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1
Fradet, Etienne. "Monitoring biochemical reactions in stationary droplets". Palaiseau, Ecole polytechnique, 2013. http://pastel.archives-ouvertes.fr/docs/00/92/97/15/PDF/fradet_thesis_2013.pdf.
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La microfluidique de gouttes - i. E. L'emploi de gouttelettes comme microréacteurs - offre de nombreux avantages pour l'étude des systèmes biologiques. Dans ce travail de thèse, nous présentons une nouvelle approche pour la production et la manipulation de gouttelettes au sein de microcanaux afin de suivre l'avancement de réactions biochimiques au cours du temps. Contrairement aux approches existantes, notre dispositif utilise des gradients de confinement afin de produire et guider une unique goutte vers son lieu de stockage. Ce faisant, deux gouttes de contenus différents peuvent être appariées et fusionnées afin de déclencher une réaction chimique. Les réactifs n'étant pas activement mélangés, un front de réaction se propage alors le long de la goutte fille duquel on peut extraire la cinétique de la réaction. Nous commençons par l'étude de réactions simples ayant lieu en une étape. Un modèle 1D de réaction-diffusion permet de représenter la dynamique du front de réaction ce qui est vérifié en confrontant les solutions de ce modèle, obtenues numériquement ou analytiquement, à des mesures effectuées en gouttes. Puis, nous nous intéressons au cas des réactions enzymatiques. Nous démontrons d'abord la parallélisation de notre technique d'appariement de gouttes afin de reproduire en microcanal différents tests enzymatiques usuellement effectués en plaque multipuits. Finalement, nous étudions le cas des réactions enzymatiques rapides à l'aide de notre modèle de réaction-diffusion. Là encore, la comparaison d'expériences tenues en gouttes et de prédiction issues de notre modèle nous permet d'extraire une mesure des paramètres cinétiques de la réaction mise en jeuDroplet microfluidics - i. E. The use of droplets as microreactors - offers significant advantages for the study of biological systems. In this work, we present a new platform for the production and manipulation of microfluidic droplets in view of measuring the evolution of biochemical reactions. Contrary to existing approaches, our device uses gradients of confinement to produce a single drop on demand and guide it to a pre-determined location. In this way, two nanoliter drops containing different reagents can be placed in contact and merged together in order to trigger a chemical reaction. Then, an analysis of the observed reaction front yields the reaction rate. We start with the case of one step reactions. We derive a one dimensional reaction-diffusion model for the reaction front and compare numerical and analytical solutions of our model to experiments held in our microsystem. Then, we turn our attention to the case of enzymatic reactions. First, we show how the device operation can be parallelized in order to react an initial sample with a range of compounds or concentrations and we perform standard well-mixed enzyme assays with our parallelized chip, thereby mimicking titer plate assays in droplets. Second, we build onto our reaction-diffusion model to predict the rate of fast enzymatic reactions held in our device. Again, numerical and analytical solutions of our model are compared to experiments done in droplets which yields measurements of the kinetic parameters of the reaction at play
2
Marrone, April. "THE BIOCHEMICAL REACTIONS OF DRY STATE DNA". Doctoral diss., University of Central Florida, 2009. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/3622.
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The biochemistry of dry state DNA is of interest to the fields of forensics, ancient DNA, and DNA storage. The exact chemical nature of the degradation of the DNA molecule in the dry state has not been studied prior. If determined what chemical changes the DNA molecule undergoes, to what degree and in what time frame then protocols can be implemented to bypass the impact of this damage or to repair it when necessary. It is suspected that similar reactions occur to the dry state DNA molecule as does to the hydrated molecule. It cannot be assumed, however that these types of chemical processes occur to the same extent and at the same rates. In general the generic process of hydrolysis encompasses two important reactions, that of deamination and of base loss from the 2’-deoxyribose backbone. Base loss is believed to ultimately lead to chain scission. It is also suspect that reactive oxygen species (ROS) have an important role in the chemistry associated with DNA. Species such as hydroxyl radicals (OH·) and singlet oxygen (¹O₂) can lead to strand scissions and chemically modified bases. Throughout this project various techniques were used to determine damage to DNA and its molecular constituents under conditions leading to hydrolytic and oxidative damage. Novel techniques used in this study include ion-pairing chromatography and denaturing HPLC (DHPLC) to measure glycosidic bond cleavage and strand breaks. The extent to which the macromolecule haemoglobin (Hb) can lead to oxidative damage of DNA in dried blood stains by acting as a Fenton chemistry catalyst was evaluated. Additionally the enzymatic activity of the extracellular nuclease from Alteromonas espejiana, BAL 31 was studied as it pertains to the degradation of single-stranded short homopolymeric oligonucleotides. This study serves as the basis for future, more in depth experimentation into the more specific nature of dry state DNA biochemistry.
It was found that to a large extent the same degradation reactions (base hydrolysis, base modifications, and strand breaks) do occur in the dry state as in the hydrated state when heat and UV radiation are used as energy sources. Reaction rates indicate that base hydrolysis and deamination occur much more slowly, yet have the same energies of activation in both states. Single strand breaks of dry state duplex DNA occur with a half life of 24 ± 2 days and appears to occur in a mechanistic manner which could be of interest when attempting to repair such damage. In addition, base loss alone does not correlate with the extent of single strand breaks detected. Thermodynamic data can lead to the conclusion that DNA degradation in both dry and hydrated states is not a spontaneous process. It is also concluded that though the Hb molecule undergoes oxidative changes over time, these changes do not impact its ability to become a more aggressive Fenton reagent. However, the presence of Hb in the vicinity of DNA does create the opportunity for OH· induced damage to the deoxyribose sugar, and most likely the DNA bases themselves. This study also reveals that the general purpose BAL 31 nuclease commonly used in molecular genetics exhibits a hithertofore non-characterized degree of substrate specificity with respect to single-stranded DNA oligomers. Specifically, BAL 31 nuclease activity was found to be affected by the presence of guanine in ssDNA oligomers.Ph.D.
Department of Chemistry
Sciences
Chemistry PhD
3
Mistry, Dharmit. "Mechanistic studies of some chemical and biochemical reactions". Thesis, University of Huddersfield, 2014. http://eprints.hud.ac.uk/id/eprint/23444/.
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Three aspects of chemical and biochemical reactions were investigated. 1. The relative reactivities of pyrophosphate (phosphorus(V)) and pyro-di-H-phosphonate (phosphorus(III)) and its derivatives have been analysed at various pHs. The hydrolysis rate of pyro-di-H-phosphonate (PP(III)) was found to be higher than pyrophosphate at all pHs. Using ITC and NMR, pyrophosphate showed metal-ion complexing abilities whereas pyro-di-H-phosphonate showed weak or no complexing to metal-ions, although the rate of hydrolysis at pH 7 slightly increased compared to the spontaneous hydrolysis of PP(III). The enzymatic hydrolysis of pyrophosphate, which is thought to occur via MgPP(V)2-, occurs efficiently and is close to being diffusion controlled. Pyro-di-H-phosphonate on the other hand does not act as a substrate or as an inhibitor of pyrophosphatase. 2. Dichloromethane (DCM) is an alkylating agent for pyridine, producing methylene bis-pyridinium dication (MDP) upon refluxing the solution. The kinetics and mechanism of hydrolysis of methylene bis-pyridinium dication have been studied. Below pH 7 MDP is extremely stable and hydrolysis is first-order in hydroxide-ion. Above pH 9 an unusual intermediate is formed on hydrolysis which has a chromophore at 366 nm in water and its formation is second-order in hydroxide-ion. The carbon acidity of the central methylene group was also investigated kinetically using H/D exchange and the pKa was surprisingly high at 21.2 at 25oC (I = 1.0 M). 3. Isothermal titration calorimetry (ITC) is a technique mainly used by biochemists to obtain a range of physical and thermodynamic properties of a reaction. Analysing the data can become difficult when investigating complex reactions involving more than one step, for instance metal-ions binding to an enzyme. In this work models have been developed to simulate sequential reactions. These were used to simulate experimental ITC data for metal-ions: Zn2+, Co2+ and Cd2+ complexing to the active sites of BcII, a metallo β-lactamase responsible for antibiotic resistance, providing additional information on the mechanism by which this enzyme acts to deactivate β-lactam antibiotics. The simulations suggest that BcII has two very similar binding affinities to metal-ions which are filled sequentially.
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Dubey, Nidhi Chandrama. "Smart hydrogels based platforms for investigation of biochemical reactions". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-184082.
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Polyketides are natural products with complex chemical structures and immense pharmaceutical potential that are synthesized via secondary metabolic pathways. The in-vitro synthesis of these molecules requires high supply of building blocks such as acetyl Co-enzyme A, and cofactors (adenosine triphosphate (ATP). These precursor and cofactor are synthesized from respective soluble enzymes. Owing to the expensive nature of the enzymes, it is important to immobilize enzymes to improve the process economics by enabling multiple uses of catalyst and improving overall productivity and robustness. The polymer-based particles of nano and submicron size have become attractive material for their role in the life sciences. With the advances in synthetic protocols of the microgels and commercial availability of many of the monomers, it is feasible to tune the properties of the particles as per the process requirement. The core shell microgel with functional shell allows high loading of ligands onto the microgel particles due to increased availability of functional group on the outer surface. The aim of the thesis thus was to study biochemical reactions on the smart microgels support using single (acetyl CoA synthetase (Acs)) and dual (pyruvate kinase (Pk) and L-lactic dehydrogenase (Ldh)) enzyme/s systems.
