La désintégration $B_{ (s)}$ → τμ est supprimée dans le SM, où le nombre leptonique est conservé. Son observation serait donc une preuve non ambiguë de la physique au-delà du SM. Des résultats récents [1,2] ont ravivé l'intérêt pour la recherche de tels processus [3]. Cette thèse présente la recherche des désintégrations $B_{ (s)}$→ τμ dans l'expérience LHCb, l'une des 4 grandes expériences menées au Large Hadron Collider (LHC) du CERN.Le lepton τ se désintègre avant d'atteindre le détecteur LHCb et est reconstruit en utilisant le canal τ → πππν. Le neutrino provenant de la désintégration du τ échappe à la détection. Une technique de reconstruction spécifique est utilisée pour déduire l'énergie du neutrino et donc la masse invariante du méson B qui s'est désintégré.Afin de séparer le signal du bruit de fond, une sélection hors ligne composée de différentes étapes est appliquée. Des techniques d'analyse multivariées, telles que les arbres de décision boostés (BDT), sont utilisées pendant le processus de sélection.La stratégie d'analyse est complétée par un ajustement simultané à la distribution de masse invariante des mésons B dans différentes régions d'un BDT final. Selon les prédictions du SM, aucun événement de signal n'est attendu. Dans ce cas, la méthode CLs sera utilisée pour extraire les limites supérieures des rapports de branchement BR($B_{ (s)}$→ τμ).[1] Test of lepton universality using $B^+$→$K^+$$l ^+$$l ^-$ decaysPhys. Rev. Lett. 113, 151601 (2014)[2] Measurement of the ratio of branching fractions BR(B → D*τ ν)/BR(B → D*μν)Phys. Rev. Lett. 115 (2015) 111803[3] Lepton Flavour Violation in B Decays ? Phys. Rev. Lett. 114, 091801 (2015) / The decay $B_{ (s)}$→τμ is suppressed in the SM, in which lepton flavour is conserved. Its observation would therefore be an unambiguous evidence of physics beyond the SM. Recent results [1,2] revived the interest for the search of such processes [3]. This thesis presents the search for the $B_{ (s)}$→τμ decays within the LHCb experiment, one of the 4 large experiments operated at the CERN Large Hadron Collider (LHC).The τ lepton decays before reaching the LHCb detector and is reconstructed using the τ→πππν channel. The neutrino from the τ decay escapes detection. A specific reconstruction technique is used in order to infer the energy of the ν and thus the invariant mass of the decaying B meson. This way, the complete kinematics of the process can be solved up to a two fold ambiguity.In order to disentangle signal from background, an offline selection consisting of different steps is applied. Data driven and multivariate analysis techniques, such as Boosted Decision Trees (BDT), are used during the selection process. The analysis strategy is completed by a simultaneous fit to the B meson invariant mass distribution over the different bins of a final BDT. According to the SM expectations, no signal events should be observed. In this case, the CLs method will be used to extract the upper limits on the branching fractions.[1] Test of lepton universality using $B^+$→$K^+$$l ^+$$l ^-$ decaysPhys. Rev. Lett. 113, 151601 (2014)[2] Measurement of the ratio of branching fractions BR(B → D*τ ν)/BR(B → D*μν)Phys. Rev. Lett. 115 (2015) 111803[3] Lepton Flavour Violation in B Decays ? Phys. Rev. Lett. 114, 091801 (2015)

Streptococcus mutans is a recognized principal etiologic agent in coronal caries. Although S. mutans has the ability to bind collagen and degrade FALGPA, a synthetic peptide mimicking collagen substrate, its role in dental root caries has not yet been fully elucidated. Degradation of collagen fibrils in dentin was attributed to S. mutans, but a collagenase enzyme has not yet been isolated from this organism. Considering the increased incidence of dental root decay among the elderly, an understanding of the role of the pathogenic factors is necessary to the development of preventive measures. The present study has focused on the cloning and analysis of S. mutans collagenase enzyme. Toward this goal, a putative collagenase gene was identified in S. mutans UA159 by genomic analysis and a primer set was designed and used to amplify the corresponding gene in S. mutans GS-5 used as a model organism. The PCR product was cloned into the vector pCR 2.1 TOPO-TA, and the gene sequenced and analyzed. Alignment of the S. mutans GS-5 and UA159 putative collagenase genes showed 99% homology. The gene was next cloned in frame into the inducible expression vector pET100/D TOPO. Induction and expression of recombinant protein in E. coli were confirmed by SDS-PAGE and Western immunoblotting, while biochemical analysis indicated that it was a calcium- dependent metalloproteinase. Enzyme analysis of the recombinant enzyme showed both gelatinolytic and collagenolytic activity. Further analysis of the GS5 gene using databases such as ExPASy, Pfam, and SMART indicated that it was highly homologous to the U32 peptidase family, which includes the PrtC collagenase of Porphyromonas gingivalis, a bacterium causing periodontitis. The present study was the first to unequivocally demonstrate the existence of a collagenase gene in S. mutans, and to identify it as a member of the U32 peptidase family. The obtaining of the S. mutans collagenase gene should help in further investigation of the role of this enzyme in dental root decay and its potential use as a dental root caries vaccine.

