Un des enjeux majeurs de la biologie moderne est de comprendre les mécanismes complexes régissant l’expression de gènes d’un organisme en développement. Alors que les activateurs (enhancers) ont été abondamment étudiés et analysés, seul un relatif petit nombre de répresseurs (silencers) a été identifié à ce jour et restent jusqu’à présent assez mal compris. Un nombre non négligeable de CRMs jouent par ailleurs un double rôle à la fois d’amplificateurs et d’inactivateurs de transcription en fonction de l’état ou du type cellulaire dans lequel ils se trouvent, rajoutant un niveau supplémentaire de à la régulation génique dans différents types cellulaires et tissus. De façon surprenante, nous avons découvert que tous les éléments ayant une activité de répression transcriptionnelle que nous avons identifiés, s’avèrent aussi avoir une activité d’activation transcriptionnelle dans d’autres contextes cellulaires. Nos résultats remettent donc en question le paradigme de deux catégories distinctes de CRMs et suggèrent que des milliers, ou plus, d’éléments bifonctionnels restent à être découverts chez la Drosophile et potentiellement 104-105 chez l’humain. Le référencement et la caractérisation de ces éléments devraient s’avérer utiles, si ce n’est cruciaux, afin de comprendre la façon par laquelle ces motifs d’expression sont encodés au sein des génomes d'organismes métazoaires et donc éventuellement chez l’Homme. / A major challenge in biology is to understand how complex gene expression patterns in organismal development are encoded in the genome. While transcriptional enhancers have been studied extensively, few transcriptional silencers have been identified and they remain poorly understood. Here we used a novel strategy to screen hundreds of sequences for tissue-specific silencer activity in whole Drosophila embryos. Strikingly, 100% of the tested elements that we found to act as transcriptional silencers were also active enhancers in other cellular contexts. These elements were enriched in highly occupied target (HOT) region overlap (Roy et al., 2010) and specific transcription factor (TF) motif combinations. CRM bifunctionality complicates the understanding of how gene regulation is specified in the genome and how it is read out differently in different cell types. Our results challenge the common practice of treating elements with enhancer activity identified in one cell type as serving exclusively activating roles in the organism and suggest that thousands or more bifunctional CRMs remain to be discovered in Drosophila and perhaps 104-105 in human (Heintzman et al., 2009). Characterization of bifunctional elements should aid in investigations of how precise gene expression patterns are encoded in the genome.

This diploma thesis deals with the basic theoretical overview of air-conditioning noise, the description of individual devices used in ventilation and active ventilation during storage of cereals. It also describes the possibilities of application of silencers for these devices. In the practical part, it focuses on the noise measurement in the post-harvest line and the design of appropriate noise measures to meet the under-noise levels.

Large silencers used in the power generation industry usually have a very large cross section at the inlet and outlet. Higher-order modes will populate the inlet and outlet even at very low frequencies. Although the silencer itself is often modeled by a three-dimensional analysis tool such as the boundary element method (BEM) or finite element method (FEM), a direct computation of the transmission loss (TL) from the BEM or FEM model can be challenging without incorporating certain forms of modal expansion. A so-called “impedance-to-scattering matrix method” is proposed to extract the modes at the inlet and outlet from the BEM impedance matrix based on the point collocation method. The BEM impedance matrix relates the sound pressures at the inlet and outlet to the corresponding particle velocities, while the scattering matrix relates the modes at the inlet and outlet. Normally there are more boundary elements than the total number of modes at the inlet and outlet, and a least-squares procedure is used to condense the element-based impedance matrix to the mode-based scattering matrix. The TL computation will follow if a certain form of the incident wave is assumed and the outlet is non-reflective. Several commonly used inlet/outlet configurations are considered in this dissertation, which include axisymmetric, non-axisymmetric circular, and rectangular inlet/outlet shapes. In addition to the single inlet and outlet silencers, large multi-inlet and multi-outlet silencers are also investigated. Besides the collocation-based impedance-to-scattering matrix method, an integral-based impedance-to-scattering matrix method based on the reciprocal identity is also proposed for large silencer analysis. Although it may be more time-consuming to perform the additional numerical integration, an integral-based method is free of any uncertainties associated with collocation points. The computational efficiency, accuracy and stability are compared between two proposed methods. One bonus effect of producing the scattering matrix is that it can also be used to combine subsystems in series connection. The Redheffer’s star product is introduced to combine scattering matrices of subsystems. In the design stage, rapid assessment of the silencer performance is always preferred. However, the existing analytical approaches are only suitable for simple dissipative silencers such as straight lined ducts. A two-dimensional first-mode semi-analytical solution is developed to quickly evaluate the performance of tuned dissipative silencers below the cut-off frequency. The semi-analytical solution can also serve as a validation tool for the BEM.

