998 resultados para Homology modeling
Resumo:
The disintegration of recovered paper is the first operation in the preparation of recycled pulp. It is known that the defibering process follows a first order kinetics from which it is possible to obtain the disintegration kinetic constant (KD) by means of different ways. The disintegration constant can be obtained from the Somerville index results (%lsv and from the dissipated energy per volume unit (Ss). The %slv is related to the quantity of non-defibrated paper, as a measure of the non-disintegrated fiber residual (percentage of flakes), which is expressed in disintegration time units. In this work, disintegration kinetics from recycled coated paper has been evaluated, working at 20 revise rotor speed and for different fiber consistency (6, 8, 10, 12 and 14%). The results showed that the values of experimental disintegration kinetic constant, Ko, through the analysis of Somerville index, as function of time. Increased, the disintegration time was drastically reduced. The calculation of the disintegration kinetic constant (modelled Ko), extracted from the Rayleighs dissipation function, showed a good correlation with the experimental values using the evolution of the Somerville index or with the dissipated energy
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RESUME Les btalanes sont des pigments chromo-alcalodes violets et jaunes prsents dans les plantes appartenant l'ordre des Caryophyllales et dans les champignons des genres Amanita et Hygrocybe. Leur courte voie de biosynthse est lucide chimiquement depuis de nombreuses annes, mais les enzymes impliques dans cette biosynthse chez les plantes ne sont toujours pas caractrises. L'enzyme de la DOPA-dioxygnase d' Amanita muscaria a t identifie (Girod et Zryd, 1991a), mais de nombreuses tentatives d'isolation d'un homologue chez les plantes ont chou. Afin d'isoler les gnes spcifiques des btalanes chez les plantes, nous avons construit des banques soustraites d'ADNc partir d'ARN total de ptales immatures de Portulaca grandiflora (Pg) de gnotypes jaunes et blancs, respectivement violets et blancs. Les clones couleur- spcifiques ont t dtects en premier par analyse Northem du RNA de ptales blancs et colors. Les candidats positifs ont alors t soumis une analyse de transcription au niveau des tiges colores, vertes et des feuilles, afin d'tablir leur expression spcifique. Deux ARNs messagers complets ont une expression corrle avec l'accumulation des btalanes dans les tissus. Le premier de ces clones, A.16, code pour une oxydase de l'acyl-Coenzyme A (ACX) putative, mais le domaine de liaison du FAD essentiel pour l'activit d'ACX est absent. Toutes nos tentatives pour dmontrer sa fonction ont chou. Le rle de cette protine dans la voie de synthse des btalanes reste inconnu. Le deuxime de ces clones spcifique aux btalanes, L.6 (isol par Zaiko, 2000), a t renomm DODA en raison de son homologie avec le domaine LigB (pfam02900) d'une 4,5-dioxygnase extradiol bactrienne. DODA a t identifi in silico comme une dioxygnase extradiol en raison de la conservation stricte, au niveau de sa squence peptidique, des rsidus catalytiques de LigB et de ceux liant le cofacteur fer. Une analyse de transfert Southem a montr que ce gne est unique dans Pg. L'expression transitoire de DODA par transformation biolistique dans des ptales blancs de Pg a produit des taches violettes ou jaunes dans des cellules transformes. Une analyse HPLC de ces taches a dmontr leur identit avec les btalanes prsentes naturellement dans les ptales violets et jaunes de Pg, confirmant ainsi la complmentation par le gne Pg DODA de l'allle rcessif cc prsent dans les ptales blancs de Pg. Des homologues de DODA (DOPA-dioxygnase) ont t identifis dans de nombreuses espces de plantes, y compris dans celles sans btalane. L'alignement de ces homologues a permis l'identification d'un motif spcifique aux btalanes ct d'une histidine catalytique conserve. Ce motif [H-P-(S,A)-(N,D)-x-T-P] remplace le motif [H-N-L-R] conserv dans les plantes sans btalane et le motif [H-N-L-x] prsent dans tous les homologues bactriens et archaebactriens. Une modlisation tridimensionnelle prliminaire du site actif de Pg DODA et de son homologue dans la mousse