Dissertations / Theses on the topic 'Interaction functionals'

This thesis is a contribution to the mathematical theory of Hyperbolic Conservation Laws. Three are the main results which we collect in this work. The first and the second result (denoted in the thesis by Theorem A and Theorem B respectively) deal with the following problem. The most comprehensive result about existence, uniqueness and stability of the solution to the Cauchy problem \begin{equation}\tag{$\mathcal C$} \label{E:abstract} \begin{cases} u_t + F(u)_x = 0, \\u(0, x) = \bar u(x), \end{cases} \end{equation} where $F: \R^N \to \R^N$ is strictly hyperbolic, $u = u(t,x) \in \R^N$, $t \geq 0$, $x \in \R$, $\TV(\bar u) \ll 1$, can be found in [Bianchini, Bressan 2005], where the well-posedness of \eqref{E:abstract} is proved by means of vanishing viscosity approximations. After the paper [Bianchini, Bressan 2005], however, it seemed worthwhile to develop a \emph{purely hyperbolic} theory (based, as in the genuinely nonlinear case, on Glimm or wavefront tracking approximations, and not on vanishing viscosity parabolic approximations) to prove existence, uniqueness and stability results. The reason of this interest can be mainly found in the fact that hyperbolic approximate solutions are much easier to study and to visualize than parabolic ones. Theorems A and B in this thesis are a contribution to this line of research. In particular, Theorem A proves an estimate on the change of the speed of the wavefronts present in a Glimm approximate solution when two of them interact; Theorem B proves the convergence of the Glimm approximate solutions to the weak admissible solution of \eqref{E:abstract} and provides also an estimate on the rate of convergence. Both theorems are proved in the most general setting when no assumption on $F$ is made except the strict hyperbolicity. The third result of the thesis, denoted by Theorem C, deals with the Lagrangian structure of the solution to \eqref{E:abstract}. The notion of Lagrangian flow is a well-established concept in the theory of the transport equation and in the study of some particular system of conservation laws, like the Euler equation. However, as far as we know, the general system of conservations laws \eqref{E:abstract} has never been studied from a Lagrangian point of view. This is exactly the subject of Theorem C, where a Lagrangian representation for the solution to the system \eqref{E:abstract} is explicitly constructed. The main reasons which led us to look for a Lagrangian representation of the solution of \eqref{E:abstract} are two: on one side, this Lagrangian representation provides the continuous counterpart in the exact solution of \eqref{E:abstract} to the well established theory of wavefront approximations; on the other side, it can lead to a deeper understanding of the behavior of the solutions in the general setting, when the characteristic field are not genuinely nonlinear or linearly degenerate.

The emergence of genomics as a discrete field of biology has changed humanity’s understanding of our relationship with bacteria. Sequencing the genome of each newly-discovered bacterial species can reveal novel gene sequences, though the genome may contain genes coding for hundreds or thousands of proteins of unknown function (PUFs). In some cases, these coding sequences appear to be conserved across nearly all bacteria. Exploring the functional roles of these cases ideally requires an integrative, cross-species approach involving not only gene sequences but knowledge of interactions among their products. Protein interactions, studied at genome scale, extend genomics into the field of interactomics. I have employed novel computational methods to provide context for bacterial PUFs and to leverage the rich genomic, proteomic, and interactomic data available for hundreds of bacterial species. The methods employed in this study began with sets of protein complexes. I initially hypothesized that, if protein interactions reveal protein functions and interactions are frequently conserved through protein complexes, then conserved protein functions should be revealed through the extent of conservation of protein complexes and their components. The subsequent analyses revealed how partial protein complex conservation may, unexpectedly, be the rule rather than the exception. Next, I expanded the analysis by combining sets of thousands of experimental protein-protein interactions. Progressing beyond the scope of protein complexes into interactions across full proteomes revealed novel evolutionary consistencies across bacteria but also exposed deficiencies among interactomics-based approaches. I have concluded this study with an expansion beyond bacterial protein interactions and into those involving bacteriophage-encoded proteins. This work concerns emergent evolutionary properties among bacterial proteins. It is primarily intended to serve as a resource for microbiologists but is relevant to any research into evolutionary biology. As microbiomes and their occupants become increasingly critical to human health, similar approaches may become increasingly necessary.

Made available in DSpace on 2016-12-12T20:15:51Z (GMT). No. of bitstreams: 1 Marsal Eduardo Bento.pdf: 1108751 bytes, checksum: c5c36b13c56d8d4fadcee9ddc5a9098e (MD5) Previous issue date: 2014-12-16
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
The development of Density Functional Theory (DFT) has been focused primarily on two main pillars: (1) the pursuit of more accurate exchange-correlation (XC) density functionals; (2) the feasibility of computational implementation when dealing with many-body systems. In this context, this work is aimed on using one-dimensional quantum systems as theoretical laboratories to investigate the implementation of orbital functionals (OFs) of density. By definition, OFs are those which depend only implicitly on the density, via an explicit formulation in terms of Kohn-Sham orbitals. Typical examples are the XC functionals arising from the Perdew-Zunger self-interaction correction (PZSIC). Formally, via Kohn-Sham equations, the implementation of OFs must be performed by means of the optimized effective potential method (OEP), which is known by requiring an excessive computational effort even when dealing with few electrons systems (N ̴ 10). Here, we proceed a systematical investigation aiming to simplify or avoid the OEP procedure, taking as reference the implementation of the PZSIC correction applied to one-dimensional Hubbard chains.
O desenvolvimento da Teoria do Funcional da Densidade (DFT) tem se concentrado, sobretudo, em dois pilares fundamentais: (1) a busca por funcionais de troca e correlação (XC) mais precisos; (2) a viabilidade de implementação computacional diante de sistemas com muitos elétrons. Nesse contexto, o objetivo principal deste trabalho consiste em utilizar sistemas quânticos unidimensionais, mais simples de serem tratados numericamente, como laboratórios teóricos para o desenvolvimento de alternativas de implementação numérica de funcionais orbitais (OFs) da densidade. Por definição, OFs são todos aqueles que dependem apenas implicitamente da densidade, via formulação explícita em termos dos orbitais Kohn-Sham. Exemplos típicos são os funcionais XC advindos da correção de auto-interação de Perdew e Zunger (PZSIC). Formalmente, via equações de Kohn-Sham, a implementação de OFs deve ser procedida por meio do método do potencial efetivo otimizado (OEP) que, no contexto computacional, é conhecido por se tornar demasiadamente custoso, inclusive para sistemas com poucos elétrons (N ̴ 10). Sendo assim, investigamos, de forma sistemática, alternativas de simplificar ou evitar o procedimento OEP, tomando como referência a implementação da correção PZSIC aplicada a cadeias de Hubbard unidimensionais.

