地震波场模拟及叠前深度偏移的李群方法

The processes of seismic wave propagation in phase space and one way wave extrapolation in frequency-space domain, if without dissipation, are essentially transformation under the action of one parameter Lie groups. Consequently, the numerical calculation methods of the propagation ought to be Lie group transformation too, which is known as Lie group method. After a fruitful study on the fast methods in matrix inversion, some of the Lie group methods in seismic numerical modeling and depth migration are presented here. Firstly the Lie group description and method of seismic wave propagation in phase space is proposed, which is, in other words, symplectic group description and method for seismic wave propagation, since symplectic group is a Lie subgroup and symplectic method is a special Lie group method. Under the frame of Hamiltonian, the propagation of seismic wave is a symplectic group transformation with one parameter and consequently, the numerical calculation methods of the propagation ought to be symplectic method. After discrete the wave field in time and phase space, many explicit, implicit and leap-frog symplectic schemes are deduced for numerical modeling. Compared to symplectic schemes, Finite difference (FD) method is an approximate of symplectic method. Consequently, explicit, implicit and leap-frog symplectic schemes and FD method are applied in the same conditions to get a wave field in constant velocity model, a synthetic model and Marmousi model. The result illustrates the potential power of the symplectic methods. As an application, symplectic method is employed to give synthetic seismic record of Qinghai foothills model. Another application is the development of Ray+symplectic reverse-time migration method. To make a reasonable balance between the computational efficiency and accuracy, we combine the multi-valued wave field & Green function algorithm with symplectic reverse time migration and thus develop a new ray+wave equation prestack depth migration method. Marmousi model data and Qinghai foothills model data are processed here. The result shows that our method is a better alternative to ray migration for complex structure imaging. Similarly, the extrapolation of one way wave in frequency-space domain is a Lie group transformation with one parameter Z and consequently, the numerical calculation methods of the extrapolation ought to be Lie group methods. After discrete the wave field in depth and space, the Lie group transformation has the form of matrix exponential and each approximation of it gives a Lie group algorithm. Though Pade symmetrical series approximation of matrix exponential gives a extrapolation method which is traditionally regarded as implicit FD migration, it benefits the theoretic and applying study of seismic imaging for it represent the depth extrapolation and migration method in a entirely different way. While, the technique of coordinates of second kind for the approximation of the matrix exponential begins a new way to develop migration operator. The inversion of matrix plays a vital role in the numerical migration method given by Pade symmetrical series approximation. The matrix has a Toepelitz structure with a helical boundary condition and is easy to inverse with LU decomposition. A efficient LU decomposition method is spectral factorization. That is, after the minimum phase correlative function of each array of matrix had be given by a spectral factorization method, all of the functions are arranged in a position according to its former location to get a lower triangular matrix. The major merit of LU decomposition with spectral factorization (SF Decomposition) is its efficiency in dealing with a large number of matrixes. After the setup of a table of the spectral factorization results of each array of matrix, the SF decomposition can give the lower triangular matrix by reading the table. However, the relationship among arrays is ignored in this method, which brings errors in decomposition method. Especially for numerical calculation in complex model, the errors is fatal. Direct elimination method can give the exact LU decomposition But even it is simplified in our case, the large number of decomposition cost unendurable computer time. A hybrid method is proposed here, which combines spectral factorization with direct elimination. Its decomposition errors is 10 times little than that of spectral factorization, and its decomposition speed is quite faster than that of direct elimination, especially in dealing with a large number of matrix. With the hybrid method, the 3D implicit migration can be expected to apply on real seismic data. Finally, the impulse response of 3D implicit migration operator is presented.

