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Dissertations / Theses on the topic 'Systems biophysics'
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Schwab, David Jason. "Topics in biophysics and disordered quantum systems." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1971489301&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Iram, Shamreen. "Characterization and Control of Cellular Systems." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1607450707990284.
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Huff, Alison. "A Hydrostatic Pressure Perfusion System for Biological Systems." Miami University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=miami1343970397.
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Lee, Choon-Hwan. "Multilinear analysis of fluorescence spectra of photosynthetic systems /." The Ohio State University, 1988. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487594970651308.
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Barrass, David Bryan. "Mathematical modelling of pulsatility in neuroendocrine systems." Thesis, Sheffield Hallam University, 1993. http://shura.shu.ac.uk/19321/.
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The work described in this thesis concerns the mathematical description of the characteristic oscillatory electrical behaviour of certain neurosecretory cells found in the hypothalamus of the mammalian brain. This study concentrates on those cells which secrete the hormone oxytocin. A model first described by Hodgkin and Huxley is used as a starting point for the derivation of a description comprising a system of coupled non-linear partial differential equations. The equations have been based wherever possible on experimental data relevant to the system being studied. Where this has not been possible, alternative models based on data from other, related systems have been used. The thesis starts with a discussion of the physiology of the system under study and presents some background material. The second chapter discusses the process of mathematical modelling of neurones and presents some of the relevant work in the area. The model due to Hodgkin and Huxley is significant and is discussed in detail. The research methodology is then outlined. Experimental procedures for recording the electrical behaviour of nerve cells and methods of recording selected ionic currents are the subject of chapter three. Chapter four presents a discussion of oscillatory behaviour in nerve cells at a general level and outlines the features necessary for a nerve cell to exhibit oscillation. The next three chapters discuss the characteristics of the different ionic currents involved and describe the author's derivation of models of these currents. Chapter Five presents the author's model of the sodium current, Chapter Six, the potassium currents and Chapter Seven, the calcium current. The experimental work undertaken and the results obtained are then presented and discussed. During the course of this study a number of computer programs were written and tested by the author. The program listings appear in the appendix. The thesis is significant and contributes to the body of knowledge in that no other mathematical model of the unique bursting behaviour of oxytocin-secreting cells exists as far as the author is aware.
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Czudek, Carole. "Post-mortem studies of neurotransmitter systems in schizophrenia." Thesis, University of Nottingham, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305142.
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Axelrod, Kevin Connor. "Bistable dynamics in microbial ecology and systems biology." Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493470.
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Bistability, in which a system has two stable states, is a common property of many dynamic systems. This thesis explores the properties of such systems across a range of length scales, from gene circuits to ecosystems. Cells often store memories of environmental stimuli using bistable gene circuits. High fidelity memory storage requires that a state has a long lifetime. However, an underappreciated aspect of stable memory is that the distance from a bifurcation could determine how sensitive a state is to perturbations in the extracellular environment. We predict that cell memory should become increasingly sensitive to perturbations near a bifurcation and test this idea in three different gene circuits: a toggle switch, the yeast galactose utilization network, and the E. coli lactose utilization network.
In a second study, we explore how the environmental context in which two species interact can influence their mode of interaction. Two species in nature often form reciprocally beneficial partnerships termed mutualisms, but in certain environmental regimes the species might shift to competing with one another for resources. This mutualism-competition transition has been understudied in experimental ecosystems. Using a synthetic yeast cross-feeding mutualism, we modulate the degree to which two partners rely on each other by supplementing the cells with variable amounts of nutrients. Surprisingly, we find that as the amount of supplemented nutrients is increased, the system passes through eight qualitatively distinct dynamic regimes: extinction, obligatory mutualism, obligatory/facultative mutualism, facultative mutualism, parasitism, amensalism, competition, and competitive exclusion.
In a third study, we probe how population growth dynamics can influence the probability of evolutionary rescue. Natural populations frequently face harsh environments in which their death rate exceeds their birth rate and population size tends toward zero. In such scenarios, populations can either go extinct, migrate to a better habitat, or adapt to the harsh environment. Natural populations often exhibit an “Allee effect,” in which populations grow slowly at low density due to struggles with such behaviors as finding a mate or collective hunting. We hypothesize that the presence of an Allee effect could impede evolutionary rescue and confirm this hypothesis in a model laboratory yeast ecosystem.<br>Biophysics
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Bradford, Justin A. "Stochastic innovation: Functional self-organization in simple systems." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3297812.
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Plett, Timothy Stephen. "Ion Transport Phenomena at the Nanoscale in Different Model Battery Systems." Thesis, University of California, Irvine, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10287815.
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<p> Lithium ion battery technology has flourished since its introduction into the consumer market. Not only has it helped revolutionize consumer electronics, it also compliments R&D into clean forms of energy harvest e.g. solar, wind, and hydro-electric. As demand for the technology grows, innovative approaches have been taken to improve capacity, output, and lifetime in Li-ion batteries. The approach studied in this research involves the inclusion of nanostructures, which have the potential to significantly increase capacity. While several techniques to fabricate nanostructures are understood, underlying phenomena governing ion transport in and around these nanostructures is only partially understood, which could directly impact design principles for such devices. </p><p> This thesis examines a variety of model systems which could serve to simulate environments found in proposed devices and answer questions regarding ion transport phenomena. The main components we studied from such battery systems were electrolyte and cathode materials. The electrolyte experiences different ion transport phenomena arising from the nanoconfinement of the cathode structures both around and inside the electrode material. Thus, having model systems to examine electrolyte and cathode material separately and in tandem is useful for elucidating phenomena without the challenge of deconvolution resulting from other current-carrying mechanisms. </p><p> Our main tools for carrying out our research were synthetic nanopores. The nanopore structures afforded means to access nanoscale, control environment, and even fabricate components for study. By studying the current-voltage curves in these systems, we were able to draw meaningful conclusions about mechanisms of ion transport in these model systems. The main findings of this research include the inducement of positive surface charge on nanopore structures by organic solvent-based electrolytes by means of dipole and/or ion adsorption, positive evidence of gel electrolyte fitting current models of ion current rectification, and the impact of oxidation state and cycling in cathode material on ion transport through its porous media. Each of these findings is directly related to the thrust of the research and potentially provide insights for future battery design.</p><p>
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Singh, K. D. "The development of biomagnetic systems : planar gradiometers and software tools." Thesis, Open University, 1991. http://oro.open.ac.uk/19786/.
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This thesis is concerned with two aspects of the design and construction of biomagnetic systems. Firstly, it considers the optimum design of planar gradiometers. The modelling of gradiometers is discussed and an algorithm for optimising the sensitivity of a specific type of gradiometer is presented. A test thin-film procedure for the manufacture of a planar gradiometer is outlined. The performance of three different types of gradiometer in recovering test current distributions, using a distributed current analysis technique, is assessed. Secondly, four major software tools that are essential in the analysis of data from large multi-channel biomagnetic systems are presented. These tools are then used to analyze data from a visual evoked response experiment. The system used to collect data was the Helsinki multi-channel system which consists of 24 planar gradiometers. The results confirm the retinotopic mapping of visual field information, and suggest that the time evolution of activity in different parts of the visual cortex is similar for early latencies.
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Mallory, Donald Paul. "Co-diffusion of particles in biological systems studied using PIE-FCCS." University of Akron / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=akron1627666937482877.
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Hammond, K. "Investigations into the physical properties of some selected synthetic phospholipid bilayer systems." Thesis, University of Manchester, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376588.
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Sellers, Benjamin D. "Physics-based refinement of proteins in model systems." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3311345.
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Guillet, Dominique. "Spatio-temporal image correlation spectroscopy: Extension to three dimensions and application to biological systems." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110545.