There is an intense interest in the availability of radioactive isotopes that could be developed into nuclear batteries. Promethium-147 is one of the isotopes of interest for use in nuclear batteries as well as in other compact low power applications. Pm-147 is a pure beta (β-) emitter with a half-life of 2.62 years. For this research, Pm-147 was produced from enriched Nd-146 via the neutron capture method in the Hydraulic Tube facility of HFIR at the Oak Ridge National Laboratory. Radioisotopic impurities produced via the neutron capture method have significant effects on its potential final use for nuclear battery applications. This research provides information on the co-production levels of the radioisotopic impurities in the samples containing Pm-147 and their effects on the required shielding. Gamma spectroscopy analysis served as the primary method in the evaluation of the impurities. Previous research had identified the presence of these impurities but it had not studied them in detail.

The purpose of this report is to present the results of the study and analysis of loss-of-coolant and loss-of-flow simulations performed on the Modular Helium Reactor developed by General Atomics using the thermal-hydraulics code RELAP5-3D/ATHENA. The MHR is a high temperature gas cooled reactor. It is a prismatic core concept for New Generation Nuclear Plant (NGNP). Very few reactors of that kind have been designed in the past. Furthermore, the MHR is supposed to be a highly passively safe concept. So there are high needs for numerical simulations in order to confirm the design. The project is dedicated to the assessment of the passive decay heat capabilities of the reactor under abnormal transient conditions. To comply with the requirements of the NGNP, fuel and structural temperatures must be kept under design safety limits under any circumstances. During the project, the MHR has been investigated: first under steady-state conditions and then under transient settings. The project confirms that satisfying passive decay heat removal by means of natural heat transfer mechanisms (convection, conduction and radiation) occurs.

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.

ABSTRACT Chemotherapy is a common method used for cancer treatment. Especially when it concerns cancers that have grown invasively it seems to be the only efficient treatment due to the substances ability to reach and affect almost the entire body. One major obstacle regarding chemotherapy is that the patients often develop resistance to the cytotoxic substances used. Fluorometric microculture cytotoxicity assay (FMCA) is a method developed to measure sensitivity of tumor cells to different cytotoxic substances in vitro. The assay is based on hydrolysis of fluorescein diacetate to fluorescein by cells with intact cell membranes after incubation with drugs for 72 hours. This study investigated the impact of two methodological factors that may cause errors in the achieved results; namely the possible occurrence of drug decay during incubation and the use of an inappropriate amount of cells. These factors were tested by exposing the cytotoxic drugs to pre-incubation in absence of tumor cells for different times and to use suspensions with different concentrations of cells. The results indicated occurrence of drug decay in 3 of the 18 substances tested and that the amount of cells affected the results for most of the drugs tested but to different extent.

This dissertation investigates characteristics of the vertical distributions of mass flux observed in field and laboratory experiments. Thirty vertical mass flux profiles were measured during a field experiment in Jericoacoara, Brazil from October to November, 2008. These data were supplemented with 621 profiles gathered from an extensive review of the aeolian literature. From the field experiment, the analysis of the grain-size statistics for the flux caught in each trap shows that a reverse in grain-size trends occurs at an inflection zone located 0.05 ? 0.15 m above the bed. Below this inflection, mean grain-size decreases steeply with elevation in the near bed region dominated by reptation and saltation modes of transport. Above the inflection there is a coarsening of grain size with elevation; as saltation becomes the dominant transport mode. These results indicate that the coarsest grains are found close to and farthest from the bed. Using a data set comprising 274 vertical flux profiles, the performance of the exponential, power and logarithmic functions were tested to see which provided the best fit to the vertical flux distributions. The exponential function performed best 88% of the time. The average r2 value for the grouped exponential, logarithmic, and power function fits are 0.98, 0.85 and 0.91, respectively. The populations of the exponent coefficients, representing the relative rate of decrease with height above the surface, or slope of the vertical mass flux profiles, are statistically different in wind tunnels and field experiments. The slopes of the vertical flux profiles observed in wind tunnel experiments are steeper compared to field environments, which infers that saltation is suppressed in wind tunnels. These differences are magnified in wind tunnels with small working cross section areas, and in wind tunnel experiments that use extreme environmental conditions, such as very high shear velocities. The Rouse concentration model, widely used in water studies, was tested to see if it could replicate the observed vertical flux distributions and transport rates. A fall velocity (w0) equation for particles falling in air was derived using a grain size (d) dependency: w0 (in m/s) = 4.23d (in mm) + 0.1956 (r^2=0.88). The Rouse model performs poorly when the value of the beta (a form of the Schmidt number in the Rouse number exponent) is assumed to be unity. The values of beta were modeled using a relationship derived from a dependency of beta on the w0/u* ratio: beta = 3.2778(w0/u*) - 0.4133 (r^2=0.65). The values of beta ranged from 6.11 ? 17.83 for all the experiments. The Rouse profiles calculated using this approach predict very similar vertical distributions to the observed data and predicted 86% and 81% of the observed transport rate in field and wind tunnel experiments respectively. The Rouse approach is more physically meaningful than current approaches that use standard curve fitting functions to represent the vertical flux data but do not provide any explanatory power for the shape or magnitude of the profile.