<p>Heterochromatin, or condensed chromatin, is a transcriptionally repressive form of chromatin that occurs in many eukaryotic organisms. At its natural locations, heterochromatin is thought to play important roles in genome organization as well as gene expression. Just as important is the restriction of this repressive form of chromatin to appropriate regions of the genome. In the budding yeast <italic>Saccaromyces cerevisiae</italic>, domains of condensed, transcriptionally silenced chromatin are found at telomeres and at the silent-mating type cassettes, <italic>HML<italic/> and <italic>HMR</italic>. At these locations, a complex of Silent Information Regulator (SIR) proteins gets recruited to DNA through discrete silencer elements. Once recruited, the Sir protein complex then spreads along chromosomes in a step-wise manner. This process results in the silencing of gene expression. It is unclear whether silenced chromatin is established in the same manner at different genomic locations. Understanding how silenced chromatin is formed is important for determining how these chromatin structures are regulated.</p><p>To better understand how silenced chromatin is established in different genomic contexts, I used chromatin immuoprecipitation to follow the rate of silenced chromatin formation at different locations. The rates of Sir protein assembly were compared at two locations, telomere VI-R and <italic>HMR</italic>. I discovered that the silencers at these two locations were equally proficient at recruiting Sir proteins. However, the rate of Sir protein assembly onto nucleosomes was far more rapid at <italic>HMR</italic> than at the telomere VI-R. Furthermore, the rate of Sir protein assembly was more rapid on one side of the <italic>HMR-E</italic> silencer at <italic>HMR</italic> than the other. Moreover, insertion of the <italic>HMR-E</italic> silencer adjacent to the telomere VI-R significantly improved the rate of Sir protein assembly onto nucleosomes. Additionally, observations that the association of Sir protein occurs simultaneously across several kilobases at <italic>HMR</italic> and that silencing at <italic>HMR</italic> is insensitive to co-expression of wild-type and catalytically inactive Sir2 proteins suggest that <italic>HMR-E</italic> enables the assembly of silenced chromatin in a non-linear fashion. These results suggest that <italic>HMR-E</italic> functions to both recruit Sir proteins and promote their assembly across several kilobases.</p><p>In addition to the <italic>HMR-E</italic> silencer, <italic>HMR</italic> is also characterized by the presence of a second auxiliary <italic>HMR-I</italic> silencer and a tRNA gene that functions as a boundary element to restrict the spread of silenced chromatin. I used chromatin immunoprecipitation to determine how each of these regulatory elements contribute to the steady-state levels of Sir protein association with chromatin. Consistent with a role for <italic>HMR-E</italic> beyond recruitment, I discovered that the <italic>HMR-E</italic> silencer alone promoted higher levels of Sir proteins on nucleosomes compared to the telomere VI-R. The levels of Sir protein association with <italic>HMR</italic> were further elevated by the <italic>HMR-I</italic> silencer, even though this silencer does not recruit Sir proteins on its own and does not contribute to any of the known functions of silenced chromatin at <italic>HMR</italic>. Additionally, although the tRNA gene did block the spread Sir proteins, I discovered that the capacity for Sir proteins to spread beyond a few kilobases was severely limited even in the absence of the boundary.</p><p>The results of this thesis work provide new insights into the mechanisms of silenced chromatin establishment and regulation in budding yeast. I show here that the capacity of Sir proteins to assemble onto nucleosomes is inherently limited. Additionally, silencers vary in their ability to promote this assembly. I conclude that the silencer is a key factor in determining the relative size, efficiency, and location of silenced chromatin domains in the cell.</p> / Dissertation

No description available.