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The object of this thesis is to present work done using spatio-temporal image correlation spectroscopy (STICS), a technique that uses fluorescence intensity fluctuations in a microscopy image time series to calculate a complete space-time correlation function in order to measure transport dynamics in cells. The time evolution of this correlation function gives information on the magnitude and direction of a flow of fluorescent particles sampled in the image series. First, a new application of STICS to plant cell biology is shown. In dividing plant cells, delivery of new cell wall material to the forming cell plate requires intricate coordination of secretory vesicle trafficking and delivery. In this work, STICS is used to measure vesicle dynamics during plant cell division. It was discovered that vesicle transport to the plane of division occurs in three phases, each with its characteristic flow patterns and range of velocities, which directly reflect the rate of growth of the forming cell plate. The second part of this thesis presents the extension of the STICS technique to a third spatial dimension. The development of this new technique, called 3D STICS, allows the study of transport dynamics in three dimensions, which is more relevant in tissues and non adherent cells which are inherently 3D. Computer simulations were performed to test the accuracy and precision of the technique under a range of parameters such as particle density of immobile and moving populations; and number of images, velocity and resolution in the third spatial dimension. A comparison between values of velocities in a 2D plane recovered using STICS and its new 3D version is also presented.<br>L'objet de cette thèse est de présenter des travaux faits à l'aide de la spectroscopie par corrélation spatiotemporelle d'images (STICS), une technique qui utilise les fluctuations d'intensité dans une série d'images capturées à l'aide d'un microscope par fluorescence pour calculer la fonction complète de corrélation spatiotemporelle, et ainsi mesurer la dynamique du transport de protéines à l'intérieur de cellules vivantes. L'évolution temporelle de cette fonction de corrélation donne de l'information sur la direction et la vitesse d'un flot de particules fluorescentes présentes dans la série d'images. Tout d'abord, une nouvelle application de la technique en biologie végétale est présentée. Lors de la division cellulaire végétale, le transport du matériel membranaire nécessaire à la formation de la plaque cellulaire requiert une grande précision dans la coordination du transport et de la livraison des vésicules de sécrétion. Dans cette thèse, STICS est utilisée pour mesurer la dynamique de ces vésicules pendant la division cellulaire végétale. Les résultats obtenus révèlent l'existence de trois phases dans le transport des vésicules de sécrétion au site de division cellulaire, chacune présentant une échelle de vitesse et des motifs de mouvement caractéristiques qui se reflètent dans le taux de croissance de la plaque cellulaire. Dans un deuxième temps, le développement de STICS pour inclure l'analyse de la troisième dimension spatiale est présenté. Cette nouvelle technique, appelée STICS 3D, permet l'étude de dynamiques en trois dimensions, ce qui est plus pertinent que la version deux-dimensionnelle pour les tissus et les cellules non adhérentes, qui ont un environnement intrinsèquement 3D. Des simulations par ordinateur ont été effectuées pour déterminer l'exactitude, la précision et les limites de la technique pour un éventail de paramètres comme la vitesse, le nombre d'images et la résolution dans la troisième dimension spatiale ainsi que la densité des populations immobiles et en mouvement. Une comparaison entre les résultats obtenus avec STICS et la nouvelle version 3D de la technique est également présentée.
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Dyle, Michael Christopher. "Systems-based discovery of tomatidine as a small molecule inhibitor of skeletal muscle atrophy." Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/3076.
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Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, reduced adiposity and diet-induced obesity, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy.
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Baldwin, Janet Alison. "An investigation of the effects of pulsed magnetic fields on some in vitro biological systems." Thesis, University of Sheffield, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333242.
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Nordling, Torbjörn E. M. "Issues on modelling of large-scale cellular regulatory networks." Thesis, KTH, Numerical Analysis and Computer Science, NADA, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4182.
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<p>Vi har identifierat flexibelt utbyte och lagring av data i databaser, tillsammans med långvarig satsning på olika existerande och framtida modeller som nyckar till förståelse av det regler nätverk som utgör bron mellan geno- och fenotyp. Denna pilot studie av modellering av stora cellulära kontroll nätverk utgår från en intressant medicinsk frågeställning inom molekylär cellbiologi: Är framtvingad expression av Cdc6, aktivering av Cdk4/6 och Cdk2 tillräcklig för förankringsfri entré av cell cykelns S fas? Vi försöker konstruera en modell för att besvara denna fråga, på så sätt att vi kan detektera problem vid modellering av stora kontroll nätverk, diskutera implikationer och möjliga lösningar.</p><p>Vår modell är baserad på 1447 reaktioner och innehåller 1343 olika molekyler. Vi använde graf teori för att studera dess topologi och gjorde följande fynd: Nätverket är skalfritt och avtar enligt en potensfunktion, som var väntat baserat på tidigare arbeten. Nätverket består av ett stort väl förenat kluster. Det kan inte bli modulariserat i form av starka komponenter eller block i en användbar form. Detta eftersom vi fann en stor komponent eller ett stort block som innehöll majoriteten av alla molekyler och mer än hundra små komponenter eller block med en eller några molekyler. Vårt nätverk stämmer inte överens med en hierarkisk nätverks modell bestående av block förenade av cut-vertices.</p><br><p>We have identified flexible exchange and storage of data in databases, together with prolonged investment in different existing and future modelling formalisms as key issues in successful understanding of the regulatory network responsible for the connection between geno- and phenotype. This pilot study of modelling of large-scale regulatory networks starts with a medically interesting question from molecular cell biology: Is enforced expression of Cdc6, activation of Cdk4/6 and Cdk2 sufficient for anchorage-independent entry of the S phase of the cell cycle? We try to construct a model for answering this question, in such a way that we can reveal obstacles of large-scale regulatory modelling, discuss their implications and possible solutions.</p><p>Our model is based on 1447 reactions and contains 1343 different molecules. We used graph theory to study its topology and made the following findings: The network is scale-free and decays as a power-law, as could be expected based on earlier works. The network consists of one huge well connected cluster. It cannot be modularised into strong components or blocks in a useful way, since we get one big component or block containing a majority of all molecules and more than a hundred tiny components or blocks with one or a few molecules. Our network does not agree with a hierarchical network model consisting of blocks linked by cut-vertices.</p>
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Salveson, Patrick J. "Exploring and Controlling the Supramolecular Assembly of Amyloid-Forming Peptides and Proteins with Chemical Model Systems." Thesis, University of California, Irvine, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10928791.
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<p> Chapter 1 overviews the phenomenon of the self-assembly of small peptides and proteins in several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. This chapter provides context for the rest of the dissertation. The aberrant assembly of peptides and proteins into large structures defines a class of human pathologies, which are collectively known as amyloid diseases. In these diseases, native peptides and proteins misfold and proceed to assemble into structures that mediate the disease. The characterization of these assemblies is particularly challenging due to their heterogeneity and metastability. Within this cornucopia of assemblies, a subset known as soluble oligomers have emerged as likely neurotoxic species responsible for the progression of neurodegenerative diseases. The structures of these oligomers remain unknown. This dissertation describes my efforts to explore and control the structures of these oligomers with chemical model systems. </p><p> Chapter 2 presents the X-ray crystallographic structure and biological characterization of oligomers formed by a macrocyclic β-hairpin peptide derived from α-synuclein. The peptide adopts a β-hairpin structure, which assembles in a hierarchical fashion. Three β-hairpins assemble to form a triangular trimer. Three copies of the triangular trimer assemble to form a basket-shaped nonamer. Two nonamers pack to form an octadecamer. Molecular modeling suggests that full-length α-synuclein may also be able to assemble in this fashion. Circular dichroism spectroscopy demonstrates that the peptide interacts with anionic lipid bilayer membranes, like oligomers of full-length α-synuclein. LDH and MTT assays demonstrate that the peptide is toxic toward SH-SY5Y cells. Comparison of the peptide to homologues suggests that this toxicity results from nonspecific interactions with the cell membrane. The oligomers reported are fundamentally different than the proposed models of the fibrils formed by α-synuclein and suggest that α-Syn<sub> 36–55</sub>, rather than the NAC, may nucleate oligomer formation. </p><p> Chapter 3 explores the effect of shifting the residue pairing of Aβ-derived β-hairpins on the structures of the oligomers that form through X-ray crystallography. Three residue pairings were investigated using constrained macrocyclic β-hairpins in which Aβ<sub>30–36</sub> is juxtaposed with Aβ<sub>17–23 </sub>, Aβ<sub>16–22</sub>, and Aβ<sub>15–21</sub>. X-ray crystallography reveals that the Aβ<sub>16–22</sub>–Aβ<sub> 30–36</sub> pairing forms a compact ball-shaped dodecamer composed of fused triangular trimers, the Aβ<sub>17–23</sub>–Aβ<sub> 30–36</sub> forms a spherical dodecamer composed of triangular trimers, and that the Aβ<sub>15–21</sub>–Aβ<sub>30–36</sub> pairing forms a fibril-like assembly. Both the compact dodecamer and the spherical dodecamer may help explain the structures of the trimers and dodecamers formed by full-length Aβ. </p><p> Chapter 4 describes the design, synthesis, and characterization of macrocyclic β-hairpins that contain the <i>N</i>-2-nitrobenzyl photolabile protecting group. Each peptide contains two heptapeptide segments from Aβ<sub>16–22 </sub> or Aβ<sub>17–23</sub> constrained into β-hairpins. The N -2-nitrobenzyl group is appended to the amide backbone of Gly<sub>33 </sub> to disrupt the oligomerization of the peptides by disrupting intermolecular hydrogen bonds. X-ray crystallography reveals that <i>N</i>--nitrobenzyl groups can either block assembly into discrete oligomers or permit formation of trimers, hexamers, and dodecamers. Photolysis of the <i>N</i>--nitrobenzyl groups with long-wave UV light unmasks the amide backbone and alters the assembly and the biological properties of the macrocyclic β-hairpin peptides. SDS–PAGE studies show that removing the <i>N</i>--nitrobenzyl groups alters the assembly of the peptides. MTT conversion and LDH release assays show that decaging the peptides induces cytotoxicity. Circular dichroism studies and dye leakage assays with liposomes reveal that decaging modulates interactions of the peptides with lipid bilayers. Collectively, these studies demonstrate that incorporating N -2-nitrobenzyl groups into macrocyclic β-hairpin peptides provides a new strategy to probe the structures and the biological properties of amyloid oligomers. </p><p> Chapter 5 presents the discovery that crystal violet and other <i> C3</i> symmetric triphenylmethane dyes bind to triangular trimers derived from Aβ. Although many small molecules bind to these assemblies, the details of how these molecules interact with Aβ oligomers remain unknown. This chapter reports that crystal violet, and other <i>C3</i> symmetric triphenylmethane dyes, bind to <i>C3</i> symmetric trimers derived from Aβ. Binding changes the color of the dyes from purple to blue, and causes them to fluoresce red when irradiated with green light. Job plot and analytical ultracentrifugation experiments reveal that two trimers complex with one dye molecule. Studies with several triphenylmethane dyes reveal that three <i>N,N</i>-dialkylamino substituents are required for complexation. Several mutant trimers, in which Phe<sub>19</sub>, Phe<sub>20</sub>, and Ile<sub> 31</sub> were mutated to cyclohexylalanine, valine, and cyclohexylglycine, were prepared to probe the triphenylmethane dye binding site. (Abstract shortened by ProQuest.) </p><p>
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Stefferson, Michael W. "Dynamics of Crowded and Active Biological Systems." Thesis, University of Colorado at Boulder, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10823834.
