result, very fast (on the order of milliseconds) changes in the temperature of the electrolyte solution surrounding the electrode can be achieved. Due to the size of the heated microelectrodes, the hot zone in solution is small. Therefore, the solution can be easily overheated and temperatures above the boiling point can be reached.<p> The purpose of this research was to investigate and understand the phenomena occurring at ac polarized microelectrodes and to propose new applications of these electrodes. Using both steady-state and fast-scan (10 V/s) cyclic voltammetry measurements, mass transport of redox species has been studied at ac heated microelectrodes. It has been established that the convection at hot-disk microelectrodes is driven primarily by the electrothermal flow of an electrolyte solution. In addition, other effects such as ac dielectrophoresis and Soret (nonisothermal) diffusion are also observed. Numerical simulations have been employed to predict the distribution of temperature in the hot zone, the direction and magnitude of the electrothermal force and the solution flow rate, as well as the voltammetric response of hot-disk microelectrodes. The results of the simulations agree well with the experimental observations. Theoretical findings of this PhD work are very important for the understanding of the fundamentals of high temperature electrochemistry, particularly mass transport. The proposed explanation of the convection mechanism is most likely applicable not only to ac polarized microelectrodes, but also to the microwave heated microelectrodes, since the only difference between these two heating methods is in the way of delivering electrical energy (wired vs. wireless). The results of the studies of Soret diffusion indicate that it contributes significantly to mass transfer of redox species at hot microelectrodes. Taking into account that the magnitude of the Soret effect has been considered negligible by other electrochemists, the results obtained in this work prove the opposite and show that Soret diffusion affects both the faradaic current and the half-wave potential of the redox reaction. Therefore, the Soret effect can not be ignored if working with hot microelectrodes.<p> Hot microelectrodes can have a number of interesting applications. The results of the initial investigations indicate that these electrodes can be successfully used in the arrangement for Scanning Electrochemical Microscopy (such a novel technique is termed Hot-Tip SECM). In addition, the observed dielectrophoretic and electrothermal convection effects can enhance the performance of the electrochemical sensors based on hot microelectrodes. This can lead to the improvement of the detection limits of many biologically important analytes, such as proteins, bacteria and viruses.