Protein-protein interaction networks provide important information about what the biological function of proteins whose roles are unknown might be in a cell. These interaction networks were analyzed by a variety of approaches by running them on a single computer and the roles of the proteins identified were used to predict the function of the proteins unidentified. The functional flow is an approach that takes the network connectivity, distance effect, topology of the network with local and global views into account. With these advantages, that the functional flow produces more accurate results on the prediction of protein functions was presented by the previos conducted researches. However, the application implemented for this approach could not be practically applied on the large and complex network produced for the complex species because of memory limitation. The purpose of this thesis is to provide a new application be implemented on the high computing performance where the application can be scaled on the large data sets. Therefore, Hadoop, one of the open source map/reduce environments, was installed on 18 hosts each of which has eight cores. Method
the first map/reduce job distributes the protein interaction network as a format which allows parallel distributed computing to all the worker nodes, the other map/reduce job generates flows for each known protein function and the role of the proteins unidentified are predicted by accumulating all of these generated flows. It has been observed in the experiments we performed that the application requiring high performance computing can be decomposed into worker nodes efficiently and the application can provide better performance as the resources increase.

We propose a new kind of execution environment where applications can be debugged and re-programmed while they are being used. We call our overall concept interactive programming. We develop some of the key components of interactive programming in the setting of a pure, call-by-value functional language. We illustrate our ideas via a proof-of-concept implementation called lambdaCalc, but leave several important components of the overall vision, including efficient incremental update and scaling to large programs, for future work. Our specific achievements are as follows. First, we show how to reify the execution of a program into a live document which can be interactively decomposed into both sequential steps and parallel slices. We give a novel characterisation of forward and backward dynamic slicing and show that for a fixed computation the two problems describe a Galois connection. Second, we introduce a novel execution indexing scheme which derives execution differences from program differences. Our scheme supports the wholesale reorganisation of a computation via operations such as moves and splices. The programmer is able to see the consequences of edits on the intensional structure of the execution. Where possible, node identity is preserved, allowing an edit to be made whilst an execution is being explored and the changes to be reflected in the user's current view of the execution.

The present study explores the use of interactions for a communicative purpose, when it comes to communicate banking brand values through a website. By establishing important banking values, trust, sincerity and transparency this study investigates how interaction can be used to communicate those values, through the theory of interaction attributes. Using interaction attributes to communicate emotions as well as brand values has been previously investigated. However, not in the setting of banking. Through designing and exploring interactions this study established some important qualities to consider when designing for banking, with the goal of communicating trust, sincerity and transparency. Attributes consistency, expectedness and apparent are favourable, whilst pliability is found to have a negative effect. In addition to these attributes established by previous work, the findings suggest the importance of a new quality, to design interactions that animate slowly over time, as a way to guide the user through the interaction.

Neste trabalho utilizamos sistemas modelos no desenvolvimento, implementação e análise de funcionais orbitais da densidade, focando, em particular, nas correções de autointeração de Perdew-Zunger (PZSIC) e Lundin-Eriksson (LESIC). Aplicamos as correções de auto-interação ao funcional local (LDA) do modelo de Hubbard e de poços quânticos semicondutores, ambos unidimensionais, no caso estático e dependente do tempo, respectivamente. Para o modelo de Hubbard unidimensional, comparamos a LDA, LDA+PZSIC e LDA+LESIC, identificando o desempenho para energias e densidades do estado fundamental, com e sem impurezas locais, além do gap fundamental de energia. Em adição, averiguamos o desempenho diante de cargas fracionárias, estabelecendo conexões com o erro de delocalização da LDA. Mostramos a possibilidade da correta descrição das freqüências das oscilações de Friedel no modelo de Hubbard, além de investigar como a falha da LDA em reproduzir esse aspecto pode estar relacionada com os erros de auto-interação e delocalização. Investigamos ainda as diferentes possibilidades de implementação autoconsistente de qualquer funcional orbital da densidade, analisando a relação entre funcionais aproximados e suas implementações aproximadas. Nos poços quânticos, sob o enfoque dependente do tempo, analisamos a descontinuidade do potencial de troca e correlação ao variarmos o número de partículas, em dois processos distintos: a ionização eletrônica em um poço simples e dissociação de um poço duplo assimétrico. No último caso, avaliamos os efeitos da descontinuidade no número total de partículas em cada poço, revelando os mecanismos que resgatam a neutralidade elétrica durante processos de dissociação, com a correta carga final inteira.
In this work we use model systems to develop, implement and analyse orbital-dependent density functionals, focusing, specifically, on the self-interaction corrections (SICs) of Perdew and Zunger (PZSIC) and of Lundin and Eriksson (LESIC). These self-interaction corrections are applied to the local-density approximation (LDA) for the one-dimensional Hubbard model and for semiconductor quantum wells, in one-dimensional static and time-dependent situations. For the one-dimensional Hubbard model we compare LDA, LDA+PZSIC and LDA+LESIC, and investigate the performance of these approaches for ground-state energies, densities and energy gaps, with and without impurities in the system. We also consider the case of fractional charges, where a connection to the delocalization error of the LDA can be made. We show that in principle a correct description of the frequences of Friedel oscillations in the Hubbard model can be obtained from DFT, and investigate how the failure of the LDA in reproducing this is related to the selfinteraction and delocalization errors. Moreover, we investigate different procedures for the selfconsistent implementation of any orbital-dependent functional, and analyse the question of the interplay between an approximate functional and its approximate implementation. For quantum wells sytems we analyse, in a time-dependent framework, the discontinuity of the exchange-correlation potential under variation of the particle number in two different processes: the ionization of a simple quantum well and the dissociation of an asymmetric double well. In the latter case, we also consider the effect of changes in the particle number in each subwell, thus revealing the mechanism that restores electric neutrality during dissociation, with correct final charge.

ABSTRACT Functional foods can positively influence functions of the body, by improving the health or reducing the risk of disease. Some functional foods contain ‘probiotics’, defined as ‘live microorganisms which when administered in adequate amounts confer a health benefit on the host’. The development and use of in vitro and in vivo protocols to assess the probiotic efficacy of microorganisms are highly encouraged by FAO and WHO. In this thesis, the probiotic potential of the lactic acid bacterium Lactobacillus plantarum, wild type and derivative mutant strains, was investigated. The distinctive cell surface features exhibited by stress gene mutants prompted us to produce, by gene knockout, other L. plantarum defective strains and led us to investigate whether these characteristics could affect host-microbe interaction. The bacterial survival of L. plantarum strains and commercial probiotics was evaluated by designing an in vitro system simulating the transit along the human oro-gastrointestinal tract. Different carrier matrices were assayed in relation to possible prebiotic effects. The bacterial molecular response to such stresses was monitored by analysing the expression of stress, adhesion and probiosis genes. Interaction with the host was studied in vitro by i) assessing bacterial adhesive ability to gut epithelial cells; ii) investigating anti-inflammatory properties and induction of innate immunity genes in human host cells. L. plantarum strains were resistant to the combined stress at the various steps of the simulated oro-gastrointestinal tract. Major decreases in viability were observed mainly under drastic acidic conditions (pH ≤ 2.0) of the gastric compartment. Abiotic stresses associated to the intestinal environment (small intestine) poorly affected bacterial vitality. The protective effect of vehicle matrices correlated with composition and bacterial nutritional needs. A relationship was found between bacterial survival and stress gene pattern. All strains significantly adhered to human intestinal epithelial cells, with the ΔctsR L. plantarum mutant exhibiting the highest adhesion. Colonization ability was improved by addition of prebiotics. Supernatants from all strains of L. plantarum reduced proinflammatory cytokine secretion by activated human immune cells. Induction of immune-related genes resulted generally higher upon incubation with heat-inactivated bacteria, rather than with live ones. For specific genes, a differential transcriptional pattern was observed upon stimulation with the different L. plantarum strains, pointing to a possible role of the knocked out bacterial genes in modulation of host cells response. Particularly, cells from Δhsp18.55 and ΔftsH mutants strongly triggered immune defence genes. This study highlights the relevance of the microbial genetic background in host-probiotic interaction and might contribute to: i) define selection criteria and/or conditions for probiotic screening and delivery; ii) identify candidate bacterial genes and/or molecules involved in probiosis, so to tailor probiotics for specific clinical applications.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2012.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (p. 117-136).
In this thesis, I implemented a method for performing electronic structure calculations, "Constrained Density Functional Theory-- Configuration Interaction" (CDFT-CI), which builds upon the computational strengths of Density Functional Theory and improves upon it by including higher level treatments of electronic correlation which are not readily available in Density-Functional Theory but are a keystone of wavefunction-based electronic structure methods. The method involves using CDFT to construct a small basis of hand-picked states which suffice to reasonably describe the static correlation present in a particular system, and efficiently computing electronic coupling elements between them. Analytical gradients were also implemented, involving computational effort roughly equivalent to the evaluation of an analytical Hessian for an ordinary DFT calculation. The routines were implemented within Q-Chem in a fashion accessible to end users; calculations were performed to assess how CDFT-CI improves reaction transition state energies, and to assess its ability to produce conical intersections, as compared to ordinary DFT. The analytical gradients enabled optimization of reaction transition-state structures, as well as geometry optimization on electronic excited states, with good results.
by Benjamin James Kaduk.
Ph.D.

