A characteristic EEG pattern in 4p-syndrome: case report and review of the literature.

Deletions on the short arm of chromosome 4 cause Wolf-Hirschhorn syndrome (WHS) and Pitt-Rogers-Danks syndrome (PRDS). WHS is associated with severe growth and mental retardation, microcephaly, a characteristic facies and congenital malformations. The PRDS phenotype is similar to WHS but generally less severe. Seizures occur in the majority of WHS and PRDS patients. Sgrò et al. [17] described a stereotypic electroclinical pattern in four unrelated WHS patients, consisting of intermittent bursts of 2-3 Hz high voltage slow waves with spike wave activity in the parietal areas during drowsiness and sleep associated with myoclonic jerks. We report a patient with PRDS and the typical EEG pattern and review 14 WHS patients with similar EEG findings reported in the literature. CONCLUSION: Awareness and recognition of the characteristic electroclinical findings in Wolf-Hirschhorn syndrome and Pitt-Rogers-Danks syndrome might help in the early diagnosis of such patients.

Continuous assessment of electrical epileptic activity in acute stroke.

OBJECTIVE: To determine the incidence and risk factors of electrical seizures and other electrical epileptic activity using continuous EEG (cEEG) in patients with acute stroke. METHODS: One hundred consecutive patients with acute stroke admitted to our stroke unit underwent cEEG using 10 electrodes. In addition to electrical seizures, repetitive focal sharp waves (RSHWs), repetitive focal spikes (RSPs), and periodic lateralized epileptic discharges (PLEDs) were recorded. RESULTS: In the 100 patients, cEEG was recorded for a mean duration of 17 hours 34 minutes (range 1 hour 12 minutes to 37 hours 10 minutes). Epileptic activity occurred in 17 patients and consisted of RSHWs in seven, RSPs in seven, and PLEDs in three. Electrical seizures occurred in two patients. On univariate Cox regression analysis, predictors for electrical epileptic activity were stroke severity (high score on the National Institutes of Health Stroke Scale) (hazard ratio [HR] 1.12; p = 0.002), cortical involvement (HR 5.71; p = 0.021), and thrombolysis (HR 3.27; p = 0.040). Age, sex, stroke type, use of EEG-modifying medication, and cardiovascular risk factors were not predictors of electrical epileptic activity. On multivariate analysis, stroke severity was the only independent predictor (HR 1.09; p = 0.016). CONCLUSION: In patients with acute stroke, electrical epileptic activity occurs more frequently than previously suspected.

Regulation of chromosomal replication in Caulobacter crescentus.

The alpha-proteobacterium Caulobacter crescentus is characterized by its asymmetric cell division, which gives rise to a replicating stalked cell and a non-replicating swarmer cell. Thus, the initiation of chromosomal replication is tightly regulated, temporally and spatially, to ensure that it is coordinated with cell differentiation and cell cycle progression. Waves of DnaA and CtrA activities control when and where the initiation of DNA replication will take place in C. crescentus cells. The conserved DnaA protein initiates chromosomal replication by directly binding to sites within the chromosomal origin (Cori), ensuring that DNA replication starts once and only once per cell cycle. The CtrA response regulator represses the initiation of DNA replication in swarmer cells and in the swarmer compartment of pre-divisional cells, probably by competing with DnaA for binding to Cori. CtrA and DnaA are controlled by multiple redundant regulatory pathways that include DNA methylation-dependent transcriptional regulation, temporally regulated proteolysis and the targeting of regulators to specific locations within the cell. Besides being critical regulators of chromosomal replication, CtrA and DnaA are also master transcriptional regulators that control the expression of many genes, thus connecting DNA replication with other events of the C. crescentus cell cycle.