The study indicated that the enzyme immobilization significantly depends on the enzyme, conjugation strategy and the support. The covalent immobilization provides rigidity to the enzyme structure as in case of Acs immobilized on PNIPAm-AEMA microgels but at the same time leads to loss in enzyme activity. Whereas, in the case of covalent immobilization of Ldh on microgel showed improved in enzyme activity. On the other hand adsorption of the enzyme via ionic interaction provide better kinetic profile of enzymes hence the membrane reactor was prepared using PNIPAm-PEI conjugates for acetyl CoA synthesis. The better outcome of work with PNIPAm-PEI resulted in its further evaluation for dual enzyme system. This work is unique in the view that the immobilization strategies were well adapted to immobilize single and dual enzymes to achieve stable bioconjugates for their respective applications in precursor biosynthesis (Acetyl Co enzyme A) and co-factor dependent processes (ACoA and ATP).
The positive end results of microgels as the support (particles in solution and as the thin film (membrane)) opens further prospective to explore these systems for other precursor biomolecule production.
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Davis, Aaron Vincent Tarn. "Chemical and Biochemical Redox Reactions of the Anticancer Drug Streptonigrin". Thesis, Queen Mary, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504553.
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Streptonigrin has shown activity against several tumours (e.g. breast and lung). The drug induces cytotoxicity by impairing DNA synthesis via inhibition of Topoisomerase II and direct damage to DNA through attack by ROS (reactive oxygen species), the latter of which has been linked to the aminoquinone domain [Bolzc'm and Bianchi 2001]. Streptonigrin exists in one of three possible oxidation states, the oxidised quinone, the le- reduced semiquinone radical and a 2e- reduced hydroquinone. The semiquinone radical has been linked to the production of ROS species through redox cycling in the presence of oxygen. The superoxide and hydroxyl radicals cause damage to various cellular constituents e.g. proteins and nucleic acids (HO· is the primary source of the drug's toxicity). In addition to this streptonigrin has a high affinity for different metal ions e.g. iron and copper. The drug-metal complexes are known to increase streptonigrin's binding affinity to DNA [Bolzfm and Bianchi 2001]. Little is known about the effects of the metal on the chemical and biological activity of the drug. Most of the research on the redox chemistry of streptonigrin (SN) has consisted of NMR studies of SN metal complexes in organic solvents at concentrations which are not feasible at physiological conditions. This research focused on determining the precise mechanism involved in streptonigrin semiquinone formation; the precise role of different metal ions in semiquinone formation and the affect of different pH via two buffers with different pHs (5.5 and 9.5). The experimental data showed that semiquinone formation occurred via complete reduction followed by oxidation rather than I e- reduction . Subsequent EPR experiments also confirmed that metal ions had a direct affect on semlqumone formatIon, wuh streptol1lgrm metal bmdmg ratios greater than I: I mhlbumg semiquinone formation. Experiments carried out to measure reactive oxygen species formation by the drug showed limited evidence of superoxide formation by the different drug metal complexes; however there was clear evidence of hydroxyl radical formation which appeared to change in concentration with metal ion concentration in a similar fashion to the semiquinone. The experimental work should assist future drug analogue development.
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Greenfield, Daniel Leo Computer Science & Engineering Faculty of Engineering UNSW. "New and hybrid methods for simulating biochemical systems". Awarded by:University of New South Wales. Computer Science and Engineering, 2006. http://handle.unsw.edu.au/1959.4/23990.
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It is a dream of Systems-Biology to efficiently simulate an entire cell on a computer. The potential medical and biological applications of such a tool are immense, and so are the challenges to accomplish it. At the level of a cell, the number of reacting molecules is so low that stochastic effects can be crucial in deciding the system-level behaviour of the cell. Despite the recent development of many new and hybrid stochastic approaches, exact stochastic simulation algorithms are still needed, and are widely employed in most current biochemical simulation packages. Unfortunately, the performance of these algorithms scales badly with the number of reactions. It is shown that this is especially the case for hubs and scale-free networks. This is worrying because hubs are an important component of biochemical systems, and it is widely suspected that biochemical networks are scale-free. It is shown that the scalability issue in these algorithms is due to the high interdependency between reactions. A general method for arbitrarily reducing this interdependency is introduced, and it is shown how it can be used for many classes of simulation processes. This is applied to one of the fastest algorithms currently, the Next Reaction Method. The resulting algorithm, the Reactant-Margin Method, is tested on a wide range of hub sizes and shown to be asymptotically faster than the current best algorithms. Hybrid versions of the Reactant-Margin Method and the Next Reaction Method are also compared on a real biological model - the Lambda-Phage virus, and the new algorithm is again shown to perform better. The problems inherent in the hybridization are also shown to be more exactly and efficiently handled in the Reactant-Margin framework than in the Next-Reaction Method framework. Finally, a software tool called GeNIV is introduced. This GUI-based biochemical modelling and simulation tool is an embodiment of a mechanistic-representation philosophy. It is implements the Reactant Margin and Next Reaction hybrid algorithms, and has a simple representation system for gene-state occupancy and their subsequent biochemical reactions. It is also novel in that it translates the graphical model into Javacode which is compiled and executed for simulation.
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Liu, Yang y 刘洋. "Free energy simulations of important biochemical processes". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196036.
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Free energy simulations have been widely employed to compute the thermodynamic properties of many important biochemical processes. In the first part of this dissertation, two important biochemical processes, protonation/deprotonation of acid in solution and solvation of small organic molecules, are investigated using free energy simulations.
Accurate computation of the pKa value of a compound in solution is important and challenging. To efficiently simulate the free energy change associated with the protonation/deprotonation processes in solution, a new method of mixing Hamiltonian, implemented as an approach using a fractional protonin the hybrid quantum mechanics/molecular mechanics (QM/MM) scheme, is developed. This method is a combination of a large class of λ-coupled free-energy simulation methods and the linear combination of atomic potential approach. Theoretical and technical details of this method, along with the calculation results of the pKa value of methanol and methanethiol molecules in aqueous solution, are discussed. The simulation results show satisfactory agreement with experimental data.
Though the QM/MM method is one of the most useful methods in the modeling of biochemical processes, little attention has been paid to the accuracy of QM/MM methods as an integrated unit. Therefore, the solvation free energies of a set of small organic molecules are simulated as an assessment of ab initio QM/MM methods. It shows that the solvation free energy from QM/MM simulations can vary over a broad range depending on the level of QM theory / basis sets employed. Diffuse functions tend to over-stabilize the solute molecules in aqueous solution. The deviations pose a pressing challenge to the future development of new generation of MM force fields and QM/MM methods if consistency with QM methods becomes a natural requirement.
In the second part of the dissertation, the dynamic and energetic properties of two molten globule (MG) protein molecules, α-lactalbumin(α-LA) and monomeric chorismate mutase (mCM) are investigated using molecular dynamics simulations. The exploring of the molecular mechanism of protein folding is a never-settled battle while the properties of MG states and their roles in protein folding become an important question. The MGs show increased side chain flexibility while maintain comparable side-chain coupling compared to the native state, which partially explains the preserving of native-like overall conformation. The enhanced sampling method, temperature-accelerated molecular dynamics (TAMD), is used for the study of the hydrophobic interactions inside both biomolecules. The results suggest that these hydrophobic cores could overcome energy barriers and repack into new conformation states with even lower energies.
The repacking of the hydrophobic cores in MGs might be served as a criterion for recognizing the MGs in large class of biomolecules.published_or_final_version
Chemistry
Doctoral
Doctor of Philosophy
8
Möller, Mark. "A hybrid algorithm for the simulation of biochemical reactions and diffusion". [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=982994052.
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Gomez, David [Verfasser] y Stefan [Akademischer Betreuer] Klumpp. "Mechanisms of biochemical reactions within crowded environments / David Gomez ; Betreuer: Stefan Klumpp". Potsdam : Universität Potsdam, 2016. http://d-nb.info/1218400757/34.
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Rajanayagam, Kavitha. "Chemical and biochemical redox reactions of the anthra quinone anticancer drug Mitoxantrone". Thesis, Queen Mary, University of London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417075.
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Flach, Edward H. "Reactions in open systems : pattern formation with convection, and open biochemical pathways". Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496888.
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Yee, Yao-Chung. "Novel design of a passive microfluidic mixer for biochemical reactions and biosensing". [College Station, Tex. : Texas A&M University, 2007. http://hdl.handle.net/1969.1/ETD-TAMU-1500.
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Zimmer, Christoph [Verfasser] y Hans Georg [Akademischer Betreuer] Bock. "Parameter estimation for stochastic models of biochemical reactions / Christoph Zimmer ; Betreuer: Hans Georg Bock". Heidelberg : Universitätsbibliothek Heidelberg, 2012. http://d-nb.info/1179785401/34.
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Dahl, Helen. "Ethyl glucuronide, a new biochemical marker for acute alcohol intake : studies on possible causes for false-negative or false-positive results /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-644-1/.