鄂尔多斯盆地西缘中生代构造与地层分析及盆地演化研究

Through the detailed analyses of Mesozoic tectono-stratigraphy and basin formation dynamic mechanism and the styles of different units in the western margin of Ordos Basin(Abbreviated to "the western margin"), while some issues of the pre-Mesozoic in the western margin and central part of Ordos Basin also be discussed, the main views and conclusion as follows: 1. There are three types of depositional systems which are related with syndepositional tectonic actions and different tectonic prototype basins, including: alluvial fan systems, river system (braided river system and sinuosity river system), lacustrine-river delta system and fan delta system. They have complex constitutions of genetic facies. For the tectonic sequence VI, the fan sediments finning upper in the north-western margin and coarse upper in the south-western margin respectively. 2. In order to light the relationship between basin basement subsidence rate and sediment supply and the superposed styles, five categories of depositional systems tracts in different prototype basins were defined: aggrading and transgressive systems tracts during early subsidence stage, regressive and aggrading systems tracts during rapid subsidence, upper transgessive systems tracts during later subsidence stage. Different filling characteristics and related tectonic actions in different stages in Mesozoic period were discussed. 3. In order to determined the tectonic events of the provenance zones and provenance strata corresponding to basins sediments, according the clastics dispersal style and chemical analyses results of sediments in different areas, the provenance characteristics have been described. The collision stage between the "Mongolia block" and the north-China block may be the late permian; The sediments of Mesozoic strata in the north-western margin is mainly from the Alex blocks and north-Qilian Paleozoic orogeny, while the south-western margin from Qinling orogeny. The volcanic debris in the Yan'an Formation may be from the arc of the north margin of north-China block, although more study needed for the origin of the debris. The provenance of the Cretaceous may be from the early orogeny and the metamorphic basement of Longshan group. 4. The subsidence curve and subsidence rate and sedimentary rate in different units have been analyzed. For different prototype basin, the form of the subsidence curves are different. The subsidence of the basins are related with the orogeny of the basins.The beginning age of the foreland basin may be the middle Triassic. The change of basement subsidence show the migration of the foredeep and forebulge into the basin. The present appearance of the Ordos basin may be formed at the late stage of Cretaceous, not formed at the late Jurassic. 5. The structure mode of the west margin is very complex. Structure transfer in different fold-thrust units has been divided into three types: transfer faults, transition structures and intersected form. The theoretic explanations also have been given for the origin and the forming mechanism. The unique structure form of Hengshanpu is vergent west different from the east vergence of most thrust faults, the mechanism of which has been explained. 6. In Triassic period, the He1anshan basin is extensional basin while the Hengshanbu is "forland", and the possible mechanism of the seemingly incompatible structures has been explained. First time, the thesis integrate the Jurassic—early Cretaceous basins of west margin with the Hexi corridor basins and explain the unitive forming mechanism. The model thinks the lateral extrusion is the main mechanism of the Hexi corridor and west margin basins, meanwhile, the deep elements and basement characters of the basins. Also, for the first time, we determine the age of the basalt in Helanshan area as the Cretaceous period, the age matching with the forming of the Cretaceous basins and as the main factor of the coal metamorphism in the Helanshan area. 7. The Neoprotterozoic aulacogen is not the continuation of the Mesozoic aulacogen, while it is another new rift stage. In the Paleozoic, the Liupanshan—southern Helanshan area is part of the back-arc basins of north Qilian ocean. 8. The Helanshan "alacogen" is connected with the north margin of north China block, not end at the north of Zhouzishan area like "appendices". Also, I think the upper Devonian basin as the beginning stage of the extensional early Carboniferous basins, not as a part of the foreland basins of Silurian period, not the collision rift. 9. The controlling factor of the difference of the deformation styles of the north-west margin and the south-west margin is the difference of the basements and adjacent tectonic units of the two parts.