With an abundance of data resulting from high-throughput technologies, like DNA microarrays, a race has been on the last few years, to determine the structures and functions of genes and their products, the proteins. Inference of gene interactions, lies in the core of these efforts. In all this activity, three important research issues have emerged. First, in much of the current literature on gene regulatory networks, dependencies among variables in our case genes - are assumed to be linear in nature, when in fact, in real-life scenarios this is seldom the case. This disagreement leads to systematic deviation and biased evaluation. Secondly, although the problem of undersampling, features in every piece of work as one of the major causes for poor results, in practice it is overlooked and rarely addressed explicitly. Finally, inference of network structures, although based on rigid mathematical foundations and computational optimizations, often displays poor fitness values and biologically unrealistic link structures, due - to a large extend - to the discovery of pairwise only interactions. In our search for robust, nonlinear measures of dependency, we advocate that mutual information and related information theoretic functionals (conditional mutual information, total correlation) are possibly the most suitable candidates to capture both linear and nonlinear interactions between variables, and resolve higher order dependencies. To address these issues, we researched and implemented under a common framework, a selection nonparametric estimators of mutual information for continuous variables. The focus of their assessment was, their robustness to the limited sample sizes and their expansibility to higher dimensions - important for the detection of more complex interaction structures. Two different assessment scenaria were performed, one with simulated data and one with bootstrapping the estimators in state-of-the-art network inference algorithms and monitor their predictive power and sensitivity. The tests revealed that, in small sample size regimes, there is a significant difference in the performance of different estimators, and naive methods such as uniform binning, gave consistently poor results compared with more sophisticated methods. Finally, a custom, modular mechanism is proposed, for the inference of gene interactions, targeting the identi cation of some of the most common substructures in genetic networks, that we believe will help improve accuracy and predictability scores.

La nucléoline, une des protéines non-ribosomique les plus abondantes du nucléole, semble être impliquée dans de nombreux aspects du métabolisme de l'ADN en plus de son rôle dans la régulation de la transcription par l'ARN polymérase I, la maturation du pré-ARNr et l’assemblage des ribosomes. L'objectif de cette thèse est d'étudier l'interaction de la nucléoline avec la chromatine, et de déchiffrer la fonction de la nucléoline dans la régulation de l’expression génique. Il a été rapporté que la nucléoline est nécessaire pour la transcription des gènes codant pour l'ADN ribosomal in vivo, mais le mécanisme par lequel la nucléoline module la transcription d’ARN polymérase I (Pol I) est inconnue. Dans cette thèse, je montre que l’inhibition de l’expression de la nucléoline par siRNAconduit dans les gènes de l’ADNr à une augmentation de la marque hétérochromatine et une diminution des marques caractéristiques de l’euchromatine. La nucléoline est associée à des gènes ADNr non méthylés et ChIP-seq montrent un fort enrichissement de la nucléoline dans le promoteur et la région codante de l'ADNr. La nucléoline est capable d'interférer avec la liaison de TTF-1 sur le terminateur T0 proches du promoteur inhibant ainsi le recrutement du sous-unité NoRC TIP5 et HDAC1 et la création d'un état répressif hétérochromatine. Cette invasion de macroH2A1 dans le nucléole joue un rôle majeur dans l'inhibition de la transcription par la RNA Polymérase I en l'absence de la nucléoline. Ces résultats révèlent l'importance de la nucléoline pour le maintien de l'état euchromatien de l'ADNr et le rôle de macroH2A1 dans la régulation de la transcription de l'ADNr
Besides the well-known role of the nucleolus in ribosome biogenesis, nucleoli play important roles in the regulation of many fundamental cellular processes, including cell cycle regulation, apoptosis, telomerase production, RNA processing and therefore it is not surprising that many nucleolar proteins appear to be multifunctional proteins. Nucleolin, one of the most abundant non-ribosomal proteins of the nucleolus, has been the focus of many studies since it was first described 35 years ago. It seems to be involved in many aspects of DNA metabolism, chromatin regulation and appeared to be a good pharmacological target for drug development in addition to its role in RNA polymerase I transcription and pre-ribosomal processing and assembly in pre-ribosomes. In eukaryotic cells, DNA is packed into nucleosomes to form chromatin in the nucleus. The cells develop a variety of strategies to overcome the nucleosomal barriers. These strategies include DNA methylation, histone post-translational modifications, incorporation of histone variants and ATP dependent chromatin remodeling. The aim of this thesis is to study the interaction of nucleolin with chromatin, and to decipher the mechanism of nucleolin in gene regulation. It was reported that nucleolin possesses a histone chaperone activity, helps the transcription through nucleosomes, and it is required for ribosomal DNA gene (rDNA) transcription in vivo, but the mechanism by which nucleolin modulates RNA polymerase I (Pol I) transcription is unknown. In the thesis it is shown that nucleolin knockdown results in an increase of the heterochromatin mark H3K9me2 and a decrease of H4K12Ac and H3K4me3 euchromatin histone marks in rDNA genes. Nucleolin is associated with unmethylated rDNA genes and ChIP-seq experiments identified a strong enrichment of nucleolin in the promoter and coding regions of rDNA. Nucleolin is able to interfere with the binding of TTF-1 on the promoter-proximal terminator T0 thus inhibiting the recruitment of the nucleolar remodeling complex (NoRC) subunit TIP5 and HDAC1 and the establishment of a repressive heterochromatin state. In addition, in absence of nucleolin or after inhibition of Pol I by actinomycin D, a strong relocalization of the histone variant macroH2A1 to the nucleolus and on the rDNA genes was observed. This invasion of macroH2A1 in the nucleolus plays a major role in the inhibition of Pol I transcription in absence of nucleolin, as knockdown of macroH2A1 eliminates the repressive effect of nucleolin depletion. These results reveal the importance of nucleolin for the maintenance of the euchromatin state of rDNA required for an efficient production of ribosomal RNAs and the role of macroH2A1 in rDNA transcription