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Hinzpeter, Florian [Verfasser] y Ulrich [Akademischer Betreuer] Gerland. "Kinetics of spatially organized biochemical reactions : optimal strategies and underlying physical principles / Florian Hinzpeter ; Betreuer: Ulrich Gerland". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1191691330/34.
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Ozogur, Sureyya. "Mathematical Modelling Of Enzymatic Reactions, Simulation And Parameter Estimation". Master's thesis, METU, 2005. http://etd.lib.metu.edu.tr/upload/12605856/index.pdf.
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A deep and analytical understanding of the human metabolism grabbed attention of scientists from biology, medicine and pharmacy. Mathematical models of metabolic pathways offer several advances for this deep and analytical understanding due to their incompensable potential in predicting metabolic processes and anticipating appropriate interventions when required. This thesis concerns mathematical modeling analysis and simulation of metabolic pathways. These pathways include intracellular and extracellular compounds such as enzymes, metabolites, nucleotides and cofactors. Experimental data and available knowledge on metabolic pathways are used in constituting a mathematical model. The models are either in the form of nonlinear ordinary differential equations (ode's) or differential algebraic equations (dae'
s). These equations are composed of kinetic parameters such as kinetic rate constants, initial rates and concentrations of metabolites. The non-linear nature of enzymatic reactions and large number of parameters cause trouble in efficient simulation of those reactions. Metabolic engineering tries to simplify these equations by reducing the number of parameters. In this work, enzymatic system which includes Creatine Kinase, Hexokinase and Glucose 6-Phosphate Dehydrogenase (CK-HK-G6PDH) is modeled in the form of dae'
s, solved numerically and the system parameters are estimated. The numerical results are compared with the results from an existing work in literature. We demonstrated that, our solution method based on direct solution of the CK-HK-G6PDH system significantly from simplified solutions. We also showed that genetic algorithm(GA) for parameter estimation, provides much clear results to the experimental values of the metabolite, especially with NADPH. Keywords: metabolic engineering, kinetic modelling, biochemical reactions, enzymatic reactions, differential algebraic equations, parameter estimation, genetic algorithm.
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Hatcher, Anthony. "Comparison of Micrscan Identification and Susceptibility Testing Methods for Streptococcus Dysgalactiae to Conventional Biochemical Reactions and Kirby-Bauer Susceptibility Testing Methods". TopSCHOLAR®, 1994. http://digitalcommons.wku.edu/theses/970.
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A total of 100 isolates of Streptococcus dysgalact iae from bovine mastitis infections was used to evaluate and compare the biochemical reactions of the gram positive Combo Type 6 panel on the MicroScan autoSCANR system to a conventional procedure for identification of streptococci. Of the 100 isolates, 83.3% was identified as "Very Rare Biotype" by the MicroScan and classified as S. dysgalactiae by conventional methods. Of the remaining 16.7%, MicroScan identified 3.3% as Streptococcus morbillorum, 3.3% as Aerococcus viridians, 3.3% as Streptococcus constellatum/milleri, 1.7% as Streptococcus agalactiae, 1.7% as Streptococcus mitis, 1.7% as Streptococcus sanguis, and 1.7% as Streptococcus intermidis/rni 1 leri. The identification of bacteria other than Very Rare Biotype can be attributed to code profiles listed in the MicroScan which demonstrate biochemical reactions similar to S. dysgalact iae. The antimicrobial susceptibility of 94 S. dysgalactiae isolates to 16 antibiotics was determined by the MicroScan system. Of the antibiotics tested, each demonstrated greater than 85% susceptibility against the 94 strains of S. dysgalactiae. Of the 16 antibiotics used in the MicroScan, nine were compared to the standard Kirby-Bauer method and/or results obtained from the literature. S. dysgalactiae was reported as sensitive to penicillin on 89.4% of the strains tested by the MicroScan, 98.4% by the Kirby-Bauer method, and 98.0% by the literature references. In testing 94 strains for susceptibility to gentamicin by two methods, MicroScan resulted in 98.0% comparability to literature values but 83.6% to the Kirby-Bauer technique. The other antibiotics tested on the MicroScan and compared to the Kirby-Bauer and/or literature values illustrated a comparison of greater than 90%. In this study, 36 isolates of S. dysgalactiae demonstrating resistance to tetracycline, single, and multiple antibiotics were analyzed for plasmids. The evidence of plasmids was not detected as analyzed by agarose gel electrophoresis. All 100 isolates of S. dysgalactiae, with the exception of one, were tested serologically for the presence of C antigen. Each isolate tested was classified as a Group C streptococci. Each of the 100 isolates was stored in 5% sheep red blood cells at -20°C for one year. Each isolate was revived, with the exception of one, and demonstrated characteristic streptococcal colony morphology. The storage recovery rate was 99% and is an acceptable storage method for streptococci.
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Dubey, Nidhi Chandrama [Verfasser], Manfred [Akademischer Betreuer] Stamm y Pée Karl-Heinz [Akademischer Betreuer] van. "Smart hydrogels based platforms for investigation of biochemical reactions / Nidhi Chandrama Dubey. Betreuer: Manfred Stamm. Gutachter: Manfred Stamm ; Karl-Heinz van Pée". Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://d-nb.info/1079468110/34.
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Dubey, Nidhi C. [Verfasser], Manfred [Akademischer Betreuer] Stamm y Pée Karl-Heinz [Akademischer Betreuer] van. "Smart hydrogels based platforms for investigation of biochemical reactions / Nidhi Chandrama Dubey. Betreuer: Manfred Stamm. Gutachter: Manfred Stamm ; Karl-Heinz van Pée". Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-184082.
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Kagel, Heike [Verfasser], Frank Fabian [Akademischer Betreuer] Bier, Marcus [Akademischer Betreuer] Frohme, Jörn [Akademischer Betreuer] Glökler, Frank Fabian [Gutachter] Bier, Ilko [Gutachter] Bald y Michel [Gutachter] Köhler. "Light-induced pH cycle : a non-invasive method to control biochemical reactions / Heike Kagel ; Gutachter: Frank Fabian Bier, Ilko Bald, Michel Köhler ; Frank Fabian Bier, Marcus Frohme, Jörn Glökler". Potsdam : Universität Potsdam, 2019. http://d-nb.info/1218405104/34.
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Akintoye, Ayodele. "Continuous chromatographic biochemical reaction-separation". Thesis, Aston University, 1989. http://publications.aston.ac.uk/9739/.
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Combined bioreaction separation studies have been carried out for the first time on a moving port semi-continuous counter-current chromatographic reactor-separator (SCCR-S1) consisting of twelve 5.4cm id x 75cm long columns packed with calcium charged cross-linked polystyrene resin (KORELA V07C). The inversion of sucrose to glucose and fructose in the presence of the enzyme invertase and the biochemIcal synthesis of dextran and fructose from sucrose in the presence of the enzyme dextransucrase were investigated. A dilute stream of the appropriate enzyme in deionised water was used as the eluent stream. The effect of switch time, feed concentration, enzyme activity, eluent rate and enzyme to feed concentration ratio on the combined bioreaction-separation were investigated. For the invertase reaction, at 20.77% w/v sucrose feed concentrations complete conversions were achieved. The enzyme usage was 34% of the theoretical enzyme amount needed to convert an equivalent amount of sucrose over the same time period when using a conventional fermenter. The fructose rich (FRP) and glucose rich (GRP) product purities obtained were over 90%. By operating at 35% w/v sucrose feed concentration and employing the product splitting and recycling techniques, the total concentration and purity of the GRP increased from 32% w/v to 4.6% and from 92.3% to 95% respectively. The FRP concentration also increased from 1.82% w/v to 2.88% w/v. A mathematical model was developed for the combined reaction-separation and used to simulate the continuous inversion of sucrose and product separation using the SCCR-S1. In the biosynthesis of dextran studies, 52% conversion of a 2% w/v sucrose concentration feed was achieved. An average dextran molecular weight of 4 millIon was obtained in the dextran rich (DRP) product stream. The enzyme dextransucrase was purifed successfully using centrifugation and ultrafiltration techniques.
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Khoshnaw, Sarbaz Hamza Abdullah. "Model reductions in biochemical reaction networks". Thesis, University of Leicester, 2015. http://hdl.handle.net/2381/32442.
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Many complex kinetic models in the field of biochemical reactions contain a large number of species and reactions. These models often require a huge array of computational tools to analyse. Techniques of model reduction, which arise in various theoretical and practical applications in systems biology, represent key critical elements (variables and parameters) and substructures of the original system. This thesis aims to study methods of model reduction for biochemical reaction networks. It has three goals related to techniques of model reduction. The primary goal provides analytical approximate solutions of such models. In order to have this set of solutions, we propose an algorithm based on the Duhamel iterates. This algorithm is an explicit formula that can be studied in detail for wide regions of concentrations for optimization and parameter identification purposes. Another goal is to simplify high dimensional models to smaller sizes in which the dynamics of original models and reduced models should be similar. Therefore, we have developed some techniques of model reduction such as geometric singular perturbation method for slow and fast subsystems, and entropy production analysis for identifying non–important reactions. The suggested techniques can be applied to some models in systems biology including enzymatic reactions, elongation factors EF–Tu and EF–Ts signalling pathways, and nuclear receptor signalling. Calculating the value of deviation at each reduction stage helps to check that the approximation of concentrations is still within the allowable limits. The final goal is to identify critical model parameters and variables for reduced models. We study the methods of local sensitivity in order to find the critical model elements. The results are obtained in numerical simulations based on Systems Biology Toolbox (SBToolbox) and SimBiology Toolbox for Matlab. The simplified models would be accurate, robust, and easily applied by biologists for various purposes such as reproducing biological data and functions for the full models.