Sea state effect on the sea surface emissivity at L-band

In May 1999, the European Space Agency (ESA) selected the Earth Explorer Opportunity Soil Moisture and Ocean Salinity (SMOS) mission to obtain global and frequent soil moisture and ocean salinity maps. SMOS' single payload is the Microwave Imaging Radiometer by Aperture Synthesis (MIRAS), an L-band two-dimensional aperture synthesis radiometer with multiangular observation capabilities. At L-band, the brightness temperature sensitivity to the sea surface salinity (SSS) is low, approximately 0.5 K/psu at 20/spl deg/C, decreasing to 0.25 K/psu at 0/spl deg/C, comparable to that to the wind speed /spl sim/0.2 K/(m/s) at nadir. However, at a given time, the sea state does not depend only on local winds, but on the local wind history and the presence of waves traveling from far distances. The Wind and Salinity Experiment (WISE) 2000 and 2001 campaigns were sponsored by ESA to determine the impact of oceanographic and atmospheric variables on the L-band brightness temperature at vertical and horizontal polarizations. This paper presents the results of the analysis of three nonstationary sea state conditions: growing and decreasing sea, and the presence of swell. Measured sea surface spectra are compared with the theoretical ones, computed using the instantaneous wind speed. Differences can be minimized using an "effective wind speed" that makes the theoretical spectrum best match the measured one. The impact on the predicted brightness temperatures is then assessed using the small slope approximation/small perturbation method (SSA/SPM).

A model of the wind direction signature in the Stokes emission vector from the ocean surface at microwave frequencies

This paper presents a model of the Stokes emission vector from the ocean surface. The ocean surface is described as an ensemble of facets with Cox and Munk's (1954) Gram-Charlier slope distribution. The study discusses the impact of different up-wind and cross-wind rms slopes, skewness, peakedness, foam cover models and atmospheric effects on the azimuthal variation of the Stokes vector, as well as the limitations of the model. Simulation results compare favorably, both in mean value and azimuthal dependence, with SSM/I data at 53° incidence angle and with JPL's WINDRAD measurements at incidence angles from 30° to 65°, and at wind speeds from 2.5 to 11 m/s.

Bud dormancy in apple trees after thermal fluctuations

The objective of this work was to evaluate the effect of heat waves on the evolution of bud dormancy, in apple trees with contrasting chilling requirements. Twigs of 'Castel Gala' and 'Royal Gala' were collected in orchards in Papanduva, state of Santa Catarina, Brazil, and were exposed to constant (3°C) or alternating (3 and 15°C for 12/12 hours) temperature, combined with zero, one or two days a week at 25°C. Two additional treatments were evaluated: constant temperature (3°C), with a heat wave of seven days at 25°C, in the beginning or in the middle of the experimental period. Periodically, part of the twigs was transferred to 25°C for daily budburst evaluation of apical and lateral buds. Endodormancy (dormancy induced by cold) was overcome with less than 330 chilling hours (CH) of constant cold in 'Castel Gala' and less than 618 CH in 'Royal Gala'. A daily 15°C-temperature cycle did not affect the endodormancy process. Heat waves during endodormancy resulted in an increased CH to achieve bud requirements. The negative effect of high temperature depended on the lasting of this condition. Chilling was partly cancelled during dormancy when the heat wave lasted 36 continuous hours or more. Therefore, budburst prediction models need adjustments, mainly for regions with mild and irregular winters, such as those of Southern Brazil.

