No description available.

In eukaryotes, mRNA decay pathways are important for cellular response to various physiological conditions and also function in co-translational quality control systems that target translationally aberrant mRNAs for degradation. My work on identification and characterization of novel components and pathways of mRNA degradation and quality control in Saccharomyces cerevisiae is summarized below.I have identified Edc3p as a novel protein important for mRNA decay. Deletion of Edc3p leads to a defect in mRNA decay in strains deficient in decapping enzymes and, in combination with a block to the 3' to 5' decay pathway, causes exaggerated growth defects and synthetic lethality. An Edc3p-GFP fusion protein localizes in processing bodies, which are specialized cytoplasmic foci containing decapping proteins. Together, these observations indicate that Edc3p directly interacts with the decapping complex to stimulate the mRNA decapping rate.Quality control during mRNA translation is critical for regulation of gene expression. My work shows that yeast mRNAs with defects in translation elongation, due to strong translational pauses, are recognized and targeted for degradation via an endonucleolytic cleavage in a novel process referred to as No-Go Decay (NGD). The cellular mRNA decay machinery degrades the 5' and 3' cleavage products produced by NGD. NGD is translation-dependent, occurs in a range of mRNAs and can be induced by a variety of elongation pauses. These results indicate NGD may occur at some rate in response to any stalled ribosome.I also show that two highly conserved proteins, Dom34p and Hbs1p, homologous to the eukaryotic release factors eRF1 and eRF3 respectively, are required for NGD. Further characterization of the No-Go decay pathway indicates that Dom34p function during NGD is conserved across species. Identification of RPS30, a small ribosomal protein as a trans-acting factor during NGD suggests that the ribosome may have a novel role during NGD. Other experiments indicate that the No-Go decay pathway may cross talk with the unfolded protein response pathway. The identification of No-Go decay as a novel quality control pathway during translation elongation supports the existence of a global cellular mechanism for maintenance of translational quality control.

This dissertation contains research directed at investigating the behavior and properties of a class of composite materials known as phononic crystals. Two categories of phononic crystals are explicitly investigated: (I) elastic phononic crystals and (II) nano-scale phononic crystals. For elastic phononic crystals, attention is directed at two-dimensional structures. Two specific structures are evaluated (1) a two-dimensional configuration consisting of a square array of cylindrical Polyvinylchloride inclusions in air and (2) a two-dimensional configuration consisting of a square array of steel cylindrical inclusions in epoxy. For the first configuration, a theoretical model is developed to ascertain the necessary band structure and equi-frequency contour features for the realization of phase control between propagating acoustic waves. In contrasting this phononic crystal with a reference system, it is shown that phononic crystals with equifrequency contours showing non-collinear wave and group velocity vectors are ideal systems for controlling the phase between propagating acoustic waves. For the second configuration, it is demonstrated that multiple functions can be realized of a solid/solid phononic crystal. The epoxy/steel phononic crystal is shown to behave as (1) an acoustic wave collimator, (2) a defect-less wave guide, (3) a directional source for elastic waves, (4) an acoustic beam splitter, (5) a phase-control device and (6) a k-space multiplexer. To transition between macro-scale systems (elastic phononic crystals) and nano-scale systems (nano-phononic crystals), a toy model of a one-dimensional chain of masses connected with non-linear, anharmonic springs is utilized. The implementation of this model introduces critical ideas unique to nano-scale systems, particularly the concept of phonon mode lifetime. The nano-scale phononic crystal of interest is a graphene sheet with periodically spaced holes in a triangular array. It is found through equilibrium molecular dynamics simulation techniques, that phonon-boundary collision effects and coherent phononic effects (band-folding) are two competing scattering mechanisms responsible for the reduction of acoustic and optical phonon lifetimes. Conclusions drawn about the lifetime of thermal phonons in phononic crystal patterned graphene are linked with the anharmonic, one-dimensional crystal model.

No description available.