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Lawson, Christopher Peter Abiodun Tevi. "The development of novel myosin inhibitors". Thesis, University of St Andrews, 2011. http://hdl.handle.net/10023/2123.
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This thesis describes a structure activity relationship (SAR) study on the recently discovered small molecule tool blebbistatin (S)-21 with particular emphasis on the development of novel synthetic protocols suitable for the rapid synthesis of libraries of blebbistatin analogues. These analogues are potentially of use as novel myosin inhibitors Chapter 1 introduces the concept of chemical biology with particular emphasis on chemical genetics. This approach has rekindled the search for new chemical tools for the investigation of biological systems. The success of blebbistatin (S)-21, which was identified in a chemical genetic study, as a research tool was also discussed. The link between several myosin classes and genetic diseases such as coeliac disease, Crohn’s disease, deafness, dermatitis, familial hypertrophic cardiomyopathy, Griscelli disease and ulcerative colitis indicate that potent inhibitors which show selectivity towards specific myosin isoforms may be of great value as tools for the study of these conditions. The plan for the SAR study around (S)-21 was outlined. Chapter 2 describes the studies undertaken to develop an efficient synthetic route to N1-alkyl analogues of (S)-21 suitable for the parallel synthesis of chemical collections. These studies culminated in the synthesis of an intermediate (S)-66 from which novel N1-alkyl analogues were synthesised. The biological evaluation of these N1-alkyl analogues was discussed. Chapter 3 describes the development of a protocol suitable for the parallel synthesis of collections of N1-aryl analogues of (S)-21 via the intermediate 66. The application of this protocol to the synthesis of a collection of racemic N1-aryl and heteroaryl analogues of (S)-21 and their biological evaluation was presented. Chapter 4 describes the successful rational design and synthesis of a novel fused thiophene ring containing inhibitor of myosin II. The structure of this compound was proposed by modelling of the existing co-crystal structure of (S)-21 bound to the metastable state of Dictyostelium discoideum myosin II (S1dC) and sought to optimise the π-π stacking interaction displayed by (S)-21 with the tyrosine 261 residue within its binding site. The biological evaluation of this novel analogue was discussed. In Chapter 5 the studies conducted to investigate the contribution of ring-C to the binding affinity of (S)-21 were described. The development of alternate routes to (S)-21, in an attempt to avoid difficulties experienced during the synthesis of some analogues of (S)-21, are described. The synthesis and biological investigation of the fluorescent dye PPBA whose binding site has been suggested to overlap with that of (S)-21 was also reported.
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Lester, Christopher. "Efficient simulation techniques for biochemical reaction networks". Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:bb804e01-b1de-409f-b843-4806c2c990c2.
Texto completoResumen
Discrete-state, continuous-time Markov models are becoming commonplace in the modelling of biochemical processes. The mathematical formulations that such models lead to are opaque, and, due to their complexity, are often considered analytically intractable. As such, a variety of Monte Carlo simulation algorithms have been developed to explore model dynamics empirically. Whilst well-known methods, such as the Gillespie Algorithm, can be implemented to investigate a given model, the computational demands of traditional simulation techniques remain a significant barrier to modern research. In order to further develop and explore biologically relevant stochastic models, new and efficient computational methods are required. In this thesis, high-performance simulation algorithms are developed to estimate summary statistics that characterise a chosen reaction network. The algorithms make use of variance reduction techniques, which exploit statistical properties of the model dynamics, so that the statistics can be computed efficiently. The multi-level method is an example of a variance reduction technique. The method estimates summary statistics of well-mixed, spatially homogeneous models by using estimates from multiple ensembles of sample paths of different accuracies. In this thesis, the multi-level method is developed in three directions: firstly, a nuanced implementation framework is described; secondly, a reformulated method is applied to stiff reaction systems; and, finally, different approaches to variance reduction are implemented and compared. The variance reduction methods that underpin the multi-level method are then re-purposed to understand how the dynamics of a spatially-extended Markov model are affected by changes in its input parameters. By exploiting the inherent dynamics of spatially-extended models, an efficient finite difference scheme is used to estimate parametric sensitivities robustly. The new simulation methods are tested for functionality and efficiency with a range of illustrative examples. The thesis concludes with a discussion of our findings, and a number of future research directions are proposed.
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Huang, Xin. "Simulation of biochemical reaction and biophysical process". Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491955.
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The density functional theory (DFT) and molecular mechanics (MM) are used to study biochemical reactions and biophysical processes. The mechanism of DNA backbone hydrolysis by specific enzyme is studied. It is found that the Mg2 + cation can polarize the breaking P-O bond while a histidine acts as both the stabilizer and activator of the attacking water. Moreover, the water dissociation and formation ofnew bond should be coinstantaneous. In order to understand the nitrosylation ~f target thiol group in cells, we study oxygen-dependent thiol nitrosylating pathway. A general trend of the mixed pathway is found. Different intermediate (N203 or N02) can perform the nitrosylation of the target thiol group. Water can diminish the N20 3pathway through hydrolyzing N20 3, but it is capable of enhancing the effect of agent N02. Selectivity of target thiol is also studied. By this means, the thiol group which. is the easiest to accept the NO group would be nitrosylated rather than others. Aiming to further understanding of the fidelity transformation during the process in which tRNA is bound to aminoacyl-tRNA synthetases (aaRS), the mechanism is studied using molecular mechanics calculations. The effects of anticodon, positive arginines and crucial alanine site are analysed. The binding sequence is outlined. The fidelity of genetics information in DNA replication is studied by DFT and molecular mechanics. We find that the correct nucleotide insertion has nothing to do with'its complementary part, but determined by nearby essential residues. The match base pair can allow the residue to be fully positioned in the reactive pocket. Thus a new mechanism of DNA replication is proposed: it is the match base pair induced hydrophobic domain that determines the fidelity in the reaction.
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Steiner-Oliveira, Carolina 1981. "Uso do laser de 'C'O IND. 2' ('lambda'=10,6 'mu') na prevenção da carie e erosão dentarias : estudos in vitro". [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288091.
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Orientador: Marines Nobre dos Santos UchoaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
Made available in DSpace on 2018-08-13T08:04:08Z (GMT). No. of bitstreams: 1 Steiner-Oliveira_Carolina_D.pdf: 11802864 bytes, checksum: 338ee3278fb157bb1cb37edb2e6d1a5d (MD5) Previous issue date: 2009
Resumo: Os efeitos causados pelas modificações promovidas pela irradiação com laser de CO2 podem inibir a desmineralização dos tecidos dentários e podem ser potencializados quando associados ao fluoreto. Apesar de amplo uso do fluoreto e da redução da prevalência de cárie, essa doença ainda acomete grupos de alto risco. Por outro lado, tem sido observado um aumento da prevalência da erosão dentária. Os objetivos dessa tese, composta por 4 manuscritos, foram: (1) descrever as características do laser de CO2 e seus mecanismos de ação na inibição da desmineralização do esmalte; (2) desenvolver um modelo microbiológico, in vitro, de produção de lesão de cárie em dentina e testar duas hipóteses: (a) de que não há diferença na produção de cárie artificial em dentina utilizando um modelo microbiológico com regimes de 3 e 6 imersões ao dia em sacarose, avaliados por contagem bacteriana da dentina (UFC), análise microrradiográfica (AM) e análise de polissacarídeo insolúvel (API); (b) de que não há diferença no pH do biofilme antes e após sua imersão em sacarose; (3) avaliar, in vitro, a efetividade do laser de CO2 (? = 10,6 µm) pulsado, associado ou não ao fluoreto, na redução da desmineralização da dentina radicular usando um modelo microbiológico, avaliado por AM; (4) avaliar, in vitro, o efeito do mesmo laser, associado ou não ao fluoreto, na redução da desmineralização do esmalte e da dentina submetidos a um desafio erosivo, pela mensuração da perda de superfície e análise da concentração de cálcio, fósforo e fluoreto das soluções desmineralizadoras. Os dados foram analisados quanto à normalidade e testes apropriados foram realizados com nível de significância de 5%. No estudo 1, os efeitos do laser no esmalte, seu mecanismo de ação na redução da desmineralização, combinados ou não ao fluoreto, foram discutidos. No estudo 2, o pH do biofilme diminuiu imediatamente após a imersão em sacarose, mas aumentou novamente 5 min depois. Lesões em dentina foram produzidas com sucesso e a adição de sacarose mostrou as maiores perdas minerais, no entanto não diferiu entre os dois regimes de sacarose. A UFC não mostrou nenhuma diferença e a API dos tratamentos foram maiores que a do grupo controle. No estudo 3, os espécimes radiculares foram tratados ou não com laser de CO2 e com ou sem fluoreto antes ou após a irradiação com laser. O modelo microbiológico utilizado foi efetivo em produzir lesões dentinárias e as terapias combinadas mostraram as lesões dentinárias mais rasas. No estudo 4, espécimes de esmalte e dentina foram tratados com fluoreto, laser e fluoreto/laser e submetidos a um desafio erosivo. Os resultados de desgaste indicaram que o tratamento combinado interferiu com as perdas minerais do esmalte e da dentina, mesmo sem mostrar efeito sinérgico. Houve uma tendência de retenção de fluoreto no esmalte pelo tratamento combinado e também de liberação de menores quantidades de cálcio, fósforo e fluoreto para as soluções desmineralizadoras. Em conclusão, o mecanismo de ação do laser de CO2 na inibição da desmineralização do esmalte ainda não está completamente esclarecido e seu efeito pode ser aumentado quando associado ao fluoreto. O modelo microbiológico foi efetivo em produzir lesões de cárie dentinária. A irradiação da dentina radicular com laser inibiu a desmineralização dessa superfície apenas quando associado com o fluoreto; no entanto, não foi observado efeito sinérgico. O tratamento isolado com laser não foi capaz de prevenir a perda de superfície do esmalte e da dentina devido à erosão. Sua combinação com fluoreto mostrou alguma proteção, mas principalmente devido ao efeito do fluoreto. Não foi observada interação sinérgica significativa ou proteção duradoura com a terapia de laser.