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<p> Interactions between particles and their environment can alter the dynamics of biological systems. In crowded media like the cell, interactions with obstacles can introduce anomalous subdiffusion. Active matter systems, <i>e.g. </i>, bacterial swarms, are nonequilibrium fluids where interparticle interactions and activity cause collective motion and dynamical phases. In this thesis, I discuss my advances in the fields of crowded media and active matter. For crowded media, I studied the effects of soft obstacles and bound mobility on tracer diffusion using a lattice Monte Carlo model. I characterized how bound motion can minimize the effects of hindered anomalous diffusion and obstacle percolation, which has implications for protein movement and interactions in cells. I extended the analysis of binding and bound motion to study the effects of transport across biofilters like the nuclear pore complex (NPC). Using a minimal model, I made predictions on the selectivity of the NPC in terms of physical parameters. Finally, I looked at active matter systems. Using dynamical density functional theory, I studied the temporal evolution of a self-propelled needle system. I mapped out a dynamical phase diagram and discuss the connection between a banding instability and microscopic interactions.</p><p>
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Zou, Rui Ghosh Avijit. "Automated sensitivity analysis on spatio-temporal biochemical systems /." Philadelphia, Pa. : Drexel University, 2007. http://hdl.handle.net/1860/1565.
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Nielsen, Morten. "Numerical studies of Ising models defined on a random lattice as applied to the phase behaviour of lipid bilayer systems." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=35924.
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We examine complex fluid systems where both translational and conformational degrees of freedom are present and focus on systems in which the interplay between the two sets of degrees of freedom is manifested in the macroscopic phase behaviour. We develop an efficient random lattice algorithm describing the translational degrees of freedom and analyze a series of microscopic models defined on a two dimensional fluid surface. Different degrees of complexity in the description of the microscopic coupling between the translational and conformational degrees of freedom allow us to study a variety of models related to pure lipid membrane and lipid-sterol membrane systems.<br>The phase equilibrium described by the models is calculated by use of Monte Carlo simulation techniques. The different models are shown to exhibit a rich phase behaviour. Depending on the specific model parameters, the phase transition associated with the conformational degrees of freedom is found to be either coupled to, or uncoupled from, that associated with the conformational degrees of freedom.<br>Specifically, the order-disorder transition of an Ising model defined on a fluid surface is shown to be of first order, when the two sets of degrees of freedom are strongly coupled. In contrast, the transition falls in the universality class of the two-dimensional Ising model when the two sets of degrees of freedom are weakly coupled.<br>We next analyze a model for pure lipid bilayers which is shown to exhibit a phase behaviour with different types of macroscopic coupling between the two sets of degrees of freedom. Depending on the strength of the microscopic interactions the lipid chain melting transition and the lattice melting transition may be either macroscopically coupled or uncoupled.<br>A related model for lipid-sterol mixtures is shown to provide a consistent interpretation of the various phases of lipid-cholesterol and lipid-lanosterol binary mixtures based on the microscopic dual action of the sterol molecule on the lipid-chain degrees of freedom. We discuss the results for the systems in the context of membrane evolution and suggest that evolution has tended to optimize the lipid-sterol interaction so as to stabilize optimally the mechanical properties of the membrane. Furthermore, a specific small-scale structure is identified and characterized in the liquid-ordered phase in lipid-cholesterol mixtures. This structure is found to be absent in lipid-lanosterol mixtures.<br>Finally, a model for membrane lysis gives evidence for the high mechanical stabilizing effect of cholesterol on the membrane. The inclusion of cholesterol is shown to inhibit lysis whereas lanosterol only has little stabilizing effect.
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Xu, Yuanda. "Thermodynamic and Hydrodynamic Coupling Effects on Compositional Lipid Domains in Membrane Stack Systems." Thesis, Princeton University, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10642189.
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<p> This dissertation will focus on my work in biophysics, and my work in mean field games and glucose predictive analysis will not be presented. Several problems relating to the effects of thermodynamic coupling and hydrodynamic coupling within the membrane stack system are discussed. Three theoretical approaches are employed and proposed to study the membrane stack system: a diffuse-interface approach is utilized for numerical simulations; a coarse-grained sharp-interface approach is utilized to provide physical understanding of various kinetics; a hybrid intermediate sharp-interface approach is adopted to study the domain coalescence in the absence of diffusion. </p><p> In the first part of the thesis, we discuss the thermodynamic coupling in membrane stack systems. Comprehensive analyses are presented to understand the accelerated coarsening kinetics with respect to single layer and long-range alignment. Numerical simulations are conducted for three systems, namely a diffusion dominated system, an advective interlayer friction dominated system, and an advective membrane viscosity dominated system. Experimental results regarding the advective interlayer friction dominated system are supported by simulations. We investigate the mechanism of the enhanced coarsening kinetics in membrane stack systems and the relationship between the coarsening process and vertical alignment. An intuitive understanding along with analytical explanations are further presented. Moreover, numerical results regarding the critical mixture are also discussed. </p><p> We then investigate the interfacial fluctuation behavior within membrane stack systems. The hydrodynamic coupling is found to play a significant role and several physical length scales are found to be crucial. Both a sharp-interface approach and a diffuse-interface approach are employed to numerically simulate decay of interface fluctuations in representative two-membrane systems. </p><p> To measure the thermodynamic coupling in experiments, the hydrodynamic force needs to be quantified, especially for the non-circular domains. In the last part of this thesis, the drag coefficient relating domain velocity and force acting on the domain is calculated using perturbation theory within two limits: the first limit refers to a domain much larger than the hydrodynamic screening length; the second limit refers to a domain that is much smaller than the hydrodynamic screening length.</p><p>
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Moreno-Cantú, Jorge J. "Optimization of positron imaging systems through the use of tapered collimators." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=60652.
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A Monte Carlo simulation system was enhanced in order to analyze photon transport in tapered geometries. This system was used to evaluate the performance of new tapered collimator designs, for multi-slice positron emission tomography (MS-PET) and positron volumetric imaging systems (PVI-Systems). For each imaging modality, the performance of the new collimators was compared to those of the current collimators of choice. Collimators were evaluated based upon their: (1) trues detection efficiencies; (2) scatter detection efficiencies; (3) scatter fractions; and (4) total singles to trues events ratios. In MS-PET, collimators with a diamond-like cross section--double tapered collimators--were introduced and their performance compared to those of single tapered and cylindrical collimators. Double tapered collimators yielded better performance than single tapered ones. In PVI systems, external tapered collimators were simulated and their performance compared to those of cylindrical ones. External tapered collimators did not improve the scanner performance.
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Rieth, Monica D. "Investigating Detergent and Lipid Systems for the Study of Membrane Protein Interactions| Characterizing Caveolin Oligomerization." Thesis, Lehigh University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3638680.
