<p><strong>Apstrakt je obrađen tehnologijama za optičko prepoznavanje teksta (OCR).</strong></p><p>U radu je spektrofotometrijski ispitivana brzina oksidacije L-askorbinske kiseline. Tok reakcije je praćen snimanjem UV apsorpcionih spektara termostatiranih rastvora L-askorbinske kiseline u puferima različitih vrednosti rN: acetatnom (4-6). fosfatnom (5-8). fosfatno-citratnom (6-8), boratnom (8-11). glicinskom (9-11) i univerzalnom (4-11) !zveden je jednostavan oblik kinetičke jednačine reakcije vi&scaron;eg i razlomljenog reda. Dobijena jednačina je univerzalna, jer obuhvata jednačine nultog, prvog, drugog, trećeg i razlomljenog reda izračunate su vrednosti reda reakcije i one variraju sa promenom vrednosti rN unutar jednog puferskog sistema. Veza između vrednosti konstanti brzine oksidacije L-askorbinske kiseline i vrednosti rN ispitivanih pufera je linearna do vrednosti rN=10.00. Vrednosti koeficijenta pravca prave su različite za ispitivane pufere. Vrsta anjona prisutna u puferu kao i prisusutvo jona metala u kori&scaron;ćenim hemikalijama utiču na vrednosti konstante brzine oksidacije L-askorbinske kiseline i one su različite u raznim puferima istih vrednosti rN. Vrednosti konstante brzine oskidacije L-askorbinske kiseline su največe u univerzalnom puferu pri svim vrednostima rN. Prisutna sme&scaron;a anjona manje utiče na oksidaciju L-askorbinske kiseline nego pojedinačni anjoni, verovatno zbog među- sobnih interakcija.</p> / <p><strong>Abstract was processed by technology for Optical character recognition (OCR).</strong></p><p>The paper deats with the spectrophotometric study of L-ascorbic acid oxidation rate. The course of reaction has been observed by recording the UV absorption spectra of thermostated solution of L-ascorbic acid in buffers with different рН values: acetate (4-6), phosphate (5-8), phosphate-citrate (6-8), borate (8-11), glycine (9-11) and universal (4-11). A simple form of kinetic eguation of higher and fractional order reaction has been observed. The obtained eguation is universal as it comprises the eguations of zero, first, second, third and fractional order. The reaction order values have been calculated and they vary with change of рН values within each buffer system. The relation between the values of L-ascorbic acid oxidation rate constants and рН value of the studied buffers is linear up to рН value = 10.00. The straight line stopes are different for investigated buffers. The anion type present in a buffer as wett as the presence of metal ions in applied chemicals affect the values of L-ascorbic acid oxidation rate constant and they are different in different buffers with the same рН values. The values of L-ascorbic acid oxidation rate constant are the highest in the universal buffer at all рН values. The present anion mixture affects the L-ascorbtc acid oxidation to a tesser degree than single anions, presumabty due to mutuat interactions.</p>

Due to the ever increasing concerns about pollutants and contaminants found in water, new treatment technologies have been developed. Ozonation is one of such technologies. It has been widely applied in the treatment of pollutants in water and wastewater treatment processes. Ozone has many applications such as oxidation of organic components, mineral matter, inactivation of viruses, cysts, bacteria, removal of trace pollutants like pesticides and solvents, and removal of tastes and odours. Ozone is the strongest conventional oxidant that can result in complete mineralisation of the organic pollutants to carbon dioxide and water. Because ozone is unstable, it is generally produced onsite in gas mixtures and is immediately introduced to water using gas/liquid type reactors (e.g. bubble columns). The ozone reactions are hence of the type gas liquid reactions, which are complex to model since they involve both chemical reactions, which occur in the liquid phase, and mass transfer from the gas to the liquid phase. This study focuses on two aspects: mass transfer and chemical reactions in multicomponent systems. The mass transfer parameters were determined by experiments under different conditions and the chemical reactions were studied using single component and multicomponent systems. Two models obtained from the literature were adapted to the systems used in this study. Mass transfer parameters in the semi-batch reactor were determined using oxygen and ozone at different flow rates in the presence and absence of t-butanol. t-Butanol is used as a radical scavenger in ozonation studies and it has been found to affect the gas¿liquid mass transfer rates. An experimental study was carried out to investigate the effects of t-butanol concentrations on the physical properties of aqueous solutions, including surface tension and viscosity. It was found that t-butanol reduced both properties by 4% for surface tension and by a surprising 30% for viscosity. These reductions in the solution physical properties were correlated to enhancement in the mass transfer