Abstract: The effects caused by the modifications promoted by the CO2 laser irradiation can inhibit the dental tissues demineralization and may be enhanced when associated with fluoride. Despite the widespread use of the fluoride and the reduction of the caries prevalence, this disease still occurs in the high risk groups. On the other hand, an increase of the dental erosion prevalence was observed. This thesis, comprised by 4 manuscripts, aimed: (1) to describe the CO2 laser characteristics and its action mechanisms in the enamel demineralization inhibition; (2) to develop an in vitro microbial model to produce dentin caries lesions and test two hypotheses - (a) that there is no difference in the artificial caries production in dentin using a microbial model with 3 and 6 sucrose bath immersions, as assessed by bacterial counts on the dentin (CFU), microradiographic analysis (TMR) and extracellular polysaccharide analysis (EPS); (b) that there is no difference in the biofilm pH before and after each sucrose bath; (3) to assess, in vitro, the effectiveness of a pulsed CO2 laser (? = 10.6 µm) associated or not with fluoride, in reducing the root demineralization using a microbial model, as assessed by TMR; (4) to assess, in vitro, the effect of the same laser, associated or not with fluoride, on the prevention of the enamel and dentin erosions by means of surface loss measurement and analysis of the calcium, phosphorus and fluoride concentrations in the demineralizing solutions. The data were checked for normality and appropriated tests were performed with a significance level of 5%. In study 1, the laser effects on the enamel and its action mechanisms in the demineralization reduction, combined or not with fluoride, were discussed. In study 2, the biofilm pH decreased immediately after the sucrose bath but increased again after 5 min. Dentin lesions were successfully produced, and the sucrose addition showed the highest mineral losses, even though there was no difference between the sucrose regimens. The CFU did not show any difference and the EPS from the treatment groups were higher than for the control. In study 3, root specimens were treated with/without CO2 laser and with/without fluoride prior or after the laser irradiation. The microbial model utilized was effective in developing dentin lesions and the combined therapies showed the shallowest dentin lesions. In study 4, specimens of enamel and root dentin were treated with fluoride, laser and fluoride/laser and submitted to an erosive challenge. The wear results indicated that the combined treatment interfered with the enamel or dentin surface losses, although no synergistic effect was observed. There was a trend for the combined treatment to retain more fluoride in enamel and release lower amounts of calcium and phosphorus into the demineralizing solutions. In conclusion, the CO2 mechanism action on the enamel demineralization reduction is still not elucidated and its effects can be increased when associated with fluoride. The microbial model was effective in producing dentin caries lesions. However, it did not reproduce the remineralizing phase of the caries process. Irradiation of the root dentin with laser inhibited the root surface demineralization only when associated with fluoride; however, no synergic effect was observed. The laser treatment alone was not able to prevent enamel or dentin surface losses due to erosion. Its combination with fluoride showed some protection, but mostly due to the fluoride effect. No significant synergistic interaction or lasting protection could be observed for the laser therapy.
Doutorado
Odontopediatria
Doutor em Odontologia
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Wu, Jialiang. "Hybrid modeling and analysis of multiscale biochemical reaction networks". Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/47723.
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This dissertation addresses the development of integrative modeling strategies capable of combining deterministic and stochastic, discrete and continuous, as well as multi-scale features. The first set of studies combines the purely deterministic modeling methodology of Biochemical Systems Theory (BST) with a hybrid approach, using Functional Petri Nets, which permits the account of discrete features or events, stochasticity, and different types of delays. The efficiency and significance of this combination is demonstrated with several examples, including generic biochemical networks with feedback controls, gene regulatory modules, and dopamine based neuronal signal transduction.
A study expanding the use of stochasticity toward systems with small numbers of molecules proposes a rather general strategy for converting a deterministic process model into a corresponding stochastic model. The strategy characterizes the mathematical connection between a stochastic framework and the deterministic analog. The deterministic framework is assumed to be a generalized mass action system and the stochastic analogue is in the format of the chemical master equation. The analysis identifies situations where internal noise affecting the system needs to be taken into account for a valid conversion from a deterministic to a stochastic model. The conversion procedure is illustrated with several representative examples, including elemental reactions, Michaelis-Menten enzyme kinetics, a genetic regulatory motif, and stochastic focusing.
The last study establishes two novel, particle-based methods to simulate biochemical diffusion-reaction systems within crowded environments. These simulation methods effectively simulate and quantify crowding effects, including reduced reaction volumes, reduced diffusion rates, and reduced accessibility between potentially reacting particles. The proposed methods account for fractal-like kinetics, where the reaction rate depends on the local concentrations of the molecules undergoing the reaction. Rooted in an agent based modeling framework, this aspect of the methods offers the capacity to address sophisticated intracellular spatial effects, such as macromolecular crowding, active transport along cytoskeleton structures, and reactions on heterogeneous surfaces, as well as in porous media.
Taken together, the work in this dissertation successfully developed theories and simulation methods which extend the deterministic, continuous framework of Biochemical Systems Theory to allow the account of delays, stochasticity, discrete features or events, and spatial effects for the modeling of biological systems, which are hybrid and multiscale by nature.
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Geffen, Dara. "Parameter identifiability of biochemical reaction networks in systems biology". Thesis, Kingston, Ont. : [s.n.], 2008. http://hdl.handle.net/1974/1347.
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Li, Fei. "Stochastic Modeling and Simulation of Reaction-Diffusion Biochemical Systems". Diss., Virginia Tech, 2016. http://hdl.handle.net/10919/64913.
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Reaction Diffusion Master Equation (RDME) framework, characterized by the discretization of the spatial domain, is one of the most widely used methods in the stochastic simulation of reaction-diffusion systems. Discretization sizes for RDME have to be appropriately chosen such that each discrete compartment is "well-stirred" and the computational cost is not too expensive.
An efficient discretization size based on the reaction-diffusion dynamics of each species is derived in this dissertation. Usually, the species with larger diffusion rate yields a larger discretization size. Partitioning with an efficient discretization size for each species, a multiple grid discretization (MGD) method is proposed. MGD avoids unnecessary molecular jumping and achieves great simulation efficiency improvement.
Moreover, reaction-diffusion systems with reaction dynamics modeled by highly nonlinear functions, show large simulation error when discretization sizes are too small in RDME systems. The switch-like Hill function reduces into a simple bimolecular mass reaction when the discretization size is smaller than a critical value in RDME framework. Convergent Hill function dynamics in RDME framework that maintains the switch behavior of Hill functions
with fine discretization is proposed.
Furthermore, the application of stochastic modeling and simulation techniques to the spatiotemporal regulatory network in Caulobacter crescentus is included. A stochastic model
based on Turing pattern is exploited to demonstrate the bipolarization of a scaffold protein, PopZ, during Caulobacter cell cycle. In addition, the stochastic simulation of the spatiotemporal histidine kinase switch model captures the increased variability of cycle time in cells depleted of the divJ genes.Ph. D.
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Jenkins, Robert. "Deterministic and stochastic modelling of chemical and biochemical reaction kinetics". Thesis, University of Nottingham, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.495585.
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We analyse various chemical reaction schemes both deterministically and stochastically. The reactions are considered to demonstrate the rich, mathematical behaviour apparent in the systems, rather than to represent realistic chemical reactions. The deterministic analysis is carried out to provide insights into the behaviour of the systems that we can then consider stochastically.
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Leising, Sophie. "Nonlinear controller synthesis for complex chemical and biochemical reaction systems". Link to electronic thesis, 2005. http://www.wpi.edu/Pubs/ETD/Available/etd-050205-152657/.
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Thesis (M.S.) -- Worcester Polytechnic Institute.Keywords: model predictive control; discrete-time model; continuous-time model; nonlinear systems; Lyapunov design. Includes bibliographical references (p. 99-102).
