No description available.

The Langevin equation is a stochastic differential equation frequently used in molecular dynamics for simulating systems with a constant temperature. Recent developments have given rise to wide uses of Langevin dynamics at different levels of spatial resolution, which necessitate time step and friction parameter choices outside of the range for which many existing temporal discretization methods were originally developed. We first study the GJ--F, BAOAB and BBK numerical algorithms, originally developed for atomistic simulations, on a coarse-grained polymer melt, paying close attention to the large time step regime. The results of this study then inspire our search for new algorithms and lead to a general class of velocity Verlet-based time-stepping schemes designed to perform well for all parameter regions, by ensuring that they faithfully reproduce statistical quantities for the case of a free particle and harmonic oscillator. This family of methods depends on the choice of a single free parameter function and we explore some of the methods defined for certain choices of this parameter on realistic coarse-grained and atomistic molecular systems relevant in material and bio-molecular science. In addition, we provide an equivalent splitting formulation of this one-parameter family which allows for enhanced insight into the hidden time scaling induced by the choice of the free parameter in the Hamiltonian and stochastic time scales. / Mathematics

Plasticizers are a commonly used additive used in the polymer industry to make the plastic more pliable by reducing the glass transition temperature, Tg and Young's modulus, Y. As the plasticizer aids in polymer process-ability and making it suitable for applications from industrial cables to sensitive medical equipment, the mechanism of plasticization is not fully understood. There are three theories used to explain plasticization: lubricity theory, gel theory, and free volume theory. The latter is a fundamental concept of polymer science that is used to calculate many polymer properties, but they all do not give a clear picture on plasticization. With molecular dynamics (MD) simulation, a coarse-grained (CG) model - which consist of a simple bead-spring model that generalizes particles as a bead and connects them via a finite spring – is used to explore the impact of plasticizer size throughout the polymer system. The interaction characteristics of the plasticizer is explored by representing the plasticizer molecules as a single bead of varying size. This gives better control on the variability of the mixture and pinpoint the significant contributions to plasticization. A path to understanding the the mechanism of plasticization will give insight in glass formation, and can later be used to find an optimal plasticizer architecture to minimize the migration of the additive by tuning the compatibility. Current results show a decoupling between the Tg and Y of the polymer-additive system. The overall understanding of finite-size effects shows: as additive of increasing size is added, the polymer free volume increases which in-turn would decrease the Y, but Tg is shown to increase because the polymer and additive are not as mobile to reduce caging effect of monomeric units. / Thesis / Master of Applied Science (MASc)

Yes / Inhaled nanoparticles (NPs) are experienced by the first biological barrier inside the alveolus known as lung surfactant (LS), a surface tension reducing agent, consisting of phospholipids and proteins in the form of the monolayer at the air-water interface. The monolayer surface tension is continuously regulated by the alveolus compression and expansion and protects the alveoli from collapsing. Inhaled NPs can reach deep into the lungs and interfere with the biophysical properties of the lung components. The interaction mechanisms of bare gold nanoparticles (AuNPs) with the LS monolayer and the consequences of the interactions on lung function are not well understood. Coarse-grained molecular dynamics simulations were carried out to elucidate the interactions of AuNPs with simplified LS monolayers at the nanoscale. It was observed that the interactions of AuNPs and LS components deform the monolayer structure, change the biophysical properties of LS and create pores in the monolayer, which all interfere with the normal lungs function. The results also indicate that AuNP concentrations >0.1 mol% (of AuNPs/lipids) hinder the lowering of the LS surface tension, a prerequisite of the normal breathing process. Overall, these findings could help to identify the possible consequences of airborne NPs inhalation and their contribution to the potential development of various lung diseases. / University of Technology Sydney (UTS) FEIT Research Scholarship, UTS IRS (S.I.H.), 2018 Blue Sky scheme–Suvash Saha (Activity 2232368), N.S.G is supported by the Vice-Chancellor fellowship funded by QUT.