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<p> Membrane proteins represent an important class of proteins that closely associate or reside within the plasma membrane of the cell. They play a multitude of roles in cell function such as signaling, trafficking, and recently discovered, scaffolding and shaping of the plasma membrane itself. For example, caveolin is a membrane protein that is believed to have the ability to curve the plasma membrane forming invaginations that serve as signaling platforms called caveolae. The curvature of the plasma membrane is believed to be a result of caveolin oligomerization. Caveolin oligomerization was characterized using sedimentation equilibrium analytical ultracentrifugation. Due to the extremely hydrophobic nature of caveolin it was necessary to explore different detergents and lipid systems that support membrane protein structure and function. Not all detergents are conducive to studies of membrane proteins and it is often necessary to determine empirically the best detergent / lipid mimic best suited for biophysical studies. One membrane mimic that has been well-characterized and used successfully to study membrane proteins are bicelles. Bicelles are discoidal phospholipid structures comprised of a long-chain and short-chain phospholipid, typically 1,2-dimyristoyl-<i>sn</i>-glycero-3-phosphocholine (DMPC) and 1,2-dihexanoyl-<i> sn</i>-glycero-3-phosphocholine (DHPC), respectively. Bicelles provide a true bilayer environment in which to study membrane protein structure and function. These lipid structures were successfully density matched using the method of sedimentation equilibrium in the analytical ultracentrifuge by adding 71.7% D<sub>2</sub>O as a density modifier. We explored the utility of bicelles as a medium for studying membrane protein interactions in the analytical ultracentrifuge (AUC) by investigating the interactions of caveolin-1. The results of this work show that caveolin-1 does not have the capacity to oligomerize in detergent micelles or in a bilayer environment (bicelles). On the other hand, a naturally-occuring breast cancer mutant, P132L, forms a strong dimer in detergent micelles. A close investigation of the mutant reveals that an extension of helix 2 in the intramembrane region of the protein where dimerization was shown to occur may play a key role in the dimerization of the mutant.</p><p> An alternative bicelle system was also investigated using pentaethylene glycol monooctyl ether (C<sub>8</sub>E<sub>5</sub>) instead of DHPC to form the rim of the bicelle. The C<sub>8</sub>E<sub>5</sub> / DMPC lipid aggregates were density matched and their properties were characterized using <sup> 31</sup>P-phosphorus NMR to assess the heterogeneity of the lipid / detergent arrangement, which confirms a bicellar-like arrangement. C<sub>8</sub>E<sub> 5</sub> has a density similar to water (1.007 g / mL) and was shown to form lipid aggregate structures with DMPC that are less dense and require significantly lower quantity of D<sub>2</sub>O to density match in the AUC making them better suited to the study of membrane protein interactions of small peptides.</p>
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Jennings, Joel Nicholas. "A new computational model for multi-cellular biological systems." Thesis, University of Cambridge, 2014. https://www.repository.cam.ac.uk/handle/1810/245334.
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The early development of an animal results from a highly complex sequence of interactions within and between cells to transform a fertilised egg into a functional embryo. A major challenge in the field of morphogenesis is explaining how coordinated cell shape change, growth and movement create the structures that we are familiar with, and what drives the processes that pattern and control this behaviour. Embryos are complicated mechanical systems for which we have a wealth of morphological data about the shapes and movements of cells but it is diffcult to understand how these movements emerge as a result of force-generating mechanisms within the embryo. A new, force-based modelling technique designed to test hypotheses about dynamic processes within an embryo is presented. The model focusses on how the mechanical properties of a cell and inter-cellular forces affect the movements we see within a tissue. It is designed to probe the relationships between cellular and tissue behaviours; such as how forces propagate through a system or the response of a tissue to applied forces. The novel features of the model are discussed along with analysis of tissue and cellular behaviours for different idealised systems, describing how the parameters of the model affect experimental observables. The model is applied to two real world systems. Firstly examining the role of boundary conditions on the patterning seen in the formation of the zebrafish forebrain neural plate. Secondly, two proposed hypotheses for the formation of the primitive streak in the chick embryo are investigated and compared. These applications demonstrate how the model can be used to complement experimental studies and help to tease out the mechanical processes driving morphogenesis.
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Xu, Xiaohua. "Modeling of nucleation-based stochastic processes in cellular systems." Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/28784.
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Molecular cell biology has been an intensively studied interdisciplinary field with the rapid development of experimental techniques and fast upgrade of computational hardware and numerical tools. Recent technological developments have led to single-cell experiments which allow us to probe the role of stochasticity in cellular processes. Stochastic modeling of the corresponding processes is thus an essential ingredient for the understanding and interpretation of cellular systems of interest. In this thesis, we explore several nucleation-based stochastic cellular processes, i.e. Min protein oscillation in Escherichia coli, pausing phenomena in DNA transcription, and single-molecule enzyme kinetics. We focus on the key experimental results and build up stochastic models accordingly to provide quantitative insights to the underlying physical mechanisms for the corresponding biological processes. We utilize specific mathematical methods and computational algorithms to gain a better understanding and make predictions for further experimental explorations in the relevant fields.<br>Ph. D.
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Johnson, Eachan Oliver Daniel. "Protein-protein recognition in biological systems exhibiting highly-conserved tertiary structure : cytochrome P450." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:d19f5f52-d1ce-4ec2-be83-fd52f01124f8.
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Protein tertiary structure is more conserved than amino acid sequence, leading to a diverse range of functions observed in the same fold. Despite < 20 % overall sequence identity, cytochromes P450 all have the same fold. Bacterial Class I P450s receive electrons from a highly specific, often unidentified, ferredoxin, in which case the hemoprotein is termed “orphaned”. CYP199A2, a Class I P450, accepts electrons from ferredoxins Pux and HaPux. Five orientation-dependent and one orientation-independent DEER measurements on paramagnetic HaPux and spin-labelled CYP199A2 yielded vector restraints, which were applied to building a model of the CYP199A2:HaPux complex in silico. A different binding mode was observed compared to P450cam:Pdx and P450scc:Adx, both recently elucidated by X-ray crystallography. This protocol was also applied to the CYP101D1:Arx complex. The first three measurements indicate that this heterodimer does not have a similar orientation to CYP199A2:HaPux, P450cam:Pdx, or P450scc:Adx. P450cam was fused to putidatredoxin reductase (PdR) to explore the kinetic effects with a view to improving electron transfer to orphan P450s. Heme incorporation of this enzyme depends on linker length. In whole cells, the fusion was more active after longer incubations. In vitro kinetics of the fusion exhibited some co-operativity and enhanced kinetics over the unfused system under steady-state conditions. The putative iron-sulfur biosynthesis ferredoxin PuxB had been engineered by rational mutagenesis to support catalysis by CYP199A2. It was confirmed this arose from improved protein-protein recognition. Engineering of E. coli ferredoxin based on these findings was carried out, resulting in electron-transfer to CYP199A4 from a novel engineered alien ferredoxin.
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Harland, Christopher William 1983. "Desiccation resistance and viscoelasticity in model membrane systems." Thesis, University of Oregon, 2010. http://hdl.handle.net/1794/10993.
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xii, 89 p. : ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number.<br>Lipid membranes are a basic structural element of all cells. They provide a framework for the physical organization of the cell, act as a scaffold for numerous proteins, and serve as the host site for countless chemical reactions integral to cell function. Several key problems in membrane biophysics hinge on reliable methods for measuring membrane material properties. Properties such as rigidity, fluidity, charge density, etc., are important factors that govern membrane structure and function. As such, we need controllable, reliable, and quantitative methods of probing membrane material properties. In pursuit of such methods, we completed two related projects that, while distinct, aimed to create and apply quantitative measures of membrane material properties to current problems in biophysics.
The first of these two lines of inquiry centered on the pervasive, pathogenic family of mycobacteria that is known to not only cause several diseases but also to survive prolonged periods of dehydration. We developed an experimental model system that mimics the structure of the mycobacterial envelope consisting of an immobile hydrophobic layer supporting a two-dimensionally fluid, glycolipid-rich outer monolayer. With this system, we show that glycolipid containing monolayers, in great contrast to phospholipid monolayers, survive desiccation with no loss of integrity, as assessed by both fluidity and protein binding, revealing a possible cause of mycobacterial persistence.
In the second line of inquiry, we developed another general platform for probing membrane material properties that has produced the first reported observations of viscoelasticity in lipid membranes. We utilized recently developed microrheological techniques on freestanding lipid bilayer systems using high speed video particle tracking. The complex shear modulus of the bilayers was extracted at a variety of temperatures that span the liquid-ordered to disordered phase transition of the membranes. At many temperatures measured, the membranes displayed viscoelastic behavior reminiscent of a Maxwell material, namely elastic at high frequencies and viscous at low frequencies. Moreover, the viscoelastic behavior was suppressed at the critical phase transition temperature where the membranes behave as a purely viscous fluid. Surprisingly, the viscoelastic behavior was found in all of several distinct membrane compositions that were examined.<br>Committee in charge: Dr. Daniel Steck, Chair;
Dr. Raghuveer Parthasarathy, Research Advisor;
Dr. Darren Johnson;
Dr. Heiner Linke;
Dr. John Toner
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Afzal, Nasrin. "Aging processes in complex systems." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/23901.