Lg尾波衰减成像研究——北京及邻区衰减成像

With the development of the technology of earthquake observation, more and more researchers work at many fields' of seismicity using seismic kinetic property, as the result, the study of attenuation has also made great progress, especially in the mechanism of the attenuation and the physical process. Aki put forward single back scattering theory to explain the forming of the seismic coda wave in 1969. Then, researchers started to develop the study in seismic scattering and attenuation. My thesis is also based on that theory. We assume that the Lg wave is a superposition fo high-mode surface waves, the coda of Lg is caused by scattering. Sato proposed Single Isotropic Scattering model (SIS model) to interpreted the scatter property, and he also formulated the geometrical spreading term. Then Xie (1988) developed the single spectral-ratio (SSR) method to obtain the Lg coda Q and the frequency dependent factor n. Later, he get to lateral images in the area of scatter ellipse. SSR method is explored and used in the study of Lg coda waves of regional earthquakes in my thesis. Choosing the earthquakes records with high ratio of signal-noise ,which were recorded at the stations from 1989 to 1999, we obtain the single trace Lg coda Q and its frequency dependent factor n. The results proved that SIS model is the reasonable model to explain the Lg coda wave, and SSR method also can be used to process Lg coda of regional earthquakes to get to the satisfied Lg coda Q. Based on the Lg coda Q we obtained using the former method, we explore the programs to inverse the regional Lg coda Q independently, and then make use of them to inverse the Lg coda Q of Beijing and adjacent area. The inversion result is satisfied. We conclude that the distribution of Qo (Q in lHz) is marked by the inhomogeneity, which is related to the tectonic structure: The value of Qo in uplift area, for example, Yanshan uplift, Taihang uplift, Luxi Uplift, is higher than the depression area, for example, Jizhong depression, Huanghua depression, and Jiyang depression, and the border between the higher Q area and lower Q area is very clear; Lg coda Q is also related to the velocity structure, higher velocity area is also with higher Q, lower velocity area is with lower Q; and higher heat-flow area is companied with lower Q. All in all, the value of Q reflects the difference of characteristics of lithofaces, porosity, the liquid content between the pores and heat flow. So, the Q value difference between uplift area and depression area reveals the difference of tectonic structure, lithology and physical character of the rock. So, the study of Lg coda Q is help to understand the earthquakes propagation mechanism through the inhomogenous medium, the cause of the coda, attenuation mechanism of the coda. Making use of the lateral images of Q, with velocity images, heat flow results, and other experimental result, we will be promoted to understand the complex structure of the crust, its inhomogenous character, and so on.

地震反射系数成像方法研究

Reflectivity sequences extraction is a key part of impedance inversion in seismic exploration. Although many valid inversion methods exist, with crosswell seismic data, the frequency brand of seismic data can not be broadened to satisfy the practical need. It is an urgent problem to be solved. Pre-stack depth migration which developed in these years becomes more and more robust in the exploration. It is a powerful technology of imaging to the geological object with complex structure and its final result is reflectivity imaging. Based on the reflectivity imaging of crosswell seismic data and wave equation, this paper completed such works as follows: Completes the workflow of blind deconvolution, Cauchy criteria is used to regulate the inversion(sparse inversion). Also the precondition conjugate gradient(PCG) based on Krylov subspace is combined with to decrease the computation, improves the speed, and the transition matrix is not necessary anymore be positive and symmetric. This method is used to the high frequency recovery of crosswell seismic section and the result is satisfactory. Application of rotation transform and viterbi algorithm in the preprocess of equation prestack depth migration. In equation prestack depth migration, the grid of seismic dataset is required to be regular. Due to the influence of complex terrain and fold, the acquisition geometry sometimes becomes irregular. At the same time, to avoid the aliasing produced by the sparse sample along the on-line, interpolation should be done between tracks. In this paper, I use the rotation transform to make on-line run parallel with the coordinate, and also use the viterbi algorithm to complete the automatic picking of events, the result is satisfactory. 1. Imaging is a key part of pre-stack depth migration besides extrapolation. Imaging condition can influence the final result of reflectivity sequences imaging greatly however accurate the extrapolation operator is. The author does migration of Marmousi under different imaging conditions. And analyzes these methods according to the results. The results of computation show that imaging condition which stabilize source wave field and the least-squares estimation imaging condition in this paper are better than the conventional correlation imaging condition. The traditional pattern of "distributed computing and mass decision" is wisely adopted in the field of seismic data processing and becoming an obstacle of the promoting of the enterprise management level. Thus at the end of this paper, a systemic solution scheme, which employs the mode of "distributed computing - centralized storage - instant release", is brought forward, based on the combination of C/S and B/S release models. The architecture of the solution, the corresponding web technology and the client software are introduced. The application shows that the validity of this scheme.