coefficient, kL. The mass transfer coefficient increased by about 60% for oxygen and by almost 50% for ozone. The hydrodynamic behaviour of the system used in this work was characterised by a homogeneous bubbling regime. It was also found that the gas holdup was significantly enhanced by the addition of t-butanol. Moreover, the addition of t-butanol was found to significantly reduce the size of gas bubbles, leading to enhancement in the volumetric mass transfer coefficient, kLa. The multicomponent ozonation was studied with two systems, slow reactions when alcohols were used and fast reactions when endocrine disrupting compounds were used. ii These experiments were simulated by mathematical models. The alcohols were selected depending on their volatilization at different initial concentrations and different gas flow rates. The degradation of n-propanol as a single compound was studied at the lowest flow rate of 200 mL/min. It was found that the degradation of n-propanol reached almost 60% within 4 hours. The degradation of the mixture was enhanced with an increase in the number of components in the mixture. It was found that the degradation of the mixture as three compounds reached almost 80% within four hours while the mixture as two compounds reached almost 70%. The effect of pH was studied and it was found that an increase in pH showed slight increase in the reaction. Fast reactions were also investigated by reacting endocrine disrupting chemicals with ozone. The ozone reactions with the endocrine disrupters were studied at different gas flow rates, initial concentrations, ozone concentrations and pH. The degradation of 17¿-estradiol (E2) as a single compound was the fastest, reaching about 90% removal in almost 5 minutes. However estrone (E1) degradation was the lowest reaching about 70% removal at the same time. The degradation of mixtures of the endocrine disruptors was found to proceed to lower percentages than individual components under the same conditions. During the multicomponent ozonation of the endocrine disruptors, it was found that 17¿-estradiol (E2) converted to estrone (E1) at the beginning of the reaction. A MATLAB code was developed to predict the ozone water reactions for single component and multicomponent systems. Two models were used to simulate the experimental results for single component and multicomponent systems. In the case of single component system, good simulation of both reactions (slow and fast) by model 1 was obtained. However, model 2 gave good agreement with experimental results only in the case of fast reactions. In addition, model 1 was applied for multicomponent reactions (both cases of slow and fast reaction). In the multicomponent reactions by model 1, good agreement with the experimental results was also obtained for both cases of slow and fast reactions. / Ministry of Higher Education in Libya and the Libyan Cultural Centre and Educational Bureau in London.

This thesis is concerned with methodologies for the accurate quantitative modelling of molecular biological systems. The first part is devoted to the chemical Langevin equation (CLE), a stochastic differential equation driven by a multidimensional Wiener process. The CLE is an approximation to the standard discrete Markov jump process model of chemical reaction kinetics. It is valid in the regime where molecular populations are abundant enough to assume their concentrations change continuously, but stochastic fluctuations still play a major role. We observe that the CLE is not a single equation, but a family of equations with shared finite-dimensional distributions. On the theoretical side, we prove that as many Wiener processes are sufficient to formulate the CLE as there are independent variables in the equation, which is just the rank of the stoichiometric matrix. On the practical side, we show that in the case where there are m_1 pairs of reversible reactions and m_2 irreversible reactions, there is another, simple formulation of the CLE with only m_1+m_2 Wiener processes, whereas the standard approach uses 2m_1+m_2. Considerable computational savings are achieved with this latter formulation. A flaw of the CLE model is identified: trajectories may leave the nonnegative orthant with positive probability. The second part addresses the challenge when alternative, structurally different ordinary differential equation models of similar complexity fit the available experimental data equally well. We review optimal experiment design methods for choosing the initial state and structural changes on the biological system to maximally discriminate between the outputs of rival models in terms of L_2-distance. We determine the optimal stimulus (input) profile for externally excitable systems. The numerical implementation relies on sum of squares decompositions and is demonstrated on two rival models of signal processing in starving Dictyostelium amoebae. Such experiments accelerate the perfection of our understanding of biochemical mechanisms.