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Woo, Sung Sik Ph D. Massachusetts Institute of Technology. "Fast simulation of stochastic biochemical reaction networks on cytomorphic chips". Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/107292.
Texto completoResumen
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2016.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 169-181).
The large-scale simulation of biochemical reaction networks in cells is important in pathway discovery in medicine, in analyzing complex cell function in systems biology, and in the design of synthetic biological circuits in living cells. However, cells can undergo many trillions of reactions over just an hour with multi-scale interacting feedback loops that manifest complex dynamics; their pathways exhibit non-modular behavior or loading; they exhibit high levels of stochasticity (noise) that require ex- pensive Gillespie algorithms and random-number generation for accurate simulations; and, they routinely operate with nonlinear statics and dynamics. Hence, such simulations are extremely computationally intensive and have remained an important bottleneck in computational biology over decades. By exploiting common mathematical laws between electronics and chemistry, this thesis demonstrates that digitally programmable analog integrated-circuit 'cytomorphic' chips can efficiently run stochastic simulations of complex molecular reaction networks in cells. In a proof-of-concept demonstration, we show that 0.35 [mu]m BiC- MOS cytomorphic gene and protein chips that interact via molecular data packets with FPGAs (Field Programmable Gate Arrays) to simulate networks involving up to 1,400 biochemical reactions can achieve a 700x speedup over COPASI, an efficient bio- chemical network simulator. They can also achieve a 30,000x speedup over MATLAB. The cytomorphic chips operate over five orders of magnitude of input concentration; they enable low-copy-number stochastic simulations by amplifying analog thermal noise that is consistent with Gillespie simulations; they represent non-modular load- ing effects and complex dynamics; and, they simulate zeroth, first, and second-order linear and nonlinear gene-protein networks with arbitrary parameters and network connectivity that can be flexibly digitally programmed. We demonstrate successful stochastic simulation of a p53 cancer pathway and glycolytic oscillations that are consistent with results obtained from conventional digital computer simulations, which are based on experimental data. We show that unlike conventional digital solutions, an increase in network scale or molecular population size does not compromise the simulation speed and accuracy of our completely parallel cytomorphic system. Thus, commonly used circuit improvements to future chips in our digital-to-analog converters, noise generators, and biasing circuits can enable further orders of magnitude of speedup, estimated to be a million fold for large-scale networks.
by Sung Sik Woo.
Ph. D.
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Koyama, M., R. Imai, M. Shikida, M. Okochi, H. Tsuchiya, H. Honda, K. Sato y 一雄 佐藤. "Micromachined sample divider for analyzing biochemical reaction based on single molecules". IEEE, 2008. http://hdl.handle.net/2237/11138.
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Allen, Nicholas A. "Computational Software for Building Biochemical Reaction Network Models with Differential Equations". Diss., Virginia Tech, 2005. http://hdl.handle.net/10919/30059.
Texto completoResumen
The cell is a highly ordered and intricate machine within which a wide variety of chemical processes take place. The full scientific understanding of cellular physiology requires accurate mathematical models that depict the temporal dynamics of these chemical processes. Modelers build mathematical models of chemical processes primarily from systems of differential equations. Although developing new biological ideas is more of an art than a science, constructing a mathematical model from a biological idea is largely mechanical and automatable.
This dissertation describes the practices and processes that biological modelers use for modeling and simulation. Computational biologists struggle with existing tools for creating models of complex eukaryotic cells. This dissertation develops new processes for biological modeling that make model creation, verification, validation, and testing less of a struggle. This dissertation introduces computational software that automates parts of the biological modeling process, including model building, transformation, execution, analysis, and evaluation. User and methodological requirements heavily affect the suitability of software for biological modeling. This dissertation examines the modeling software in terms of these requirements.
Intelligent, automated model evaluation shows a tremendous potential to enable the rapid, repeatable, and cost-effective development of accurate models. This dissertation presents a case study that indicates that automated model evaluation can reduce the evaluation time for a budding yeast model from several hours to a few seconds, representing a more than 1000-fold improvement. Although constructing an automated model evaluation procedure requires considerable domain expertise and skill in modeling and simulation, applying an existing automated model evaluation procedure does not. With this automated model evaluation procedure, the computer can then search for and potentially discover models superior to those that the biological modelers developed previously.Ph. D.
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Allen, Nicholas Alexander. "Computational Software for Building Biochemical Reaction Network Models with Differential Equations". Diss., Virginia Tech, 2003. http://hdl.handle.net/10919/30059.
Texto completoResumen
The cell is a highly ordered and intricate machine within which a wide variety of chemical processes take place. The full scientific understanding of cellular physiology requires accurate mathematical models that depict the temporal dynamics of these chemical processes. Modelers build mathematical models of chemical processes primarily from systems of differential equations. Although developing new biological ideas is more of an art than a science, constructing a mathematical model from a biological idea is largely mechanical and automatable.
This dissertation describes the practices and processes that biological modelers use for modeling and simulation. Computational biologists struggle with existing tools for creating models of complex eukaryotic cells. This dissertation develops new processes for biological modeling that make model creation, verification, validation, and testing less of a struggle. This dissertation introduces computational software that automates parts of the biological modeling process, including model building, transformation, execution, analysis, and evaluation. User and methodological requirements heavily affect the suitability of software for biological modeling. This dissertation examines the modeling software in terms of these requirements.
Intelligent, automated model evaluation shows a tremendous potential to enable the rapid, repeatable, and cost-effective development of accurate models. This dissertation presents a case study that indicates that automated model evaluation can reduce the evaluation time for a budding yeast model from several hours to a few seconds, representing a more than 1000-fold improvement. Although constructing an automated model evaluation procedure requires considerable domain expertise and skill in modeling and simulation, applying an existing automated model evaluation procedure does not. With this automated model evaluation procedure, the computer can then search for and potentially discover models superior to those that the biological modelers developed previously.Ph. D.
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Sarmidi, M. R. "Simultaneous biochemical reaction and separation in a continuous rotating annular chromatograph". Thesis, Aston University, 1993. http://publications.aston.ac.uk/9767/.
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The aim of this work has been to investigate the behaviour of a continuous rotating annular chromatograph (CRAC) under a combined biochemical reaction and separation duty. Two biochemical reactions have been employed, namely the inversion of sucrose to glucose and fructose in the presence of the enzyme invertase and the saccharification of liquefied starch to maltose and dextrin using the enzyme maltogenase. Simultaneous biochemical reaction and separation has been successfully carried out for the first time in a CRAC by inverting sucrose to fructose and glucose using the enzyme invertase and collecting continuously pure fractions of glucose and fructose from the base of the column. The CRAC was made of two concentric cylinders which form an annulus 140 cm long by 1.2 cm wide, giving an annular space of 14.5 dm3. The ion exchange resin used was an industrial grade calcium form Dowex 50W-X4 with a mean diameter of 150 microns. The mobile phase used was deionised and dearated water and contained the appropriate enzyme. The annular column was slowly rotated at speeds of up to 240oh-1 while the sucrose substrate was fed continuously through a stationary feed pipe to the top of the resin bed. A systematic investigation of the factors affecting the performance of the CRAC under simultaneous biochemical reaction and separation conditions was carried out by employing a factorial experimental procedure. The main factors affecting the performance of the system were found to be the feed rate, feed concentrations and eluent rate. Results from the experiments indicated that complete conversion could be achieved for feed concentrations of up to 50% w/v sucrose and at feed throughputs of up to 17.2 kg sucrose per m3 resin/h.
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Nguyen, Vu ngoc tung. "Analysis of biochemical reaction graph : application to heterotrophic plant cell metabolism". Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0023/document.