[EN] This thesis deals with the development of a living biointerface between synthetic substrates and living cells to engineer cell-material interactions for tissue engineering purposes. This living biointerface is made of Lactococcus lactis, a non-pathogenic lactic bacteria widely used as starter in the dairy industry and, recently, in the expression of heterologous proteins in applications such as oral vaccine delivery or membrane-bound expression of proteins. L. lactis has been engineered to display the III 7-10 fragment of the fibronectin fused to GFP as reporter protein. Fibronectin is a ubiquitous protein present in the extracellular matrix, a complex mesh of structural and adhesive proteins which serve as mechanical support and development niche for cells of a wide variety of tissues. This fragment contains two important sequences, RGD and PHSRN. RGD is an adhesive sequence that interacts with a wide range of integrins, membrane-bound receptors that play a role in cellular processes such as adhesion, migration, proliferation and differentiation. On the other hand, PHSRN binds synergistically with RGD to some integrins such as alpha-5-beta-1 and others, increasing the specificity of this interaction. Genetically engineered L. lactis has been thoroughly characterized to test its capabilities as a living interface. This strain was found to express the FNIII 7-10-GFP fragment covalently linked to the cell wall and biological activity and expression levels of this fragment was assessed with techniques such as Western blot, ELISA and immunofluorescence. Moreover, this strain still holds the ability to develop biofilms, communities of sessile, attached bacteria to abiotic surfaces which helps greatly in the generation of a stable monolayer of bacteria between synthetic substrates and mammalian cells. Mammalian cell behaviour in response to the expressed fibronectin fragment on L. lactis membrane was also assessed. Several cell lines were tested, such as Fn-/Fn- and NIH3T3 fibroblasts, C2C12 myoblasts and human bone-marrow derived mesenchymal cells. This living biointerface was found to trigger cell adhesion and FAK phosphorylation, a marker for intracellular integrin-mediated signalling in all of the tested cell lines. It also triggered myoblast-to-myotube differentiation on C2C12 cells. In hMSCs, the cell-wall exposed fibronectin fragment was found to enhance the phosphorylation of ERK1/2, a kinase involved in the MAPK pathway, which is deeply involved in a multitude of cellular processes related to differentiation, proliferation and migration. Nevertheless, this thesis is a proof of concept that this novel system can be further exploited to express almost any desired protein or small molecule to help in the development of new tissues from progenitor cells. These molecules can be either secreted in the medium or displayed in the membrane, and can also be constitutively expressed or in-demand, due to the great flexibility of L. lactis and the wide variety of expression systems available. This interface based on living bacteria establishes a new paradigm in surface functionalization for biomedical engineering applications.
[ES] Esta tesis aborda el desarrollo de una biointerfase viviente entre materiales sintéticos y células vivas con el objetivo de dirigir la interacción célula-material en aplicaciones de ingeniería tisular. Esta biointerfase está compuesta de Lactococcus lactis, una bacteria láctica no patógena, ampliamente usada en la industria láctea como inóculo, y, recientemente, en la expresión heteróloga de proteínas para su uso como vacunas de administración oral o su expresión en membrana. L. lactis ha sido genéticamente modificado para expresar el fragmento III 7-10 de la fibronectina, unida a GFP como reporter. La fibronectina es una proteína presente de forma ubicua en la matriz extracelular, una compleja red de proteínas adhesivas y estructurales cuyo propósito es servir como soporte estructural y como nicho de desarrollo para diversos tejidos. Este fragmento contiene dos secuencias importantes, RGD y PHSRN. RGD es una secuencia adhesiva de unión que interacciona con una amplia variedad de integrinas, receptores de membrana que juegan muchos e importantes papeles en diferentes procesos celulares, como adhesión, proliferación, migración o diferenciación. Por otra parte, PHSRN se une a las integrinas de forma sinérgica con RGD facilitando aún más estos procesos y aumentando la especificidad de esta interacción. Esta cepa de L. lactis modificada ha sido ampliamente caracterizada para estudiar su idoneidad como interfaz funcional viviente. Se ha demostrado que L. lactis es capaz de expresar el fragmento FNIII7-10-GFP covalentemente anclado a la pared celular bacteriana, habiéndose caracterizado también su actividad biológica con técnicas como Western blot, ELISA e inmunofluorescencia. Esta cepa mantiene la capacidad de desarrollo de biofilms presente en la gran mayoría de microorganismos. Los biofilms son comunidades de bacterias sésiles adheridas a un sustrato que pueden ser usadas como interfase física entre células de mamífero y sustratos abióticos. También se ha estudiado la respuesta celular a la fibronectina expuesta en la membrana de L. lactis. Se estudiaron varias líneas celulares, como fibroblastos Fn-/Fn- y NIH3T3, mioblastos C2C12 y células mesenquimales humanas derivadas de médula ósea. Esta interfase viviente fue capaz de provocar respuesta celular en forma de adhesión en todas las líneas estudiadas, además de inducir diferenciación de mioblastos a miotubos en C2C12 y de provocar la fosforilación de FAK, un marcador de señalización celular mediada por integrinas. En células mesenquimales humanas se demostró la capacidad del fragmento de fibronectina expuesto para fosforilar ERK1/2, una kinasa perteneciente a la ruta de señalización MAPK, ruta que forma parte de muchos procesos celulares importantes como diferenciación, proliferación y migración. Pese a todo, esta tesis es sólo una prueba de concepto de un sistema que puede ser utilizado para expresar casi cualquier proteína o molécula pequeña deseada, que puede ser muy útil en el desarrollo de nuevos tejidos a partir de sus células progenitoras. Estas moléculas pueden ser secretadas en el medio o ancladas en la pared celular, de forma constitutiva o bajo demanda, debido a la flexibilidad y amplia variedad de sistemas de expresión disponibles para L. lactis. Esta biointerfase basada en bacterias vivas establece un nuevo paradigma en el campo de la funcionalización de superficies para aplicaciones de ingeniería biomédica.
[CAT] Aquesta tesi aborda el desenvolupament d'una interfase viva entre materials sintètics i cèl·lules vives amb l'objectiu de dirigir la interacció cèl·lula-material, per al seu ús en aplicacions d'enginyeria tissular. Aquesta interfase està composta de Lactococcus lactis, un bacteri làctic, no patogènic i àmpliament utilitzat en l'industria làctica com a inòcul, i, recentment, en l'expressió heteròloga de proteïnes per al seu ús com vacunes d'administració oral o per a la seva expressió en membrana. L. lactis ha sigut genèticament modificada per a expressar el fragment III7-10 de la fibronectina, unida a GFP com a reporter. La fibronectina és una proteïna present de forma ubiqua en la matriu extracel·lular, una complexa xarxa de proteïnes adhesives i estructurals que s'utilitzen com a suport estructural i com a nínxol de desenvolupament per a diversos teixits. Aquest fragment conté dos seqüències importants, RGD i PHSRN. RGD és una seqüència adhesiva d'unió a integrines, receptors de membrana que juguen molts i molt importants papers en diferents processos cel·lulars, com poden ser adhesió, proliferació, migració o diferenciació. Per altra banda, PHSRN s'uneix a les integrines de forma sinèrgica amb RGD facilitant encara més aquests processos i augmentant l'especificitat d'aquesta interacció. Aquesta modificació genètica de L. lactis ha estat àmpliament caracteritzada per provar les seves característiques com a interfase funcional vivent. S'ha demostrat que L. lactis és capaç d'expressar el fragment FNIII 7-10-GFP covalentment ancorat a la paret cel·lular bacteriana, havent-se caracteritzat també la seva activitat biològica amb tècniques com Western blot, ELISA i immunofluorescència. A més, aquest cep manté la capacitat de desenvolupament de biofilms, comunitats de bacteris sèssils adherits a un substrat que poden ser utilitzades com a interfase física entre cèl·lules de mamífer i substrats abiòtics. També s'ha estudiat la resposta cel·lular a la fibronectina expressada en la paret cel·lular de L. lactis. El estudi es va fer utilitzant diverses línies cel·lulars, com fibroblasts Fn-/Fn- i NIH3T3, mioblasts C2C12 i cèl·lules mesenquimals humanes derivades de medul·la òssia. Aquesta interfase vivent va ser capaç de provocar resposta cel·lular en forma d'adhesió a totes les línies estudiades, a més d'induir diferenciació de mioblasts a miotubs en C2C12 i de provocar la fosforilació de FAK, un marcador de senyalització cel·lular mediat per integrines, en les línies assajades. En cèl·lules mesenquimals humanes es va demostrar la capacitat del fragment de fibronectina exposat per fosforilar ERK1/2, una kinasa pertanyent a la ruta de senyalització MAPK, ruta que forma part de molts processos cel·lulars importants com diferenciació, proliferació i migració. Malgrat tot, aquesta tesi mostra només una prova de concepte d'un sistema que pot ser utilitzat per expressar gairebé qualsevol proteïna o molècula petita desitjada, que pot ser molt útil en el desenvolupament de nous teixits a partir de les seves cèl·lules progenitores. Aquestes molècules poden ser secretades en el medi o ancorades a la paret cel·lular, de manera constitutiva o sota demanda, a causa de la flexibilitat i àmplia varietat de sistemes d'expressió disponibles per L. lactis Aquesta biointerfase basada en bacteris vius estableix un nou paradigma en el camp de la funcionalització de superfícies per a aplicacions d'enginyería biomèdica.
Rodrigo Navarro, A. (2015). Functional living biointerfaces to direct cell-material interaction [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/51461
TESIS