人工源频率域大地电磁法正反演研究

The CSAMT method is playing an important role in the exploration of geothermal and the pre-exploration in tunnel construction project recently. In order to instruct the interpretation technique for the field data, the forward method from ID to 3D and inversion method in ID and 2D are developed in this paper for the artificial source magnetotelluric in frequency domain. In general, the artificial source data are inverted only after the near field is corrected on the basis of the assumption of half-homogeneous space; however, this method is not suitable for the complex structure because the assumption is not valid any more. Recently the new idea about inversion scheme without near field correction is published in order to avoid the near field correction error. We try to discuss different inversion scheme in ID and 2D using the data without near field correction.The numerical integration method is used to do the forward modeling in ID CSAMT method o The infinite line source is used in the 2D finite-element forward modeling, where the near-field effect is occurred as in the CSAMT method because of using artificial source. The pseudo-delta function is used to modeling the source distribution, which reduces the singularity when solving the finite-element equations. The effect on the exploration area is discussed when anomalous body exists under the source or between the source and exploration area; A series of digital test show the 2D finite element method are correct, the results of modeling has important significant for CSAMT data interpretation. For 3D finite-element forward modeling, the finite-element equation is derived by Galerkin method and the divergence condition is add forcedly to the forward equation, the forward modeling result of the half homogeneous space model is correct.The new inversion idea without near field correction is followed to develop new inversion methods in ID and 2D in the paper. All of the inversion schemes use the data without near field correction, which avoid introducing errors caused by near field correction. The modified grid parameter method and the layer-by-layer inversion method are joined in the ID inversion scheme. The RRI method with artificial source are developed and finite-element inversion method are used in 2D inversion scheme. The inversion results using digital data and the field data are accordant to the model and the known geology data separately, which means the inversion without near field correction is accessible. The feasibility to invert the data only in exploration area is discussed when the anomalous body exists between the source and the exploration area.

Enterococcus sp. considerações clínicas e microbiológicas em endodontia

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Use of a coupled mechanical-acoustic computational model to identify failure mechanisms in paper production

In this paper, a couple mechanical-acoustic system of equations is solved to determine the relationship between emitted sound and damage mechanisims in paper under controlled stress conditions. The simple classical expression describing the frequency of a plucked string to its material properties is used to generate a numberical representation of the microscopic structue of the paper, and the resulting numerical model is then used to simulate the vibration of a range of simple fibre structures when undergoing two distinct types of damange mechanisms: (a)fibre/fibre bond failure, (b) fibre failure. The numercial results are analysed to determine whether there is any detectable systematic difference between the resulting acoustic emissions of the two damage processes. Fourier techniques are then used to compare th computeed results against experimental measurements. Distinct frequency components identifying each type of damage are shown to exist, and in this respect theory and experiments show good correspondece. Hence, it is shown, that althrough the mathematical model represents a grossly-simplified view of the complex structure of the paper, it nevertheless provides a good understanding of the underlying micro-mechanisms characterising its proeperties as a stress-resisting structure. Use of the model and acoompanying software will enable operators to identify approaching failure conditions in the continuous production of paper from emitted sound signals and take preventative action.

Numerical optimisation techniques applied to evacuation analysis

A common problem faced by fire safety engineers in the field of evacuation analysis concerns the optimal design of an arbitrarily complex structure in order to minimise evacuation times. How does the engineer determine the best solution? In this study we introduce the concept of numerical optimisation techniques to address this problem. The study makes user of the buildingEXODUS evacuation model coupled with classical optimisation theory including Design of Experiments (DoE) and Response Surface Models (RSM). We demonstrate the technique using a relatively simple problem of determining the optimal location for a single exit in a square room.

Arp2p, a potential substrate for NatB acetyltransferase in fission yeast, is important in actin patch nucleation and motility in arp2-1 and arm1 ts mutants

The actin cytoskeleton is a dynamic and complex structure in fission yeast that plays a major function in many cell processes including cellular growth, septa formation, endocytosis and cellular division. Computational studies have shown that Arp2p, which forms part of the Arp2/3 complex, is a potential substrate of NatB acetyltransferase which has specificity for proteins possessing an N-terminal Met-Asp or Met-Glu sequence motif. In arm1- mutants the loss of function of Arm1p, an auxillary subunit required for NatB activity, results in a temperature sensitive phenotype characterized by multiple septa, failure of endocytosis, and the inability to form actin cables. A temperature sensitive mutant of Schizosaccharomyces pombe arp2 gene exhibits a similar phenotype as seen by the formation of improper septa, slow growth, and the delocalization of actin patches. Four expression vectors encoding the open reading frames of arp2 and cdc8 (tropomyosin) were constructed with a modification changing the second residue to a Histidine, believed to mimic the charge distribution of natural acetylation by NatB. Constructs tested in normal yeast strains remained viable and grew normally in the presence of Met-His Arp2p and tropomyosin. Analysis of their ability to suppress the mutant phenotypes of arp2-1 and arm1- mutants is an area of research to be explored in future studies.