[pt] A simulação da adsorção da prednisolona em um modelo de surfactante pulmonar foi realizada com sucesso usando dinâmica molecular coarse grained a uma temperatura de 310 K. O modelo coarse grained da prednisolona foi parametrizado usando o modelo do colesterol e validado utilizando cálculos de coeficientes de partição octanol-água e coeficientes de difusão lateral. O coeficiente de partição octanol-água calculado para prednisolona a 298 K é 3,9 mais ou menos 1,6 que possui um acordo razoável com o valor experimental. O coeficiente de difusão lateral da prednisolona na monocamada mista de DPPC/POPC é estimado ser (6 mais ou menos 4) x10(-7) cm(2) s(-1) a 20 mN m(-1), o que está de acordo com o encontrado para o colesterol. A monocamada mista de DPPC/POPC foi utilizada como modelo de surfactante pulmonar onde moléculas de prednisolona foram adsorvidas formando nanoagregados. Os nanoagregados de prednisolona foram transferidos dentro da monocamada mista DPPC/POPC sendo espalhados na tensão superficial de 20 mN m(-1). A 0 e 10 mN m(-1) os nanoagregados de prednisolona induzem o colapso da monocamada mista DPPC/POPC formando bicamadas. A implicação deste trabalho é que a prednisolona pode apenas ser administrada com surfactante pulmonar utilizando baixas frações em massa de prednisolona por lipídio (menor que 10 por cento). Com frações elevadas, o colapso inativa as propriedades do surfactante pulmonar pela formação de uma bicamada. Os resultados desta pesquisa podem ser utilizados para o desenvolvimento de novos tratamentos clínicos de doenças como a síndrome da angústia respiratória do recém-nascido, asma e doença pulmonar obstrutiva crônica. / [en] The simulation of prednisolone adsorption on a lung surfactant model was successfully performed using coarse grained molecular dynamics at 310 K (dynamics first performed). The coarse grained model for prednisolone was parameterized using a well-established cholesterol model and validated by using calculations of octanol–water partition coefficients and lateral diffusion coefficients. The calculated octanol–water partition coefficient of prednisolone at 298 K is 3.9 more or less 1.6, which is in reasonable agreement with experiment. The lateral diffusion coefficient of prednisolone in the DPPC/POPC mixed monolayer is estimated to be (6 more or less 4) x10(-7) cm(2) s(-1) at 20 mN m(-1), which is in agreement with that found for cholesterol. The DPPC/POPC mixed monolayer was used as lung surfactant model where prednisolone molecules were adsorbed forming nanoaggregates. The nanoaggregates of prednisolone were transferred into the DPPC/POPC mixed monolayer being spread at the surface tension of 20 mN m(-1). At 0 and 10 mN m(-1) , the prednisolone nanoaggregates induce the collapse of the DPPC/POPC mixed monolayer forming a bilayer. The implications of this work are that prednisolone may only be administered with lung surfactant by using low mass fractions of prednisolone per lipid (less than 10 percent). And, with high fractions, the collapse inactivates the properties of the lung surfactant by forming a bilayer. The results of this research can be used to develop new clinical treatments for diseases such as respiratory distress syndrome of the newborn, asthma and chronic obstructive pulmonary disease.

Nous avons tous l'intuition qu'un travail peut être réalisé en beaucoup moins de temps s'il est réparti entre plusieurs personnes ou sur plusieurs machines. Cette notion se nomme le parallélisme qui peut se définir comme l'état de ce qui se développe dans la même direction ou en même temps. C'est naturellement que la notion de parallélisme a été appliquée aux ordinateurs. De ce fait, il a été possible de répondre aux besoins de puissance nécessaire à la réalisation de projets gourmands en temps de calculs et en taille mémoire. Le parallélisme combiné à une algorithmique performante permet de gagner du temps afin de répondre au mieux à d'importants besoins. Il rompt avec l'approche classique qui consiste à gagner de la vitesse en effectuant plus rapidement chaque opération, approche bornée par les lois de la physique. La notion de parallélisme a donc grandement contribué à la multiplication des modèles informatiques. <br /><br />Nous nous intéresserons au modèle systolique et au modèle parallèle à gros grains baptisé (Coarse Grained Multicomputers). Le modèle CGM a été proposé par F. Dehne et al. et il possède des propriétés qui le rendent très intéressant d'un point de vue pratique. Il est parfaitement adapté à la modélisation des architectures existantes pour lesquelles le nombre de processeurs peut être de plusieurs milliers et la taille des données peut atteindre plusieurs milliards d'octets. Un algorithme développé pour ce modèle est constitué de calculs locaux utilisant, si possible, des algorithmes séquentiels optimaux et de rondes de communication dont le nombre doit être indépendant de la taille des données à traiter. Le modèle CGM est donc très intéressant d'un point de vue économique. En effet, ce modèle est indépendant des architectures réelles et permet de réutiliser des algorithmes séquentiels efficaces, ce qui le rend très portable. <br /><br />Dans cette thèse nous nous intéressons à des problèmes d'algorithmique du texte. Ces problèmes peuvent améliorer la compression de données ou bien être utilisés en bio-informatique. Ainsi, nous proposons des solutions CGM aux problèmes de recherche de la plus longue sous-suite croissante, de la plus longue sous-suite commune à deux mots, du plus long suffixe répété en chaque caractère d'un mot et de répétitions. Pour cela, nous sommes partis de solutions systoliques existantes que nous avons adaptées au modèle CGM. Le but de ce travail est en fait double. D'une part, nous proposons pour la première fois des solutions CGM à ces quatre problèmes. D'autre part, nous montrons comment des solutions systoliques peuvent être dérivées en algorithmes CGM. En effet, de nombreux problèmes ont été étudiés sur des architectures systoliques, c'est à dire des machines dédiées, non réutilisables pour d'autres problèmes. Le modèle CGM quant à lui permet de travailler avec des machines peu coûteuses et réutilisables à souhaits. De plus, l'expérience acquise au cours de ces travaux nous permet d'avoir une bonne idée des solutions systoliques adaptables au modèle CGM. Ceci pourrait permettre de consolider le pont existant entre modèles à grains fins et modèles à gros grains. <br /><br />Nous finissons cette thèse par une discussion sur l'équilibrage de charge des solutions proposées et sur la prédictivité de l'adaptation d'autres solutions systoliques au modèle CGM.

