In this study, we consider electrostatics contributed from the molecules in the ionic solution. It plays a significant role in determining the binding affinity of molecules and drugs. We develop the overall framework of computing electrostatic properties for three-dimensional molecular structures, including potential, energy, and forces. These properties are derived from Poisson-Boltzmann equation, a partial differential equation that describes the electrostatic behavior of molecules in ionic solutions. In order to compute these properties, we derived new boundary integral equations and designed a boundary element algorithm based on the linear time fast multipole method for solving the linearized Poisson-Boltzmann equation. Meanwhile, a higher-order parametric formulation called algebraic spline model is used for accurate approximation of the unknown solution of the linearized Poisson-Boltzmann equation. Based on algebraic spline model, we represent the normal derivative of electrostatic potential by surrounding electrostatic potential. This representation guarantees the consistent relation between electrostatic potential and its normal derivative. In addition, accurate numerical solution and fast computation for electrostatic energy and forces are also discussed. In addition, we described our hierarchical modeling and parameter optimization of molecular structures. Based on this technique, we can control the scalability of molecular models for electrostatic computation. The numerical test and experimental results show that the proposed techniques offer an efficient and accurate solution for solving the electrostatic problem of molecules. / text

Sediment transport at the watershed scale in the Bluegrass Region of Kentucky is dominated by surface fine grained laminae, streambed, and streambank erosion; high instream sediment storage; and surface erosion processes. All these processes can be impacted by agricultural, urban, and suburban land-uses as well as hydrologic forcing. Understanding sediment transport processes at the watershed scale is a need for budgeting and controlling sediment pollution, and watershed modeling enables investigation of the cumulative effect of sediment processes and the parameters controlling these processes upon the entire sediment budget for a watershed. Sediment transport is being modeled by coupling the hydrologic model Hydrologic Simulations Program-FORTRAN (HSPF) with an in-house conceptually based hydraulic and sediment transport model. The total yield at the watershed outlet as well as the source fractions from surface fine grained lamina, streambed, and streambank sources; deposition; and biological generation within the streambed are predicted with the sediment transport model. Urbanization scenarios are then run on the calibrated model so as to predict the sediment budget for the South Elkhorn watershed for present and future conditions.

Structure and mechanical properties of DNA play a key role in its biological functioning. A lot of well-established conclusions about the DNA structure and its sequence-dependent variabil- ity came from various experimental and computational studies of the Dickerson-Drew dodecamer (DD), a prototypic B-DNA molecule of the sequence (5')CGCGAATTCGCG(3'). In this study we present a detailed analysis of structural and mechan- ical properties of DD based on extensive atomistic molecular dynamics (MD) simulations with explicit representation of wa- ter and ionic environment. We analyze three simulated systems covering different ionic conditions and water models. Two MD trajectories are reported for the first time, one of them being 2.4 µs long. An extensive comparsion with one recent NMR struc- ture and four recent X-ray structures is made. It is found that the end basepairs can adopt two different pairing motifs dur- ing the simulation: the canonical Watson-Crick pair or a non- canonical trans Watson-Crick/Sugar Edge pair. These states can significantly influence the structure of DD even at the third step from the end. A clear relationship is found between the BI/BII backbone substates and the basepair step conformation. A model of rigid bases is used to study mechanical properties of the DNA. The non-local...

Fine-grained access control is a conceptual approach to addressing database security requirements. In relational database management systems, fine-grained access control refers to access restrictions enforced at the row, column, or cell level. While a number of commercial implementations of database fine-grained access control are available, there are presently no generalized approaches to implementing fine-grained access control for relational database management systems. Fine-grained access control is potentially a good solution for database professionals and system architects charged with designing database applications that implement granular security or privacy protection features. However, in the oral tradition of the database community, fine-grained access control is spoken of as imposing significant performance penalties, and is therefore best avoided. Regardless, there are current and emerging social, legal, and economic forces that mandate the need for efficient fine-grained access control in relational database management systems. In the study undertaken, the author was able to quantify the performance costs associated with four common implementations of fine-grained access control for relational database management systems. Security benchmarking was employed as the methodology to quantify performance costs. Synthetic data from the TPC-W benchmark as well as representative data from a real-world application were utilized in the benchmarking process. A simple graph-base performance model for Fine-grained Access Control Evaluation (FACE) was developed from benchmark data collected during the study. The FACE model is intended for use in predicting throughput and response times for relational database management systems that implement fine-grained access control using one of the common fine-grained access control mechanisms - authorization views, the Hippocratic Database, label-based access control, and transparent query rewrite. The author also addresses the issue of scalability for fine-grained access control mechanisms that were evaluated in the study.