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Aujourd’hui, la biologie des systèmes est confrontée aux défis de l’analyse de l’énorme quantité de données biologiques et à la taille des réseaux métaboliques pour des analyses à grande échelle. Bien que plusieurs méthodes aient été développées au cours des dernières années pour résoudre ce problème, ce sujet reste un domaine de recherche en plein essor. Cette thèse se concentre sur l’analyse des propriétés structurales, le calcul des modes élémentaires de flux et la détermination d’ensembles de coupe minimales du graphe formé par ces réseaux. Dans notre recherche, nous avons collaboré avec des biologistes pour reconstruire un réseau métabolique de taille moyenne du métabolisme cellulaire de la plante, environ 90 noeuds et 150 arêtes. En premier lieu, nous avons fait l’analyse des propriétés structurelles du réseau dans le but de trouver son organisation. Les réactions points centraux de ce réseau trouvés dans cette étape n’expliquent pas clairement la structure du réseau. Les mesures classiques de propriétés des graphes ne donnent pas plus d’informations utiles. En deuxième lieu, nous avons calculé les modes élémentaires de flux qui permettent de trouver les chemins uniques et minimaux dans un réseau métabolique, cette méthode donne un grand nombre de solutions, autour des centaines de milliers de voies métaboliques possibles qu’il est difficile de gérer manuellement. Enfin, les coupes minimales de graphe, ont été utilisés pour énumérer tous les ensembles minimaux et uniques des réactions qui stoppent les voies possibles trouvées à la précédente étape. Le nombre de coupes minimales a une tendance à ne pas croître exponentiellement avec la taille du réseau a contrario des modes élémentaires de flux. Nous avons combiné l’analyse de ces modes et les ensembles de coupe pour améliorer l’analyse du réseau. Les résultats montrent l’importance d’ensembles de coupe pour la recherche de la structure hiérarchique du réseau à travers modes de flux élémentaires. Nous avons étudié un cas particulier : qu’arrive-t-il si on stoppe l’entrée de glucose ? En utilisant les coupes minimales de taille deux, huit réactions ont toujours été trouvés dans les modes élémentaires qui permettent la production des différents sucres et métabolites d’intérêt au cas où le glucose est arrêté. Ces huit réactions jouent le rôle du squelette / coeur de notre réseau. En élargissant notre analyse aux coupes minimales de taille 3, nous avons identifié cinq réactions comme point de branchement entre différent modes. Ces 13 réactions créent une classification hiérarchique des modes de flux élémentaires fixés et nous ont permis de réduire considérablement le nombre de cas à étudier (approximativement divisé par 10) dans l’analyse des chemins réalisables dans le réseau métabolique. La combinaison de ces deux outils nous a permis d’approcher plus efficacement l’étude de la production des différents métabolites d’intérêt par la cellule de plante hétérotrophiqueNowadays, systems biology are facing the challenges of analysing the huge amount of biological data and large-scale metabolic networks. Although several methods have been developed in recent years to solve this problem, it is existing hardness in studying these data and interpreting the obtained results comprehensively. This thesis focuses on analysis of structural properties, computation of elementary flux modes and determination of minimal cut sets of the heterotrophic plant cellmetabolic network. In our research, we have collaborated with biologists to reconstructa mid-size metabolic network of this heterotrophic plant cell. This network contains about 90 nodes and 150 edges. First step, we have done the analysis of structural properties by using graph theory measures, with the aim of finding its owned organisation. The central points orhub reactions found in this step do not explain clearly the network structure. The small-world or scale-free attributes have been investigated, but they do not give more useful information. In the second step, one of the promising analysis methods, named elementary flux modes, givesa large number of solutions, around hundreds of thousands of feasible metabolic pathways that is difficult to handle them manually. In the third step, minimal cut sets computation, a dual approach of elementary flux modes, has been used to enumerate all minimal and unique sets of reactions stopping the feasible pathways found in the previous step. The number of minimal cut sets has a decreasing trend in large-scale networks in the case of growing the network size. We have also combined elementary flux modes analysis and minimal cut sets computation to find the relationship among the two sets of results. The findings reveal the importance of minimal cut sets in use of seeking the hierarchical structure of this network through elementary flux modes. We have set up the circumstance that what will be happened if glucose entry is absent. Bi analysis of small minimal cut sets we have been able to found set of reactions which has to be present to produce the different sugars or metabolites of interest in absence of glucose entry. Minimal cut sets of size 2 have been used to identify 8 reactions which play the role of the skeleton/core of our network. In addition to these first results, by using minimal cut sets of size 3, we have pointed out five reactions as the starting point of creating a new branch in creationof feasible pathways. These 13 reactions create a hierarchical classification of elementary flux modes set. It helps us understanding more clearly the production of metabolites of interest inside the plant cell metabolism
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Cheng, Yuhui. "Multiscale simulations of biochemically reacting systems". Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3274520.
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Thesis (Ph. D.)--University of California, San Diego, 2007.Title from first page of PDF file (viewed Oct. 3, 2007). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 117-134).
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Liu, Gu. "Target identification and validation studies in chemical biology & Synthesis of medium-sized ring containing compounds via oxidative fragmentation". Thesis, University of St Andrews, 2010. http://hdl.handle.net/10023/986.
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Part I of this thesis describes the development of bioactive small molecules of relevance to the study of the apicomlexan parasite Toxoplasma gondii into useful chemical tools. The research includes the target identification and validation studies, using both chemical and biological methods. Chapter 1 provides an overview of chemical genetics with a particular emphasis on methods for the identification of the protein targets of bioactive small molecules. The concept of biochemical protein target identification techniques was introduced with a detailed discussion of interesting applications from the literature. Chapter 2 focuses on the development of a tetrahydro-β-carboline based lead molecule into a chemical tool through target identification studies. The structure activity relationship (SAR) data associated with this core structure, the design of a chemical inducer of dimerisation (CID) and the synthesis of this CID are discussed in detail. Chapter 3 described work done to identify the potential protein target(s) of Conoidin A. Experiments to assess whether Conoidin A can inhibit a proposed target in vitro are also included. Further optimisation of this structural class to develop more potent inhibitors is discussed in the second part of this chapter. Part II of this thesis describes the development of methods for the synthesis of medium-sized ring containing compounds using oxidative fragmentation and rearrangement strategies. Chapter 5 provides an overview of the existing oxidative fragmentation methodology, with an emphasis on the use of oxidative fragmentation reactions for the synthesis of medium-sized ring systems (8-11 ring atoms). Chapter 6 focuses on using the established oxidative fragmentation method in the oxizino carbazolone system to investigate the diasteroselectivity of this reaction. Possible mechanisms for this transformation are investigated and discussed using both chemical and computational methods. An interesting rearrangement reaction has also been observed during this study. Chapter 7 focuses on developing an asymmetric oxidative fragmentation method, for use in the diazabenz[e]aceathrylenes system. Asymmetric oxidative fragmentation reactions using [Ru(pybox)(pydic)] catalysts are discussed. Attempts to optimise the enantiomeric excesses of the reaction by varying reaction conditions and substituents in the substrate are also included.
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Hughes, Alistair Paul. "The accuracy of linear flux models in predicting reaction rate profiles in a model biochemical reaction system". Master's thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/9116.
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Includes bibliographical referencesMetabolic flux analysis is commonly used in the modelling of biochemical reactions. The use of MFA models has gained large amounts of interest due to the simplicity of the computational procedures required for the model, and the exclusion of difficult to measure intracellular reaction data. There are many examples of the use of MFA models in literature studies in a number of applications, ranging from the medical industry through to the development of novel biochemical processes. Little to no mention is provided in literature studies regarding the applicability of the MFA model to a specified set of reaction data. Furthermore, the techniques and routines used to compute the flux models are not well described in these studies. The objectives of this research were to determine the sensitivity of the MFA models to various operating and kinetic parameters and to highlight the considerations required when setting up the computational routine used to solve the flux balances. The study was conducted using a model pathway populated with a set of hypothetical elemental reactions and branch points. The model pathway was used in this study to negate the affects of complex regulatory biochemical architectures which are not well described in literature. The use of the model pathway ensured that the reaction system was thermodynamically feasible and there was consistency in the mass balances. The exclusion of the complex regulatory reactions did not affect the accuracy of the results generated in this study. A set of reaction mechanisms were used to describe each reaction step and were populated with parameters reference from literature. The cellular and reactor mass balances were generated using correlations presented in literature.
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Ng, Sau-wah. "Population genetics study on the variable number of Tandem repeats (VNTR) loci of a Han Chinese population in Hong Kong and its application in human identity". Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B2292582X.
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Hauser, Anett. "Chemical Approaches to Elucidate Lysine Phosphorylation". Doctoral thesis, Humboldt-Universität zu Berlin, 2021. http://dx.doi.org/10.18452/22287.
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Reversible Phosphorylierung ist die bekannteste posttranslationale Modifikation (PTM) und die O-Phosphomonoester von Serin, Threonin und Tyrosin galten lange als die einzigen relevanten Vertreter. Vor kurzem wurden erste Erkenntnisse über die biologische Relevanz von labilen Phosphorylierungen veröffentlicht, z.B. die Phosphorylierung von Histidin, Arginin und Cystein sowie die Pyrophosphorylierung von Serin und Threonin. Auch die Aufklärung von Phospho-Lysin (pLys) wurde mit der Etablierung einer chemoselektiven Synthese zur Darstellung ortsselektiv phosphorylierter Lysinpeptide und der Entwicklung massenspektrometrischer Protokolle zur eindeutigen pLys-Identifizierung in Angriff genommen. Dennoch wurde bisher kein endogenes pLys beschrieben oder eingehende Untersuchungen mit interagierenden Enzymen durchgeführt.