CO2:n käyttö puhdistuksessa ja inerttinä kaasuna öljynjalostusympäristössä

Tutkimuksen tavoitteena on löytää CO2:lle puhdistus- ja inertointikohteita öljynjalostusympäristöstä. CO2:na käytettäisiin Porvoon vetylaitokselta sivutuotteena tulevaa CO2:a. Vetylaitokselta saatava CO2-virta ei ole riittävän puhdasta käytettäväksi suoraan pesuissa ja inertoinnissa. CO2:n eri olomuotoja voidaan käyttää puhdistuksessa. Tutkimuksen lähtökohtana olleen ylikriittisen CO2:n tehokkuus perustuu sen liuottavuuteen. Huonosti liukenevien aineiden liukoisuus ylikriittiseen CO2:in paranee lisäaineiden ja pinta-aktiivisten aineiden käytöllä. Kiinteä CO2 jäädyttää ja poistaa epäpuhtauden sublimoitumisesta aiheutuvan paineaallon voimasta. Kuivajääpuhdistus soveltuu parhaiten tasaisten pintojen puhdistamiseen. Ylikriittisellä CO2:lla onnistuu nykyisellä teknologialla vain pienien kappaleiden puhdistaminen. Kuivajääpuhdistuksen toimivuutta kokeiltiin käytännössä Neste Oilin Porvoon jalostamolla hyvin tuloksin. Tasaisilta pinnoilta saatiin poistetuksi bitumia ja rasvakerros. Käyttökustannusvertailussa osoittautui ylikriittistä CO2:a käyttävä laitteisto halvemmaksi ja kuivajääpuhallus kalliimmaksi kuin konventionaaliset menetelmät. Säiliöiden paineistamiseen ja inertointiin käytetään yleisesti N2:ä. N2:llä inertoitavia kohteita voitaisiin korvata CO2:lla. CO2:n käyttöä rajoittavia seikkoja on hinta ja sen reaktiivisuus alkalimetallien kanssa. Vertailtaessa näiden kahden liukoisuuksia hiilivetyihin osoittautui CO2 monin kerroin liukoisemmaksi. Tämän ominaisuuden ansiosta CO2 voisi olla hyvä väliaine laitteiden hiilivetyvapaaksi saattamisessa.

Riskianalyysistäohjeelliseen panostussuunnitelmaan

Nykytekniikalla kyetään tehokkaaseen ja turvalliseen työn toteuttamiseen. Suorituksen aikaansaanti edellyttää ympäristön kartoittamista niin, että urakoitsija tuntee ne seikat, jotka ovat tarpeen, jotta työ voidaan suorittaa vaurioittamatta olevia rakennuksia ja aiheuttamatta asukkaille vaaratilanteita. Riskianalyysi tuo esille ne seikat, jotka on syytä tietää työn laskenta- ja suoritustilanteessa. On tunnettava käytettävät räjähdysaineet ja mitä tapahtuu räjähdysprosessissa. Prosessin ideaalimallin (harmoninen värähtely) pohjalta on kehitetty teorioita, joiden avulla kyetään pitämään suorituksen aiheuttama tärinätaso sellaisena, ettei ympäristössä olevia entisiä rakennuksia vaurioiteta eikä teknisestä suorituksesta aiheudu vaaratilanteita ihmisille. Riskianalyysi- ja rakennuskatselmustietojen perusteella mitoitetaan käytettävä panos sellaiseksi, että asetetut turvallisuusvaateet tulevat täytetyiksi. Työn suorituksen onnistumiseksilaaditaan ohjeellinen panostussuunnitelma, jossa käytettävä panoskoko ilmoitetaan etäisyyden funktiona varottavasta kohteesta. Samassa esityksessä käy selville rakenteille sallittu tärinäaallon heilahdusnopeus mm/s:ssa. Muuttunut etäisyys ja se tosiasia, etteivät räjäytyskentät ole tärinätasoltaan identtisiä, vaikka etäisyys ja panoskoko ovat samat, tarvitsee muutostentekoa varten teoreettistasoisen esityksen tuekseen. Tuo tuki on ohjeellinen panostussuunnitelma. Muutosten perusteena ei ole mutu - menettely, vaan teoreettinen, yleisesti hyväksyttyihin menettelytapoihin perustuva malli.

Juego 2D para Android

El proyecto consistirá en diseñar desde cero un juego para smartphones que utilicen el sistema operativo Android. El objetivo del juego será sobrevivir a las oleadas de enemigos, que aparecerán en el extremo derecho de la pantalla y se dirigirán al lado opuesto, durante el tiempo suficiente para superar el nivel actual. Al mismo tiempo tendremos que tratar de esquivar los obstáculos y recoger los objetos que nos proporcionarán un bonus de puntos. En el juego habrá un número finito de niveles, cada uno más difícil que el anterior.