Structural and mechanical properties of nucleic acids play a key role in a wide range of biological processes, as well as in the field of nucleic acid nanotechnology. The thesis presents results of several studies focused on modelling these properties. Extensive unrestrained atomic-resolution molecular dynamics (MD) simulations are used to investigate structural dynamics of nucleic acids, and to parametrize their mechanical models. The deformation energy is assumed to be a general quadratic function of suitably chosen internal coordinates. Two types of models are employed which differ in the level of coarse- graining. The first one is based on the description of conformation at the level of individual bases and the second, coarser one is used to study global bending and twisting flexibility. The models are applied to explain mechanical properties of A-tracts in the context of DNA looping and nucleosome positioning, to characterize twist-stretch cou- pled deformations in DNA and RNA, and to predict changes in the properties of damaged DNA that are likely to be relevant for damage recognition and repair. Besides that, we propose a general model of DNA allostery, applied to study the effect of minor groove binding of small ligands and the allosteric coupling between proteins mediated by the DNA. A careful...

La complexité des systèmes embarqués et des applications impose des besoins croissants en puissance de calcul et de consommation énergétique. Couplé au rendement en baisse de la technologie, le monde académique et industriel est toujours en quête d'accélérateurs matériels efficaces en énergie. L'inconvénient d'un accélérateur matériel est qu'il est non programmable, le rendant ainsi dédié à une fonction particulière. La multiplication des accélérateurs dédiés dans les systèmes sur puce conduit à une faible efficacité en surface et pose des problèmes de passage à l'échelle et d'interconnexion. Les accélérateurs programmables fournissent le bon compromis efficacité et flexibilité. Les architectures reconfigurables à gros grains (CGRA) sont composées d'éléments de calcul au niveau mot et constituent un choix prometteur d'accélérateurs programmables. Cette thèse propose d'exploiter le potentiel des architectures reconfigurables à gros grains et de pousser le matériel aux limites énergétiques dans un flot de conception complet. Les contributions de cette thèse sont une architecture de type CGRA, appelé IPA pour Integrated Programmable Array, sa mise en œuvre et son intégration dans un système sur puce, avec le flot de compilation associé qui permet d'exploiter les caractéristiques uniques du nouveau composant, notamment sa capacité à supporter du flot de contrôle. L'efficacité de l'approche est éprouvée à travers le déploiement de plusieurs applications de traitement intensif. L'accélérateur proposé est enfin intégré à PULP, a Parallel Ultra-Low-Power Processing-Platform, pour explorer le bénéfice de ce genre de plate-forme hétérogène ultra basse consommation. / Emerging trends in embedded systems and applications need high throughput and low power consumption. Due to the increasing demand for low power computing and diminishing returns from technology scaling, industry and academia are turning with renewed interest toward energy efficient hardware accelerators. The main drawback of hardware accelerators is that they are not programmable. Therefore, their utilization can be low is they perform one specific function and increasing the number of the accelerators in a system on chip (SoC) causes scalability issues. Programmable accelerators provide flexibility and solve the scalability issues. Coarse-Grained Reconfigurable Array (CGRA) architecture consisting of several processing elements with word level granularity is a promising choice for programmable accelerator. Inspired by the promising characteristics of programmable accelerators, potentials of CGRAs in near threshold computing platforms are studied and an end-to-end CGRA research framework is developed in this thesis. The major contributions of this framework are: CGRA design, implementation, integration in a computing system, and compilation for CGRA. First, the design and implementation of a CGRA named Integrated Programmable Array (IPA) is presented. Next, the problem of mapping applications with control and data flow onto CGRA is formulated. From this formulation, several efficient algorithms are developed using internal resources of a CGRA, with a vision for low power acceleration. The algorithms are integrated into an automated compilation flow. Finally, the IPA accelerator is augmented in PULP - a Parallel Ultra-Low-Power Processing-Platform to explore heterogeneous computing.