This dissertation examines the assessment and mitigation of airborne noise from power generation equipment. The first half of the dissertation investigates the diagnosis and treatment of combustion oscillations in boilers. Sound is produced by the flame and is reflected downstream from the combustion chamber. The reflected sound waves perturb the mixture flow or equivalence ratio increasing the heat release pulsations and the accompanying sound produced by the flame. A feedback loop model for determining the likelihood of and diagnosing combustion oscillations was reviewed, enhanced, and then validated. The current work applies the feedback loop stability model to two boilers, which exhibited combustion oscillations. Additionally, a feedback loop model was developed for equivalence ratio fluctuations and validated. For the first boiler, the combustion oscillation problem is primarily related to the geometry of the burner and the intake system. For the second boiler, the model indicated that the combustion oscillations were due to equivalence ratio fluctuations. Principles for both measuring and simulating the acoustic impedance are summarized. An approach for including the effect of structural-acoustic coupling was developed. Additionally, a method for determining the impedance above the plane wave cut-off frequency, using the acoustic FEM, of the boiler was proposed. The second half of the dissertation examines the modeling of bar silencers. Bar silencers are used to mitigate the airborne noise from large power generation equipment (especially gas turbines). Due to the large dimensions of the full cross section, a small representative cell is isolated from the entire array for analysis purposes. To predict the acoustical performance of the isolated cell for different geometric configurations, a numerical method based on the direct mixed-body boundary element method (BEM) was used. An analytical solution for a simplified circular geometry was also derived to serve as a comparison tool for the BEM. Additionally, a parametric study focusing on the effects of flow resistivity, perforate porosity, length of bars, and cross-sectional area ratio was performed. A new approach was proposed to evaluate the transmission loss based on a reciprocal work identity. Moreover, extension of the transmission loss computation above the plane wave cut-off frequency was demonstrated.

This thesis endeavors towards developing various concepts employed in analysis and design of acoustic filters for varied applications ranging from combination mufflers for automobiles to complex networks of gas carrying ducts to multiply connected complex automotive silencing devices to the noise control coatings for underwater applications. A two-dimensional wave modeling approach has been proposed to evaluate sound attenuation characteristics of dissipative mufflers of finite length with/without extended inlet and outlet tubes including very large mufflers. The correctness of the method has been validated through comparison with experimental results from literature. Two other frequently used approximate schemes have been discussed briefly with reference to the available literature. These three approaches have then been weighed against each other to show the effectiveness and limitations of each one. A thorough comparison study has been performed to investigate each one’s extent of applicability. A parametric study with different parameters suggests some useful design guidelines that can be put to use while designing such mufflers. Benefits and drawbacks of reactive and dissipative mufflers have been discussed with an intention of striking a compromise between them to achieve a better transmission quality over a broad frequency range. This has been accomplished by combining these two types of mufflers/filters explicitly. These combination mufflers are analyzed using a transfer matrix based approach by extending the aforesaid concept of two-dimensional wave modeling for finite dissipative ducts. The present approach has been used to analyze axi-symmetric circular lined plenum chambers also. The effectiveness of the bulk reaction assumption to model absorptive lining is illustrated. A parametric study has been carried out to investigate the effects of different thicknesses and placements of the absorptive lining. The contributions of reflective and absorptive portion of the combination mufflerto overall attenuation performance have been investigated from the designer’s point of view A generalized algorithm has been developed for studying the plane sound wave propa- gation in a system of interconnected rigid-walled acoustic filter elements. Interconnection between various elements is represented by a connectivity matrix. Equations of volume velocity continuity and pressure equilibrium at the interconnections are generated using this connectivity matrix and are solved using the Gauss-Jordan elimination scheme to get the overall transfer matrix of the system. The algorithm used for generalized labeling of the network and computation of Transmission Loss has also been discussed. The algorithm has been applied to investigate a multiply connected automobile mufflers as a network of acoustic elements which guides the way to a specialized application discussed next. Results for some configurations have been compared with those from the FEM analysis and experiments. A parametric study with respect to some geometric variables is carried out. The acoustical similarity between apparently different networks is discussed. The approach is flexible to incorporate any other acoustic elements, provided the acoustic variables at the junctions of the element can be related by a transfer matrix a priori. Commercial automotive mufflers are often too complex to be broken into a cascade of one dimensional elements with predetermined transfer matrices. The one dimensional (1-D) scheme presented here is based on an algorithm that uses user friendly visual volume elements to generate the system equations which are then solved using a Gauss-Jordan elimination scheme to derive the overall transfer matrix of the muffler. This work attempts and succeeds to a great extent in exploiting the speed of the one dimensional analysis with the flexibility, generality and user friendliness of three dimensional analysis using geometric modeling. A code based on the developed algorithm has been employed to demonstrate the generality of the proposed method in analyzing commercial muffers by considering three very diverse classes of mufflers with different kinds of combinations of reactive, perforated and absorptive elements. Though the examples presented in the thesis are not very complex for they are meant to be just representative cases of certain classes of mufflers, yet the algorithm can handle a large domain of commercial mufflers of high degree of complexity. Results from the present algorithm have been validated through comparisons with both the analytical and the more general, three-dimensional FEM based results. The forte of the proposed method is its power to construct the system matrix consistent with the boundary conditions from the geometrical model to evaluate the four pole parameters of the entire muffer and thence its transmission loss,etc. Thus, the algorithm can be used in conjunction with the transfer matrix based muffler programs to analyze the entire exhaust system of an automobile. A different kind of acoustic filter than the above mentioned cases is then taken up for investigation. These refer to the specialized underwater acoustic filters laid as linings on submerged bodies. These kind of underwater noise control linings have three different types of objectives, namely, Echo Reduction, Transmission Reduction (TL maximization) and a combination thereof. These coatings have been shown to be behaving very differently with different shape, size and number of air channels present in the layer. In this regard, a finite element model based methodology has been followed. An hybrid type finite element based on the Pian and Tong formulation has been modified and used so as to make the computational efforts less demanding as compared to the original one. The developed finite element has been shown to be immune to the difficulties that arise due to the near incompressible characteristics of the viscoelastic materials used and the high distortion of the elements of the FE mesh. The adequacy of this formulation has been shown by comparing its results with the analytical, FE based, and experimental results. Then, this methodology has been used to analyze and generate design curves to control various geometrical parameters for proper designing of these linings. Different unit cell representations for different types of distributions of air cavities on the linings have been discussed. Four different types of layers have been introduced and analyzed to address different objectives mentioned above. They have been termed as the Anechoic layer, Insulation layer and Combination Layer of coupled and decoupled type in this thesis. The first two layers have been designed to achieve very dissimilar characteristics and the next two layers have been designed to balance their disparities. A thorough parametric study has been carried out on the geometrical parameters of all the layers to come up with the design guidelines. For anechoic and the insulation layers, different distributions have been analyzed with different unit cell geometries and their usability in specific situations has been outlined. Effect of static pressure has also been studied by using an approximate finite element method. This method can be used to simulate deep-sea testing environment.