Das Enzym Tryptophan Synthase ist ein ausgezeichnetes Beispiel einer molekularen Fabrik auf der Nanoskala mit zwei katalytischen Zentren. Der katalytische Zyklus des Moleküls beruht zudem auf zahlreichen allosterischen Wechselwirkungen sowie der Übertragung des Intermediats Indol durch einen intramolekularen Tunnel. In dieser Arbeit wird das erste kinetische Modell eines einzelnen Tryptophan Synthase Moleküls konstruiert und analysiert. Simulationen zeigen starke Korrelationen zwischen den Zuständen der Katalysezentren sowie die Ausbildung von Synchronisation. Mit stochastischer Thermodynamik wird die experimentell unzugängliche Reaktionskonstante für die Rückübertragung des Indols aus Messdaten rekonstuiert. Methoden, die den Informationsaustausch in bipartiten Markovnetzwerken charakterisieren, werden auf beliebige Markovnetzwerke verallgemeinert und auf das Modell angewendet. Der abschließende Teil befasst sich mit chemischen Reaktionsnetzwerken von Metaboliten und Enzymen. Es werden algebraische Modelle (Halbgruppen) konstruiert, welche aufeinanderfolgende und simultane katalytische Funktionen von Enzymen und von Unternetzwerken erfassen. Diese Funktionen werden genutzt, um eine natürliche Dynamikum sowie hinreichende und notwendige Bedingungen für seine Selbsterhaltung zu formulieren. Anschließend werden die algebraischen Modelle dazu genutzt, um eine Korrespondenz zwischen Halbgruppenkongruenzen und Skalenübergängen auf den Reaktionsnetzwerken herzustellen. Insbesondere wird eine Art von Kongruenzen erörtert, welche dem Ausspuren der globalen Struktur des Netzwerkes unter vollständiger Beibehaltung seiner lokalen Komponenten entspicht. Während klassische Techniken eine bestimmte lokale Komponente fixieren und sämtliche Informationen über ihre Umgebung ausspuren, sind bei dem algebraischen Verfahren alle lokalen Komponenten zugleich sichtbar und eine Verknüpfung von Funktionen aus verschiedenen Komponenten ist problemlos möglich. / The channeling enzyme tryptophan synthase provides a paradigmatic example of a chemical nanomachine with two distinct catalytic subunits. It catalyzes the biosynthesis of tryptophan, whereby the catalytic activity in a subunit is enhanced or inhibited depending on the state of the other subunit, gates control the accessibility of the reactive sites and the intermediate product indole is directly channeled within the protein. The first single-molecule kinetic model of the enzyme is constructed. Simulations reveal strong correlations in the states of the active centers and the emergent synchronization. Thermodynamic data is used to calculate the rate constant for the reverse indole channeling. Using the fully reversible single-molecule model, the stochastic thermodynamics of the enzyme is closely examined. The current methods describing information exchange in bipartite systems are extended to arbitrary Markov networks and applied to the kinetic model. They allow the characterization of the information exchange between the subunits resulting from allosteric cross-regulations and channeling. The final part of this work is focused on chemical reaction networks of metabolites and enzymes. Algebraic semigroup models are constructed based on a formalism that emphasizes the catalytic function of reactants within the network. A correspondence between coarse-graining procedures and semigroup congruences respecting the functional structure is established. A family of congruences that leads to a rather unusual coarse-graining is analyzed: The network is covered with local patches in a way that the local information on the network is fully retained, but the environment of each patch is not resolved. Whereas classical coarse-graining procedures would fix a particular patch and delete information about the environment, the algebraic approach keeps the structure of all local patches and allows the interaction of functions within distinct patches.

Cálculos usando métodos de estrutura eletrônica (Hartree-Fock, Mõller-Plesset de segunda ordem e DFT, B3LYP) foram efetuados pelo programa Gaussian98 em microcomputadores e estações de trabalho, com o objetivo de elucidar os canais de decomposição unimolecular de éter dietílico em fase gasosa e foram comparados com valores obtidos através de aproximações baseadas na mecânica estatística pela metodologia de Benson. O éter dietílico vem sendo usado como um aditivo para o óleo diesel e combustível alternativo e o conhecimento de suas vias vias de decomposição é fundamental nestas investigações. Dezesseis modos primários, do qual, quatro ocorrem através de cisão de ligações simples C-O, C-C,C(1)-H e C(2)-H e doze ocorrendo através de estados de transição cíclicos, os quais eliminam produtos como hidrogênio etano, acetaldeído, etano, álcool etílico, metil etil éter, metano, alguns carbenos e também di-radicais, foram considerados para a determinação das barreiras de ativação, entalpias de reação, entropias de reação e energia livre de Gibbs de reação. Vias primárias ocorrendo através de cisão de ligação, não reproduziram os valores experimentais para as barreiras de ativação, mas reproduziram de modo significante, valores da entalpia da reação. Eliminação de eteno e álcool etílico, ocorrendo através de um estado de transição de quatro centros, apresentou a barreira de ativação mais baixa. Acetaldeído e eliminação de etano, ocorrendo através de quatro centros, apresentou barreira significativamente alta, mas por outro lado, a menor entalpia, ligeiramente exotérmica por -0,8 kcal.mol-1. Eliminações 1,2 de metano e carbeno ocorrendo através de três centros, junto com a eliminação 1, 1 de hidrogênio e carbeno por três centros, eliminação 2,2 hidrogênio e carbeno por três centros e eliminação 1,4 de hidrogênio, acetaldeído e eteno por seis centros, apresentaram barreiras de ativação relativamente próximas mostrando que elas são competitivas entre si. Os valores computados dos canais que ocorrem por estados de transição cíclicos foram comparados com os resultados experimentais disponíveis e discutida a validade desta abordagem computacional para o estudo de reações unimoleculares de multi-canais. Determinação