Indiana University-Purdue University Indianapolis (IUPUI) / Under normal conditions, smooth muscle cells do not replicate, or proliferate, and provide a means of contraction for many internal organs, including blood vessels and the gut. However, under abnormal or disease conditions, such as congenital heart disease and cancer, smooth muscle cells acquire the ability to replicate, to make extracellular matrix proteins and to migrate. Thus, determining how smooth muscle cells regulate these processes is crucial to understanding how the cells can switch between normal and diseased states. Serum response factor (SRF) is a widely expressed protein that plays a key role in the regulation of smooth muscle differentiation, proliferation and migration. It is generally accepted that one way that SRF can distinguish between these functions is through pathway-specific co-factor interactions. A novel SRF co-factor, chromodomain helicase DNA binding protein 8 (CHD8), was originally isolated from a yeast two-hybrid assay. CHD8 is widely expressed in adult tissues including smooth muscle. Data from in vitro binding assays indicate that the N-terminus of CHD8 can interact directly with the MADS domain of SRF. Co-immunoprecipitation assays verified the ability of these two proteins to interact within cells. Adenoviral-mediated shRNA knockdown of CHD8 in smooth muscle cells resulted in statistically significant 10-20% attenuation of expression of SRF-dependent, smooth muscle-specific genes. Similar experiments revealed that knockdown of CHD8 did not affect the SRF-dependent induction of immediate early genes required to promote proliferation. In contrast, knockdown of CHD8 in A10 vascular smooth muscle cells resulted in a marked induction in of apoptosis, characterized by increases in apoptotic markers such as phospho-H2A.X, cleaved PARP and activated caspase-3. These data suggest that CHD8 may play a specific role in modulating SRF’s activity toward anti-apoptotic genes, thereby regulating smooth muscle cell survival.

Radio frequency (RF) cavities are the foundational infrastructure which facilitates much of the fundamental research conducted in high energy particle physics. These RF cavities utilize their unique shape to produce resonant electromagnetic fields used to accelerate charged particles. Beside their core role in fundamental physics research, RF cavities have found application in other disciplines including material science, chemistry and biology which take advantage of their unique light sources. Industry has been keen on taking advantage of accelerator technology for a multitude of applications. Particle accelerators like the one found at Jefferson Lab’s Continuous Electron Beam Accelerator Facility must produce stable beams of high energy particles which is an incredibly costly endeavor to pursue. With the gargantuan size of these facilities, the cost of high-quality beam production is a matter of great importance. The quest to find highly efficient RF cavities has resulted in the widespread use of superconducting radio frequency (SRF) cavities which are the most efficient resonators that exploit a superconductor’s incredibly low AC surface resistance. While metals like Cu are up to the demanding job of RF cavity particle acceleration, their efficiency at transferring RF power to the particle beam is low when they are compared with SRF Nb cavities. Nb is the standard material for all SRF cavity technology particularly for its reproducibly low surface resistance, comparatively high transition temperature and thermodynamic critical field. Using superconducting Nb is not without its drawbacks. Keeping hundreds of Nb cavities in their superconducting state under extreme RF conditions is quite a daunting task. It requires the normal state not nucleate during operation. This is achieved by producing high-quality cavities with as few defects and impurities as possible while also keeping the cavities at low temperature, usually 2K. Again, due to the sheer scale of the facilities, hundred million-dollar cryogenic plants are required to handle the heat loads during SRF cavity operation. This means even small increases in maximum accelerating gradients or decrease in cavity surface resistance results in a sizably reduced operation cost. Considerable effort has been put forth to increase the efficiency of Nb cavities toward and even beyond the theoretical maximum accelerating gradients and quality factor for a clean superconductor. Recently, a new method to produce high quality factor cavities has emerged that involves nitrogen doping the cavity. The mechanism by which N doping causes the improvement is still not well understood, but the experimental research described in this dissertation shines some light into the mechanisms behind such