Status of GPCR modeling and docking as reflected by community-wide GPCR Dock 2010 assessment

The community-wide GPCR Dock assessment is conducted to evaluate the status of molecular modeling and ligand docking for human G protein-coupled receptors. The present round of the assessment was based on the recent structures of dopamine D3 and CXCR4 chemokine receptors bound to small molecule antagonists and CXCR4 with a synthetic cyclopeptide. Thirty-five groups submitted their receptor-ligand complex structure predictions prior to the release of the crystallographic coordinates. With closely related homology modeling templates, as for dopamine D3 receptor, and with incorporation of biochemical and QSAR data, modern computational techniques predicted complex details with accuracy approaching experimental. In contrast, CXCR4 complexes that had less-characterized interactions and only distant homology to the known GPCR structures still remained very challenging. The assessment results provide guidance for modeling and crystallographic communities in method development and target selection for further expansion of the structural coverage of the GPCR universe.

DRIFT and DRUV spectroscopy methods for studying the interaction of metal compounds with native cellulose

Dissertação de mestrado, Qualidade em Análises, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

L'éclatement en géométrie algébrique, différentielle et symplectique

L'éclatement est une transformation jouant un rôle important en géométrie, car il permet de résoudre des singularités, de relier des variétés birationnellement équivalentes, et de construire des variétés possédant des propriétés inédites. Ce mémoire présente d'abord l'éclatement tel que développé en géométrie algébrique classique. Nous l'étudierons pour le cas des variétés affines et (quasi-)projectives, en un point, et le long d'un idéal et d'une sous-variété. Nous poursuivrons en étudiant l'extension de cette construction à la catégorie différentiable, sur les corps réels et complexes, en un point et le long d'une sous-variété. Nous conclurons cette section en explorant un exemple de résolution de singularité. Ensuite nous passerons à la catégorie symplectique, où nous ferons la même chose que pour le cas différentiable complexe, en portant une attention particulière à la forme symplectique définie sur la variété. Nous terminerons en étudiant un théorème dû à François Lalonde, où l'éclatement joue un rôle clé dans la démonstration. Ce théorème affirme que toute 4-variété fibrée par des 2-sphères sur une surface de Riemann, et différente du produit cartésien de deux 2-sphères, peut être équipée d'une 2-forme qui lui confère une structure symplectique réglée par des courbes holomorphes par rapport à sa structure presque complexe, et telle que l'aire symplectique de la base est inférieure à la capacité de la variété. La preuve repose sur l'utilisation de l'éclatement symplectique. En effet, en éclatant symplectiquement une boule contenue dans la 4-variété, il est possible d'obtenir une fibration contenant deux sphères d'auto-intersection -1 distinctes: la pré-image du point où est fait l'éclatement complexe usuel, et la transformation propre de la fibre. Ces dernières sont dites exceptionnelles, et donc il est possible de procéder à l'inverse de l'éclatement - la contraction - sur chacune d'elles. En l'accomplissant sur la deuxième, nous obtenons une variété minimale, et en combinant les informations sur les aires symplectiques de ses classes d'homologies et de celles de la variété originale nous obtenons le résultat.

Introduction à quelques aspects de quantification géométrique.

On révise les prérequis de géométrie différentielle nécessaires à une première approche de la théorie de la quantification géométrique, c'est-à-dire des notions de base en géométrie symplectique, des notions de groupes et d'algèbres de Lie, d'action d'un groupe de Lie, de G-fibré principal, de connexion, de fibré associé et de structure presque-complexe. Ceci mène à une étude plus approfondie des fibrés en droites hermitiens, dont une condition d'existence de fibré préquantique sur une variété symplectique. Avec ces outils en main, nous commençons ensuite l'étude de la quantification géométrique, étape par étape. Nous introduisons la théorie de la préquantification, i.e. la construction des opérateurs associés à des observables classiques et la construction d'un espace de Hilbert. Des problèmes majeurs font surface lors de l'application concrète de la préquantification : les opérateurs ne sont pas ceux attendus par la première quantification et l'espace de Hilbert formé est trop gros. Une première correction, la polarisation, élimine quelques problèmes, mais limite grandement l'ensemble des observables classiques que l'on peut quantifier. Ce mémoire n'est pas un survol complet de la quantification géométrique, et cela n'est pas son but. Il ne couvre ni la correction métaplectique, ni le noyau BKS. Il est un à-côté de lecture pour ceux qui s'introduisent à la quantification géométrique. D'une part, il introduit des concepts de géométrie différentielle pris pour acquis dans (Woodhouse [21]) et (Sniatycki [18]), i.e. G-fibrés principaux et fibrés associés. Enfin, il rajoute des détails à quelques preuves rapides données dans ces deux dernières références.