Physcomitrella patens a montr l'importance de ce motif spcifique aux btalanes pour l'accessibilit du substrat au site actif. L'analyse phylogntique de DODA a confirm l'volution spare de cette protine chez les plantes btalanes par comparaison avec celle des plantes sans btalane. Nous avons donc conclu que les btalanes sont apparues par modification de l'affinit pour un substrat d'enzymes similaires DODA, chez un anctre unique des Caryophyllales qui a perdu toute capacit de biosynthse des anthocyanes. Finalement, Pg DODA n'a aucune similarit avec la protine DODA d' Amanita muscaria, bien que celle-ci complmente aussi la pigmentation des ptales blancs de Pg. La biosynthse des btalanes est un exemple remarquable de convergence volutive biochimique indpendante entre espces de rgnes diffrents. ABSTRACT Betalains are violet and yellow chromo-alkaloid pigments present in plants belonging to the order Caryophyllales and also in the fungal genera Amanita and Hygrocybe. Their short biosynthetic pathway is chemically well understood since many years, but enzymes involved in the plant pathway are still uncharacterized. The DOPA-dioxygenase from Amanita muscaria was identified (Girod and Zryd, 1991a), but numerous attempts to identify a plant homologue to the corresponding gene, failed. In order to isolate betalain-specific genes in plants, subtractive cDNA libraries were built with total RNA from white and yellow and respectively, violet immature petals from Portulaca grandiflora (Pg) genotypes. Colour-specific clones were first detected by Northern blot analysis using RNA from white and coloured petals. Positive candidates were submitted to further transcription analysis in coloured, green stems and leaves in order to assess their specific expression. Two full-length mRNAs showed a correlated expression with betalain accumulation in tissues. One of them, A.16, encodes a putative acyl-Coenzyme A oxidase (ACX), but missing the FAD binding domain essential for the ACX activity. Thus, all attempts to demonstrate its function failed. The role of this protein in the betalain biosynthesis pathway, if any, is still unknown. The second betalain-specific mRNA, L.6 (isolated by Zaiko, 2000) shows a homology with a LigB domain (pfam02900) from a bacterial extradiol 4,5-dioxygenase. It was then renamed DODA (DOPA-dioxygenase). DODA was identified in silico as a highly conserved extradiol dioxygenase due to the strict conservation of its peptidic sequence with LigB catalytic residues and iron-binding cofactor residues. Southern blot analysis showed that this gene is a single copy-gene in Pg. Transient expression of DODA protein through biolistic transformation of Pg white petals produced violet or yellow spots in individual cells. HPLC analysis of these spots showed an identity with betalain pigments present naturally in yellow and violet Pg petals, thus confirming the complementation of the recessive cc allele present in Pg white petals by Pg DODA gene. DODA homologues were identified in numerous plant species including those without betalain. Alignment of these homologues allowed the identification of a betalain-specific pattern beside a highly conserved catalytic histidine. This [H-P-(S,A)-(N,D)-x-T-P] pattern replaces a [H-N-L-R] pattern strictly conserved in non-betalain plants and a [H-N-L-x] pattern present in all bacterial and archaebacterial homologues. Preliminary three-dimensional modeling of the active site of Pg DODA and its Physcomitrella patens moss homologue revealed the importance of this betalain-specific pattern for the substrate accessibility to the DODA active site. DODA phylogenetic analysis confirmed the separate evolution of this protein in betalain-producing plants. We conclude that betalain pigments appeared in a unique ancestor of the Caryophyllales order in which anthocyanin biosynthetic pathway was impaired, by a modification of enzymes of the DODA family for substrate affinity. The Pg DODA protein has no sequence similarity with Amanita muscaria DODA, despite the fact that they both complement Pg white petals for their pigmentation. Betalain biosynthesis is an interesting example of independent biochemical evolutionary convergence between species from different kingdoms.