a drastic improvement. These insights are universal for all superconductors and may prove useful for SRF cavities beyond Nb. With Nb approaching its fundamental limits, new materials are being proposed to increase the performance of future SRF cavities which MgB2 finds itself among. MgB2 is a two-band superconductor that possesses many properties that are very attractive for the next generation of SRF cavities. One of the most important properties is MgB2’s comparatively large critical temperature which in part predicts it will have a lower surface resistance than Nb at higher operating temperatures. Such behavior of MgB2 may unlock the possibility of using cryocoolers instead of costly liquid helium plants for large scale industrial use. This dissertation starts with an introduction to superconductivity, its theory, and application to SRF cavities as well as the open questions that can be addressed in Nb and the next generation of SRF materials. A description of the experimental techniques of scanning tunneling microscopy, X-ray photoelectron spectroscopy, and atomic force microscopy is presented. Our experimental investigation into Nb SRF cavity cutouts starts with a discussion of the material’s limitations for SRF applications with an emphasis on the proximity effect which arises at the surface of this material due to its myriad of naturally forming oxides. The results of our scanning tunneling microscopy measurements for typically prepared Nb and nitrogen doped Nb follows and comparisons are made which show that the surface oxides are fundamentally different between these samples likely resulting in the profound enhancement of the cavity’s quality factor. Experimental investigation into the native oxide of hot spot nitrogen doped Nb shows a degraded oxide and superconducting properties as compared with the cold spot. The dissertation continues with a brief introduction to MgB2, followed by our scanning tunneling and electron tunneling insights into MgB2. The dissertation is concluded with a summary of our investigations and broader impact of our research on the SRF community. / Physics

The superconductivity in magnesium diboride (MgB2) was discovered in 2001. As a BCS superconductor, MgB2 has a record-high Tc of 39 K, high Jc of > 107 A/cm2 and no weak link behavior across the grain boundary. All these superior properties endorsed that MgB2 would have great potential in both power applications and electronic devices. In the past 15 years, MgB2 based power cables, microwave devices, and commercial MRI machines emerged and the next frontier are superconducting radio frequency (SRF) cavities. SRF cavities are one of the leading accelerator technologies. In SRF cavities, applied microwave power generates electrical fields that accelerate particle beams. Compared with other accelerator techniques, SRF cavity accelerators feature low loss, high acceleration gradients and the ability to accelerate continuous particle beams. However, current SRF cavities are made from high-purity bulk niobium and work at 2 K in superfluid helium. The construction and operational cost of SRF cavity accelerators are very expensive. The demand for SRF cavity accelerators has been growing rapidly in the past decade. Therefore, a lot of effort has been devoted to the enhancement of the performance and the reduction of cost of SRF cavities. In 2010, an acceleration gradient of over 50 MV/m has been reported for a Nb-based SRF cavity. The magnetic field at the inner surface of such a cavity is ~ 1700 Oe, which is close to the thermodynamic critical field of Nb. Therefore, new materials and technologies are required to raise the acceleration gradient of future SRF cavity accelerators. Among all the proposed approaches, using MgB2 thin films to coat the inner surface of SRF cavities is one of the promising tactics with the potential to raise both the acceleration gradient and the operation temperature of SRF cavity accelerators. In this work, I present my study on MgB2 thin films for their application in SRF cavities. C-epitaxial MgB2 thin films grown on SiC(0001) substrates showed Tc > 41 K and Jc > 107 A/cm2, which is superior to bulk MgB2 samples. Polycrystalline MgB2 thin films grown on metal substrates showed similar Tc and Jc compared with bulk samples, indicating MgB2 is suitable for coating a metal cavity. Large c-pitaxial MgB2 thin films were grown on 2-inch diameter c-sapphire wafers, showing our technique is capable of depositing large area samples. The lower critical field (Hc1) of MgB2 thin films was measured as well as it is know that bulk MgB2 has a small Hc1 and would suffer from vortex penetration at low magnetic fields. The penetrating magnetic vortices would result in loss in an applied RF field. However, due to the geometry barrier, thin