Spatial distribution of motor units recruited during electrical stimulation of the quadriceps muscle versus the femoral nerve.

INTRODUCTION: In this study we investigated differences in the spatial recruitment of motor units (MUs) in the quadriceps when electrical stimulation is applied over the quadriceps belly versus the femoral nerve. METHODS: M-waves and mechanical twitches were evoked using over-the-quadriceps and femoral nerve stimulation of gradually increasing intensity from 22 young, healthy subjects. Spatial recruitment was investigated using recruitment curves of M-waves recorded from the vastus medialis (VM) and vastus lateralis (VL) and of twitches recorded from the quadriceps. RESULTS: At maximal stimulation intensity (Imax), no differences were found between nerve and over-the-quadriceps stimulation. At submaximal intensities, VL M-wave amplitude was higher for over-the-quadriceps stimulation at 40% Imax, and peak twitch force was greater for nerve stimulation at 60% and 80% Imax. CONCLUSIONS: For the VM, MU spatial recruitment during nerve and over-the-quadriceps stimulation of increasing intensity occurred in a similar manner, whereas significant differences were observed for the VL. Muscle Nerve, 2013.

Isentropic Exergy and Pressure of the Shock Wave Caused by the Explosion of a Pressure Vessel

An accidental burst of a pressure vessel is an uncontrollable and explosion-like batch process. In this study it is called an explosion. The destructive effectof a pressure vessel explosion is relative to the amount of energy released in it. However, in the field of pressure vessel safety, a mutual understanding concerning the definition of explosion energy has not yet been achieved. In this study the definition of isentropic exergy is presented. Isentropic exergy is the greatest possible destructive energy which can be obtained from a pressure vessel explosion when its state changes in an isentropic way from the initial to the final state. Finally, after the change process, the gas has similar pressure and flow velocity as the environment. Isentropic exergy differs from common exergy inthat the process is assumed to be isentropic and the final gas temperature usually differs from the ambient temperature. The explosion process is so fast that there is no time for the significant heat exchange needed for the common exergy.Therefore an explosion is better characterized by isentropic exergy. Isentropicexergy is a characteristic of a pressure vessel and it is simple to calculate. Isentropic exergy can be defined also for any thermodynamic system, such as the shock wave system developing around an exploding pressure vessel. At the beginning of the explosion process the shock wave system has the same isentropic exergyas the pressure vessel. When the system expands to the environment, its isentropic exergy decreases because of the increase of entropy in the shock wave. The shock wave system contains the pressure vessel gas and a growing amount of ambient gas. The destructive effect of the shock wave on the ambient structures decreases when its distance from the starting point increases. This arises firstly from the fact that the shock wave system is distributed to a larger space. Secondly, the increase of entropy in the shock waves reduces the amount of isentropic exergy. Equations concerning the change of isentropic exergy in shock waves are derived. By means of isentropic exergy and the known flow theories, equations illustrating the pressure of the shock wave as a function of distance are derived. Amethod is proposed as an application of the equations. The method is applicablefor all shapes of pressure vessels in general use, such as spheres, cylinders and tubes. The results of this method are compared to measurements made by various researchers and to accident reports on pressure vessel explosions. The test measurements are found to be analogous with the proposed method and the findings in the accident reports are not controversial to it.

Selective catalytic reduction of nitrogen oxides with ammonia in forced unsteady state reactors - Case based reasoning and mathematical model simulation reasoning