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Malgr son importance dans notre vie de tous les jours, certaines proprits de l?eau restent inexpliques. L'tude des interactions entre l'eau et les particules organiques occupe des groupes de recherche dans le monde entier et est loin d'tre finie. Dans mon travail j'ai essay de comprendre, au niveau molculaire, ces interactions importantes pour la vie. J'ai utilis pour cela un modle simple de l'eau pour dcrire des solutions aqueuses de diffrentes particules. Rcemment, l?eau liquide a t dcrite comme une structure forme d?un rseau alatoire de liaisons hydrognes. En introduisant une particule hydrophobe dans cette structure basse temprature, certaines liaisons hydrognes sont dtruites ce qui est nergtiquement dfavorable. Les molcules d?eau s?arrangent alors autour de cette particule en formant une cage qui permet de rcuprer des liaisons hydrognes (entre molcules d?eau) encore plus fortes : les particules sont alors solubles dans l?eau. A des tempratures plus leves, l?agitation thermique des molcules devient importante et brise les liaisons hydrognes. Maintenant, la dissolution des particules devient nergtiquement dfavorable, et les particules se sparent de l?eau en formant des agrgats qui minimisent leur surface expose l?eau. Pourtant, trs haute temprature, les effets entropiques deviennent tellement forts que les particules se mlangent de nouveau avec les molcules d?eau. En utilisant un modle bas sur ces changements de structure forme par des liaisons hydrognes j?ai pu reproduire les phnomnes principaux lis l?hydrophobicit. J?ai trouv une rgion de coexistence de deux phases entre les tempratures critiques infrieure et suprieure de solubilit, dans laquelle les particules hydrophobes s?agrgent. En dehors de cette rgion, les particules sont dissoutes dans l?eau. J?ai dmontr que l?interaction hydrophobe est dcrite par un modle qui prend uniquement en compte les changements de structure de l?eau liquide en prsence d?une particule hydrophobe, plutt que les interactions directes entre les particules. Encourage par ces rsultats prometteurs, j?ai tudi des solutions aqueuses de particules hydrophobes en prsence de co-solvants cosmotropiques et chaotropiques. Ce sont des substances qui stabilisent ou dstabilisent les agrgats de particules hydrophobes. La prsence de ces substances peut tre incluse dans le modle en dcrivant leur effet sur la structure de l?eau. J?ai pu reproduire la concentration leve de co-solvants chaotropiques dans le voisinage immdiat de la particule, et l?effet inverse dans le cas de co-solvants cosmotropiques. Ce changement de concentration du co-solvant proximit de particules hydrophobes est la cause principale de son effet sur la solubilit des particules hydrophobes. J?ai dmontr que le modle adapt prdit correctement les effets implicites des co-solvants sur les interactions de plusieurs corps entre les particules hydrophobes. En outre, j?ai tendu le modle la description de particules amphiphiles comme des lipides. J?ai trouv la formation de diffrents types de micelles en fonction de la distribution des regions hydrophobes la surface des particules. L?hydrophobicit reste galement un sujet controvers en science des protines. J?ai dfini une nouvelle chelle d?hydrophobicit pour les acides amins qui forment des protines, base sur leurs surfaces exposes l?eau dans des protines natives. Cette chelle permet une comparaison meilleure entre les expriences et les rsultats thoriques. Ainsi, le modle dvelopp dans mon travail contribue mieux comprendre les solutions aqueuses de particules hydrophobes. Je pense que les rsultats analytiques et numriques obtenus claircissent en partie les processus physiques qui sont la base de l?interaction hydrophobe.<br/><br/>Despite the importance of water in our daily lives, some of its properties remain unexplained. Indeed, the interactions of water with organic particles are investigated in research groups all over the world, but controversy still surrounds many aspects of their description. In my work I have tried to understand these interactions on a molecular level using both analytical and numerical methods. Recent investigations describe liquid water as random network formed by hydrogen bonds. The insertion of a hydrophobic particle at low temperature breaks some of the hydrogen bonds, which is energetically unfavorable. The water molecules, however, rearrange in a cage-like structure around the solute particle. Even stronger hydrogen bonds are formed between water molecules, and thus the solute particles are soluble. At higher temperatures, this strict ordering is disrupted by thermal movements, and the solution of particles becomes unfavorable. They minimize their exposed surface to water by aggregating. At even higher temperatures, entropy effects become dominant and water and solute particles mix again. Using a model based on these changes in water structure I have reproduced the essential phenomena connected to hydrophobicity. These include an upper and a lower critical solution temperature, which define temperature and density ranges in which aggregation occurs. Outside of this region the solute particles are soluble in water. Because I was able to demonstrate that the simple mixture model contains implicitly many-body interactions between the solute molecules, I feel that the study contributes to an important advance in the qualitative understanding of the hydrophobic effect. I have also studied the