de parâmetros termoquímicos, como calor de formação para espécies radicalares dos canais de decomposição primário e alguns radicais alcóxidos, junto com a estimativa de afinidade eletrônica e protônica (com a abordagem ab initio Gaussian 2 a qual estima energias eletrônicas muito precisas) foram efetuados e seus resultados foram comparados com os valores experimentais disponíveis e valores obtidos através de energias de ligação e da regra de aditividade de Benson. / Calculations using methods of electronic structure(Hartree-Fock, second order Moller-Plesset and DFT: B3LYP) had been effected through the Gaussian98 program in microcomputers and workstations, with the objective to elucidate the unimolecular decomposition channels of diethyl ether in gaseous phase. These results also had been compared to those obtained by the methodology based in statistical mechanics through Benson\'s approach. Sixteen primary ways, which, four occur through the break of simple bonds C-O, C-C,C(1)-H, C(2)-H, and twelve occur through cyclical transistion states, which eliminate products as hydrogen, ethene, acetaldehyde, ethane, ethyl alcohol, methyl ethyl ether, methane, some carbenes and also diradicals. These products had been considered to the determination of the activation barriers, enthalpies of reaction, entropies of reaction and free energy of Gibbs of reaction. Primary ways occurring through the break of bonds, had not reproduced experimental values for the activation barriers, however they had reproduced in a significant way, values of the enthalpy of the reaction. Elimination of ethene and ethyl alcohol, occurring by a transition state of four centers, presented the lowest activation barrier. Acetaldehyde and ethane elimination occurring through four centers, presented a high significantly barrier, but on the other hand it presented the smallest enthalpy, lightly exothermic above -0,8 kcal.mol-1. Eliminations 1,2 of methane and carbene occurring through three centers, together with the elimination 1,1 of hydrogen and carbene through three centers, elimination 2,2 of hydrogen and carbene through three centers and elimination 1,4 of hydrogen, acetaldehyde and ethene through six centers, had presented relatively next activation barriers, showing that they are competitive among themselves. The computed values of the channels that occur through cyclical transition states had been compared with the available experimental results and the trustworthiness of this computational boarding for the study of unimolecular reactions in multi-channel had been dicussed. Determination of thermochemical parameters, as heat of formation for radicalar species of the primary channel of decomposition and some alcoxyde radicais, together with the estimative of the electronic and protonic affinities,( with the ab initio Gaussian 2 boarding which estimate very precise eletronic energies ) and their results had been compared with the available experimental values and with values gotten through energies of bond and Benson\'s additivity rule.

J'ai mis au point une méthodologie pour annoter les superfamilles d'enzymes, en décrire l'histoire et les replacer dans l'évolution de leurs voies métaboliques. J'en ai étudié trois : (1) les amidohydrolases cycliques, dont les DHOases (dihydroorotases, biosynthèse des pyrimidines), pour lesquelles j'ai proposé une nouvelle classification. L'arbre phylogénétique inclut les dihydropyrimidinases (DHPases) et allantoïnases (ALNases) qui ont des réactions similaires dans d'autres voies (dégradation des pyrimidines et des purines respectivement). (2) L'étude de la superfamille des DHODases (qui suivent les DHOases) montre une phylogénie semblable aux DHOases, avec également des enzymes d'autres voies, dont les DHPDases (qui suivent les DHPases). De cette observation est né le concept de module réactionnel, qui correspond à la conservation de l’enchaînement de réactions semblables dans différentes voies métaboliques. Cela a été utilisé lors de (3) l'étude des carbamoyltransférases (TCases) qui incluent les ATCases (précédant les DHOases). J'ai d'abord montré l'existence d'une nouvelle TCase potentiellement impliquée dans la dégradation des purines et lui ai proposé un nouveau rôle en utilisant le concept de module réactionnel (enchaînement avec l'ALNase). Dans ces trois grandes familles j'ai aussi mis en évidence trois groupes de paralogues non identifiés qui se retrouvent pourtant dans un même contexte génétique appelé « Yge » et qui formeraient donc un module réactionnel constitutif d'une nouvelle voie hypothétique. Appliqué à diverses voies, le concept de modules réactionnels refléterait donc les voies métaboliques ancestrales dont ils seraient les éléments de base. / I designed a methodology to annotate enzyme superfamilies, explain their history and describe them in the context of metabolic pathways evolution. Three superfamilies were studied: (1) cyclic amidohydrolases, including DHOases (dihydroorotases, third step of the pyrimidines biosynthesis), for which I proposed a new classification. The phylogenetic tree also includes dihydropyrimidinases (DHPases) and allantoinases (ALNases) which catalyze similar reactions in other pathways (pyrimidine and purine degradation, respectively). (2) The DHODases superfamily (after DHOases) show a similar phylogeny as DHOases, including enzymes from other pathways, DHPDases in particular (after DHPases). This led to the concept of reaction module, i.e. a conserved series of similar reactions in different metabolic pathways. This was used to study (3) the carbamoyltransferases (TCases) which include ATCases (before DHOases). I first isolated a new kind of TCase, potentially involved in the purine degradation, and I proposed a new role for it in the light of reaction modules (linked with ALNase). In those three superfamilies I also found three groups of unidentified paralogs that were remarkably part of the same genetic context called “Yge” which would be a reaction module part of an unidentified pathway. The concept of reactions modules may then reflect the ancestral metabolic pathways for which they would be basic elements.