The application of forced unsteady-state reactors in case of selective catalytic reduction of nitrogen oxides (NOx) with ammonia (NH3) is sustained by the fact that favorable temperature and composition distributions which cannot be achieved in any steady-state regime can be obtained by means of unsteady-state operations. In a normal way of operation the low exothermicity of the selective catalytic reduction (SCR) reaction (usually carried out in the range of 280-350°C) is not enough to maintain by itself the chemical reaction. A normal mode of operation usually requires supply of supplementary heat increasing in this way the overall process operation cost. Through forced unsteady-state operation, the main advantage that can be obtained when exothermic reactions take place is the possibility of trapping, beside the ammonia, the moving heat wave inside the catalytic bed. The unsteady state-operation enables the exploitation of the thermal storage capacity of the catalyticbed. The catalytic bed acts as a regenerative heat exchanger allowing auto-thermal behaviour when the adiabatic temperature rise is low. Finding the optimum reactor configuration, employing the most suitable operation model and identifying the reactor behavior are highly important steps in order to configure a proper device for industrial applications. The Reverse Flow Reactor (RFR) - a forced unsteady state reactor - corresponds to the above mentioned characteristics and may be employed as an efficient device for the treatment of dilute pollutant mixtures. As a main disadvantage, beside its advantages, the RFR presents the 'wash out' phenomena. This phenomenon represents emissions of unconverted reactants at every switch of the flow direction. As a consequence our attention was focused on finding an alternative reactor configuration for RFR which is not affected by the incontrollable emissions of unconverted reactants. In this respect the Reactor Network (RN) was investigated. Its configuration consists of several reactors connected in a closed sequence, simulating a moving bed by changing the reactants feeding position. In the RN the flow direction is maintained in the same way ensuring uniformcatalyst exploitation and in the same time the 'wash out' phenomena is annulated. The simulated moving bed (SMB) can operate in transient mode giving practically constant exit concentration and high conversion levels. The main advantage of the reactor network operation is emphasizedby the possibility to obtain auto-thermal behavior with nearly uniformcatalyst utilization. However, the reactor network presents only a small range of switching times which allow to reach and to maintain an ignited state. Even so a proper study of the complex behavior of the RN may give the necessary information to overcome all the difficulties that can appear in the RN operation. The unsteady-state reactors complexity arises from the fact that these reactor types are characterized by short contact times and complex interaction between heat and mass transportphenomena. Such complex interactions can give rise to a remarkable complex dynamic behavior characterized by a set of spatial-temporal patterns, chaotic changes in concentration and traveling waves of heat or chemical reactivity. The main efforts of the current research studies concern the improvement of contact modalities between reactants, the possibility of thermal wave storage inside the reactor and the improvement of the kinetic activity of the catalyst used. Paying attention to the above mentioned aspects is important when higher activity even at low feeding temperatures and low emissions of unconverted reactants are the main operation concerns. Also, the prediction of the reactor pseudo or steady-state performance (regarding the conversion, selectivity and thermal behavior) and the dynamicreactor response during exploitation are important aspects in finding the optimal control strategy for the forced unsteady state catalytic tubular reactors. The design of an adapted reactor requires knowledge about the influence of its operating conditions on the overall process performance and a precise evaluation of the operating parameters rage for which a sustained dynamic behavior is obtained. An apriori estimation of the system parameters result in diminution of the computational efforts. Usually the convergence of unsteady state reactor systems requires integration over hundreds of cycles depending on the initial guess of the parameter values. The investigation of various operation models and thermal transfer strategies give reliable means to obtain recuperative and regenerative devices which are capable to maintain an auto-thermal behavior in case of low exothermic reactions. In the present research work a gradual analysis of the SCR of NOx with ammonia process in forced unsteady-state reactors was realized. The investigation covers the presentationof the general problematic related to the effect of noxious emissions in the environment, the analysis of the suitable catalysts types for the process, the mathematical analysis approach for modeling and finding the system solutions and the experimental investigation of the device found to be more suitable for the present process. In order to gain information about the forced unsteady state reactor design, operation, important system parameters and their values, mathematical description, mathematicalmethod for solving systems of partial differential equations and other specific aspects, in a fast and easy way, and a case based reasoning (CBR) approach has been used. This approach, using the experience of past similarproblems and their adapted solutions, may provide a method for gaining informations and solutions for new problems related to the forced unsteady state reactors technology. As a consequence a CBR system was implemented and a corresponding tool was developed. Further on, grooving up the hypothesis of isothermal operation, the investigation by means of numerical simulation of the feasibility of the SCR of NOx with ammonia in the RFRand in the RN with variable feeding position was realized. The hypothesis of non-isothermal operation was taken into account because in our opinion ifa commercial catalyst is considered, is not possible to modify the chemical activity and its adsorptive capacity to improve the operation butis possible to change the operation regime. In order to identify the most suitable device for the unsteady state reduction of NOx with ammonia, considering the perspective of recuperative and regenerative devices, a comparative analysis of the above mentioned two devices performance was realized. The assumption of isothermal conditions in the beginningof the forced unsteadystate investigation allowed the simplification of the analysis enabling to focus on the impact of the conditions and mode of operation on the dynamic features caused by the trapping of one reactant in the reactor, without considering the impact of thermal effect on overall reactor performance. The non-isothermal system approach has been investigated in order to point out the important influence of the thermal effect on overall reactor performance, studying the possibility of RFR and RN utilization as recuperative and regenerative devices and the possibility of achieving a sustained auto-thermal behavior in case of lowexothermic reaction of SCR of NOx with ammonia and low temperature gasfeeding. Beside the influence of the thermal effect, the influence of the principal operating parameters, as switching time, inlet flow rate and initial catalyst temperature have been stressed. This analysis is important not only because it allows a comparison between the two devices and optimisation of the operation, but also the switching time is the main operating parameter. An appropriate choice of this parameter enables the fulfilment of the process constraints. The level of the conversions achieved, the more uniform temperature profiles, the uniformity ofcatalyst exploitation and the much simpler mode of operation imposed the RN as a much more suitable device for SCR of NOx with ammonia, in usual operation and also in the perspective of control strategy implementation. Theoretical simplified models have also been proposed in order to describe the forced unsteady state reactors performance and to estimate their internal temperature and concentration profiles. The general idea was to extend the study of catalytic reactor dynamics taking into account the perspectives that haven't been analyzed yet. The experimental investigation ofRN revealed a good agreement between the data obtained by model simulation and the ones obtained experimentally.