aggregation of hydrophobic particles in aqueous solutions in the presence of cosolvents. Here I have demonstrated that the important features of the destabilizing effect of chaotropic cosolvents on hydrophobic aggregates may be described within the same two-state model, with adaptations to focus on the ability of such substances to alter the structure of water. The relevant phenomena include a significant enhancement of the solubility of non-polar solute particles and preferential binding of chaotropic substances to solute molecules. In a similar fashion, I have analyzed the stabilizing effect of kosmotropic cosolvents in these solutions. Including the ability of kosmotropic substances to enhance the structure of liquid water, leads to reduced solubility, larger aggregation regime and the preferential exclusion of the cosolvent from the hydration shell of hydrophobic solute particles. I have further adapted the MLG model to include the solvation of amphiphilic solute particles in water, by allowing different distributions of hydrophobic regions at the molecular surface, I have found aggregation of the amphiphiles, and formation of various types of micelle as a function of the hydrophobicity pattern. I have demonstrated that certain features of micelle formation may be reproduced by the adapted model to describe alterations of water structure near different surface regions of the dissolved amphiphiles. Hydrophobicity remains a controversial quantity also in protein science. Based on the surface exposure of the 20 amino-acids in native proteins I have defined the a new hydrophobicity scale, which may lead to an improvement in the comparison of experimental data with the results from theoretical HP models. Overall, I have shown that the primary features of the hydrophobic interaction in aqueous solutions may be captured within a model which focuses on alterations in water structure around non-polar solute particles. The results obtained within this model may illuminate the processes underlying the hydrophobic interaction.<br/><br/>La vie sur notre plante a commenc dans l'eau et ne pourrait pas exister en son absence : les cellules des animaux et des plantes contiennent jusqu' 95% d'eau. Malgr son importance dans notre vie de tous les jours, certaines proprits de l?eau restent inexpliques. En particulier, l'tude des interactions entre l'eau et les particules organiques occupe des groupes de recherche dans le monde entier et est loin d'tre finie. Dans mon travail j'ai essay de comprendre, au niveau molculaire, ces interactions importantes pour la vie. J'ai utilis pour cela un modle simple de l'eau pour dcrire des solutions aqueuses de diffrentes particules. Bien que l?eau soit gnralement un bon solvant, un grand groupe de molcules, appeles molcules hydrophobes (du grecque "hydro"="eau" et "phobia"="peur"), n'est pas facilement soluble dans l'eau. Ces particules hydrophobes essayent d'viter le contact avec l'eau, et forment donc un agrgat pour minimiser leur surface expose l'eau. Cette force entre les particules est appele interaction hydrophobe, et les mcanismes physiques qui conduisent ces interactions ne sont pas bien compris l'heure actuelle. Dans mon tude j'ai dcrit l'effet des particules hydrophobes sur l'eau liquide. L'objectif tait d'claircir le mcanisme de l'interaction hydrophobe qui est fondamentale pour la formation des membranes et le fonctionnement des processus biologiques dans notre corps. Rcemment, l'eau liquide a t dcrite comme un rseau alatoire form par des liaisons hydrognes. En introduisant une particule hydrophobe dans cette structure, certaines liaisons hydrognes sont dtruites tandis que les molcules d'eau s'arrangent autour de cette particule en formant une cage qui permet de rcuprer des liaisons hydrognes (entre molcules d?eau) encore plus fortes : les particules sont alors solubles dans l'eau. A des tempratures plus leves, l?agitation thermique des molcules devient importante et brise la structure de cage autour des particules hydrophobes. Maintenant, la dissolution des particules devient dfavorable, et les particules se sparent de l'eau en formant deux phases. A trs haute temprature, les mouvements thermiques dans le systme deviennent tellement forts que les particules se mlangent de nouveau avec les molcules d'eau. A l'aide d'un modle qui dcrit le systme en termes de restructuration dans l'eau liquide, j'ai russi reproduire les phnomnes physiques lis l?hydrophobicit. J'ai dmontr que les interactions hydrophobes entre plusieurs particules peuvent tre exprimes dans un modle qui prend uniquement en compte les liaisons hydrognes entre les molcules d'eau. Encourage par ces rsultats prometteurs, j'ai inclus dans mon modle des substances frquemment utilises pour stabiliser ou dstabiliser des solutions aqueuses de particules hydrophobes. J'ai russi reproduire les effets ds la prsence de ces substances. De plus, j'ai pu dcrire la formation de micelles par des particules amphiphiles comme des lipides dont la surface est partiellement hydrophobe et partiellement hydrophile ("hydro-phile"="aime l'eau"), ainsi que le repliement des protines d l'hydrophobicit, qui garantit le fonctionnement correct des processus biologiques de notre corps. Dans mes tudes futures je poursuivrai l'tude des solutions aqueuses de diffrentes particules en utilisant les techniques acquises pendant mon travail de thse, et en essayant de comprendre les proprits physiques du liquide le plus important pour notre vie : l'eau.