film MgB2 would have a higher Hc1 than the bulk material. In my experiments, the Hc1 of MgB2 thin films increased with decreasing film thickness. At 5 K, a 100 nm epitaxial MgB2 thin film showed enhanced Hc1 ~ 1880 Oe, which is higher than Hc1 of Nb at 2 K. This showed that MgB2 coated SRF cavities have the potential to work at higher magnetic fields and higher temperature. Because the magnetic field distribution in the thin film Hc1 measurement is different from the magnetic field in a real SRF cavity, a few Nb ellipsoids were machined and coated with MgB2. The ellipsoid only has a magnetic field outside its surface and can serve as an inverse SRF cavity in the vortex penetration measurement. In the experiments, vortices penetrate into the bulk Nb ellipsoid at a magnetic field 400 Oe lower than the vortex penetration field of MgB2 coated Nb ellipsoids. This result confirmed our prediction that MgB2 coated SRF cavities could work at higher magnetic fields, thus producing higher acceleration gradients. In the last part of this thesis, I discussed how I used the dielectric resonator technique to measure the surface resistance (Rs) and Tc of MgB2 thin films. While the sensitivity of this technique was not high enough to lead to reliable Rs values, it can still serve for the determination of Tc for large area samples that are too bulky for other measurement systems. / Physics

Particle accelerators are a leading tool for frontier science. Pushing that frontier further demands more machines with higher performance, and more of a very expensive technology: superconducting radio-frequency (SRF) acceleration. From a materials perspective this means reducing residual surface resistance or raising the operating temperature (currently ~2 K) of SRF cavities. Both are pursued by materials modification: nitrogen doping/infusion in the first instance and coating with Nb3Sn in the second. Materials characterization is key to achieving understanding and directing RandD. However, very little has been done. This present work aims to fill the knowledge gap and to provide needed, validated tools to the accelerator science community. In this connection, SIMS, XPS and EBSD have proven especially valuable and represent the majority of discussion in this dissertation. / Doctor of Philosophy / Particle accelerators are a powerful tool that helps us expand our knowledge of science and how the universe works. Pushing that knowledge further requires us to use more and more powerful particle accelerators. Particle accelerators are based on a very expensive technology: superconducting radio-frequency (SRF) cavities. These cavities are hollow tubes made from niobium and shaped in such a way as to cause electromagnetic waves to form. These waves are what are used to accelerate particles. The energy input and loss of energy as heat are massive resulting in millions of dollars a year in electric bills at particle accelerator facilities. In order to build bigger and more powerful particle accelerates they most be more efficient or they become prohibitively expensive. In this dissertation I look at several next generation materials used in building particle accelerators. In particular I describe and go into detail about how to characterize these materials. In other words, how we determine the materials properties and how those properties affect the performance.

The most common failure of concrete gravity dams is sliding along the foundation surface. This thesis studies progressive failure of the Longtan dam on the upper Hongshuie river in china.Two methods are used in this thesis; the Safety Reserve Factor (SRF) method and the Overload method. The SRF-method is used as a tool to study sliding failure along the foundation weak layer of the Longtan dam. Strength reduction coefficients decrease the cohesion and friction angle values for the weak layer of the foundation. Simulations with reduced shear strength parameter values gives information about the development of the plastic zone. The ultimate bearing resistance and the failure path along the foundation are obtained. The safety reserve coefficient is established through the strength reduction coefficients, when the plastic zone of the foundation is totally coalescent. To analyse the development of the plastic zone along the dam foundation with the strength reserve method, the commercial finite element software MSC.Marc is used. The results of the Safety Reserve Factor method (SRF) show that the failure of the dam is highly related to the strength of the interface between the dam and rock foundation. The strength reserve factor is determined to 2.4. The Overload method gives a visual deformation shape of the dam structure and pressure load at the moment of failure. / Dammar har används i mer än 5000 år (Yang et al. 1999) och är fortfarande en viktig källa för energiutvinning. Det största antalet dammar finns i Kina och man tror att det finns över 80,000 dammar i landet (Shapiro 2001). En ökning av dammars kapacitet och antal sker, vilket resulterat i ett behov av bättre sätt för att utvärdera säkerhetsparametrar som betongkvalité, styvhet och homogenitet av bergmassa. Simuleringar av dammkonstruktioner kan ge värdefull information om dessa parametrar och kan därigenom bidra till att förbättra en damms stabilitet och sänka konstruktionskostnader. I det här examensarbetet utvärderas och modelleras Longtan dammen i övre Hongshui floden i Kina. Den vanligaste orsaken till haveri av betongdammar är glidning mellan betonglager och bergmassan. I den här rapporten simuleras ett svagare lager mellan betong och bergmassa och utvecklingen av kontaktbrottsvägen visualiseras och utvärderas med progressiva haveri metoden. Det svagare lagrets hållfasthetskoefficienter; friktionsvinkel och kohesion, reduceras för att analysera utbredningen av den plastiska zonen. Resultaten visar att en överskridning av draghållfastheten för betong börjar vid dammens häl och att kompressionsbristningsgränsen överskrids vid dammens tå när hållfasthetskoefficienterna reduceras. Säkerhetsreservskoefficienten för Longtan dammen erhålls då gränsytan mellan betong och berg är helt plastisk. För att analysera utbredningen av den plastiska zonen längs med dammfundamentet med progressiva haveri metoden används den kommersiella finita element mjukvaran MSC.Marc. Resultaten från säkerhetskoefficientfaktormetoden visar att ett haveri av gravitations dammar är i hög grad relaterad till hållfastheten mellan betongen och bergets gränsyta. Säkerhetskoefficientfaktorn bestäms till 2.4. För att bestämma Longtan dammens maximala vattenbelastningskapacitet används Överbelastningsmetoden. Det maximala vattentryck som Longtan dammen klarar av utan att haverera simuleras med hjälp av en vätska vars densitet ökas mellan modellkörningar. Dammens förskjutning når till sist en punkt där den ökar kraftigt och dammens mutationsdeformationstillstånd har uppnåtts. En visuell deformationsbeskrivning av dammen ges genom modellkörningar och överbelastningsfaktorn bestäms.

Rex - den nya redovisningsstandarden. Ett examensarbete för kandidatexamen i företagsekonomi.Uppsatsens syfte är att analysera auktoriserade redovisningskonsulters syn på den nya redovisningsstandarden Rex och särskilt om den kan bidra till att utveckla yrket mot en redovisningsprofession.Data har insamlats genom litteraturstudie samt genom en enkätundersökning. Respondenterna till enkäterna är auktoriserade redovisningskonsulter hos Srf konsulterna. Enkäterna skickades ut till 300 auktoriserade redovisningskonsulter varav vi erhöll 45 stycken svar. Data från enkäterna har slutligen bearbetats genom z-tester och hypotesprövningar. Genom z-tester och hypotesprövningar kom vi fram till att en signifikant andel av respondenterna anser att Rex utvecklar yrket mot en redovisningsprofession. Våra resultat tyder på att Rex bidrar till att auktoriserade redovisningskonsulter utvecklas till en redovisningsprofession.Vår uppsats har bidragit med kunskap om huruvida auktoriserade redovisningskonsulter kan anses vara en profession. Brundin Franksson och Eisersiö (2011) kom i sin kandidatuppsats fram till att Reko var ett steg som utvecklade yrkesrollen till att bli en profession. Utgångspunkten var då den tidigare redovisningsstandarden Reko. En ny redovisningsstandard har dock lanserats och den här studien har därför baserats på den nya redovisningsstandarden Rex. Med vår studie har vi kommit fram till samma slutsats som Brundin Franksson och Eisersiö. Skillnaderna har dock, förutom att vi har undersökt olika standards, varit att respondenterna i studierna har skilt sig åt. Brundin Franksson och Eisersiö undersökte både revisorer, redovisningskonsulter och auktoriserade redovisningskonsulter hos FAR medan vi endast har undersökt auktoriserade redovisningskonsulter hos Srf konsulterna. Uppsatsen har bidragit med kunskap om yrket kan komma att utvecklas till följd av den nya kontexten. Uppsatsen har även bidragit med att fylla kunskapsluckor om Rex, då vi tidigare ej funnit forskning som hunnit behandla den nya standarden. / Rex - the new accounting standard. Final assignment for bachelor’s degree in business administration.The purpose of the essay is to analyze the views of authorized accounting consultants on the new accounting standard Rex and if it can contribute to develop the profession towards an accounting profession.Data was collected through literature study and through a survey. Respondents to the questionnaires are authorized accounting consultants at the Srf consultants. The surveys were sent to 300 authorized accounting