Part I. In this work we show that P2X3 currents are acutely modulated by the GPCRs mGluR5 and P2Y2, and by the neurotrophin TrkA receptor, expressed in nociceptors, in the recombinant Xenopus oocyte system. The intracellular C-terminal domain of P2X 3 plays an important role in its functional coupling to TrkA. Preliminary studies suggest a role for PKC in the P2X3-TrkA cross-talk, but other routes may also contribute. Part II. Neurogenic and pharmacological stimulation of vascular smooth muscle P2X1 elicits a contractile response that we found was potentiated by serotonin acting through 5HT2A. We also found in Xenopus oocytes that P2X 1 currents in the desensitized state are potentiated by M1 ACh receptors and by phorbol ester stimulation of PKC. Part III. We have shown in Boue-Grabot et al. (2003) that there was an intracellular negative cross-talk and physical interaction between P2X2 and 5HT3A receptors. We also found a functional interaction between P2X2 and GABAA alpha2beta 3 receptor subtypes in HEK293 mammalian cells and in Xenopus oocytes; and we confirmed the findings of Sokolova et al. , (2001) in primary cultures of DRG neurons. (Abstract shortened by UMI.)

Gambling is a popular pastime in the United States, and it is important that we understand the class of behaviors in a behavior analytic context. The relationship between the function and preference of gambling behavior remains yet to be explored. The purpose of these two studies is to examine this relationship. Participants were asked to play a set of four computerized slot machines. Each slot machine was tied to a separated function-based outcome which they could win. In study 1, 80% of participants had a distinct preference for a single outcome. In study 2, the participants were also administered the GFA. Seven participants completed the MSWO. The relationship between the results of the GFA and the results of the free operant preference assessment did not support the hypothesis. Among other results, was data suggesting that those who score 0's on their GFA's may significantly affect the data and that the MSWO and free operant preference assessment have a strong high correlation.

Chez S. Cerevisiae, les nutriments, les lipides et les protéines membranaires sont internalisés par endocytose. Ce processus requiert des filaments d’actine dynamiques. Un facteur clé pour la polymérisation de l’actine est le nucléateur Arp2/3, activé par des facteurs de promotion de la nucléation (NPF). Pendant l’endocytose, la polymérisation de l’actine est initiée, entre autre, par les NPFs Las17 et les myosines de type I. Nous avons caractérisé deux protéines, Lsb1 et Lsb2 qui lient Las17 par leurs domaines SH3 et qui inhibent in vitro la polymérisation de l’actine dépendante du complexe Arp2/3. Lsb1 et Lsb2 colocalisent avec des protéines du cytosquelette, Las17, Abp1 et Sla1 et influencent la stabilité de Las17 in vivo. Nous avons ainsi identifié deux nouveaux régulateurs négatifs de l’activité NPF de Las17 ce qui permet de mieux comprendre son rôle dans la polymérisation de l’actine et l’endocytose. Nous avons également caractérisé chez des levures S. Cerevisiae, A. Gossypii, C. Albicans et S. Pombe des réseaux d’interactions protéine-protéine à travers des spécificités de liaison des domaines SH3 par la technique SPOT. Une conservation de la spécificité des myosines de type I, connu par ailleurs, a été montrée par analyse bioinformatique et valide notre méthode. De plus, nous montrons que la fonction de la myosine I de recruter la machinerie de polymérisation dans un extrait de S. Cerevisiae est conservée de S. Cerevisiae à A. Gossypii. Nous faisons des analyses similaires pour de nombreuses autres protéines à domaine SH3 ce qui nous permettra de prédire des interactions protéines-protéines ainsi de mieux comprendre l’évolution des réseaux d’interaction protéique
In S. Cerevisiae, nutrients, lipids and membrane proteins are internalized by endocytosis. These processes require dynamic actin filament assembly. A key factor for actin polymerization is the nucleating complex Arp2/3 that is activated by nucleation promoting factors (NPF). During the process of endocytosis, a strong NPF activity is exhibited by Las17, the unique S. Cerevisiae homolog of WASP and the type I myosin, Myo5, among others. Here, we characterize two SH3 domain containing proteins Lsb1 and Lsb2. We could show that both proteins bind to the proline rich sequence of the NPF Las17 via their SH3 domains and efficiently inhibit Las17 induced Arp2/3-dependent actin polymerization in vitro. We could also show that Lsb1 and Lsb2 partially colocalize with Las17 and that they influence the stability of Las17 in vivo. However, we did not detect any defect in endocytosis for the single or double deletion mutants of LSB1 and LSB2. In conclusion, we identified two new negative regulators of the NPF activity of Las17 that will help us to further understand actin nucleation and endocytosis. The characterization of the SH3 domain binding specificity in four yeast species S. Cerevisiae, A. Gossypii, C. Albicans and S. Pombe showed high conservation of the type I myosin specificity during evolution, validating our method. The ability of type I myosin to recruit the actin polymerization machinery in S. Cerevisiae is conserved from S. Cerevisiae to A. Gossypii. Similar analysis of numerous other SH3 domains, including Lsb1 and Lsb2, is in progress, which will allow us to predict new protein-protein interactions and to gain insights into the evolution of protein interaction networks