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The accumulation of aqueous pollutants is becoming a global problem. The search for suitable methods and/or combinations of water treatment processes is a task that can slow down and stop the process of water pollution. In this work, the method of wet oxidation was considered as an appropriate technique for the elimination of the impurities present in paper mill process waters. It has been shown that, when combined with traditional wastewater treatment processes, wet oxidation offers many advantages. The combination of coagulation and wet oxidation offers a new opportunity for the improvement of the quality of wastewater designated for discharge or recycling. First of all, the utilization of coagulated sludge via wet oxidation provides a conditioning process for the sludge, i.e. dewatering, which is rather difficult to carry out with untreated waste. Secondly, Fe2(SO4)3, which is employed earlier as a coagulant, transforms the conventional wet oxidation process into a catalytic one. The use of coagulation as the post-treatment for wet oxidation can offer the possibility of the brown hue that usually accompanies the partial oxidation to be reduced. As a result, the supernatant is less colored and also contains a rather low amount of Fe ions to beconsidered for recycling inside mills. The thickened part that consists of metal ions is then recycled back to the wet oxidation system. It was also observed that wet oxidation is favorable for the degradation of pitch substances (LWEs) and lignin that are present in the process waters of paper mills. Rather low operating temperatures are needed for wet oxidation in order to destruct LWEs. The oxidation in the alkaline media provides not only the faster elimination of pitch and lignin but also significantly improves the biodegradable characteristics of wastewater that contains lignin and pitch substances. During the course of the kinetic studies, a model, which can predict the enhancements of the biodegradability of wastewater, was elaborated. The model includes lumped concentrations suchas the chemical oxygen demand and biochemical oxygen demand and reflects a generalized reaction network of oxidative transformations. Later developments incorporated a new lump, the immediately available biochemical oxygen demand, which increased the fidelity of the predictions made by the model. Since changes in biodegradability occur simultaneously with the destruction of LWEs, an attempt was made to combine these two facts for modeling purposes.
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A rigorous unit operation model is developed for vapor membrane separation. The new model is able to describe temperature, pressure, and concentration dependent permeation as wellreal fluid effects in vapor and gas separation with hydrocarbon selective rubbery polymeric membranes. The permeation through the membrane is described by a separate treatment of sorption and diffusion within the membrane. The chemical engineering thermodynamics is used to describe the equilibrium sorption of vapors and gases in rubbery membranes with equation of state models for polymeric systems. Also a new modification of the UNIFAC model is proposed for this purpose. Various thermodynamic models are extensively compared in order to verify the models' ability to predict and correlate experimental vapor-liquid equilibrium data. The penetrant transport through the selective layer of the membrane is described with the generalized Maxwell-Stefan equations, which are able to account for thebulk flux contribution as well as the diffusive coupling effect. A method is described to compute and correlate binary penetrantmembrane diffusion coefficients from the experimental permeability coefficients at different temperatures and pressures. A fluid flow model for spiral-wound modules is derived from the conservation equation of mass, momentum, and energy. The conservation equations are presented in a discretized form by using the control volume approach. A combination of the permeation model and the fluid flow model yields the desired rigorous model for vapor membrane separation. The model is implemented into an inhouse process simulator and so vapor membrane separation may be evaluated as an integralpart of a process flowsheet.
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Thisresearch deals with the dynamic modeling of gas lubricated tilting pad journal bearings provided with spring supported pads, including experimental verification of the computation. On the basis of a mathematical model of a film bearing, a computer program has been developed, which can be used for the simulation of a special type of tilting pad gas journal bearing supported by a rotary spring under different loading conditions time dependently (transient running conditions due to geometry variations in time externally imposed). On the basis of literature, different transformations have been used in the model to achieve simpler calculation. The numerical simulation is used to solve a non-stationary case of a gasfilm. The simulation results were compared with literature results in a stationary case (steady running conditions) and they were found to be equal. In addition to this, comparisons were made with a number of stationary and non-stationary bearing tests, which were performed at Lappeenranta University of Technology using bearings designed with the simulation program. A study was also made using numerical simulation and literature to establish the influence of the different bearing parameters on the stability of the bearing. Comparison work was done with literature on tilting pad gas bearings. This bearing type is rarely used. One literature reference has studied the same bearing type as that used in LUT. A new design of tilting pad gas bearing is introduced. It is based on a stainless steel body and electron beam welding of the bearing parts. It has good operation characteristics and is easier to tune and faster to manufacture than traditional constructions. It is also suitable for large serial production.