The resonance spectrum of the nucleon gives direct information on the dynamics and interactions of its constituents. This offers an important challenge to the theoretical models of nucleon structure, including the emerging Lattice QCD predictions, conformal field theories and more phenomenological, QCD-based approaches. Although the various models predict different features for the excitation spectra, the experimental information is currently of too poor quality to differentiate between these models. Pion photoproduction from the nucleon is a powerful probe of the spectrum as most resonances are expected to couple to the pion decay channel. However, cross-sections alone are not sensitive enough to allow identification of the underlying excitation spectrum, as the resonances have energy widths larger than their separations. A major world effort is underway to additionally measure polarisation observables in the production process. For a model-independent analysis a “complete” set of single- and doublepolarisation observables needs to be measured in experiments involving polarised beams, targets and a means of determining recoil nucleon polarisation. In particular, the beam asymmetry is a critical observable for the constraint of partial wave analyses (PWA) used to extract the nucleon excitation spectrum from the data. Almost all of the available world data on the beam asymmetry has been taken on the proton, with the neutron dataset sparse, containing only three experiments at fixed angles and in a limited photon energy range. The lack of extensive data on the neutron is a major deficiency, as different resonances have very different electromagnetic couplings to the proton and neutron. As a result, the data from the two targets will have very different relative contributions from, and sensitivities to, the spectrum of nucleon resonances. Moreover, neutron data is essential for the separation of the isoscalar and isovector components of the reaction amplitudes. This thesis presents a very high statistics measurement of the photon beam asymmetry on the neutron with close-to-complete angular coverage and a wide range of invariant mass (1610 – 2320 MeV) extending over the third resonance region, where the excitation spectrum is particularly ill defined. The experiment was conducted at the Thomas Jefferson National Accelerator Facility (JLab) using a tagged, linearly polarised photon beam, a liquid deuterium target and the CEBAF Large Acceptance Spectrometer (CLAS). The quality and quantity of the data has allowed an invariantmass resolution of 10 MeV and an angular resolution of 0.1 in the cosine of the centre-of-mass pion production angle, θ. Good agreement is evident in the regions where there is kinematic overlap with sparse previous data. Comparison of the new data is made with the two main partial wave analyses, SAID andMAID. Significant discrepancy is observed at backward θ with SAID (across most of the energy range) and MAID (up to ∼ 1750 MeV) and also below ∼ 35◦ in θ with both analyses. This extensive new dataset will help significantly to constrain partial wave analyses and will be a crucial part of the current world effort to use meson photoproduction to tackle long-standing uncertainties in the fundamental excitation spectrum of the nucleon. As a first step towards this the refitting of the SAID partial wave analysis incorporating the new data was carried out and shows very significant changes in the properties of the magnetic P11, P13, D13, D35, F15, G17 and G19 partial waves.

SuperNEMO est un projet de détecteur de nouvelle génération pour la recherche de la décroissance double bêta sans émission de neutrinos. La technique expérimental déployée est dans la lignée du son prédécesseur NEMO3, combinant un trajectographe et un calorimètre, afin d’identifier non seulement les électrons des décroissances double bêta, mais également pour mesurer l’ensemble des composantes de bruit de fond du détecteur. Le projet vise ainsi une sensibilité de 10^26 ans sur la période du 82Se, ce qui permettrait de sonder une masse effective du neutrino de 50 meV. Pour atteindre cette sensibilité, le projet prévoit notamment de mettre en place un calorimètre composé d’un millier de compteur à scintillation de basse radioactivité, dont la résolution en énergie serait meilleure que 8 % FWHM pour des électrons de 1 MeV.Ce travail de thèse apporte une contribution importante dans les travaux de Recherche et Développements pour améliorer les performances des scintillateurs et photomultiplicateurs, et pour réduire leur radioactivité, avec notamment la conception d’un nouveau photomultiplicateur en collaboration avec Photonis. / SuperNEMO is a next generation double beta decay experiment which will extend the successful “tracko-calo” technique employed in NEMO 3. The main characteristic of this type of detector is to identify not only double beta decays, but also to mesure its own background components. The projet aims to reach a sensitivity up to 1026 years on the half-life of 82Se. One of the main challenge of the Research and Development is to achieve an unprecedented energy resolution for the electron calorimeter, better than 8 % FWHM at 1 MeV.This thesis contributes to improve scintillators and photomultiplicators performances and reduce their radioactivity, including in particular the development of a new photomultiplier in collaboration with Photonis.

The aim of this thesis was to identify genetic factors involved in frontotemporal lobar degeneration (FTLD), a neurodegenerative disorder clinically characterised by a progressive change in personality, behaviour and language. FTLD is a genetically complex disorder and a positive family history is found in up to 40% of the cases. In 10-20% of the familial cases the disease can be explained by mutations in the gene encoding the microtubule associated protein tau (MAPT). In the first study we describe the clinical and neuropathological features of a Finnish family with FTLD caused by a mutation in MAPT. We also provide evidence that the pathogenic mechanism of this mutation is through altered splicing of MAPT transcripts. Recently, mutations in the gene encoding progranulin (PGRN) were identified as a major cause of FTLD. In the second study we describe a Swedish family with FTLD caused by a frameshift mutation in PGRN. We provide a clinical and neuropathological description of the family, as well as evidence that the pathogenicity of this mutation is through nonsense-mediated decay of the mutant mRNA transcripts and PGRN haploinsufficiency. In the third study we describe a novel PGRN splice site mutation and a previously described PGRN frameshift mutation, found in a mutation screen of 51 FTLD patients. We describe the clinical and neuropathological characteristics of the mutation carriers and demonstrate that haploinsufficiency is the pathogenic mechanism of the two mutations. In the fourth study we investigate the prevalence of PGRN and MAPT gene dosage alterations in 39 patients with FTLD. No gene dosage alterations were identified, indicating that variations in copy number of the PGRN and MAPT genes are not a common cause of disease, at least not in this FTLD patient collection.