Thesis (Ph.D. in Molecular Biology) -- University of Colorado at Denver and Health Sciences Center, 2005.
Typescript. Includes bibliographical references (leaves 165-185). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

This thesis describes the development of a diagnostic tool to identify potential weaknesses in the interfaces between the key functions involved in new product development within manufacturing organisations. It comprises three parts: Part One introduces the field and reviews the literature. It discusses the subject of new product development (NPD), describes how the NPD process has evolved and outlines the key success factors which have been found to apply. It identifies and summarises the key issues which have influenced NPD and discusses the role that teams have had within the field. Key functions and their respective interfaces are identified and the barriers which exist between these functions assessed. A theoretical framework is presented which proposes that problems within these functional interfaces can be overcome by developing appropriate solutions based on accurate diagnosis of imbalance of functional perceptions within organisations. Associated research hypotheses and methodology for the research programme are also presented. Part Two describes the development and testing of a questionnaire to achieve this diagnosis. This details the identification of core issues through interviews in sample companies, initial testing of a questionnaire and the subsequent revision and retesting. Rationalisation of the questionnaire using both item and factor analysis techniques are then described and, following final testing, the use of these same techniques to develop a scoring system are also detailed. Part Three discusses the findings from the research programme and draws conclusions. The results obtained from the use of the diagnostic questionnaire within the participating organisations are compared with the literature and the development of the diagnostic questionnaire is evaluated. Finally the research hypotheses are examined and tested and conclusions relating to both the findings and the questionnaire development are drawn. Finally recommendations for the future use of the developed diagnostic tool are made.

Previously functional plasma polymers have been demonstrated to act as protective films for reinforcing fibres and provide adhesion to matrix resins in the formation of composite. In this work, the model interphase surface from the allylamine (AAm)1 1,7-octadiene (Oct) plasma copolymer treated with DGEBA-Br epoxy was produced in order to simulate the formation of an interphase region under differing cure regimes. The fundamental interaction of epoxy with a plasma polymer coating deposited onto an electrical grade (E-glass) substrate was investigated to understand the nature of interpenetrating network. X-ray photoelectron spectroscopy (XPS) was utilised to quantify the surface chemistry of the deposited coating and the model interphase surfaces. With a complementary of ARXPS, the penetration of epoxy into the plasma polymer coating was examined. It was found that the ratio of C-N/C increased in all model interphase surfaces in comparison to control AAm plasma copolymer. This confirmed that the chemical reaction between amine functional groups of the plasma polymer and epoxide groups of the epoxy had occurred through the formation of cross-links to form a semi-interpenetrating network (IPN). It therefore resulted in the presence of interphase region in which the AAm plasma copolymer and the epoxy formed the IPN. It was also observed that the interphase was principally formed at the outermost surface. However at a higher post-heat treatment temperature (80°C 2hl 120°C 3hl ISO °c 4h) the chemical bond was found to create through all analysis depth, thus enabling a thicker interphase to be formed. Time of flight secondary ion mass spectrometry (ToF-SIMS) images from the fracture surfaces of model surfaces were used to establish the mode of failure as well as uniformity of the epoxy overlayer. It was demonstrated that the locus of failure occurred at the interface between the AAm plasma copolymer coating and the E-glass substrate. This can confirm a strong interfacial bond between the coating and the epoxy.

Calcium (Ca2+)/calmodulin-dependent kinase 2 (CaMK-II) is a multifunctional member of a family of Ca2+/calmodulin-dependent serine/threonine protein kinases that respond to transient intracellular calcium signaling. CaMK-II has been reported to be involved with transcription regulation, cell motility, neuronal development, cell cycle regulation, and more recently early development of vertebrates (Easley et al., 2008; Rothschild et al., 2009; Francescatto et al., 2010). Through previous work in the lab using tandem mass spectrometry and “substrate-trapping mutants”, tumor suppressor protein 53 (p53) was identified as a novel CaMK-II binding partner in tissue culture. In this study, I sought to provide characterization of the functional interaction of p53 and CaMK-II. First, a stable p53 knockdown human cell line (HEK) was established through lentiviral transduction of p53 shRNA and verified with immunoblots and immunostaining assays. Next, the localization of CaMK-II and the cell growth rate in these cells was determined. In wild type HEK cells, catalytically inactive CaMK-II inhibited cell growth, which is consistent with previous studies in mouse fibroblasts with pharmacological inhibition. p53-deficient cells were less sensitive to CaMK-II deficiencies using dominant negative CAMK-II, but not pharmacological disruption. The overall results of this study have provided significant clues to the mechanism between CaMK-II and p53 in the control of cell cycle progression.

It is widely believed that Quantum Chromodynamics (QCD) is the theory that describes the strong interaction. In the infrared region of the theory, the perturbative expansion breaks down and so, other techniques must be used. One such technique is the study of the Schwinger-Dyson equations. In this thesis is presented such a study. It is shown that the ghost sector of QCD may be crucial to the understanding of the infrared behaviour. Conventionally, the Slavnov- Taylor identity is used to truncate the Schwinger-Dyson equations but it is found that for the ghost-gluon vertex, such an identity cannot be used in an appropriate manner. In order to extract information, a new technique is presented, based on the powerlaw behaviour of the two-point functions in the infrared. By demanding consistency in the full equations in Landau gauge and multiplicative renormalisability, it is found that in general, the gluon propagator dressing function cannot diverge and the ghost propagator function cannot vanish in the infrared. Further, it is shown that the powerlaw behaviour depends on a certain kinematical limit of only one function connected with the ghost-gluon vertex.

1. Z. M. Abbas Bhaya and all. Impact of Logistics Activities For Improving Marketing Performance Via Bayesian Quantile Regression: An Analytical Study In Omnnea Telecom Iraq: Bucharest, Romania, 2017, p 462-473 2. Ciesielski, M. Logistyka w strategiach firm, PWN, Poznań, 1999, p 159 3. BLAIK, P. Logistyka. Koncepcja zintegrowanego zarządzania, wyd. II, PWE, Warszawa, 2001, p 239 4. Liubovyna D. Rol lohystyky na sovremennom predpryiatyy. Yzdanye «fynansovaia hazeta-ekspo», №5, 2007.
Marketing and logistics represent some of the key areas of companies’ activities that have direct impacts on the volume of goods sold and establish distribution strategy for the company. They directly affect each other's activities and can dramatically change the company's market position through the integrated development of the both areas. The main purpose of the above types of activities is the distribution and sale of goods. Effective supply chain and logistics management play a key role for customers, suppliers, owners and investors of any company as this activity coordinates and connects all structures of the organization. The field of logistics covers the management of a wide variety of objects – flow of documents, information, finance, people, and, of course, goods and materials flow. Decisions made in the distribution area must go primarily in accordance with the decisions in the production and marketing area. Logistics experts make decisions on such issues as distribution routes, store`s type and location, sales format etc.
Маркетинг та логістика представляють деякі ключові сфери діяльності компаній, які мають прямий вплив на обсяг реалізованих товарів і встановлюють стратегію розподілу для компанії. Вони безпосередньо впливають на діяльність один одного і можуть кардинально змінити позиції компанії на ринку завдяки інтегрованому розвитку обох напрямків. Основною метою вищезазначених видів діяльності є розподіл та продаж товарів. Ефективний ланцюг поставок та управління логістикою відіграють ключову роль для споживачів, постачальників, власників та інвесторів будь-якої компанії, оскільки ця діяльність координує та пов'язує всі структури організації. Галузь логістики охоплює управління найрізноманітнішими об'єктами - потоком документів, інформації, фінансів, людей і, звичайно, потоком товарів і матеріалів. Рішення, що приймаються у сфері розподілу, повинні прийматися переважно відповідно до рішень у галузі виробництва та збуту. Експерти з логістики приймають рішення з таких питань, як маршрути розподілу, тип і місце розташування магазину, формат продажів тощо.