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Static process simulation has traditionally been used to model complex processes for various purposes. However, the use of static processsimulators for the preparation of holistic examinations aiming at improving profit-making capability requires a lot of work because the production of results requires the assessment of the applicability of detailed data which may be irrelevant to the objective. The relevant data for the total assessment gets buried byirrelevant data. Furthermore, the models do not include an examination of the maintenance or risk management, and economic examination is often an extra property added to them which can be performed with a spreadsheet program. A process model applicable to holistic economic examinations has been developed in this work. The model is based on the life cycle profit philosophy developed by Hagberg and Henriksson in 1996. The construction of the model has utilized life cycle assessment and life cycle costing methodologies with a view to developing, above all, a model which would be applicable to the economic examinations of complete wholes and which would require the need for information focusing on aspects essential to the objectives. Life cycle assessment and costing differ from each other in terms of the modeling principles, but the features of bothmethodologies can be used in the development of economic process modeling. Methods applicable to the modeling of complex processes can be examined from the viewpoint of life cycle methodologies, because they involve the collection and management of large corpuses of information and the production of information for the needs of decision-makers as well. The results of the study shows that on the basis of the principles of life cycle modeling, a process model can be created which may be used to produce holistic efficiency examinations on the profit-making capability of the production line, with fewer resources thanwith traditional methods. The calculations of the model are based to the maximum extent on the information system of the factory, which means that the accuracyof the results can be improved by developing information systems so that they can provide the best information for this kind of examinations.
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Globalization and new information technologies mean that organizations have to face world-wide competition in rapidly transforming, unpredictable environments, and thus the ability to constantly generate novel and improved products, services and processes has become quintessential for organizational success. Performance in turbulent environments is, above all, influenced by the organization's capability for renewal. Renewal capability consists of the ability of the organization to replicate, adapt, develop and change its assets, capabilities and strategies. An organization with a high renewal capability can sustain its current success factors while at the same time building new strengths for the future. This capability does not only mean that the organization is able to respond to today's challenges and to keep up with the changes in its environment, but also that it can actas a forerunner by creating innovations, both at the tactical and strategic levels of operation and thereby change the rules of the market. However, even though it is widely agreed that the dynamic capability for continuous learning, development and renewal is a major source of competitive advantage, there is no widely shared view on how organizational renewal capability should be defined, and the field is characterized by a plethora of concepts and definitions. Furthermore,there is a lack of methods for systematically assessing organizational renewal capability. The dissertation aims to bridge these gaps in the existing research by constructing an integrative theoretical framework for organizational renewal capability and by presenting a method for modeling and measuring this capability. The viability of the measurement tool is demonstrated in several contexts, andthe framework is also applied to assess renewal in inter-organizational networks. In this dissertation, organizational renewal capability is examined by drawing on three complimentary theoretical perspectives: knowledge management, strategic management and intellectual capital. The knowledge management perspective considers knowledge as inherently social and activity-based, and focuses on the organizational processes associated with its application and development. Within this framework, organizational renewal capability is understood as the capacity for flexible knowledge integration and creation. The strategic management perspective, on the other hand, approaches knowledge in organizations from the standpoint of its implications for the creation of competitive advantage. In this approach, organizational renewal is framed as the dynamic capability of firms. The intellectual capital perspective is focused on exploring how intangible assets can be measured, reported and communicated. From this vantage point, renewal capability is comprehended as the dynamic dimension of intellectual capital, which consists of the capability to maintain, modify and create knowledge assets. Each of the perspectives significantly contributes to the understanding of organizationalrenewal capability, and the integrative approach presented in this dissertationcontributes to the individual perspectives as well as to the understanding of organizational renewal capability as a whole.
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Both the intermolecular interaction energies and the geometries for M thiophene, M pyrrole, M n+ thiophene, and M n+ pyrrole with M = Li, Na, K, Ca, and Mg; and M n+ = Li+ , Na+ , K+ , Ca2+, and Mg2+ have been estimated using four commonly used density functional theory DFT methods: B3LYP, B3PW91, PBE, and MPW1PW91. Results have been compared to those provided by HF, MP2, and MP4 conventional ab initio methods. The PBE and MPW1PW91 are the only DFT methods able to provide a reasonable description of the M complexes. Regarding M n+ complexes, the four DFT methods have been proven to be adequate in the prediction of these electrostatically stabilized systems, even though they tend to overestimate the interaction energies.