"Secondary teachers across the United States are being asked to use formative assessment data to inform their classroom instruction. At the same time, critics of US government’s No Child Left Behind legislation are calling the bill “No Child Left Untested”. Among other things, critics point out that every hour spent assessing students is an hour lost from instruction. But, does it have to be? What if we better integrated assessment into classroom instruction and allowed students to learn during the test? This dissertation emphasizes using the intelligent tutoring system as an assessment system that just so happens to provide instructional assistance during the test. Usually it is believed that assessment get harder if students are allowed to learn during the test, as it’s then like trying to hit a moving target. So, my results are somewhat shocking that by providing tutoring to students while they are assessed I actually improve the assessment of students’ knowledge. Most traditional assessments treat all questions on the test as sampling a single underlying knowledge component. Yet, teachers want detailed, diagnostic reports to inform their instruction. Can we have our cake and eat it, too? In this dissertation, I provide solid evidence that a fine-grained skill model is able to predict state test scores better than coarser-rained models, as well as being used to give teachers more informative feedback that they can reflect on to improve their instruction. The contribution of the dissertation lies in that it established novel assessment methods to better assess students in intelligent tutoring systems. Through analyzing data of more than 1,000 students across two years, it provides strong evidence implying that it is possible to develop a continuous assessment system that can do all three of these things at the same time: 1) accurately and longitudinally assesses students, 2) gives fine grained feedback that is more cognitively diagnostic, and 3) saves classroom instruction time by assessing students while they are getting tutoring. "

"Recently, hydrogel have found to be promising biomaterials since their porous structure and hydrophilicity enables them to absorb a large amount of water. In this study the role of water on the mechanical properties of hydrogel are studied using ab-initio molecular dynamics (MD) and coarse-grained simulations. Condensed-Phased Optimized Molecular Potential (COMPASS) and MARTINI force fields are used in the all-atom atomistic models and coarse-grained simulations, respectively. The crosslinking process is modeled using a novel approach by cyclic NPT and NVT simulations starting from a high temperature, cooling down to a lower temperature to model the curing process. Radial distribution functions for different water contents (20%, 40%, 60% and 80%) have shown the crosslinks atoms are more hydrophilic than the other atoms. Diffusion coefficients are quantified in different water contents and the effect of crosslinking density on the water diffusion is studied. Elasticity parameters are computed by constant strain energy minimization in mechanical deformation simulations. It is shown that an increase in the water content results in a decrease in the elastic. Finally, continuum hyper elastic model of contact lens is studied for three different loading scenarios using Finite Element Model. "