Characterization of semi-permeable films promotes the systematic selection of membranes and process design. When acquiring the diffusive and sorption properties of gas transport in non-porous membranes, the time lag method is considered the conventional method of characterization. The time lag method involves monitoring the transient accumulation of species due to permeation on a fixed volume present in a downstream reservoir. In the thesis at hand, an alternative approach to the time lag technique is proposed, termed as the short cut method. The short cut method appoints the use of a two reservoir system, where the species decay in the upstream face of the membrane is monitored, in combination with the accumulation on the downstream end. The early and short time determination of membrane properties is done by monitoring the inflow and outflow flux profiles, including their respective analytical formulas. The newly proposed method was revealed to have estimated the properties at 1/10 the required time it takes for the classical time lag method, which also includes a better abidance to the required boundary conditions. A novel design of the upstream reservoir, consisting of a reference and working volume, is revealed, which includes instructional use, and the mechanics involved with its operation. Transient pressure decay profiles are successfully obtained when the reference and working volumes consisted of only tubing. However when tanks were included in the volumes, large errors in the decay were observed, in particular due to a non-instantaneous equilibration of the pressure during the start up. This hypothesis was further re-enforced by examining different upstream tank-based configurations. iii In the end, a validated numerical model was constructed for the purpose of simulating the two reservoir gas permeation system. A modified form of the finite differences scheme is utilized, in order to account for a concentration-dependent diffusivity of penetrants within the membrane. Permeation behavior in a composite membrane system was disclosed, which provided a new perspective in analyzing the errors associated with the practical aspect of the system.

The 87Rb-86Sr system is a widely used long-lived isotope geochronometer. 87Rb, the naturally occurring radioactive isotope of Rb, undergoes beta-decay to stable 87Sr with a half-life of approximately 50 Ga. Decay of 87Rb to 87Sr results in variable 87Sr/86Sr in minerals with different Rb/Sr, and measurement of 87Rb/86Sr and 87Sr/86Sr allows for the determination of the age of the rock. Accurate ages depend both on the quality of the isotopic analysis and on the accuracy of the 87Rb decay constant, lambda87. Although the currently accepted value for lambda87 of 1.42 × 10-11a-1 has been in use for over 30 years, there is growing evidence that it is not accurate. Recent attempts to refine lambda87 and its precision have not reached a consensus. This thesis describes a new experiment to measure lambda87 by 87Sr accumulation over a period of about 30 years, and the preparation of a 84-86Sr double-spike in conjunction with that experiment. Radiogenic 87Sr produced in aliquots of a RbClO4 salt was measured by isotope dilution thermal ionization mass spectrometry. An average of 31 measurements yields a value of 1.398 ± 0.003 × 10-11a-1 . This requires a substantial revision from the previously accepted decay constant and makes Rb-Sr ages calculated with it 1.5% older. A Rb-Sr and U-Pb isotopic chronometry study was carried out on thirteen ordinary chondrites – the most common type of meteorite, the origin and history of which are still unclear. Some meteorites appear disturbed, possibly by recent shock during breakup of the parent body, whereas others yielded accurate and precise U-Pb and Pb-Pb ages. For example, L5 Elenovka yielded distinct ages for silicates (4555 Ma) and phosphates (4535 Ma), allowing the cooling rate of this meteorite from approximately 1055 K to 759 K to be constrained to 15 ± 3 K/Ma. Rb-Sr yielded less precise ages than U-Pb, but using the new decay constant allows accurate comparison between the two methods. This study creates a firm foundation for future studies in thermal history of chondrites and terrestrial metamorphic complexes using Rb-Sr together with other isotopic chronometers.

Graduation date: 1992