The cell cycle–regulated genes of schizosaccharomyces pombe

Many genes are regulated as an innate part of the eukaryotic cell cycle, and a complex transcriptional network helps enable the cyclic behavior of dividing cells. This transcriptional network has been studied in Saccharomyces cerevisiae (budding yeast) and elsewhere. To provide more perspective on these regulatory mechanisms, we have used microarrays to measure gene expression through the cell cycle of Schizosaccharomyces pombe (fission yeast). The 750 genes with the most significant oscillations were identified and analyzed. There were two broad waves of cell cycle transcription, one in early/mid G2 phase, and the other near the G2/M transition. The early/mid G2 wave included many genes involved in ribosome biogenesis, possibly explaining the cell cycle oscillation in protein synthesis in S.pombe. The G2/M wave included at least three distinctly regulated clusters of genes: one large cluster including mitosis, mitotic exit, and cell separation functions, one small cluster dedicated to DNA replication, and another small cluster dedicated to cytokinesis and division. S. pombe cell cycle genes have relatively long, complex promoters containing groups of multiple DNA sequence motifs, often of two, three, or more different kinds. Many of the genes, transcription factors, and regulatory mechanisms are conserved between S. pombe and S. cerevisiae. Finally, we found preliminary evidence for a nearly genome-wide oscillation in gene expression: 2,000 or more genes undergo slight oscillations in expression as a function of the cell cycle, although whether this is adaptive, or incidental to other events in the cell, such as chromatin condensation, we do not know.

Interviewer and Respondent Survey Quality Effects in a CATI Panel

Especially in panel surveys, respondent attrition, respondent learning, and interviewer experience effects play a crucial role with respect to data quality. We examine three interview survey quality indicators in the same survey in a cross sectional as well as in a longitudinal way. In the cross sectional analysis we compare data quality in the mature original sample with that in a refreshment sample, surveyed in the same wave. Because in the same wave an interviewer survey was conducted, collecting attitudes on their socio demography, survey attitudes and burden measures, we are able to consider interviewer fixed effects as well. The longitudinal analysis gives more insight in the respondent learning effects with respect to the quality indicators considered by considering the very same respondents across waves. The Swiss Household Panel, a CATI survey representative of the Swiss residential population, forms an ideal modelling database: the interviewer - respondent assignment is random, both within and across waves. This design avoids possible confusion with other effects stemming from a non-random assignment of interviewers, e.g. area effects or effects from assigning the best interviewers to the hard cases. In order to separate interviewer, respondent and wave effects, we build cross-classified multilevel models.