By indirections find directions out : thinkable worlds in Abbott and Vonnegut

This thesis is concerned with the interaction between literature and abstract thought. More specifically, it studies the epistemological charge of the literary, the type of knowledge that is carried by elements proper to fictional narratives into different disciplines. By concentrating on two different theoretical methods, the creation of thought experiments and the framing of possible worlds, methods which were elaborated and are still used today in spheres as varied as modal logics, analytic philosophy and physics, and by following their reinsertion within literary theory, the research develops the theory that both thought experiments and possible worlds are in fact short narrative stories that inform knowledge through literary means. By using two novels, Abbott’s Flatland and Vonnegut’s The Sirens of Titan, that describe extra-dimensional existence in radically different ways, respectively as a phenomenologically unknowable space and as an outward perspective on time, it becomes clear that literature is constitutive of the way in which worlds, fictive, real or otherwise, are constructed and understood. Thus dimensions, established through extensional analogies as either experimental knowledge or modal possibility for a given world, generate new directions for thought, which can then take part in the inductive/deductive process of scientia. By contrasting the dimensions of narrative with the way that dimensions were historically constituted, the research also establishes that the literary opens up an infinite potential of abstract space-time domains, defined by their specific rules and limits, and that these different experimental folds are themselves partaking in a dimensional process responsible for new forms of understanding. Over against science fiction literary theories of speculation that posit an equation between the fictive and the real, this thesis examines the complex structure of many overlapping possibilities that can organise themselves around larger compossible wholes, thus offering a theory of reading that is both non-mimetic and non-causal. It consequently examines the a dynamic process whereby literature is always reconceived through possibilities actualised by reading while never defining how the reader will ultimately understand the overarching structure. In this context, the thesis argues that a causal story can be construed out of any one interaction with a given narrative—underscoring, for example, the divinatory strength of a particular vision of the future—even as this narrative represents only a fraction of the potential knowledge of any particular literary text. Ultimately, the study concludes by tracing out how novel comprehensions of the literary, framed by the material conditions of their own space and time, endlessly renew themselves through multiple interactions, generating analogies and speculations that facilitate the creation of new knowledge.

Homéostasie des histones en réponse au dommage à l’ADN et étude d’inhibiteurs de désacétylases d’importance clinique