In dieser Arbeit werden mehrere Ansätze zur Erweiterung des Wissens über pLys vorgestellt. Dazu gehören das Design einer alternativen Syntheseroute zu pLys-Peptiden und die Entwicklung sowie Evaluierung von zwei stabilen Analoga als Bausteine für die Peptidsynthese. Weiterhin wurde die Protonierung des Phosphoramidatstickstoffs untersucht. In systematischen Enzymaktivitätsassays wurden die Wechselwirkungen zwischen Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) und verschiedenen Phospho-Substraten untersucht. Dabei zeigte sich eine ausgeprägte Selektivität für pLys, eine hohe Sequenzabhängigkeit der LHPP-Aktivität und ein klares Bindungsmotiv. Darüber hinaus wurden proteomische Methoden hinsichtlich ihrer Eignung für pLys-Peptide evaluiert. Im Laufe dieser Untersuchung wurden mehrere pLys-Immunogene für die Generierung von monoklonalen anti-pLys-Antikörpern und ein Workflow für die Histontrennung und -analyse entwickelt. Des Weiteren wurde die chelationsverstärkte Fluoreszenz von markierten Phospho-Peptiden als Werkzeug zur Bestimmung des Phosphorylierungsgrades in Enzymaktivitäts- oder Stabilitätsassays untersucht.Reversible phosphorylation is the most prominent post-translational modification (PTM) and the O-phosphomonoesters of serine, threonine and tyrosine have been considered as the only notable forms for long time. Recent developments have paved the way to insights into the biological relevance of labile phosphorylations, e.g. phosphorylation of histidine, arginine and cysteine as well as pyrophosphorylation of serine and threonine. Also, the elucidation of phospho-lysine (pLys) was tackled with the establishment of a chemoselective synthesis to obtain site-selectively phosphorylated lysine peptides and the development of mass spectrometric protocols to unambiguously identify modification sites. Nonetheless, no endogenous pLys site has been described or in-depth investigations of interacting enzymes have been conducted. In this thesis, several approaches to enhance the knowledge about pLys are introduced. These include the design of an alternative synthesis route to pLys peptides and the development as well as evaluation of two stable analogues as building blocks for peptide synthesis. Furthermore, the protonation of the phosphoramidate-nitrogen was investigated. In systematic phosphoramidate hydrolase and phosphatase activity assays, the interactions between phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) and various phospho-substrates were examined. Thereby, distinct selectivity for pLys, high sequence dependence of LHPP activity and a distinct binding motif were revealed. In addition to that, proteomic methods were evaluated regarding their suitability for pLys peptides. Over the course of this investigation, several pLys immunogens for the generation of monoclonal anti-pLys antibodies and a workflow for histone separation and analysis were developed. Furthermore, chelation-enhanced fluorescence of labeled phospho-peptides was studied as a tool for determining the degree of phosphorylation in enzyme activity or stability assays.
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Linar, Mikeev [Verfasser] y Verena [Akademischer Betreuer] Wolf. "Numerical analysis of stochastic biochemical reaction networks / Mikeev Linar ; Betreuer: Verena Wolf". Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2018. http://d-nb.info/1160938695/34.
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Hajiaghayi, Monir. "Study of two biochemical models : chemical reaction networks, and nucleic acid systems". Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/63311.
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The contributions of this thesis are motivated by an exciting challenge at
the intersection of computer science and biochemistry: Can we program
molecules to do interesting or useful computations? There has been significant progress in programming nucleic acids - particularly DNA molecules -
thanks in part to availability of models and algorithms for predicting nucleic
acid structure and folding kinetics. At a higher level of abstraction, Chemical
Reaction Networks (CRNs) have proven to be valuable as a molecular programming
model that enables researchers to understand the potential and
limitations of computing with molecules, unencumbered by low-level details.
These two levels of abstraction are linked; it is possible to "compile" CRN
programs into nucleic acid systems that make the programs implementable
in a test tube.
We design and analyze CRN algorithms for two purposes. First, we
show how any semilinear function can be computed by CRNs, even when
no "leader" species (i.e., initial species with constant but non-zero counts)
is present. Our results improve earlier results of Chen et al. (2012) who
showed that only semilinear functions are computable by error-free CRNs
using leaders. Our new CRN construction can be done in expected time
O(n), which is faster than O(n log n) bound achieved by Chen et al. Second,
we provide the most intuitive proofs of correctness and efficiency for three
different CRNs computing Approximate Majority: Given a mixture of two
types of species with an initial gap between their counts, a CRN computation
must reach totality on the majority species with high probability. The CRNs
of our interest have the ability to start with an initial gap of Ω(√n log n).
In the second part of this thesis, we study the problem of predicting the
Minimum Free Energy secondary structure (the set of base pairs) of a given
set of nucleic acid strands with no pseudoknots (crossing base pairs). We
show that this problem is APX-hard which implies that there does not exist
a polynomial time approximation scheme for this problem, unless P = NP.
We also propose a new Monte-Carlo based method to efficiently estimate
nucleic acid folding kinetics.Science, Faculty of
Computer Science, Department of
Graduate
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Hellander, Andreas. "Numerical simulation of well stirred biochemical reaction networks governed by the master equation". Licentiate thesis, Uppsala universitet, Avdelningen för teknisk databehandling, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-85856.
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Numerical simulation of stochastic biochemical reaction networks has received much attention in the growing field of computational systems biology. Systems are frequently modeled as a continuous-time discrete space Markov chain, and the governing equation for the probability density of the system is the (chemical) master equation. The direct numerical solution of this equation suffers from an exponential growth in computational time and memory with the number of reacting species in the model. As a consequence, Monte Carlo simulation methods play an important role in the study of stochastic chemical networks. The stochastic simulation algorithm (SSA) due to Gillespie has been available for more than three decades, but due to the multi-scale property of the chemical systems and the slow convergence of Monte Carlo methods, much work is currently being done in order to devise more efficient approximate schemes. In this thesis we review recent work for the solution of the chemical master equation by direct methods, by exact Monte Carlo methods and by approximate and hybrid methods. We also describe two conceptually different numerical methods to reduce the computational time when studying models using the SSA. A hybrid method is proposed, which is based on the separation of species into two subsets based on the variance of the copy numbers. This method yields a significant speed-up when the system permits such a splitting of the state space. A different approach is taken in an algorithm that makes use of low-discrepancy sequences and the method of uniformization to reduce variance in the computed density function.
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Samal, Satya Swarup [Verfasser]. "Analysis of Biochemical Reaction Networks using Tropical and Polyhedral Geometry Methods / Satya Swarup Samal". Bonn : Universitäts- und Landesbibliothek Bonn, 2016. http://d-nb.info/1124540091/34.
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Menz, Stephan [Verfasser]. "Hybrid stochastic-deterministic approaches for simulation and analysis of biochemical reaction networks / Stephan Menz". Berlin : Freie Universität Berlin, 2013. http://d-nb.info/1031667121/34.
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Ürgüplü, Belma Asli. "Contributions to symbolic effective qualitative analysis of dynamical systems : application to biochemical reaction networks". Thesis, Lille 1, 2010. http://www.theses.fr/2010LIL10013/document.
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Le but de mes travaux de recherche est de rendre, autant que possible, algorithmique l'étude des modèles composés par des équations différentielles paramétriques. Je me concentre aux algorithmes basés sur les symétries de Lie étendues pour les modèles de taille moyenne (environ vingt variables). Je présente deux méthodes de simplification exacte : la réduction du nombre des variables d'un modèle et sa reparamétrisation pour distinguer le rôle de ses paramètres. Les systèmes simplifiés sont équivalents aux systèmes originaux par des relations implicites ou explicites (suivant la méthode choisie). Ces algorithmes, grâce aux stratégies de calcul utilisées et aux restrictions sur les objets étudiés, ont une compléxité temporelle polynomiale en la taille de l'entrée. Ils sont implémentés dans les paquetages MABSys et ExpandedLiePointSymmetry. Les modèles simplifiés issus de ces algorithmes facilitent diverses études comme l'analyse qualitative symbolique ou numérique. J'illustre mes travaux sur une famille de réseaux génétiques avec un seul gène auto-régulé en faisant une analyse qualitative symbolique complète. Mon exemple principal appartient au domaine des réseaux de régulation génétique mais l'application des méthodes que je présente n'est pas limitée à la biologie intracellulaireThe goal of my research is to make algorithmic, as much as possible, the study of models composed by parametric differential equations. I focus on the algorithms based on expanded Lie point symmetries for medium size (about twenty variables) models. I present two exact simplification methods: the reduction of the number of variables of a model and its reparametrization in order to distinguish the roles of its parameters. Simplified systems are equivalent to the original ones by implicit or explicit relationships (according to the chosen method). These algorithms, thanks to some computational strategies and restriction of studied objects, are of polynomial time complexity in the input size. They are implemented in the MABSys and the ExpandedLiePointSymmetry packages. Simplified models resulting from these methods allow to perform more easily various studies such as symbolic or numerical qualitative analysis. I illustrate my work on a family of genetic networks with a single self-regulated gene by a complete symbolic qualitative analysis. Even if my principal application example belongs to genetic regulatory networks field, the methods presented in my work are not limited to intracellular biology
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Sjöberg, Paul. "Numerical Methods for Stochastic Modeling of Genes and Proteins". Doctoral thesis, Uppsala universitet, Avdelningen för teknisk databehandling, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8293.
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Stochastic models of biochemical reaction networks are used for understanding the properties of molecular regulatory circuits in living cells. The state of the cell is defined by the number of copies of each molecular species in the model. The chemical master equation (CME) governs the time evolution of the the probability density function of the often high-dimensional state space. The CME is approximated by a partial differential equation (PDE), the Fokker-Planck equation and solved numerically. Direct solution of the CME rapidly becomes computationally expensive for increasingly complex biological models, since the state space grows exponentially with the number of dimensions. Adaptive numerical methods can be applied in time and space in the PDE framework, and error estimates of the approximate solutions are derived. A method for splitting the CME operator in order to apply the PDE approximation in a subspace of the state space is also developed. The performance is compared to the most widely spread alternative computational method.
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Catti, Federica. "4,5-dihydropyrazoles : novel chemistry and biological activity". Thesis, St Andrews, 2007. http://hdl.handle.net/10023/351.
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