We use classical density functional theory to investigate the interactions between solvents and proteins. We examine a diverse experimental literature to establish thermodynamic properties of protein-cosolute interaction, particularly the compensation between transfer entropy and transfer enthalpy. We develop a method of analysing the uncertainties in such measurements and use the method to resolve a long-standing debate over entropy-enthalpy compensation. We develop a classical density functional theory for interactions between proteins and cosolutes. The theory developed here ignores the solvent-solvent interaction but is nonetheless quite accurate. We use this approach to reproduce transfer free energies reported elsewhere, and show that the cDFT model captures the desolvation barrier and the temperature dependence of the transfer free energy. We use experimental values that we have analyzed to define the parameter space of a model density functional theory approach. We then extend the classical density functional theory to capture protein-water interactions, thus developing a new implicit solvent model. Along the way we give a proof that the free energy of a bath of particles in a finite external potential is independent of the external potential in the isothermal-isobaric ensemble. We finally discuss the challenges remaining in implementing our implicit solvent model.
Science, Faculty of
Physics and Astronomy, Department of
Graduate

Previously studies used correlation of DNase I hypersensitivity sites sequencing (DNase-seq) experiments to predict interactions between enhancers and its target promoter gene. We investigate the correlation methods Pearson’s correlation and Mutual Information, using DNase-seq data for 100 cell-types in regions on chromosome one. To assess the performances, we compared our results of correlation scores to Hi-C data from Jin et al. 2013. We showed that the performances are low when comparing it to the Hi-C data, and there is a need of improved correlation metrics. We also demonstrate that the use of Hi-C data as a gold standard is limited, because of its low resolution, and we suggest using another gold standard in further studies.

The central themes of this thesis are the design aspects and function of versatile molecular assemblies that mimic the behaviour of biological compartments, such as the cell. Synthetic biomimetic compartments are designed by utilising specific molecular interactions, which direct self-assembly. Coacervates, formed by spontaneous liquid-liquid phase separation upon ionic assembly of polyelectrolytes, have been described as a novel phase of soft matter. For the first time, nucleotide small molecules (the building block of nucleic acids) have been employed in the formation of coacervate droplets through facile mixing with the polycation, poly(diallyldimethylammonium) chloride (PDDA). Coacervate formation has been shown to be dependent upon the strength of the ionic interaction between the polyvalent anion and polycation. Moreover, this novel nucleotide-based coacervate is highly stable, existing in the form of microscopic droplet dispersions in aqueous solution that are capable of sequestering chemical species, such as organic dyes, porphyrins, biopolymer-coated inorganic nanoparticles and proteins. Supramolecular assembly of porphyrin molecules and enhanced enzyme activity within the coacervate droplets has been demonstrated, highlighting the function of such a material as a biomimetic compartment. Building upon initial work, the high molecular weight polymer PDDA has been replaced with lower molecular weight poly(L-lysine) (PLys) in order to produce coacervate microdroplets using biologically-relevant components. Such nucleotide- peptide coacervate droplets are of particular interest in the search for plausible routes towards a model protocell. A wide range of nucleotide molecules (including di- and mono-phosphate species) and the redox cofactor flavin adenine dinucleotide (FAD) have been employed as coacervate building blocks. Using 24 or 3 kDa PLys coacervate droplets were formed with the characteristic stability and uptake properties previously observed. Nanoparticle or enzyme mediated catalysis within the droplets was achieved and intra-droplet porphyrin aggregation demonstrated. Finally, self-assembled nanostructures were formed using a biomimetic peptide sequence covalently tethered to a phospholipid tail. Discrete, micellar aggregates were identified, characterised and shown to preferentially solubilise hydrophobic molecules and, through ionic preorganization, could be encapsulated within a nanoscopic biomineral shell.

In recent years, interest in the cellular structures known as PM.l Oncogenic Domains (PODs) has been growing, as it has become increasingly clear that these structures may be implicated in several cellular functions, such as the regulation of the levels of active proteins in the nucleus, transcriptional regulation, suppression of growth and transformation, antiviral response, cell-cycle regulation and apoptosis. The PODs constitute large, multi-protein complexes associated with the nuclear matrix, and are visualised under immunofluorescence analysis as discrete dots numbering 10 to 20 per nucleus. A major protein component of the PODs, the promyelocytic leukaemia protein (PML), appears to be central to the function of these nuclear bodies. Notably, disruption of the PODs is observed in several malignant tissues, at the beginning of mitosis, and during infection with several viruses. During the course of a wild-type adenovirus infection, the PML protein is redistributed from the normal punctate, nuclear bodies. inr.o "track-like" structures, which colocalise with the viral protein, E40rf3. By ide itifying a mutant adenovirus defective in track formation, it was possible to ass"gn responsibility for POD reorganisation to this single viral gene product. Western blotting analysis of PML has demonstrated the existence of a characteristic pattern of PML isoforms, some apparently modified by the ubiquitinlike protein, Sl. MO-I. Analysis of the PML species present in adenovirus infected cells has shown that this characteristic pattern is altered, with the loss of SUMO-Imodified isofon 11.3, and the appearance of a novel, infection specific band. This thesis de ..cribes attempts to further investigate the nature and functional significance of the interaction between the viral E40rf3 protein and the cellular protein, PML, as occurs during adenovirus infection, by expressing Orf3 and mutants of Orf3 in eukaryotic cells through the use of plasmid based gene expression systems. By these methods, Orf3 was confirmed as necessary and sufficient for the redistribution of PML from the PODs to the "track-like" structures associated with adenovirus infection, and regions of the Orf3 protein implicated in the nuclear retention of the protein or protein stability were identified. Further, a potential link between POD redistribution and the adenovirus infection-specific PML isoform was investigated using Western blotting analysis on cell lysates derived from eukaryotic cells expressing Orf3 or mutants of Orf3 in isolation from other viral compnents. To facilitate these investigations, attempts were made to develop cell lines capable of permanent exp« ~:;10nof Orf3 protein. These experiments led to the identification of a potentially cytc pathic effect associated with the long-term expression of Orf3 in eukaryotic cells. Attempts were also made to construct whole, infectious virus, expressing mutant Orf3 proteins.