Development and application of computational methodologies in qualitative modeling

La présente thèse s'intitule "Développent et Application des Méthodologies Computationnelles pour la Modélisation Qualitative". Elle comprend tous les différents projets que j'ai entrepris en tant que doctorante. Plutôt qu'une mise en oeuvre systématique d'un cadre défini a priori, cette thèse devrait être considérée comme une exploration des méthodes qui peuvent nous aider à déduire le plan de processus regulatoires et de signalisation. Cette exploration a été mue par des questions biologiques concrètes, plutôt que par des investigations théoriques. Bien que tous les projets aient inclus des systèmes divergents (réseaux régulateurs de gènes du cycle cellulaire, réseaux de signalisation de cellules pulmonaires) ainsi que des organismes (levure à fission, levure bourgeonnante, rat, humain), nos objectifs étaient complémentaires et cohérents. Le projet principal de la thèse est la modélisation du réseau de l'initiation de septation (SIN) du S.pombe. La cytokinèse dans la levure à fission est contrôlée par le SIN, un réseau signalant de protéines kinases qui utilise le corps à pôle-fuseau comme échafaudage. Afin de décrire le comportement qualitatif du système et prédire des comportements mutants inconnus, nous avons décidé d'adopter l'approche de la modélisation booléenne. Dans cette thèse, nous présentons la construction d'un modèle booléen étendu du SIN, comprenant la plupart des composantes et des régulateurs du SIN en tant que noeuds individuels et testable expérimentalement. Ce modèle utilise des niveaux d'activité du CDK comme noeuds de contrôle pour la simulation d'évènements du SIN à différents stades du cycle cellulaire. Ce modèle a été optimisé en utilisant des expériences d'un seul "knock-out" avec des effets phénotypiques connus comme set d'entraînement. Il a permis de prédire correctement un set d'évaluation de "knock-out" doubles. De plus, le modèle a fait des prédictions in silico qui ont été validées in vivo, permettant d'obtenir de nouvelles idées de la régulation et l'organisation hiérarchique du SIN. Un autre projet concernant le cycle cellulaire qui fait partie de cette thèse a été la construction d'un modèle qualitatif et minimal de la réciprocité des cyclines dans la S.cerevisiae. Les protéines Clb dans la levure bourgeonnante présentent une activation et une dégradation caractéristique et séquentielle durant le cycle cellulaire, qu'on appelle communément les vagues des Clbs. Cet évènement est coordonné avec la courbe d'activation inverse du Sic1, qui a un rôle inhibitoire dans le système. Pour l'identification des modèles qualitatifs minimaux qui peuvent expliquer ce phénomène, nous avons sélectionné des expériences bien définies et construit tous les modèles minimaux possibles qui, une fois simulés, reproduisent les résultats attendus. Les modèles ont été filtrés en utilisant des simulations ODE qualitatives et standardisées; seules celles qui reproduisaient le phénotype des vagues ont été gardées. L'ensemble des modèles minimaux peut être utilisé pour suggérer des relations regulatoires entre les molécules participant qui peuvent ensuite être testées expérimentalement. Enfin, durant mon doctorat, j'ai participé au SBV Improver Challenge. Le but était de déduire des réseaux spécifiques à des espèces (humain et rat) en utilisant des données de phosphoprotéines, d'expressions des gènes et des cytokines, ainsi qu'un réseau de référence, qui était mis à disposition comme donnée préalable. Notre solution pour ce concours a pris la troisième place. L'approche utilisée est expliquée en détail dans le dernier chapitre de la thèse. -- 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.