Coarse-grained beaches are particularly prevalent in the UK, composed of accumulations of either gravel, or mixed sand and gravel sediments. The aim of the work presented in this thesis is to improve capabilities for predicting coarse-grained beach 2D profile development. In particular, the effects of infiltration and sediment sorting are considered. In this study, the public domain numerical model, XBeach (v12) is developed further. This model was initially developed for studying sandy environments especially for the case of dune erosion. Here, the model is modified to enhance its capability to predict beach profile change on coarse-grained beaches. Improvements include: use of Lagrangian interpretation of velocity in place of Eulerian for driving sediment movement; introduction of a new morphological module based upon Soulsby’s sediment transport equation for waves and currents; incorporation of Packwood’s infiltration approach in the unsaturated area of the swash region; and implementation of a multiple sediment fraction algorithm for sediment sorting of mixed sediments. These changes are suggested and justified in order to significantly improve the application of this model to gravel and mixed beaches, especially with regard to swash velocity asymmetry which is responsible for development of the steep accretionary phase steep berm above waterline and sediment sorting. A comparison between model simulation and large scale experiments is presented with particular regard to the tendency for onshore transport and profile steepening during calm conditions; offshore transport and profile flattening during storm conditions; and sediment sorting in the swash zone. Data used for this and the model calibration comes from the Large Wave Channel (GWK) of the Coastal Research Centre (FZK) in Hannover, Germany. The results are found to agree well with the measured experimental data on gravel beach profile evolution. This is due to the inclusion of infiltration in the model which weakens the backwash volume and velocity in a more satisfying manner than through the use of asymmetric swash friction and transport coefficient. The model also simulates sediment sorting of a mixed sediment beach. However, the profile comparisons were not satisfactory due to limitations of the numerical model such as the constant permeability rate used throughout the simulation and the non-conservation of the sediment volume in the laboratory data by an order of 50%. From the simulation, it was found that the fine sediment moves offshore and the coarser sediment moves onshore. This is because of infiltration weakens the backwash velocity; the coarser sediment moving onshore barely moves back offshore while the fine sediment remains in motion. This pattern agrees with the pattern obtained from sediment samples analysis in the experiment and provides an explanation for the existence of composite beaches. The model is also shown to be capable of switching from accretionary to erosive conditions as the wave conditions become more storm-like. Again, the model simulations were in a good agreement with the observations from the GWK dataset. Numerical model simulations on the effects of the tidal cycle on coarse-grained beach profile evolution were also carried out. This preliminary investigation showed that the model was able to predict the anticipated profile change associated with a coarse-grained beach under such wave and tidal forcing. Tidally forced accretion and erosion were compared with those predicted under similar beach sediments and wave conditions for constant water level. The main differences are that the affected area is wider and the berm is located on the upper beach during flood for both gravel and mixed beaches. Therefore, the model developed in this study can be seen to be a robust tool with which to investigate cross-shore beach profile change on coarse-grained beaches and sediment sorting on mixed beaches. Further work is also indicated.

A range of simulations have been conducted to investigate the behaviour of a diverse set of complex biological membrane systems. The processes of interest have required simulations over extended time and length scales, but without sacrifice of molecular detail. For this reason, the primary technique used has been coarse-grained molecular dynamics (CG MD) simulations, in which small groups of atoms are combined into lower-resolution CG particles. The increased computational efficiency of this technique has allowed simulations with time scales of microseconds, and length scales of hundreds of nm. The membrane-permeabilizing action of the antimicrobial peptide maculatin 1.1 was investigated. This short α-helical peptide is thought to kill bacteria by permeabilizing the plasma membrane, but the exact mechanism has not been confirmed. Multiscale (CG and atomistic) simulations show that maculatin can insert into membranes to form disordered, water-permeable aggregates, while CG simulations of large numbers of peptides resulted in substantial deformation of lipid vesicles. The simulations imply that both pore-forming and lytic mechanisms are available to maculatin 1.1, and that the predominance of either depends on conditions such as peptide concentration and membrane composition. A generalized study of membrane protein aggregation was conducted via CG simulations of lipid bilayers containing multiple copies of model transmembrane proteins: either α-helical bundles or β-barrels. By varying the lipid tail length and the membrane type (planar bilayer or spherical vesicle), the simulations display protein aggregation ranging from negligible to extensive; they show how this biologically important process is modulated by hydrophobic mismatch, membrane curvature, and the structural class or orientation of the protein. The association of influenza hemagglutinin (HA) with putative lipid rafts was investigated by simulating aggregates of HA in a domain-forming membrane. The CG MD study addressed an important limitation of model membrane experiments by investigating the influence of high local protein concentration on membrane phase behaviour. The simulations showed attenuated diffusion of unsaturated lipids within HA aggregates, leading to spontaneous accumulation of raft-type lipids (saturated lipids and cholesterol). A CG model of the entire influenza viral envelope was constructed in realistic dimensions, comprising the three types of viral envelope protein (HA, neuraminidase and M2) inserted into a large lipid vesicle. The study represents one of the largest near-atomistic simulations of a biological membrane to date. It shows how the high concentration of proteins found in the viral envelope can attenuate formation of lipid domains, which may help to explain why lipid rafts do not form on large scales in vivo.