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Recent years have seen remarkable progress in our understanding of physical aging in nondisordered systems with slow, i.e. glassy-like dynamics. In many systems a single dynamical length L(t), that grows as a power-law of time t or, in much more complicated cases, as a logarithmic function of t, governs the dynamics out of equilibrium. In the aging or dynamical scaling regime, these systems are best characterized by two-times quantities, like dynamical correlation and response functions, that transform in a specific way under a dynamical scale transformation. The resulting dynamical scaling functions and the associated non-equilibrium exponents are often found to be universal and to depend only on some global features of the system under investigation.
We discuss three different types of systems with simple and complex aging properties, namely reaction diffusion systems with a power growth law, driven diffusive systems with a logarithmic growth law, and a non-equilibrium polymer network that is supposed to capture important properties of the cytoskeleton of living cells.
For the reaction diffusion systems, our study focuses on systems with reversible reaction diffusion and we study two-times functions in systems with power law growth. For the driven diffusive systems, we focus on the ABC model and a related domain model and measure two- times quantities in systems undergoing logarithmic growth. For the polymer network model, we explain in some detail its relationship with the cytoskeleton, an organelle that is responsible for the shape and locomotion of cells. Our study of this system sheds new light on the non- equilibrium relaxation properties of the cytoskeleton by investigating through a power law growth of a coarse grained length in our system.<br>Ph. D.
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Perdomo, Alejandro. "Designing and Probing Open Quantum Systems: Quantum Annealing, Excitonic Energy Transfer, and Nonlinear Fluorescence Spectroscopy." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10290.
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The 20th century saw the first revolution of quantum mechanics, setting the rules for our understanding of light, matter, and their interaction. The 21st century is focused on using these quantum mechanical laws to develop technologies which allows us to solve challenging practical problems. One of the directions is the use quantum devices which promise to surpass the best computers and best known classical algorithms for solving certain tasks. Crucial to the design of realistic devices and technologies is to account for the open nature of quantum systems and to cope with their interactions with the environment. In the first part of this dissertation, we show how to tackle classical optimization problems of interest in the physical sciences within one of these quantum computing paradigms, known as quantum annealing (QA). We present the largest implementation of QA on a biophysical problem (six different experiments with up to 81 superconducting quantum bits). Although the cases presented here can be solved on a classical computer, we present the first implementation of lattice protein folding on a quantum device under the Miyazawa-Jernigan model. This is the first step towards studying optimization problems in biophysics and statistical mechanics using quantum devices. In the second part of this dissertation, we focus on the problem of excitonic energy transfer. We provide an intuitive platform for engineering exciton transfer dynamics and we show that careful consideration of the properties of the environment leads to opportunities to engineer the transfer of an exciton. Since excitons in nanostructures are proposed for use in quantum information processing and artificial photosynthetic designs, our approach paves the way for engineering a wide range of desired exciton dy- namics. Finally, we develop the theory for a two-dimensional electronic spectroscopic technique based on fluorescence (2DFS) and challenge previous theoretical results claiming its equivalence to the two-dimensional photon echo (2DPE) technique which is based on polarization. Experimental realization of this technique confirms our the- oretical predictions. The new technique is more sensitive than 2DPE as a tool for conformational determination of excitonically coupled chromophores and o↵ers the possibility of applying two-dimensional electronic spectroscopy to single-molecules.
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Siddiqui, Jalal K. "Modeling the response of troponin C to calcium in increasingly complex systems." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1480258715871156.
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Rodgers, Christopher T. "Magnetic field effects in chemical systems." Thesis, University of Oxford, 2007. http://ora.ox.ac.uk/objects/uuid:f5878b88-c5ba-4cbd-83af-857431aef66e.
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Magnetic fields influence the rate and/or yield of chemical reactions that proceed via spin correlated radical pair intermediates. The field of spin chemistry centres around the study of such magnetic field effects (MFEs). This thesis is particularly concerned with the effects of the weak magnetic fields B₀ ~ 1mT relevant in the ongoing debates on the mechanism by which animals sense the geomagnetic field and on the putative health effects of environmental electromagnetic fields. Relatively few previous studies have dealt with such weak magnetic fields. This thesis presents several new theoretical tools and applies them to interpret experimental measurements. Chapter 1 surveys the development and theory of spin chemistry. Chapter 2 introduces the use of Tikhonov and Maximum Entropy Regularisation methods as a new means of analysing MARY field effect data. These are applied to recover details of the diffusive motion of reacting pyrene and N,N-dimethylaniline radicals. Chapter 3 gives a fresh derivation and appraisal of an approximate, semiclassical approach to MFEs. Monte Carlo calculations allow the elucidation of several "rules of thumb" for interpreting MFE data. Chapter 4 discusses recent optically-detected zero-field EPR measurements, adapting the gamma-COMPUTE algorithm from solid state NMR for their interpretation. Chapter 5 explores the role of RF polarisation in producing MFEs. The breakdown in weak fields of the familiar rotating frame approximation is analysed. Chapter 6 reviews current knowledge and landmark experiments in the area of animal magnetoreception. The origins of the sensitivity of European robins Erithacus rubecula to the Earth’s magnetic field are given particular attention. In Chapter 7, Schulten and Ritz’s hypothesis that avian magnetoreception is founded on a radical pair mechanism (RPM) reaction is appraised through calculations in model systems. Chapter 8 introduces quantitative methods of analysing anisotropic magnetic field effects using spherical harmonics. Chapter 9 considers recent observations that European robins may sometimes be disoriented by minuscule RF fields. These are shown to be consistent with magnetoreception via a radical pair with no (effective) magnetic nuclei in one of the radicals.
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Viveca, Lindahl. "Optimizing sampling of important events in complex biomolecular systems." Doctoral thesis, KTH, Fysik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-217837.
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Proteins and DNA are large, complex molecules that carry out biological functions essential to all life. Their successful operation relies on adopting specific structures, stabilized by intra-molecular interactions between atoms. The spatial and temporal resolution required to study the mechanics of these molecules in full detail can only be obtained using computer simulations of molecular models. In a molecular dynamics simulation, a trajectory of the system is generated, which allows mapping out the states and dynamics of the molecule. However, the time and length scales characteristic of biological events are many orders of magnitude larger than the resolution needed to accurately describe the microscopic processes of the atoms. To overcome this problem, sampling methods have been developed that enhance the occurrence of rare but important events, which improves the statistics of simulation data. This thesis summarizes my work on developing the AWH method, an algorithm that adaptively optimizes sampling toward a target function and simultaneously finds and assigns probabilities to states of the simulated system. I have adapted AWH for use in molecular dynamics simulations. In doing so, I investigated the convergence of the method as a function of its input parameters and improved the robustness of the method. I have also worked on a generally applicable approach for calculating the target function in an automatic and non-arbitrary way. Traditionally, the target is set in an ad hoc way, while now sampling can be improved by 50% or more without extra effort. I have also used AWH to improve sampling in two biologically relevant applications. In one paper, we study the opening of a DNA base pair, which due to the stability of the DNA double helix only very rarely occurs spontaneously. We show that the probability of opening depends on both nearest-neighbor and longer-range sequence effect and furthermore structurally characterize the open states. In the second application the permeability and ammonia selectivity of the membrane protein aquaporin is investigated and we show that these functions are sensitive to specific mutations.<br><p>QC 20171117</p>
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Mayer, Andreas. "Optimal immune systems : a ressource allocation and information processing view of immune defense." Thesis, Paris Sciences et Lettres (ComUE), 2017. http://www.theses.fr/2017PSLEE026/document.