consultants, of which we received 45 responses. Data from the surveys has finally been processed by z-tests and hypothesis tests. We found through z-tests and hypothesis tests, that a significant part of the respondents believes that Rex develops the profession towards an accounting profession. Our results indicate that Rex contributes to the development of authorized accounting consultants into an accounting profession.Our essay contributes with knowledge of whether authorized accounting consultants can be considered a profession. Brundin Franksson and Eisersiö (2011) concluded that Reko was one step towards developing the occupational role to become a profession. The starting point was based on the previous accounting standard Reko. This study has been based on the accounting standard Rex. We came to the same conclusion as Brundin Franksson and Eisersiö. However, apart from the fact that we have examined different standards, the differences have been that we have had different respondents. The essay has contributed with knowledge that the profession may develop as a result of the new context. The essay has also contributed to filling knowledge closures about Rex, as we have previously found no research that has already dealt with the new standard. The contribution can be guaranteed even if the results are not representative of the entire population.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-05-05T18:23:07Z No. of bitstreams: 1 yuricalillouresdeoliveira.pdf: 2613361 bytes, checksum: b14d216c9e91ffe085e35724d58bc704 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-06-07T15:42:11Z (GMT) No. of bitstreams: 1 yuricalillouresdeoliveira.pdf: 2613361 bytes, checksum: b14d216c9e91ffe085e35724d58bc704 (MD5) / Made available in DSpace on 2016-06-07T15:42:11Z (GMT). No. of bitstreams: 1 yuricalillouresdeoliveira.pdf: 2613361 bytes, checksum: b14d216c9e91ffe085e35724d58bc704 (MD5) Previous issue date: 2016-01-12 / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / Esta dissertação apresenta um estudo de estratégias de alimentação de cargas hospitalares críticas utilizando conversores estáticos de energia. As cargas hospitalares escolhidas foram os equipamentos de raio x, tomografia computadorizada e ressonância magnética, sendo comparadas as seguintes formas de integração à rede: (i) estrutura com um retificador trifásico conectado à rede e três inversores monofásicos conectados às cargas ou (ii) estrutura com três retificadores monofásicos conectados à rede e três inversores monofásicos conectados às cargas. Por questões de patente, houve dificuldade em se encontrar os circuitos de front-end das fontes de alimentação das cargas hospitalares. Logo, as mesmas foram construídas dentro do ambiente de simulação do software PSIM utilizando dados de medição obtidos na literatura. O controle dos retificadores trifásico e monofásico foi realizados utilizando duas malhas de controle em cascata, com a malha interna controlando a corrente consumida da rede e a malha externa regulando a tensão no barramento CC. Para os três inversores monofásicos de saída foram implementados os controles PI RES e PI SRF visando uma comparação quanto ao desempenho. Como forma de validar o modelo matemático do sistema e o algoritmo de controle, foram feitas simulações utilizando o software PSIM. A análise feita comprovou que os resultados de simulação se mostraram coerentes com a modelagem matemática do sistema. / This master thesis presents a study about feeding strategies of critical hospital loads through power static converters. The chosen hospital loads were the x ray equipment, the computed tomography and the magnetic resonance. The following forms of grid integration were compared: (i) structure with a three-phase rectifier connected to the network and three single-phase inverters connected to the loads or (ii) structure with three single-phase rectifiers connected to the network and three single-phase inverters connected to the loads. Due to patent issues, it was difficult to find the front-end circuits for power supplies of hospital loads. Therefore, the loads were implemented in PSIM software environment using measurement data obtained from literature. The control of three-phase and single-phase rectifiers was implemented using two cascaded control loops, with the inner loop controlling the current drawn from the network and the outer loop regulating the DC bus voltage. For the single-phase inverter, PI RES and PI SRF controls were implemented, targeting a comparison in terms of performance. In order to validate the mathematical model of the system and the control algorithm, simulations were performed using the PSIM software. The analysis showed that the simulation results were consistent with the mathematical modeling of the system.

