Les ephrines et leurs récepteurs Eph constituent une famille multigénique de facteurs de guidage cellulaire et axonal. Ces facteurs jouent un rôle-clé dans l’établissement de cartes neurales topographiques, notamment au niveau des connexions thalamocorticales, réseau neuronal majeur du cerveau des mammifères. Notre projet visait initialement à étudier l’implication des ephrines corticales dans la génèse des connexions thalamocorticales par une approche de gain de fonction. Pour ce faire, nous avons généré des souris transgéniques présentant une expression ectopique spécifique de l’ephrine-A5 dans le cortex en développement, en utilisant une technique de transgénèse d’addition par chromosome artificiel de bactéries (BAC). De façon surprenante, l’analyse de ces souris nous a révélé que les ephrines, à côté de leurs rôles classiques de facteurs de guidage, influençaient la taille du cortex cérébral en régulant l’apoptose des progéniteurs neuronaux. En effet, nous avons pu montrer que l’expression ectopique du ligand ephrine-A5 par les progéniteurs corticaux exprimant son récepteur EphA7 résultait en une déplétion précoce en progéniteurs corticaux par apoptose, et une diminution subséquente de la taille du cortex. Cette vague apoptotique est observée en l’absence de toute altération détectable de la prolifération, la différenciation et la migration neurale dans le cortex. Nous avons étayé notre étude in vivo par des expériences in vitro, qui ont montré que l’ephrine-A5 recombinante était capable d’induire rapidement la mort des progéniteurs neuronaux dissociés. Nous avons également montré que cette mort cellulaire impliquait l’activation de la caspase-3, confirmant ainsi l’effet direct des ephrines et de leurs récepteurs sur une ou plusieurs cascades apoptotiques. Par contre, la stimulation des neurones post-mitotiques corticaux par l’ephrine-A5 est accompagnée d’une activation de la caspase-3 sans mort cellulaire apparente. La signalisation ephrine/Eph induirait donc l’activation de la caspase-3 dans différents types cellulaires, sans que celle-ci ne soit systématiquement le reflet d’une mort cellulaire programmée. Parallèlement, afin d’évaluer l’importance physiologique de cette voie pro-apoptotique dépendante des ephrines, nous avons étudié des souris présentant une perte de fonction du récepteur EphA7. L’analyse de ces mutants nous a permis de mettre en évidence une diminution de l’apoptose des progéniteurs corticaux, une augmentation de la taille du cortex, ainsi qu’une hypercroissance exencéphalique de tout le cerveau antérieur dans les cas les plus extrêmes. Ces observations indiquent donc que les ephrines sont nécessaires au contrôle de la mort cellulaire programmée des progéniteurs du cortex cérébral. Nous avons également observé le même phénotype exencéphalique dans des mutants déficients en ephrines-A2, -A3 et -A5, dont l’analyse préliminaire suggère également des défauts de processus apoptotiques. Nos diverses expériences, combinant une approche par gain et perte de fonction, à la fois in vivo et in vitro, ont ainsi permis de proposer un nouveau rôle des ephrines en marge de leur implication dans la guidance axonale, à savoir un rôle dans le contrôle de la taille cérébrale par induction de l’apoptose des progéniteurs corticaux. La mise en évidence de cette nouvelle voie de signalisation pro-apoptotique pourrait avoir des implications importantes dans d’autres aspects de la biologie du développement et des cellules souches, ainsi que dans l’oncogénèse.