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Vegetation has a profound effect on flow and sediment transport processes in natural rivers, by increasing both skin friction and form drag. The increase in drag introduces a drag discontinuity between the in-canopy flow and the flow above, which leads to the development of an inflection point in the velocity profile, resembling a free shear layer. Therefore, drag acts as the primary driver for the entire canopy system. Most current numerical hydraulic models which incorporate vegetation rely either on simple, static plant forms, or canopy-scaled drag terms. However, it is suggested that these are insufficient as vegetation canopies represent complex, dynamic, porous blockages within the flow, which are subject to spatially and temporally dynamic drag forces. Here we present a dynamic drag methodology within a CFD framework. Preliminary results for a benchmark cylinder case highlight the accuracy of the method, and suggest its applicability to more complex cases.
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La prsente thse s'intitule "Dveloppent et Application des Mthodologies Computationnelles pour la Modlisation Qualitative". Elle comprend tous les diffrents projets que j'ai entrepris en tant que doctorante. Plutt qu'une mise en oeuvre systmatique d'un cadre dfini a priori, cette thse devrait tre considre comme une exploration des mthodes qui peuvent nous aider dduire le plan de processus regulatoires et de signalisation. Cette exploration a t mue par des questions biologiques concrtes, plutt que par des investigations thoriques. Bien que tous les projets aient inclus des systmes divergents (rseaux rgulateurs de gnes du cycle cellulaire, rseaux de signalisation de cellules pulmonaires) ainsi que des organismes (levure fission, levure bourgeonnante, rat, humain), nos objectifs taient complmentaires et cohrents. Le projet principal de la thse est la modlisation du rseau de l'initiation de septation (SIN) du S.pombe. La cytokinse dans la levure fission est contrle par le SIN, un rseau signalant de protines kinases qui utilise le corps ple-fuseau comme chafaudage. Afin de dcrire le comportement qualitatif du systme et prdire des comportements mutants inconnus, nous avons dcid d'adopter l'approche de la modlisation boolenne. Dans cette thse, nous prsentons la construction d'un modle boolen tendu du SIN, comprenant la plupart des composantes et des rgulateurs du SIN en tant que noeuds individuels et testable exprimentalement. Ce modle utilise des niveaux d'activit du CDK comme noeuds de contrle pour la simulation d'vnements du SIN diffrents stades du cycle cellulaire. Ce modle a t optimis en utilisant des expriences d'un seul "knock-out" avec des effets phnotypiques connus comme set d'entranement. Il a permis de prdire correctement un set d'valuation de "knock-out" doubles. De plus, le modle a fait des prdictions in silico qui ont t valides in vivo, permettant d'obtenir de nouvelles ides de la rgulation et l'organisation hirarchique du SIN. Un autre projet concernant le cycle cellulaire qui fait partie de cette thse a t la construction d'un modle qualitatif et minimal de la rciprocit des cyclines dans la S.cerevisiae. Les protines Clb dans la levure bourgeonnante prsentent une activation et une dgradation caractristique et squentielle durant le cycle cellulaire, qu'on appelle communment les vagues des Clbs. Cet vnement est coordonn avec la courbe d'activation inverse du Sic1, qui a un rle inhibitoire dans le systme. Pour l'identification des modles qualitatifs minimaux qui peuvent expliquer ce phnomne, nous avons slectionn des expriences bien dfinies et construit tous les modles minimaux possibles qui, une fois simuls, reproduisent les rsultats attendus. Les modles ont t filtrs en utilisant des simulations ODE qualitatives et standardises; seules celles qui reproduisaient le phnotype des vagues ont t gardes. L'ensemble des modles minimaux peut tre utilis pour suggrer des relations regulatoires entre les molcules participant qui peuvent ensuite tre testes exprimentalement. Enfin, durant mon doctorat, j'ai particip au SBV Improver Challenge. Le but tait de dduire des rseaux spcifiques des espces (humain et rat) en utilisant des donnes de phosphoprotines, d'expressions des gnes et des cytokines, ainsi qu'un rseau de rfrence, qui tait mis disposition comme donne pralable. Notre solution pour ce concours a pris la troisime place. L'approche utilise est explique en dtail dans le dernier chapitre de la thse. -- The present dissertation is entitled "Development and Application of Computational Methodologies in Qualitative Modeling". It encompasses the diverse projects that were undertaken during my time as a PhD student. Instead of a systematic implementation of a framework defined a priori, this thesis should be considered as an exploration of the methods that can help us infer the blueprint of regulatory and signaling processes. This exploration was driven by concrete biological questions, rather than theoretical investigation. Even though the