Le cancer papillaire de la thyroïde (CPT) est la tumeur endocrine la plus fréquente. Des anomalies moléculaires activant la voie des MAPK (Mitogen-Activated Protein Kinases) sont identifiées, de façon mutuellement exclusive, dans environ 70% des cas. Il s’agit de réarrangements chromosomiques, le plus souvent de type RET/PTC (10%), de mutations ponctuelles activatrices des trois isoformes de l’oncogène RAS (H, N et K-RAS) (10%), ou de l’oncogène B-RAF (50%). La mutation « hot spot » B-RAFV600E est la plus fréquemment identifiée, elle est associée à une plus grande agressivité clinique (diagnostic à un stade tardif, risque de récidives et de décès accru). Ces évènements moléculaires ont pour conséquence commune l’activation de la voie des MAPK, se traduisant en aval par la phosphorylation de MEK (Mitogen-activated Extracellular signal-Regulated Kinase) puis de ERK (Extracellular signal-Regulated Kinase). Cette dernière est régulée négativement par des phosphatases, appartenant à la famille des Dual Specificity Phosphatases (DUSPs), d’expression ubiquitaire, et en particulier de deux phosphatases spécifiques de ERK, l’une cytoplasmique (DUSP6) et l’autre nucléaire (DUSP5). Nous avons fait l’hypothèse que ces phosphatases pouvaient être soit des gènes suppresseurs de tumeurs (leur perte d’expression conduisant à une augmentation de phosphorylation de ERK et une prolifération accrue), soit des marqueurs du degré d’activation de la voie MAPK dans le cadre d’une boucle de rétrocontrôle négatif. Ceci nous a conduits à analyser la régulation et l’expression de ces phosphatases dans trois modèles : la lignée cellulaire PCCL3 (thyroïde de rat), exprimant l’un des trois principaux oncogènes mutés dans les CPT (RET/PTC3 ou H-RASV12 ou B-RAFV600E) sous le contrôle d’un promoteur inductible par la doxycycline, des lignées cellulaires humaines dérivant de CPT et des CPT humains. (...) / Papillary thyroid cancer (PTC) is the most common endocrine malignancy. Mutually exclusive and activating alterations of the MAPK pathway (Mitogen-Activated Protein Kinases) are identified in 70% of cases. Common mutations found in PTCs are point mutation of the B-RAF (50%) and RAS genes (10%) as well as RET/PTC chromosomal rearrangements (10%). The hot spot B-RAFV600E mutation is the most frequently alteration identified and is connected with agressive clinical characteristics (high stage at diagnosis, high recurrence risk and death). These molecular events lead to constitutive activation of the MAPK pathway, resulting in MEK (Mitogen-activated Extracellular signal-Regulated Kinase) and ERK (Extracellular signal-Regulated Kinase) phosphorylation. ERK is negatively regulated by phosphatases and among them, Dual Specificity Phosphatases (DUSPs), ubiquitary expressed, in particular two ERK-specific phosphatases DUSP5 (nuclear) and DUSP6 (cytosolic). We hypothesized that these phosphatases could have tumor supressor properties (i.e. their loss would be associated with an increase in MAPK pathway activation) or may serve as a surrogate marker of MAPK pathway activation in the context of a negative feedback loop. We analysed regulation and expression of both phosphatases in 3 models: three PCCL3 cell lines (rat thyroid cells) expressing one of the most common oncogene identified in PTCs (RET/PTC3 or H-RASV12 or B-RAFV600E) under the control of a doxycycline-inducible promoter, human PTC-derived cell lines and human PTC. We demonstrated that MAPK pathway activation was correlated with induction of DUSP5 and DUSP6. These phosphatases are involved in a negative feedback loop that contributes to a tight regulation of phospho-ERK levels. DUSP5 and DUSP6 mRNA are overexpressed in human PTCs, especially in B-RAF mutated tumors suggesting a higher MAPK signaling output in these agressive PTCs. Silencing of DUSP5 and/or DUSP6 by small interfering RNA does not affect proliferation of human B-RAFV600E thyroid carcinoma-derived cell lines, suggesting the lack of tumor suppressor gene role. Compensatory changes in expression of DUSPs when a specific one is inactivated may explain this lack of effect. On the opposite, a DUSP6 pharmacological inhibitor induced a concentration dependent decrease in proliferation of human B-RAFV600E cells, suggesting « off-target » effect of this inhibitor. In a second part, we analysed the regulation of DUSP5 expression, which