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Les organismes biologiques ont développé divers mécanismes immunitaires afin de se protéger des pathogènes. Nous développons ici des modèles mathématiques de systèmes immunitaires, adaptés de façon optimale aux statistiques des pathogènes. Au delà des détails moléculaires, ces mécanismes immunitaires diffèrent dans la manière d'acquérir, de réguler et de transmettre une protection immunitaire ; différences qui pourraient s'avérer essentielles pour la survie à long terme. Afin d'expliquer la diversité des stratégies qui sont observées, nous comparons l'adaptation à long terme de populations en fonction de la dynamique des pathogènes à laquelle elles sont confrontées et de la stratégie immunitaire qu'elles adoptent. Nous démontrons que la fréquence et l'échelle de temps caractéristique des pathogènes sont les deux déterminants clés d'une stratégie immunitaire optimale. En fonction de ces deux paramètres, nous identifions des modes d'immunité distincts, comprenant immunités innées, adaptatives, ou ressemblant au système CRISPR, qui récapitulent la diversité de systèmes immunitaires naturels. Nos résultats viennent s'étendre à la question générale de l'évolution dans des environnements variables pour laquelle nous apportons de nouveaux résultats analytiques au sein d'environnements temporairement corrélés. Le système immunitaire adaptatif assure une protection à partir d'un large répertoire de cellules spécifiques à différents pathogènes. Pour prédire des propriétés statistiques de répertoires adaptés, nous étudions quel répertoire minimise au mieux le risque d'infections pour une distribution de pathogènes donnée. La théorie prédit que les cellules spécifiques contre les antigènes rares sont surreprésentées par rapport à la fréquence de leurs rencontres et que les individus, exposés aux mêmes infections, possèdent des répertoires avec des récepteurs largement différents mais exploitent la réactivité croisée afin de parvenir à la même couverture d'antigènes. Nos résultats sont issus d'une opposition entre les statistiques de détection des pathogènes, qui soutiennent l'idée d'une plus large distribution de récepteurs, et les effets de la réactivité croisée, qui tend à concentrer le répertoire optimal sur un petit nombre de clones. Nos prédictions peuvent être testées à partir d'enquêtes à haut débit sur la diversité des récepteurs et de pathogènes. Par la suite, nous examinons explicitement comment le système immunitaire adaptatif peut apprendre de manière bayésienne les statistiques de l'environnement à partir de l'historique des infections précédentes. Nous montrons que les répertoires optimaux peuvent être atteints par prolifération sélective des cellules spécifiques. La perspective bayésienne sur la dynamique des répertoires fournit un cadre conceptuel unificateur qui explique un certain nombre de caractéristiques de la mémoire immunitaire et appelle à des expériences complémentaires<br>Biological organisms have evolved diverse immune mechanisms to defend themselves against pathogens. Here we build mathematical models of immune systems optimally tuned to the statistics of pathogens. Beyond molecular details, different immune mechanisms differ in how protection is acquired, processed and passed on to subsequent generations -- differences that may be essential to long-term survival. To explain the observed diversity of strategies we compare the long-term adaptation of populations as a function of the pathogen dynamics that they experience and of the immune strategy that they adopt. We find that the two key determinants of an optimal immune strategy are the frequency and the characteristic timescale of the pathogens. Depending on these two parameters, we identify distinct modes of immunity, including adaptive, innate, bet-hedging and CRISPR-like immunities, which recapitulate the diversity of natural immune systems. Our results carry over to the general question of evolution in fluctuating environments, for which we provide novel analytical results in temporally correlated environments. The adaptive immune system provides protection through a broad repertoire of cells specific to different pathogens. To predict statistical features of well-adapted repertoires we analyze which repertoire minimizes cost of infection for a given distribution of pathogens. The theory predicts that the immune system has more receptors for rare antigens than expected from the frequency of encounters; and individuals exposed to the same infections have sparse repertoires that are largely different, but nevertheless exploit cross-reactivity to provide the same coverage of antigens. Our results follow from a tension between the statistics of pathogen detection, which favor a broader receptor distribution, and the effects of cross-reactivity, which tend to concentrate the optimal repertoire onto a few highly abundant clones. These predictions can be tested in high throughput surveys of receptor and pathogen diversity. We then explicitly consider how the adaptive immune system can learn the statistics of the environments from its past infection history in a Bayesian manner. We show that optimal repertoires can be reached by keeping memory of an infection through the selective proliferation of stimulated cells. The Bayesian perspective on repertoire dynamics provides an unifying conceptual framework to explain a number of features of immunological memory and suggests further experiments
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Marin, Boris. "Determinismo e estocasticidade em modelos de neurônios biológicos." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/43/43134/tde-23092014-154612/.
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Investigou-se a gênese de atividade irregular em neurônios de centros geradores de padrões através de modelos eletrofisiologicamente realistas. Para tanto, foram adotadas abordagens paralelas. Primeiramente, desenvolveram-se técnicas para determinar quais os mecanismos biofísicos subjacentes aos processos de codificação de informação nestas células. Também foi proposta uma nova metodologia híbrida (baseada em continuação numérica e em varreduras força bruta) para análise de bancos de dados de modelos neuronais, permitindo estendê-los e revelar instâncias de multiestabilidade entre regimes oscilatórios e quiescentes. Além disto, a fim de determinar a origem de comportamento complexo em modelos neuronais simplificados, empregaram-se métodos geométricos da teoria de sistemas dinâmicos. A partir da análise de mapas unidimensionais perturbados por ruído, foram discutidos possíveis cenários para o surgimento de caos em sistemas dinâmicos aleatórios. Finalmente mostrou-se que, levando em conta o ruído, uma classe de modelos de condutâncias reproduz padrões de disparo observados in vivo. Estas pertubações revelam a riqueza da dinâmica transiente, levando o sistema a visitar um arcabouço determinista complexo preexistente -- sem recorrer a ajustes finos de parâmetros ou a construções ad hoc para induzir comportamento caótico.<br>We investigated the origin of irregularities in the dynamics of central pattern generator neurons, through analyzing electrophysiologically realistic models. A number of parallel approaches were adopted for that purpose. Initially, we studied information coding processes in these cells and proposed a technique to determine the underlying biophysical mechanisms. We also developed a novel hybrid method (based on numerical continuation and brute force sweeps) to analyze neuronal model databases, extending them and unveiling instances of multistability between oscillatory and resting regimes. Furthermore, in order to determine the origin of irregular dynamics in simplified neuronal models, we employed geometrical methods from the theory of dynamical systems. The analysis of stochastically perturbed maps allowed us to discuss possible scenarios for the generation of chaotic behaviour in random dynamical systems. Finally we showed that, by taking noise into account, a class of conductance based models gives rise to firing patterns akin to the ones observed \\emph{in vivo}. These perturbations unveil the richness of the transient dynamics, inducing the system to populate a preexistent complex deterministic scaffolding -- without resorting to parameter fine-tuning or ad hoc constructions to induce chaotic activity.
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Asencio, Hernandez Julia. "Novel approaches in NMR and biophysics for the study of complex systems : application to the N-terminal domain of the androgen receptor." Thesis, Strasbourg, 2015. http://www.theses.fr/2015STRAJ013/document.
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Cette thèse vise à réaliser une étude approfondie sur le développement de méthodologies pour l’analyse de systèmes complexes. Cela comprend l’étude des systèmes hors d’équilibre, des systèmes d’auto-assemblage, et les systèmes biologiques désordonnés. Les méthodes développées recouvrent principalement la RMN, tel que la mesure de diffusion (DOSY) mais également d’autres techniques telles que la spectrométrie de masse, le dichroïsme circulaire (CD), la microscopie électronique (EM) et diffusion des rayons X aux petits angles (SAXS). La partie N-terminale du récepteur des androgènes (AR) est utilisée comme un système complexe. D’après la littérature, il est connu que cette région joue un rôle important pour l’activité du récepteur, et elle est également décrite comme étant intrinsèquement désordonnée. Les résultats que j’ai acquis durant la thèse m’ont permis d’identifier une courte région de ce domaine, impliquée dans la formation réversible de fibres amyloïdes, par modulation des conditions d’oxydo-réduction du milieu. Les résultats révèlent un aspect inconnu du mécanisme de AR<br>My PhD project was focused on the development of methods for the analysis of complex systems and their biophysical characterization. This includes the study of large chemical libraries, self assembly systems, protein-ligand interaction studies and disordered biological systems. A wide range of biophysical methods were used for this purpose. Specially, Nuclear Magnetic Resonance(NMR) but also other techniques such as mass spectrometry, circular dichroism (CD), electron microscopy (EM) and small angle X-ray scattering (SAXS). The N-terminal Domain of the Androgen Receptor is studied as an example of a complex system. This region plays an important role in receptor activity, and is also described as being intrinsically disordered. The results obtained during my thesis shown a short conserved region involved in the amyloid fibers formation under oxidative conditions. These results open new possibilities to understand the mechanism of the AR activity
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Lovelady, Douglas Carroll. "A Study of Complex Systems: from Magnetic to Biological." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3216.
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This work is a study of complex many-body systems with non-trivial interactions. Many such systems can be described with models that are much simpler than the real thing but which can still give good insight into the behavior of realistic systems. We take a look at two such systems. The first part looks at a model that elucidates the variety of magnetic phases observed in rare-earth heterostructures at low temperatures: the six-state clock model. We use an ANNNI-like model Hamiltonian that has a three-dimensional parameter space and yields two-dimensional multiphase regions in this space. A low-temperature expansion of the free energy reveals an example of Villain's `order from disorder' [81, 60] when an infinitesimal temperature breaks the ground-state degeneracy. The next part of our work describes biological systems. Using ECIS (Electric Cell-Substrate Impedance Sensing), we are able to extract complex impedance time series from a confluent layer of live cells. We use simple statistics to characterize the behavior of cells in these experiments. We compare experiment with models of fractional Brownian motion and random walks with persistence. We next detect differences in the behavior of single cell types in a toxic environment. Finally, we develop a very simple model of micromotion that helps explain the types of interactions responsible for the long-term and short-term correlations seen in the power spectra and autocorrelation curves extracted from the times series produced from the experiments.