projects involved divergent systems (gene regulatory networks of cell cycle, signaling networks in lung cells), as well as organisms (fission yeast, budding yeast, rat, human), our goals were complementary and coherent. The main project of the thesis is the modeling of the Septation Initiation Network (SIN) in S.pombe. Cytokinesis in fission yeast is controlled by the SIN, a protein kinase signaling network that uses the spindle pole body as scaffold. In order to describe the qualitative behavior of the system and predict unknown mutant behaviors we decided to adopt a Boolean modeling approach. In this thesis, we report the construction of an extended, Boolean model of the SIN, comprising most SIN components and regulators as individual, experimentally testable nodes. The model uses CDK activity levels as control nodes for the simulation of SIN related events in different stages of the cell cycle. The model was optimized using single knock-out experiments of known phenotypic effect as a training set, and was able to correctly predict a double knock-out test set. Moreover, the model has made in silico predictions that have been validated in vivo, providing new insights into the regulation and hierarchical organization of the SIN. Another cell cycle related project that is part of this thesis was to create a qualitative, minimal model of cyclin interplay in S.cerevisiae. CLB proteins in budding yeast present a characteristic, sequential activation and decay during the cell cycle, commonly referred to as Clb waves. This event is coordinated with the inverse activation curve of Sic1, which has an inhibitory role in the system. To generate minimal qualitative models that can explain this phenomenon, we selected well-defined experiments and constructed all possible minimal models that, when simulated, reproduce the expected results. The models were filtered using standardized qualitative ODE simulations; only the ones reproducing the wave-like phenotype were kept. The set of minimal models can be used to suggest regulatory relations among the participating molecules, which will subsequently be tested experimentally. Finally, during my PhD I participated in the SBV Improver Challenge. The goal was to infer species-specific (human and rat) networks, using phosphoprotein, gene expression and cytokine data and a reference network provided as prior knowledge. Our solution to the challenge was selected as in the final chapter of the thesis.
Resumo:
This article introduces a new interface for T-Coffee, a consistency-based multiple sequence alignment program. This interface provides an easy and intuitive access to the most popular functionality of the package. These include the default T-Coffee mode for protein and nucleic acid sequences, the M-Coffee mode that allows combining the output of any other aligners, and template-based modes of T-Coffee that deliver high accuracy alignments while using structural or homology derived templates. These three available template modes are Expresso for the alignment of protein with a known 3D-Structure, R-Coffee to align RNA sequences with conserved secondary structures and PSI-Coffee to accurately align distantly related sequences using homology extension. The new server benefits from recent improvements of the T-Coffee algorithm and can align up to 150 sequences as long as 10000 residues and is available from both http://www.tcoffee.org and its main mirror http://tcoffee.crg.cat.
Resumo:
Approximate models (proxies) can be employed to reduce the computational costs of estimating uncertainty. The price to pay is that the approximations introduced by the proxy model can lead to a biased estimation. To avoid this problem and ensure a reliable uncertainty quantification, we propose to combine functional data analysis and machine learning to build error models that allow us to obtain an accurate prediction of the exact response without solving the exact model for all realizations. We build the relationship between proxy and exact model on a learning set of geostatistical realizations for which both exact and approximate solvers are run. Functional principal components analysis (FPCA) is used to investigate the variability in the two sets of curves and reduce the dimensionality of the problem while maximizing the retained information. Once obtained, the error model can be used to predict the exact response of any realization on the basis of the sole proxy response. This methodology is purpose-oriented as the error model is constructed directly for the quantity of interest, rather than for the state of the system. Also, the dimensionality reduction performed by FPCA allows a diagnostic of the quality of the error model to assess the informativeness of the learning set and the fidelity of the proxy to the exact model. The possibility of obtaining a prediction of the exact response for any newly generated realization suggests that the methodology can be effectively used beyond the context of uncertainty quantification, in particular for Bayesian inference and optimization.