Computer simulations provide a potentially powerful complement to conventional experimental techniques in elucidating the structures, dynamics and interactions of macromolecules. In this thesis, I present three applications of computer simulations to investigate important biomolecules with sizes ranging from two-residue peptides, to proteins, and to whole chromosome structures. First, I describe the results of 441 independent explicit-solvent molecular dynamics (MD) simulations of all possible two-residue peptides that contain the 20 standard amino acids with neutral and protonated histidine. 3JHNHα coupling constants and δHα chemical shifts calculated from the MD simulations correlated quite well with recently published experimental measurements for a corresponding set of two-residue peptides. Neighboring residue effects (NREs) on the average 3JHNHα and δHα values of adjacent residues were also reasonably well reproduced. The intrinsic conformational preferences of each residue, and their NREs on the conformational preferences of adjacent residues, were analyzed. Finally, these NREs were compared with corresponding effects observed in a coil library and the average β-turn preferences of all residue types were determined. Second, I compare the abilities of three derivatives of the Amber ff99SB force field to reproduce a recent report of 3JHNHα scalar coupling constants for hundreds of two-residue peptides. All-atom MD simulations of 256 two-residue peptides were performed and the results showed that a recently-developed force field (RSFF2) produced a dramatic improvement in the agreement with experimental 3JHNHα coupling constants. I further show that RSFF2 also improved modestly agreement with experimental 3JHNHα coupling constants of five model proteins. However, an analysis of NREs on the 3JHNHα coupling constants of the two-residue peptides indicated little difference between the force fields’ abilities to reproduce experimental NREs. I speculate that this might indicate limitations in the force fields’ descriptions of nonbonded interactions between adjacent side chains or with terminal capping groups. Finally, coarse-grained (CG) models and multi-scale modeling methods are used to develop structural models of entire E. coli chromosomes confined within the experimentally-determined volume of the nucleoid. The final resolution of the chromosome structures built here was one-nucleotide-per-bead (1 NTB), which represents a significant increase in resolution relative to previously published CG chromosome models, in which one bead corresponds to hundreds or even thousands of basepairs. Based on the high-resolution final 1 NTB structures, important physical properties such as major and minor groove widths, distributions of local DNA bending angles, and topological parameters (Linking Number (Lk), Twist (Tw) and Writhe (Wr)) were accurately computed and compared with experimental measurements or predictions from a worm-like chain (WLC) model. All these analyses indicated that the chromosome models built in this study are reasonable at a microscopic level. This chromosome model provides a significant step toward the goal of building a whole-cell model of a bacterial cell.

Scheduling, placement, and routing are important steps in Very Large Scale Integration (VLSI) design. Researchers have developed numerous techniques to solve placement and routing problems. As the complexity of Application Specific Integrated Circuits (ASICs) increased over the past decades, so did the demand for improved place and route techniques. The primary objective of these place and route approaches has typically been wirelength minimization due to its impact on signal delay and design performance. With the advent of Field Programmable Gate Arrays (FPGAs), the same place and route techniques were applied to FPGA-based design. However, traditional place and route techniques may not work for Coarse-Grained Reconfigurable Architectures (CGRAs), which are reconfigurable devices offering wider path widths than FPGAs and more flexibility than ASICs, due to the differences in architecture and routing network. Further, the routing network of several types of CGRAs, including the Field Programmable Object Array (FPOA), has deterministic timing as compared to the routing fabric of most ASICs and FPGAs reported in the literature. This necessitates a fresh look at alternative approaches to place and route designs. This dissertation presents a finite domain constraint-based, delay-aware placement and routing methodology targeting an FPOA. The proposed methodology takes advantage of the deterministic routing network of CGRAs to perform a delay aware placement.