Thesis (Ph. D.)--West Virginia University, 1999.
Title from document title page. Document formatted into pages; contains viii, 157 p. : ill. (some col.) Vita. Includes abstract. Includes bibliographical references (p. 70-79).

A deeper understanding of the structural characteristics of urban settings is a prerequisite to evaluating the effects of urban design and planning proposals more efficiently. This thesis aims at shaping a new, comprehensive approach to uncover the structure of cities through the investigation of a diachronic spatio-functional process and the socio-economic impacts of such a process. It proposes a spatial network-based framework, in which individual street segments, indexed by space syntax centrality measures, are utilised to develop a series of more complex urban function connectivity measures by an analysis of the spatial network and land-use patterns in tandem. The specific application of this approach in Central Shanghai is conducted with a threefold focus: firstly, to trace the evolutionary interdependence between the spatial grids and the land-use distribution; secondly, to explain the varying economic value of the spatio-functional relationship in the housing market; and thirdly, to capture the impact of the spatiol-functional interaction on the variation of co-presence. The outputs confirm that the centrality structures of the spatial network and the land-use distribution affect each other over time; however, certain degrees of inconsistency are observed, suggesting a distinct complementary relationship between these two systems, which is further validated by the improvement of the proposed model’s predictability of urban performance. The findings verify the hypothesis that urban spatio-functional synergy is a strong determinant of the formation of urban function regions, the delineation of housing submarkets, and the discrepancy of the spatial co-presence in the city. These results demonstrate that urban performance is directly affected by the way the spatial and functional structures of the city interact. Such findings support the proposition that understanding the complexities of the spatio-functional interaction in a morphological analysis can enhance the efficiency of urban design and planning interventions, which aim to improve socioeconomic conditions in cities.

Les phonons contribuent à la diffusion inélastique résonante des rayons X (RIXS) du fait du couplage entre les degrés de liberté électronique et ceux du réseau. Contrairement à d'autres techniques sensibles aux interactions électron-phonon, la technique RIXS peut donner accès aux constantes de couplage dépendantes du moment. Des informations sur la dispersion de l'interaction électron-phonon sont très précieuses dans le contexte de la supraconductivité anisotrope conventionnelle et non conventionnelle.Nous avons considéré la contribution des phonons sur la diffusion RIXS d’un point de vue théorique. Contrairement aux études précédentes nous soulignons le rôle du couplage du réseau avec les trous de cœur. Notre modèle, avec les paramètres obtenus ab-initio, montre que même dans le cas d'un trou de coeur profond, la technique RIXS sonde le couplage exciton-phonon plutôt qu’un couplage direct électron-phonon.Cette différence conduit à des écarts quantitatifs et qualitatifs pour le couplage électron-phonon implicite par rapport à l'interprétation standard dans la littérature. Ainsi, notre objectif est de développer une approche rigoureuse pour quantifier le couplage électron-phonon dans le contexte des mesures de diffusion RIXS. La possibilité de reproduire avec précision les résultats expérimentaux à partir des calculs ab-initio, sans recourir à des paramètres ajustés, doit être considérée comme le test ultime d'une compréhension correcte de la contribution des phonons sur la diffusion RIXS.Nous commençons notre travail en considérant uniquement l’interaction trou de coeur-phonon dans le contexte de la spectroscopie par photoémission de rayons X. Nous combinons un calcul ab-initio de la fonction de réponse en espace réel avec des techniques de fonctions de Green à plusieurs corps pour reproduire les bandes latérales vibrationnelles dans les molécules SiX4 (X = H, F). L'approche que nous avons développée peut être appliquée aux matériaux cristallins.Nous examinons ensuite la contribution des phonons aux spectres d'absorption des rayons X. Contrairement aux excitations chargées générées par la photoémission par rayons X, l'absorption des rayons X crée une excitation neutre que nous approchons en tant que trou de cœur et électron excité. Nous résolvons d’abord la partie électronique du problème au niveau de l’équation de Bethe-Salpeter, puis nous habillons la quasi-particule excitonique à 2 particules résultante avec les interactions exciton-phonon en utilisant l’Ansatz des cumulants. La viabilité de cette méthode a été testée en calculant le seuil K XAS de la molécule N2 et le seuil K d’Oxygène de l’acétone. Les spectres vibrationnels obtenus concordent avec les résultats expérimentaux.Enfin, nous construisons une formulation hybride de la section transversale RIXS qui préserve la sommation explicite sur un petit nombre d'états finals, mais remplace la sommation sur les états intermédiaires, ce qui pourrait être extrêmement coûteux, par une fonction de Green. Nous avons obtenu un développement de la fonction de Green et dérivé des solutions analytiques exactes (dans la limite de non-recul) et approximatives. Le formalisme a de nouveau été testé sur le seuil K de l'acétone et est bien en accord avec l'expérience. En perspectives des travaux futurs, nous discutons de l’applicabilité de notre formalisme aux matériaux cristallins
Phonons contribute to resonant inelastic X-ray scattering (RIXS) as a consequence of the coupling between electronic and lattice degrees of freedom. Unlike other techniques that are sensitive to electron-phonon interactions, RIXS can give access to momentum dependent coupling constants. Information about the dispersion of the electron-phonon interaction is highly desirable in the context of understanding anisotropic conventional and unconventional superconductivity.We considered the phonon contribution to RIXS from the theoretical point of view. In contrast to previous studies, we emphasize the role of the core-hole lattice coupling. Our model, with parameters obtained from first principles, shows that even in the case of a deep core-hole, RIXS probes exciton-phonon coupling rather than a direct electron-phonon coupling.This difference leads to quantitative and qualitative deviations from the interpretation of the implied electron-phonon coupling from the standard view expressed in the literature. Thus, our objective is to develop a rigorous approach to quantify electron-phonon coupling within the context of RIXS measurements. The ability to accurately reproduce experimental results from first-principles calculations, without recourse to adjustable parameters, should be viewed as the ultimate test of a proper understanding of the phonon contribution to RIXS.We start by considering only the core-hole--phonon interaction within the context of X-ray photoemission spectroscopy. We combine an ab initio calculation of the real-space response function with many-body Green's functions techniques to reproduce the vibrational side-bands in SiX4 (X=H, F) molecules. The approach we developed is suitable for application to crystalline materials.We next consider the phonon contribution to X-ray absorption spectra. Unlike the charged excitations generated by X-ray photoemission, X-ray absorption creates a neutral excitation that we approximate as a core-hole and an excited electron. We first solved the electronic part of the problem on the level of the Bethe-Salpeter equation and then dressed the resulting 2-particle excitonic quasiparticle with the exciton-phonon interactions using the cumulant ansatz. The viability of this methodology was tested by calculating the N K-edge XAS of the N2 molecule and the O K-edge of acetone. The resulting vibronic spectra agreed favorably with experimental results.Finally, we construct a hybrid formulation of the RIXS cross section that preserves explicit summation over a small number of final states, but replaces the summation over intermediate states, which might be enormously expensive, with a Green's function. We develop an expansion of the Green's function and derive both analytically exact (in the no-recoil limit) and approximate solutions. The formalism was again tested on the O K-edge of acetone and agrees well with the experiment. To provide an outlook towards future work, we discuss application of the developed formalism to crystalline materials