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Kumar, Ashok Ashwin. "Density-Based Separations in Aqueous Multiphase Systems: Tools for Biological Research and Low-Cost Diagnostics." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11491.
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Cells often exist in heterogeneous mixtures. Density provides a property to separate several types of cells from the mixed sample in which they originate. Density-based separation methods provide a standard method to quickly separate or enrich specific populations of cells, such as lymphocytes from whole blood. This dissertation explores the use of aqueous multiphase systems (AMPS) as self-forming step-gradients in density for the separation of cells. AMPS were first discovered over a hundred years ago as aqueous two-phase systems. Density as a tool to separate cells is at least as old. Despite this long history, the work in this thesis is the first work to use AMPS to perform density-based separations on cells. This combination provides a powerful technique to separate cells and enable new testing at the point-of-care. Chapter 1 provides a short overview of aqueous multiphase systems and density-based separations of cells. Chapter 2 describes the process of taking technology, including AMPS, from a demonstration in a laboratory to a large scale evaluation in a field setting. In Chapter 3 and Appendix I, AMPS provide a means to enrich reticulocytes from whole blood as a means to grow malaria parasites. Chapter 4 and Appendix II describe the development and proof-of-prinicple of a density-based diagnostic test for sickle cell disease (SCD) using AMPS. Chapter 5 and Appendix III detail the results of a large scale field evaluation of a rapid test for SCD using AMPS in Zambia. Demonstrations of AMPS for density- and size-based separations are provided in Appendices IV and V. Appendix VI demonstrates the general usefulness of density to separate crystal polymorphs with another density-based separation method: magnetic levitation in a paramagnetic fluid. Beyond density, novel combinations of technology, such as electrochemistry and telecommunications provide opportunities for enabling global health (Appendix VII).<br>Engineering and Applied Sciences
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Bach, Aaron James Edward. "The evaluation of cooling systems to reduce heat strain in individuals wearing personal protective clothing." Thesis, Queensland University of Technology, 2020. https://eprints.qut.edu.au/200627/1/Aaron_Bach_Thesis.pdf.
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Personal cooling systems, worn by emergency first responders under protective clothing, are designed to minimise the risk of heat illness. This thesis reaffirms that first responder agencies (e.g. fire, police) identify heat illness as a genuine threat to worker safety. Further, it identifies that certain personal cooling systems alleviate the heat better than others, and the combination of air temperature and humidity has a direct effect on their performance. Therefore, the use of cooling systems, by first responder agencies, needs to be considered in the context of the protective clothing being worn and the environment encountered.
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Ellis, Jason Keith. "Emergent Phenomena in Classical and Quantum Systems: Cellular Dynamics in E. coli and Spin-Polarization in Fermi Superfluids." [Kent, Ohio] : Kent State University, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=kent1256932939.
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Gardel, Emily Jeanette. "Microbe-electrode interactions: The chemico-physical environment and electron transfer." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11185.
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This thesis presents studies that examine microbial extracellular electron transfer that an emphasis characterizing how environmental conditions influence electron flux between microbes and a solid-phase electron donor or acceptor. I used bioelectrochemical systems (BESs), fluorescence and electron microscopy, chemical measurements, 16S rRNA analysis, and qRT-PCR to study these relationships among chemical, physical and biological parameters and processes.<br>Engineering and Applied Sciences
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Lepp, Håkan. "Experimental studies of proton translocation reactions in biological systems : Electrogenic events in heme-copper oxidases." Doctoral thesis, Stockholm University, Department of Biochemistry and Biophysics, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-8147.
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<p>Terminal heme-copper oxidases (HCuOs) are transmembrane proteins that catalyze the final step in the respiratory chain - the reduction of O<sub>2</sub> to H<sub>2</sub>O, coupled to energy conservation by generation of an electrochemical proton gradient. The most extensively investigated of the HCuOs are the <i>aa</i><sub>3</sub>-type oxidases, to which cytochrome <i>c</i> oxidase (Cyt<i>c</i>O) belongs, which uses energy released in the O<sub>2</sub>-reduction for proton pumping. The bacterial nitric oxide reductases (NORs) have been identified as divergent members of the HCuO-superfamily and are involved in the denitrification pathway where they catalyze the reduction of NO to NO<sub>2</sub>. Although as exergonic as O<sub>2</sub>-reduction, this reaction is completely non-electrogenic. Among the traditional HCuOs, the <i>cbb</i><sub>3</sub>-type oxidases are the closest relatives to the NORs and as such provide a link between the <i>aa</i><sub>3</sub> oxidases and the NORs. The <i>cbb</i><sub>3</sub> oxidases have been shown to pump protons with nearly the same efficiency as the <i>aa</i><sub>3</sub> oxidases, despite low sequence similarity.</p><p>This thesis is focused on measurements of membrane potential generating reactions during catalysis in the Cyt<i>c</i>O and the <i>cbb</i><sub>3</sub> oxidase from <i>Rhodobacter sphaeroides</i>, and the NOR from <i>Paracoccus</i> <i>denitrificans</i>, using a time resolved electrometric technique. The pH dependence of the membrane potential generation in Cyt<i>c</i>O showed that only one proton is taken up and that no protons are pumped, at high pH. An additional kinetic phase was also detected at high pH that presumably originates to from charge-transfer within the K-pathway. Possible reasons for uncoupling, and the extent of charge-transfer, were studied using structural variants of Cyt<i>c</i>O. The measurements established that electrons and protons are taken up from the same side of the membrane in NOR. In addition, the directionality for proton uptake in <i>cbb</i><sub>3</sub> oxidase appeared to be dependent on the choice of substrate while proton pumping was indicated to occur only during O<sub>2</sub>-reduction.</p>
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Rajamani, Sathish. "Small molecule signaling and detection systems in protists and bacteria." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1155564098.
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Cucheval, Aurelie Suzanne Bernadette. "Investigations of the behaviour of pectin in casein micelle systems and their analogues : thesis presented for the degree of Doctor of Philosophy in Physics." Massey University, 2009. http://hdl.handle.net/10179/1209.
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Firstly, the effect of pectin on acid milk gels in concentrated, quiescent systems was investigated by passive microrheology using two complementary techniques: diffusive wave spectroscopy (DWS) and multiple particle tracking (MPT). DWS, by allowing probing the mechanical properties of the network at high frequency, gave information on its microstructure. The addition of high methoxyl pectins was shown to change the network structure which has been explained by bridging of the casein micelles by the polymer as the system was undergoing acidification. On the other hand, the presence of low methoxyl pectin in the acid milk gel was shown to have no effect on the microstructure of the network at low concentration of polymer (0.1%w/w) which has been attributed to the sensitivity of this low DM pectin to calcium: LM pectin are trapped by calcium and not able to interact with casein micelles anymore. Multiple particle tracking was used to probe the effect of pectin on the heterogeneity of the system by following the distribution of the displacements of added micro beads at a given time lag during the gelation using the Van Hove distribution. Furthermore, the surface chemistry of the probes was modified in an attempt to control their location in the system. Finally, the mean square displacements of the casein micelles obtained by DWS and, of k-casein coated particles obtained by MPT were shown to give good agreement for the same acid milk system. Having established that the interaction between casein micelles and low methoxyl pectin is prevented by the pectin sensitivity to calcium, the effect of the pectin fine structure was investigated on the interaction between k-casein and pectin by surface plasmon resonance (SPR). The amount of pectin binding on a k-casein coated gold surface was shown to be strongly dependant on the pectin fine structure. It was concluded that small negative patches on the pectin backbone, likely to comprise of around two consecutive unmethylesterified galacturonic acid, are the most effective for pectin binding to k-casein. The effect of the direct interaction between pectin and k- casein on ‘calcium-free casein micelle mimics’ in pectin solution was then investigated using coated latex beads. A pectin structure with a limited number of negative patches on its backbone was also shown to limit the potential for destabilization via bridging.
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Alemany, i. Arias Anna. "Dynamic force spectroscopy and folding kinetics in molecular systems." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/284197.
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Codification of genetic information; regulation of gene expression; transport of nutrients inside cells; immune protection against infectious agents; transduction of external signals... These are some of the crucial processes that take place in living organisms at the molecular level. A deep understanding of how these phenomena occur is vital to get a precise knowledge of the laws governing the microscopic world and understand, prevent and even find cures for many illnesses with an origin in the molecular scale.
Single-molecule experiments emerge as a powerful and versatile tool to investigate molecular processes at the level of individual molecules and trajectories with unprecedented spatial and temporal resolution. A paradigmatic experimental technique is given by “optical tweezers” (OT), which consist of a laser beam that captures micron-sized plastic beads using light momentum conservation. This instrument makes it possible to manipulate with nanometric precision a biomolecule and exert forces on it in the range of [0-100] pN.