Protein misfolding and aggregation are the cause of many problems within the biopharmaceutical industry and medical fields. Although many experimental studies have been implemented in vivo in order to understand this process, the mechanism occurs in time and length scales inaccessible to conventional experiments. On the other hand, computational studies have shown significant improvement in elucidating key aspects of the aggregation pathways and gain insights to the folding behavior of the proteins. Consequently, this makes computational modeling an ideal complement to experiment in understanding the generic behavior and mechanisms of aggregation. This study is concerned with DynamO, a coarse-grained, off-lattice, general event-driven discontinuous molecular-dynamics simulation package. This simulator offers a unique opportunity to gain insight into the process of protein aggregation by displaying the optimal O(N) asymptotic scaling of the computational cost with the number of particles N, rather than O(NlogN) scaling found in most standard algorithms. The study was split into two loosely related projects: in the first project, a computer model was developed in which the effect of model parameters on folding behavior and characteristics of isolated peptides is investigated. The model parameters include chain stiffness (an overlap parameter defined as the ratio of the hard-core diameter to bond length 'sigma/l'), range of interaction potential 'Gamma', sequence, and chains length 'N '. Based on the model chosen from systems of isolated chains, aggregation in multichain systems is studied. In another project, we simulate various square-well fluid systems with different ranges of interaction potential in order to understand the phase behavior of proteins due to its relevance to aggregation and many bioprocessing events. Changing the model parameters shows different folding behaviors. The model-chains with 64 residues, Gamma equal to 1.1 and sigma/l equal to 1.9 is the least computationally expensive model displaying all the characteristics found in real proteins. We introduce a new order parameter which divides the conformational space into folded and unfolded ensemble-structures, this order parameter corresponds to a transition in the folding behavior of the chains. We define a native state ensemble as an ensemble of structures with small deviation in contact maps for spheres inaccessible to the solvent defined as the core of the chain. This native ensemble corresponds to the structures exhibiting low-temperature fluctuations simulating the 'breathing motions' of real proteins which is considered responsible for their catalytic activities. On the other hand, the non-native ensemble unfolds at higher temperatures, which increases the propensity for aggregation by forming intermolecular contacts, and therefore reproduce the behavior of proteins under severe solution conditions which occurs in bio- processing (this includes high concentration, temperature, pressure, pH ...). The behavior of multichain systems shows that it is possible to correlate the aggregation propensity of chains at room temperature from the behavior of chains in isolated system at the collapse temperature, which in turn correlate with the stability of the low-T ensemble. In the second project, we developed a more efficient way of calculating the critical temperature in SW fluids even for strongly short-ranged systems which are especially difficult to simulate. In the supercritical region, every isotherm obeys the linear equation for the pressure with a high precision within the bounds of uncertainty. The linear equation pm = p0 + Rm with Rm being the constant isothermal rigidity (dp/d)T . The constant rigidity can be used to estimate directly a critical temperature (Tc) and critical pressure (pc), respectively, and also to obtain the pressures and densities of the percolation loci based on an empirical quadratic nature of change in pressure with densities outside the percolation loci. Identifying the critical temperature and how it depends on the pair potential is very important in formulations with a growing need to predict when the solution will go opalescent.

La dynamique moléculaire gros-grain nous permet d'étudier l'interface polymère / silice. En particulier, nous comparons les comportements divergents du poly(acrylamide) (PAAm) et du poly(N,Ndimethylacrylamide) (PDMA) sur la surface de silice. Tout d'abord, nous montrons que les comportements macroscopiques du PAAm et du PDMA sont correctement représentés par un modèle contenant un solvant explicite. Nous utilisons ensuite la méthode d'énergie libre umbrella sampling afin d'examiner le détachement du PAAm et du PDMA de la surface de silice et d'étudier les caractéristiques importantes qui permettent ou non à la chaîne de polymère de rester adsorbée sur la surface de silice. Nous soulignons l'importance des interactions intra moléculaires au sein du polymère ainsi que les interactions polymère/surface qui déterminent l'adsorption du polymère sur la silice. De manière surprenante, les interactions solvant/polymère et solvant/surface ne sont pas des critères discriminants lors de l'adsorption des polymères sur la surface. Les polymères sont finalement contraints de s'adsorber sur deux surfaces de silice séparées de 200 Å. Ce système nous permet d'analyser l'évolution de la labilité des monomères ainsi que la force appliquée par les monomères sur la surface quand la distance entre les deux surfaces augmente. / Polymer/silica interface is investigated using coarse-grained molecular dynamics simulations. In particular, the different behavior of poly(acrylamide) (PAAm) and of poly(N,N-dimethylacrylamide) (PDMA) on the silica surface is compared. First, we show that the macroscopic behavior of PAAm and of PDMA is correctly represented by a model containing an explicit solvent. Then, the umbrella sampling free energy method is used to probe the detachment of PAAm and of PDMA from a silica surface and to investigate important features that allow - or not - the polymer chain to remain adsorbed on the silica surface. We proved that intramolecular interactions within the polymer and polymer/surface interactions are of first importance for the polymer chain to adsorb on silica. Surprisingly, solvent/polymer as well as solvent/surface interactions are not discriminating criteria. Polymer chains are finally constrained to a particular configuration where one chain is adsorbed on two silica surfaces that are 200 Å apart. This yields interesting insights into the evolution of the monomers lability and of the surface/polymer strength interaction when the two silica surfaces are moved apart.