La chromatine possède une plasticité complexe et essentielle pour répondre à différents mécanismes cellulaires fondamentaux tels la réplication, la transcription et la réparation de l’ADN. Les histones sont les constituants essentiels de la formation des nucléosomes qui assurent le bon fonctionnement cellulaire d’où l’intérêt de cette thèse d’y porter une attention particulière. Un dysfonctionnement de la chromatine est souvent associé à l’émergence du cancer. Le chapitre II de cette thèse focalise sur la répression transcriptionnelle des gènes d’histones par le complexe HIR (HIstone gene Repressor) en réponse au dommage à l'ADN chez Saccharomyces cerevisiae. Lors de dommage à l’ADN en début de phase S, les kinases du point de contrôle Mec1, Tel1 et Rad53 s’assurent de bloquer les origines tardives de réplication pour limiter le nombre de collisions potentiellement mutagéniques ou cytotoxiques entre les ADN polymérases et les lésions persistantes dans l'ADN. Lorsque la synthèse totale d’ADN est soudainement ralentie par le point de contrôle, l’accumulation d'un excès d'histones nouvellement synthétisées est néfaste pour les cellules car les histones libres se lient de manière non-spécifique aux acides nucléiques. L'un des mécanismes mis en place afin de minimiser la quantité d’histones libres consiste à réprimer la transcription des gènes d'histones lors d'une chute rapide de la synthèse d'ADN, mais les bases moléculaires de ce mécanisme étaient très mal connues. Notre étude sur la répression des gènes d’histones en réponse aux agents génotoxiques nous a permis d’identifier que les kinases du point de contrôle jouent un rôle dans la répression des gènes d’histones. Avant le début de mon projet, il était déjà connu que le complexe HIR est requis pour la répression des gènes d’histones en phase G1, G2/M et lors de dommage à l’ADN en phase S. Par contre, la régulation du complexe HIR en réponse au dommage à l'ADN n'était pas connue. Nous avons démontré par des essais de spectrométrie de masse (SM) que Rad53 régule le complexe HIR en phosphorylant directement une de ses sous-unités, Hpc2, à de multiples résidus in vivo et in vitro. La phosphorylation d’Hpc2 est essentielle pour le recrutement aux promoteurs de gènes d’histones du complexe RSC (Remodels the Structure of Chromatin) dont la présence sur les promoteurs des gènes d'histones corrèle avec leur répression. De plus, nous avons mis à jour un nouveau mécanisme de régulation du complexe HIR durant la progression normale à travers le cycle cellulaire ainsi qu'en réponse aux agents génotoxiques. En effet, durant le cycle cellulaire normal, la protéine Hpc2 est très instable durant la transition G1/S afin de permettre la transcription des gènes d’histones et la production d'un pool d'histones néo-synthétisées juste avant l'initiation de la réplication de l’ADN. Toutefois, Hpc2 n'est instable que pour une brève période de temps durant la phase S. Ces résultats suggèrent qu'Hpc2 est une protéine clef pour la régulation de l'activité du complexe HIR et la répression des gènes d’histones lors du cycle cellulaire normal ainsi qu'en réponse au dommage à l’ADN. Dans le but de poursuivre notre étude sur la régulation des histones, le chapitre III de ma thèse concerne l’analyse globale de l’acétylation des histones induite par les inhibiteurs d’histone désacétylases (HDACi) dans les cellules normales et cancéreuses. Les histones désacétylases (HDACs) sont les enzymes qui enlèvent l’acétylation sur les lysines des histones. Dans plusieurs types de cancers, les HDACs contribuent à l’oncogenèse par leur fusion aberrante avec des complexes protéiques oncogéniques. Les perturbations causées mènent souvent à un état silencieux anormal des suppresseurs de tumeurs. Les HDACs sont donc une cible de choix dans le traitement des cancers engendrés par ces protéines de fusion. Notre étude de l’effet sur l’acétylation des histones de deux inhibiteurs d'HDACs de relevance clinique, le vorinostat (SAHA) et l’entinostat (MS-275), a permis de démontrer une augmentation élevée de l’acétylation globale des histones H3 et H4, contrairement à H2A et H2B, et ce, autant chez les cellules normales que cancéreuses. Notre quantification en SM de l'acétylation des histones a révélé de façon inattendue que la stœchiométrie d'acétylation sur la lysine 56 de l’histone H3 (H3K56Ac) est de seulement 0,03% et, de manière surprenante, cette stœchiométrie n'augmente pas dans des cellules traitées avec différents HDACi. Plusieurs études de H3K56Ac chez l’humain présentes dans la littérature ont rapporté des résultats irréconciliables. Qui plus est, H3K56Ac était considéré comme un biomarqueur potentiel dans le diagnostic et pronostic de plusieurs types de cancers. C’est pourquoi nous avons porté notre attention sur la spécificité des anticorps utilisés et avons déterminé qu’une grande majorité d’anticorps utilisés dans la littérature reconnaissent d’autres sites d'acétylation de l’histone H3, notamment H3K9Ac dont la stœchiométrie d'acétylation in vivo est beaucoup plus élevée que celle d'H3K56Ac. De plus, le chapitre IV fait suite à notre étude sur l’acétylation des histones et consiste en un rapport spécial de recherche décrivant la fonction de H3K56Ac chez la levure et l’homme et comporte également une évaluation d’un anticorps supposément spécifique d'H3K56Ac en tant qu'outil diagnostic du cancer chez l’humain.