Nous avons étudié l'effet d'une réaction chimique sur le transfert de matière pour des systèmes à deux phases sous écoulement. La phase continue est une phase fluide et la phase dispersée est constituée de particules de catalyseur au sein desquelles une réaction chimique irréversible de premier ordre a lieu. Le soluté réactif est transporté par l'écoulement externe de fluide et pénètre dans la particule par diffusion, il se produit alors une réaction chimique qui consomme cette espèce. Nous modélisons le problème par un couplage interne-externe des équations de bilan et au moyen de deux conditions limites de raccordement: continuité de la concentration et équilibre des flux de masse à la surface des particules. Le cas d'une seule sphère isolée est traitée en premier lieu de manière théorique et numérique. Nous proposons un modèle pour prédire le coefficient de transfert de masse (nombre de Sherwood «réactif») en tenant compte de la convection-diffusion externes et du couplage diffusion-réaction internes. Nous validons le modèle en le comparant à des simulations numériques directes pleinement résolues (DNS boundaryfitted) sur un maillage adapté à la géométrie des particules. Pour la simulation de systèmes multiparticules, nous mettons en œuvre une méthode d'interface «Sharp» pour traiter les fronts raides de concentration. Nous validons la mise en œuvre de la méthode sur des solutions analytiques existantes en cas de diffusion, de diffusion-réaction et par comparaison avec des corrélations de convection-diffusion disponibles dans la littérature. Dans le cas d'une réaction chimique en présence de convection-diffusion, nous validons la méthode et nous évaluons sa précision en comparant avec les simulations pleinement résolues de référence. Ensuite, nous étudions le problème de l'écoulement et du transfert autour de trois sphères alignées soumis à une réaction chimique interne. Nous proposons un modèle de nombre de Sherwood «réactif» en complément d'une prédiction de transfert pour chaque sphère disponible dans la littérature. Nous validons le modèle par comparaison avec des simulations numériques directes pour une large gamme de paramètres adimensionels. Ensuite, nous étudions la configuration du lit fixe de particules de catalyseur. Nous modélisons le profil de concentration moyenne, en tenant compte de la réaction chimique dans le lit et les profils de concentration moyenne surfacique et volumique des particules. Nous introduisons un modèle pour le nombre de Sherwood «réactif» qui est comparé à des simulations numériques pour en évaluer les limites de validité / We studied the effect of a first order irreversible chemical reaction on mass transfer for two-phase flow systems in which the continuous phase is a fluid and the dispersed phase consists in catalystspherical particles. The reactive solute is transported by the fluid flow and penetrates through the particle surface by diffusion. The chemical reaction takes place within the bulk of the particle. Wehandle the problem by coupling mass balance equations for internal-external transfer with two boundary conditions: continuity of concentration and mass flux at the particle surface. We start with the case of a single isolated sphere. We propose a model to predict mass transfer coefficient (`reactive' Sherwood number) accounting for the external convection-diffusion along with internal diffusion-reaction. We validate the model through comparison with fully resolved Direct Numerical Simulations (DNS) performed by means of a boundary-fitted mesh method. For the simulation of multi-particle systems, we implemented a Sharp Interface Method to handle strong concentration gradients. We validate the implementation of the method thoroughly thanks to comparison with existing analytical solutions in case of diffusion, diffusion-reaction and by comparison with previously established correlations for convection-diffusion mass transfer. In case of convectiondiffusion- reaction, we validate the method and we evaluate its accuracy through comparisons with single particle simulations based on the boundary-fitted method. Later, we study the problem of three aligned-interacting spheres with internal chemical reaction. We propose a `reactive' Sherwood number model based on a known non-reactive prediction of mass transfer for each sphere. We validate the model by comparison with direct numerical simulations for a wide range of dimensionless parameters. Then, we study the configuration of a fixed bed of catalyst particles. We model the cup-mixing concentration profile, accounting for chemical reaction within the bed, and the mean surface and volume concentration profiles of the particles. We introduce a model for `reactive' Sherwood number that accounts for the solid volume fraction, in addition to the aforementioned effects. We compare the model to numerical simulations to evaluate its limitations