Landscapes are comprised of multiple ecosystems shaped by disturbances varying in severity and source. Moderate disturbance from weather, pathogens, insects, and age-related senescence, in contrast to severe disturbances that fell trees, may increase standing woody debris and alter the contribution of coarse woody debris (CWD) to total ecosystem respiration (RE). However, woody debris dynamics are rarely examined following moderate disturbances that substantially increase standing dead wood stocks. We used an experimental manipulation of moderate disturbance in an upper Great Lakes forest to: 1) examine decadal changes in CWD stocks through a moderate disturbance; 2) quantify in situ CWD respiration during different stages of decay for downed and standing woody debris and; 3) estimate the annual contribution of CWD respiration to the ecosystem C balance through comparison with RE and net ecosystem production (NEP). We found that the standing dead wood mass of 24.5 Mg C ha-1 was an order of magnitude greater than downed woody debris stocks and a large source of ecosystem C flux six years following disturbance. Instantaneous in situ respiration rates from standing and downed woody debris in the earliest stages of decay were not significantly different from one another. Independently derived estimates of ecosystem CWD respiration of 1.1to 2.1 Mg C ha-1 yr-1 six years following disturbance were comparable in magnitude to NEP and 12.5 % to 23.8 % of RE, representing a substantial increase relative to pre-disturbance levels. Ecosystem respiration and NEP were stable following moderate disturbance even though ecosystem CWD respiration increased substantially, suggesting a reduction in the respiratory C contribution from other sources. We conclude that CWD is an essential component of the ecosystem C balance following a moderate forest disturbance.

In the United State today, many people do not have access to adequate dental treatment, while tooth decay is the single most common chronic childhood disease-five times more common than asthma and seven times more common than hay fever. At the same time, studies show that 80% of dental illness takes place in 25% of the population, which is comprised mostly of lower socioeconomic groups. A study undertaken by the National Health and Nutrition Examination Survey in 2000, concludes that poor children suffer five times as much tooth decay as their more affluent peers. Furthermore, in poor children with tooth decay, almost 80% remain untreated. Poor dental health there-fore is a major health concern for under privileged families.The goal of this project is to enhance and facilitate the delivery of better dental treatment by designing a new prototype for a portable dental office that will be more flexible and more usable in a variety of situations and locations. For the purpose of this study, this prototype will be considered or tested within the context of three different types of spaces: the single closed room; a large open public space; and within mobile and nonpermanent structures such as tents. Several aspects of working conditions specific to the dental office will be taken into account when developing this design including transportability, degree of flexibility, storability, hygiene, and the creation of a relaxing atmosphere all of which greatly impact both the dentists and patients experience and are essential to the creation of a successful portable dental office.

Il est établi depuis maintenant 40 ans que l'interaction nucléaire forte peut être décrite par la Chromodynamique Quantique (QCD). Le confinement des quarks dans cette théorie masque cependant ses degrés de liberté élémentaires dans les processus de basse énergie, qui doivent être calculés non-perturbativement. La QCD sur réseau est à ce jour la seule méthode permettant de mener à bien de tels calculs, et arrive dorénavant à maturité. Cependant, et alors que le spectre des hadrons stables est calculée avec précision, l'étude des désintégrations reste délicate. Nous présentons ici l'application du formalisme de Lüscher au calcul des propriétés de résonances se désintégrant sous l'interaction forte, ainsi qu'un calcul avec précision de la largeur de désintégration dans le cas particulier du meson rho. / It has been established for now 40 years that the strong nuclear interaction can be described by Quantum Chromodynamics (QCD). However, the confinement of quarks in this theory hides its elementary degrees of freedom in low-energy processes, which have to be computed non-pertubatively. Lattice QCD is, to date, the only method allowing to go through such a computation, and is now reaching maturity. However, although the spectrum of stable hadrons is computed with precision, the study of decays is still delicate. We hereby present the application of Lüscher's formalism to the study of strong-decaying resonance properties, along with a precise computation of the decay width in the particular case of the rho meson.