is a target of the MAPK pathway activation. We demonstrated, using pharmacological inhibitors, that DUSP5 is an early response gene, regulated mostly by the MAPK pathway, at the transcriptional level. Two contiguous CArG boxes that bind serum response factor (SRF) were found in a 1Kb promoter region, as well as several E twenty-six transcription factor family binding sites (EBS). These sites potentially bind Elk-1, a transcription factor activated by ERK1/2. Using wild type or mutated DUSP5 promoter reporters, we demonstrated that SRF plays a crucial role in serum induction of DUSP5 promoter activity, the proximal CArG box being important for SRF binding in vitro and in living cells. Moreover Elk-1 was bound in vitro to a promoter region containing the proximal CArG box and a putative EBS. Its specific binding to SRF was necessary to elicit promoter response to dominant positive Elk-VP16 and to enhance the response to serum stimulation. Altogether our results suggest that the MAPK pathway is more active in B-RAFV600E PTC than in PTC with other genetic alteration and could explain their clinical agressivity. DUSP5 and DUSP6, as well as phosphorylated MEK, are markers of activation of the MAPK pathway. Neither phosphatase has tumor suppressor properties in our thyroid cancer cell models. Our results suggest redundancy and functional compensation among DUSPs. (...)

This master thesis deals with the theoretical analysis of wireless sensor networks, a description of selected types of sensors, listing their features and principle of operation for intrusion detection perimeter. Then there is described design and implementation of a wireless sensor node for intrusion detection perimeter usable in wireless sensor networks.

Il a été démontré que les chevaux atteints du souffle présentent une augmentation de la masse de muscle lisse entourant les voies respiratoires comparativement à des chevaux sains (Herszberg, Ramos-Barbon et al. 2006, Leclere, Lavoie-Lamoureux et al. 2011). L’augmentation de la masse de muscle lisse ainsi observée résulte d’une hyperplasie, et possiblement, d’une hypertrophie des myocytes. Les traitements usuels du souffle ne sont que partiellement efficaces à diminuer cette augmentation. L’objectif de cette étude était d’explorer les mécanismes moléculaires impliqués dans ces changements affectant la cellule musculaire lisse dans la pathologie du souffle chez le cheval. Pour ce faire, nous avons examiné les effets d’une exposition antigénique sur l’expression du «Serum Response Factor» (SRF) dans le muscle lisse bronchique. Le SRF est un facteur de transcription localisé dans le noyau de la cellule musculaire lisse et régulant l’expression génique de celle-ci en favorisant un phénotype prolifératif ou contractile. Les résultats démontrent qu’avant exposition antigénique, les pourcentages de cellules exprimant le SRF sont faibles. Une augmentation significative du pourcentage de myocytes exprimant le SRF survient suite à une stimulation antigénique chez les chevaux atteints de souffle alors qu’aucune augmentation n’est observée chez les chevaux contrôles. Ces résultats suggèrent que le SRF pourrait contribuer au remodelage du muscle lisse péribronchique dans la pathologie du souffle. / Previous studies have shown that heaves-affected horses, when compared to age-matched control horses, have an increased smooth muscle mass surrounding their airways (Herszberg, Ramos-Barbon et al. 2006, Leclere, Lavoie-Lamoureux et al. 2011). Also, it is shown that hyperplasia, and possibly hypertrophy, contribute to this finding. Current therapies are only partially effective at reversing this finding. The goal of this study was to explore the molecular pathways involved in airway smooth muscle remodelling during heaves. We studied the Serum Response Factor (SRF), a nuclear transcriptional factor that controls gene expression in the smooth muscle cell and favour either a proliferative or a contractile phenotype. The results show that before antigenic exposition, the percentage of cells expressing SRF is low. A significant increase in the percentage of SRF-expressing myocytes occurs after antigenic stimulation in heaves-affected horses whereas no increase is observed in control subjects. These results suggest that the transcription factor SRF may contribute to airway smooth muscle remodeling in heaves-affected horses.