L'objectiu d'aquest treball es centra en el desenvolupament, comprovació i millora d'una metodologia per l'assessorament del perill tèrmic de les reaccions químiques, orientada especialment a les petites i mitjanes empreses. La metodologia està basada en un sistema de llistes de comprovació per identificar els perills, així com en altres eines senzilles d'entendre per a personal no expert en seguretat. Els orígens del desenvolupament de la metodologia es basen en dos eines existents, HarsMeth i Check Cards for Runaway. S'han pres diferents enfocaments per tal d'aconseguir una metodologia d'assessorament fiable. En primer lloc s'ha verificat l'eficàcia d'ambdues metodologies en diferents empreses dedicades al desenvolupament de productes de química fina, per determinar els punts forts i els punts febles de cada una de elles, i per aprofitar els avantatges identificats per tal de crear una unica metodologia anomenada HarsMeth version 2. A continuació, s'ha provat aquesta versió exhaustivament en dos empreses químiques per tal de millorarla, detectant fallades i allargant les llistes de comprovació amb la finalitat de cobrir el màxim número possible de qüestions per l'assessorament. Altres activitats s'han centrat en el desenvolupament d'eines per a la determinació teòrica de entalpies de reacció i per la identificació de perills tèrmics en equips de procés. La versió final de la metodologia que s'ha desenvolupat, anomenada HarsMeth New Process, està estructurada per tal de realitzar l'assessorament seguint els passos lògics en el desenvolupament d'un procés químic, començant per el disseny de la reacció química en el laboratori, seguit per l'anàlisi de la estabilitat i compatibilitat dels reactius, l'anàlisi de la perillositat de la reacció, l'escalat del procés, i la determinació de les mesures de seguretat necessàries per implementar el procés a escala industrial en funció dels perills identificats anteriorment. Un altre estratègia seguida per millorar la metodologia ha estat analitzar els accidents químics inclosos en la base de dades MARS amb la finalitat de determinar lliçons per aprendre dels accidents, així com per identificar quins aspectes de la metodologia haurien ajudat a prevenir els accidents, i a posar de relleu quins aspectes de la seguretat quimica s'han de tenir especialment en compte a les indústries de procés. / El objetivo de este trabajo se centra en el desarrollo, comprobación y mejora de una metodología para el asesoramiento del peligro térmico de las reacciones químicas, orientada especialmente a las pequeñas y medianas empresas. La metodología está basada en un sistema de listas de comprobación para identificar los peligros, así como en otras herramientas fáciles de entender para personal no experto en seguridad. Los orígenes del desarrollo de la metodología se basan en dos herramientas existentes, HarsMeth y Check Cards for Runaway. Se han seguido diferentes enfoques para llegar a una metodología de asesoramiento fiable. En primer lugar se ha verificado la eficacia de ambas metodologías en diferentes empresas dedicadas al desarrollo de productos de química fina, para determinar las fuerzas y debilidades de cada una de ellas, y para aprovechar las ventajas identificadas para crear una única metodología llamada HarsMeth version 2. A continuación, se ha probado esta versión exhaustivamente en dos empresas químicas para mejorarla, detectando fallos y expandiendo las listas de comprobación con el fin de cubrir el máximo número de cuestiones posibles en el asesoramiento. Otras actividades se han centrado en el desarrollo de herramientas para la determinación teórica de entalpías de reacción y para la identificación de peligros térmicos en equipos de proceso. La versión final de la metodología que se ha desarrollado, llamada HarsMeth New Process, está estructurada para realizar el asesoramiento siguiendo los pasos lógicos del desarrollo de un proceso químico, empezando por el diseño de la reacción química en el laboratorio, siguiendo con el análisis de la estabilidad y compatibilidad de los reactivos, el análisis de la peligrosidad de la reacción, el escalado del proceso y la determinación de medidas de seguridad necesarias para implementar el proceso a escala industrial en función de los peligros identificados anteriormente. Otra estrategia seguida para mejorar la metodología ha sido analizar los accidentes químicos incluidos en la base de datos MARS con el fin de determinar lecciones a aprender de los accidentes, así como identificar qué aspectos cubiertos por la metodología podrían haber ayudado a prevenir los accidentes, y a enfatizar qué aspectos de la seguridad química deben tener especialmente presentes las industrias de proceso. / The