The noise propagating through the truck exhaust system is often attenuated by after treatment systems including truck silencers. The acoustic simulation of the truck silencers is usually based on pressure acoustics which does not include the influence of background flow. However, background flow can affect the acoustic attenuation ability of the truck silencers a lot. This thesis presents a simulation method for investigating the influence of the background mean flow on the silencers. In this method, the fluid information is first simulated with CFD software STAR-CCM+. The fluid data is then imported into COMSOL to conduct acoustic simulation using Linearized Navier-Stokes modulus. Flow noise is not simulated in this method in order to well capture the background mean flow's effect on the performance of silencer in a relatively short calculation time. Two simple silencer model groups are studied to validate this method. The first is a Helmholtz resonator. Another model group is expansion chambers with different setups. The sensitivity of the model towards different model setup is also studied. In the last part of the work, the method is applied to a common truck silencer model CAS1 F1gen, when this method counters challenge of high calculation load. A hybrid method is then developed, combining pressure acoustics and Linearized Navier-Stokes study, to simplify the method, reduce calculation time and at the same time capture the background mean flow's influence on silencers. / Bullret som fortplantar sig genom lastbilens avgassystem dämpas ofta av efterbehandlingssystem inklusive lastbilsljuddämpare. Den akustiska simuleringen av lastbilens ljuddämpare baseras vanligtvis på tryckakustik som inte inkluderar påverkan av bakgrundsflödet. Bakgrundsflödet kan dock påverka lastbilsljuddämparnas akustiska dämpningsförmåga mycket. Denna avhandling presenterar en simuleringsmetod för att undersöka påverkan av bakgrundsmedelflödet på ljuddämparna. I den här metoden simuleras vätskeinformationen först med CFD-programvaran STAR-CCM+. Vätskedata importeras sedan till COMSOL för att genomföra akustisk simulering med linjär Navier-Stokes modul. Flödesbrus simuleras inte i denna metod för att väl fånga bakgrundsmedelflödets effekt på ljuddämparens prestanda på en relativt kort beräkningstid. Två enkla ljuddämparmodellgrupper studeras för att validera denna metod. Den första är en Helmholtz-resonator. En annan modellgrupp är expansionskammare med olika inställningar. Modellens känslighet mot olika modellupplägg studeras också. I den sista delen av arbetet tillämpas metoden på en vanlig lastbilsljuddämpare modell CAS1 F1gen, då denna metod motverkar utmaning med hög beräkningsbelastning. En hybridmetod utvecklas sedan, som kombinerar tryckakustik och linjäriserad Navier-Stokes-studie, för att förenkla metoden, minska beräkningstiden och samtidigt fånga bakgrundsmedelflödets påverkan på ljuddämpare.