The diversity of systems being studied using optical tweezers increases every day. In this thesis, OT are used to unravel the mechanisms of unfolding and folding of several small nucleic acid hairpins and a protein when a force is applied to their ends. Moreover, single antigen-antibody bonds are investigated by qualitatively measuring the correlation between bond affinity and bond elasticity. All single-molecule experiments have in common the relevant role played by thermal fluctuations. These are crucial at the microscopic scale and contain overriding thermodynamic and kinetic information of molecular systems.
The study of the characteristic forces at which molecular cooperative transitions occur, such as molecular unfolding or bond dissociation, is known as dynamic force spectroscopy (DFS). In this thesis DFS combined with Markov models are widely used to characterize the unfolding/folding reaction pathway, the transition states present in the molecular free-energy landscape, and the elastic, kinetic and thermodynamic properties of a protein, the antigen-antibody bond and nucleic acid hairpins under different conditions. A general result is that non-equilibrium DFS methods provide an excellent platform to extract thermodynamic properties of molecular states that can only be observed under dynamical conditions (that is, they are never observed in equilibrium at reasonable time scales), such as intermediate or bound configurations.
An alternative method to extract thermodynamic properties of molecular systems is the use of fluctuation relations (FR). These are mathematical identities that relate non-equilibrium work measurements to free-energy differences. When an irreversible transformation is mechanically induced in an otherwise full-equilibrated molecular system, a work is performed between an initial and a final state that differs in each independent repetition of the experiment. FR relate a collection of these work measurements to the difference in free energy between the initial and the final states, independently of the molecular reaction pathway. If the system is initially found at a partially equilibrated state, an extended version of FR can be used to measure its free energy of formation. This grants access to the thermodynamic properties of misfolded and intermediate states that are rarely sampled in full equilibrium. Additionally, the extended FR allow us to reconstruct the free-energy branches of molecular states observed during non-equilibrium experiments from irreversible work measurements. Hence, relative stabilities between molecular native, unfolded, misfolded an intermediate states can be compared at different stages of the irreversible experiment.
Results in this thesis pave the way to characterize the thermodynamics and kinetics of complex molecular process that occur under partial equilibrium conditions (as is the case in living organisms), using both DFS and FR. Examples are found in many kinetic states related to intermolecular binding or in transient non-equilibrium states occurring in polymerization reactions (e.g. translocating). Hence the influence of the findings and methods developed in this thesis remains to be seen.<br>La codificació de la informació genètica, la regulació de l'expressió dels gens, el transport de nutrients dins la cèl·lula, la protecció immunològica contra agents infecciosos... Aquests són alguns dels processos moleculars que s'esdevenen en organismes vius i són crucials per la seva supervivència. Entendre el funcionament d'aquests fenòmens és vital per conèixer les lleis que governen l'escala microscòpica i per entendre, preveure, o fins i tot trobar cures de malalties amb origen molecular, com el Parkinson, l'Alzheimer, o alguns càncers.
Els experiments amb una única molècula són una eina molt poderosa i versàtil que permet investigar molts processos moleculars a escala de molècula i trajectòria individual, amb una resolució espaio-temporal sense precedents. Una eina paradigmàtica per dur a terme aquest tipus d'estudis són les “pinces òptiques”, consistents en un feix de llum coherent focalitzat capaç d'atrapar partícules de plàstic microscòpiques utilitzant la conservació del moment. Aquest instrument permet manipular una única biomolècula amb precisió nanomètrica, i exercir-hi forces en el rang entre 0 i 100 pN.
La diversitat de sistemes estudiats amb les pinces òptiques augmenta cada dia. En aquesta tesi, s'utilitzen per desxifrar els mecanismes del plegament i desplegament d'àcids nucleics i d'una proteïna quan s'hi aplica una força. A més, les propietats d'un únic enllaç entre un antigen i un anticòs s'investiguen de manera qualitativa, mesurant la correlació entre l'afinitat i l'elasticitat de la unió.
Els resultats d'aquesta tesi obren la porta a la caracterització termodinàmica i cinètica de processos moleculars complexos que s'esdevenen en condicions d'equilibri parcial (com ocorre en organismes vius) utilitzant l'espectroscòpia dinàmica de forces (és a dir, l'estudi de les forces característiques per induir transicions moleculars) i els teoremes de fluctuació (que proporcionen estimacions de l'energia lliure mitjançant mesures irreversibles). Alguns exemples poden trobar-se en els estats cinètics i metaestables relacionats amb el plegament mecànic -com els estats intermedis i mal plegats-, en la interacció intermolecular, o en estats metaestables que es donen en reaccions de polimerització -com la translocació dels motors moleculars.
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BEGARANI, Filippo. "Capturing molecular behaviour in dynamic subcellular nanostructures." Doctoral thesis, Scuola Normale Superiore, 2020. http://hdl.handle.net/11384/91226.
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López, de Rioja Víctor. "Population range expansions, with mathematical applications to interacting systems and ancient human genetics." Doctoral thesis, Universitat de Girona, 2019. http://hdl.handle.net/10803/667171.
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The thesis studies from an analytical and computational perspective, and by using reaction-diffusion equations, the spatiotemporal evolution of different populations.
First, the dynamics of the T7 bacteriophage infecting the E. coli bacteria is studied. By adding the delayed time in diffusion and reaction terms, as well as new mathematical terms biologically sound, we can achieve results that accurately match the experimental propagation speeds.
Secondly, different mathematical models are proposed to correctly understand the expansion of VSV in Glioblastoma. The only model capable of this explanation is the system which understands the delay time for the processes of diffusion and reaction.
Finally, the Neolithic transition through Europe is explained by studying ancient genetic DNA samples alongside mathematical simulations. Focusing on haplogroup K, the model is built by analyzing the two Neolithic diffusion mechanisms: demic and cultural. The simulations show that the transition is basically demic, with only 2% of the Neolithic farmers interacting culturally<br>Aquesta tesi estudia des d’un punt de analític i computacional, gràcies a les equacions de reacció-difusió, l’evolució espaciotemporal de diferents poblacions que interactuen entre elles.
El primer article estudia la dinàmica del bacteriòfag T7 infectant el bacteri E. coli. Gràcies a la incorporació del temps de retard en els termes de difusió i reacció, així com de nous termes matemàtics amb sentit biològic, aconseguim uns resultats que s’ajusten millor a les velocitats de propagació.
El segon article aplica diferents models matemàtics per entendre millor l’expansió del VSV en Glioblastomes. L'únic model capaç d'explicar de manera correcte el sistema té en compte el temps de retard per als processos de difusió i reacció.
L’últim article explica la transició del Neolític a través d’Europa utilitzant mostres genètiques antigues i simulacions matemàtiques. Centrant-nos en l’haplogrup K, el model es construeix tenint en compte els dos mecanismes de difusió neolítica: dèmica i cultural. Les simulacions mostren que la transició és bàsicament dèmica, on només el 2% dels neolítics interaccionen culturalment
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Manathunga, Madushanka. "Impact of Electronic State Mixing on the Photoisomerization Timescale of Natural and Synthetic Molecular Systems." Bowling Green State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1541548724939953.
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Fu, Michael J. "Computational Models and Analyses of Human Motor Performance in Haptic Manipulation." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1301929982.
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Fernandez, Rodriguez Rodolfo. "Development and Implementation of Acoustic Feedback Control for Scanning Probe Microscopy." PDXScholar, 2012. https://pdxscholar.library.pdx.edu/open_access_etds/548.
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A remote-sensing acoustic method for implementing position control feedback in Scanning Probe Microscopy (SPM) is presented. The capabilities of this feedback control using the new Whispering Gallery Acoustic Sensing (WGAS) method is demonstrated in a Shear-force Scanning Probe Microscope that uses a sharp probe attached to a piezoelectric Quartz Tuning Fork (QTF) firmly mounted on the microscope's frame. As the QTF is electrically driven its mechanical response reaches the SPM frame which then acts as a resonant cavity producing acoustic modes measured with an acoustic sensor strategically placed on the SPM head. The novelty of the WGAS resides in using an SPM frame with a perimeter closely matching the intervening acoustic wavelength to act as a resonant cavity. The whispering gallery cavity constitutes an acoustic amplifier for the mechanical motion of the QTF probe. The observed monotonic behavior of the whispering gallery acoustic signal as a function of the probe sample distance is exploited here for tip-sample distance control with nanometer sensitivity, thus allowing topographic characterization as the probe is scanned across the sample's surface. This thesis includes a description of a Labview based programming for the Field Programmable Gate Array (FPGA) card used in the automated control of the WGAS feedback microscope, a solution for improving the effective resolution of the Digital to Analog Converter (DAC) and initial results towards theoretically modeling the WGAS working principle.