aim of this work is focused on the development, testing and improvement of a methodology for the assessment of thermal hazards of chemical reactions, mainly oriented to be used at small and medium enterprises. The methodology consists on a checklist based system to identify thermal hazards, including tools easy to be followed by non experts in the field of safety. The origins of the development are two already existing tools known as HarsMeth and Check Cards for Runaway. Different approaches have been followed in order to come up with a reliable assessment tool. In the first place, the two mentioned methodologies were tested at different companies working on fine chemical production, which gave the possibility to determine strengths and weaknesses for both methodologies, and to profit from the identified strengths to combine them to create one single tool called HarsMeth version 2. Later, this version was thoroughly tested at two different companies to improve it, by detecting flaws and expanding the checklists in order to cover as many issues as possible in the assessment. Further work performed aimed at the development of tools for the theoretical estimation of reaction enthalpies and for the identification of thermal hazards in process equipment. A final version of the methodology was produced, called HarsMeth New Process, structured to perform the hazard assessment at every step followed in the development of a chemical process, starting from the design of the chemical reaction at the laboratory, followed by the study of stability and compatibility of the reactants involved, the bench scale analysis of the synthesis path chosen, the scale up of the process and the determination of the necessary safety measures for the implementation of the process at industrial scale in accordance with the hazards identified. Another strategy followed in order to improve the methodology has been to analyse the chemical accidents reported to the MARS database in order to establish lessons learned from such accidents, and to identify what topics of the methodology could have helped to prevent the accidents and to emphasize what aspects of chemical safety need to be taken into account by the process industries.

In verfahrenstechnischen Anlagen der Flüssig-Flüssig-Stoffübertragung kommt es an der Phasengrenze zwischen den nicht mischbaren Flüssigphasen häufig zur Ausbildung hydrodynamischer Instabilitäten. Sie sind mit komplexen Geschwindigkeitsfeldern in den Flüssigphasen, insbesondere in den grenzschichtnahen Regionen verbunden und führen zu einem starken Anstieg der pro Zeiteinheit übertragenen Stoffmenge. Die Lösung der Diffusionsgleichung reicht in diesem Fall zur Vorausberechnung des für Auslegungszwecke bedeutsamen Stoffdurchgangskoeffizienten nicht mehr aus. Chemische Reaktionen stellen Quellen oder Senken von Wärme und Stoff dar, die das Auftreten von Instabilitäten begünstigen und die mathematische Beschreibung zusätzlich erschweren. Im Rahmen der vorliegenden Arbeit wurden experimentelle und numerische Untersuchungen zum Flüssig-Flüssig-Stoffübergang in einem vertikalen Kapillarspalt durchgeführt. Reaktionsfreie Stoffübergänge und solche mit einer exothermen chemischen Reaktion an der Phasengrenze zeigten eine große Vielfalt von Konvektionsstrukturen, wie Rollzellen, Thermiken und das doppeldiffusive Fingerregime. Die Visualisierung der Transportvorgänge erfolgte durch das Schattenschlierenverfahren. Die Beobachtungen wurden hinsichtlich geometrischer Eigenschaften von Konvektionsstrukturen sowie deren zeitlicher Änderung ausgewertet. Dazu zählten insbesondere das Längenwachstum von Thermiken und horizontale Wellenlängen von Fingerstrukturen. Zur mathematischen Beschreibung der Phänomene im Kapillarspalt wurde ein Modell entwickelt, welches auf den gekoppelten, zweidimensionalen Transportgleichungen von Impuls, Wärme und Stoff beruht. Es berücksichtigt dichte- und grenzflächenspannungsgetriebene Instabilitätsmechanismen sowie die besonderen Durchströmungseigenschaften des Kapillarspalts. Die Phasengrenze wurde als eben angenommen. Die Lösung der Modellgleichungen erfolgt auf numerischem Wege durch ein Computerprogramm. Das Modell ist in der Lage, die beobachteten Instabilitätsphänomene qualitativ richtig wiederzugeben. Mit Hilfe von Simulationsrechnungen konnte der Mechanismus aufgeklärt werden, der zum schnelleren Rückgang des Stoffdurchgangskoeffizienten im Rollzellenregime der rein grenzflächenspannungsgetrieben Instabilität im Vergleich zum Vorgang mit überlagerter Dichtekonvektion führt. Des Weiteren gelang der Nachweis des doppeldiffusiven Fingerregimes beim Stoffübergang mit exothermer Grenzflächenreaktion. Die berechnete Erhöhung des Stoffdurchgangskoeffizienten stimmt mit Angaben in experimentellen Arbeiten anderer Autoren überein.

Biological cells consist of many subunits that form distinct compartments and work together to allow for life. These compartments are clearly separated from each other and their sizes are often strongly correlated with cell size. Examples for those structures are centrosomes, which we consider in this thesis. Centrosomes are essential for many processes inside cells, most importantly for organizing cell division, and they provide an interesting example of cellular compartments without a membrane. Experiments suggest that such compartments can be described as liquid-like droplets. In this thesis, we suggest a theoretical description of the growth phase of centrosomes. We identify a possible mechanism based on phase separation by which the centrosome may be organized. Specifically, we propose that the centrosome material exists in a soluble and in a phase separating form. Chemical reactions controlling the transitions between these forms then determine the temporal evolution of the system. We investigate various possible reaction schemes and generally find that droplet sizes and nucleation properties deviate from the known equilibrium results. Additionally, the non-equilibrium effects of the chemical reactions can stabilize multiple droplets and thus counteract the destabilizing effect of surface tension. Interestingly, only a reaction scheme with autocatalytic growth can account for the experimental data of centrosomes. Here, it is important that the centrioles found at the center of all centrosomes also catalyze the production of droplet material. This catalytic activity allows the centrioles to control the onset of centrosome growth, to stabilize multiple centrosomes, and to center themselves inside the centrosome. We also investigate a stochastic version of the model, where we find that the autocatalytic growth amplifies noise. Our theory explains the growth dynamics of the centrosomes of the round worm Caenorhabditis elegans for all embryonic cells down to the eight-cell stage. It also accounts for data acquired in experiments with aberrant numbers of centrosomes and altered cell volumes. Furthermore, the model can describe unequal centrosome sizes observed in cells with disturbed centrioles. Our example thus suggests a general picture of the organization of membrane-less organelles. / Biologische Zellen bestehen aus vielen Unterstrukturen, die zusammen arbeiten um Leben zu ermöglichen. Die Größe dieser meist klar voneinander abgegrenzten Strukturen korreliert oft mit der Zellgröße. In der vorliegenden Arbeit werden als Beispiel für solche Strukturen Zentrosomen untersucht. Zentrosomen sind für viele Prozesse innerhalb der Zelle, insbesondere für die Zellteilung, unverzichtbar und sie besitzen keine Membran, welche ihnen eine feste Struktur verleihen könnte. Experimentelle Untersuchungen legen nahe, dass solche membranlose Strukturen als Flüssigkeitstropfen beschrieben werden können. In dieser Arbeit wird eine theoretische Beschreibung der Wachstumsphase von Zentrosomen hergeleitet, welche auf Phasenseparation beruht. Im Modell wird angenommen, dass das Zentrosomenmaterial in einer löslichen und einer phasenseparierenden Form existiert, wobei der Übergang zwischen diesen Formen durch chemische Reaktionen gesteuert wird. Die drei verschiedenen in dieser Arbeit untersuchten Reaktionen führen unter anderem zu Tropfengrößen und Nukleationseigenschaften, welche von den bekannten Ergebnissen im thermodynamischen Gleichgewicht abweichen. Insbesondere verursachen die chemischen Reaktionen ein thermisches Nichtgleichgewicht, in dem mehrere Tropfen stabil sein können und der destabilisierende Effekt der Oberflächenspannung unterdrückt wird. Konkret kann die Wachstumsdynamik der Zentrosomen nur durch eine selbstverstärkende Produktion der phasenseparierenden Form des Zentrosomenmaterials erklärt werden. Hierbei ist zusätzlich wichtig, dass die Zentriolen, die im Inneren jedes Zentrosoms vorhanden sind, ebenfalls diese Produktion katalysieren. Dadurch können die Zentriolen den Beginn des Zentrosomwachstums kontrollieren, mehrere Zentrosomen stabilisieren und sich selbst im Zentrosom zentrieren. Des Weiteren führt das selbstverstärkende Wachstum zu einer Verstärkung von Fluktuationen der Zentrosomgröße. Unsere Theorie erklärt die Wachstumsdynamik der Zentrosomen des Fadenwurms Caenorhabditis elegans für alle Embryonalzellen bis zum Achtzellstadium und deckt dabei auch Fälle mit anormaler Zentrosomenanzahl und veränderter Zellgröße ab. Das Modell kann auch Situationen mit unterschiedlich großen Zentrosomen erklären, welche auftreten, wenn die Struktur der Zentriolen verändert wird. Unser Beispiel beschreibt damit eine generelle Möglichkeit, wie membranlose Zellstrukturen organisiert sein können.