Investigations on post service material showed that Alloy 800H pigtails from methanol producer Methanex have service lives ranging from 3 to 18 years. Because of this variability in service life, Alloy 800H creep performance was assessed and a new criterion for its procurement developed. The current criterion recommends an ASTM grain size of 5 (72µm) or coarser with no consideration given to grain size distribution, grain boundary types, or grain boundary network topology. Results from the investigation showed that this current criterion may produce variations in steady state creep rates of an order of magnitude between ASTM grain size 1 and 5, and a 2.5 times variation in creep ductility. The ability to accurately reveal grain boundaries and assess grain boundary types is fundamental to the identification and quantification of coherent twin boundaries, and the measurement of average grain size and grain size distribution. EBSD mapping has the ability to distinguish grain boundary types using crystal orientation measurement. Grain size measurement from optical micrographs relies on morphological indicators to identify coherent twins. However, it is shown that many of the boundaries observed as straight line morphology on 2D sections did not possess {111} (coherent) interfaces. 3D reconstructions of Alloy 800H revealed the deficiencies in classifying geometry from two-dimensional (2D) sections. Σ3 Crystal volumes can be categorized as lamellar or edge structures. Lamellar structures are characterized by the appearance of parallel Σ3 boundary planes while an edge structure contains a single Σ3 interface. Sectioning plane location alters the perception of morphology. For simple twin structures, the tradition 2D classifications of morphology (complete parallel, incomplete parallel and corner Σ3) may all appear on a section plane from a single lamellar structure.

A new retrieval algorithm has been developed based on the Optimal Estimation (OE) approach, which retrieves lognormal aerosol size distribution parameters from multiwavelength aerosol extinction data, as measured by the Stratospheric Aerosol and Gas Experiment (SAGE) II in the lower stratosphere. Retrieving these aerosol properties becomes increasingly more difficult under aerosol background conditions, when tiny particles (« 0.1 µm) prevail, to which the experiment is nearly or entirely insensitive. A successful retrieval algorithm must then be able (a) to fill the 'blind spot' with suitable information about the practically invisible particles, and (b) to identify 'the best' of many possible solutions. The OE approach differs from other previously used aerosol retrieval techniques by taking a statistical approach to the multiple solution problem, in which the entire range of possible solutions are considered (including the smallest particles) and characterized by probability density functions. The three main parts of this thesis are (1) the development of the new OE retrieval algorithm, (2) the validation of this algorithm on the basis of synthetic extinction data, and (3) application of the new algorithm to SAGE II measurements of stratospheric background aerosol. The validation results indicate that the new method is able to retrieve the particle size of typical background aerosols reasonably well, and that the retrieved uncertainties are a good estimate of the true errors. The derived surface area densities (A), and volume densities (V ) tend to be closer to the correct solutions than the directly retrieved number density (N), median radius (R), and lognormal distribution width (S). Aerosol properties as retrieved from SAGE II measurements (recorded in 1999) are observed to be close to correlative in situ data. In many cases the OE and in situ data agree within the (OE and/or the in situ ) uncertainties. The retrieved error estimates are of the order of 69% (σN), 33% (σR), 14% (σS), 23% (σA), 12% (σV), and 13% (σReff ). The OE number densities are generally larger, and the OE median particle sizes are generally smaller than those N and R retrieved by Bingen et al. (2004a), who suggest that their results underestimate (N) or overestimate (R) correlative in situ data due to the 'small particle problem'. The OE surface area estimates are generally closer to correlative in situ profiles (courtesy of T. Deshler, University of Wyoming), and larger than Principal Component Analysis (PCA) retrieval solutions of A (courtesy of L. W. Thomason, NASA LaRC) that have been observed to underestimate correlative in situ data by 40-50%. These observations suggest that the new OE retrieval algorithm is a successful approach to the aerosol retrieval problem, which is able to add to the current knowledge by improving current estimates of aerosol properties in the lower stratosphere under low aerosol loading conditions.

Little is known about the spatial distribution and abundance of tree holes in New Zealand’s native forests, or the invertebrate communities that they support. I found that tree holes were common on five endemic tree species, belonging to the families Fagaceae and Podocarpaceae in the mixed broadleaf-podocarp rainforest of Orikaka Ecological Area, Buller District, New Zealand. However, tree holes were not uniformly distributed throughout the forest, with more holes found on the three podocarp species, Prumnopitys ferruginea, P. taxifolia and Dacrycarpus dacrydioides, than on Nothofagus fusca or N. menziesii. Nevertheless, Nothofagus fusca had the largest holes of any of the tree species sampled and larger trees generally had larger holes. Large, hole-bearing Nothofagus fusca trees support a specialist hole-dwelling vertebrate fauna in New Zealand and worldwide, tree holes provide habitat for a range of invertebrate species. Using specially-designed emergence traps, I collected invertebrates emerging from naturally-occurring dry tree holes and compared this assemblage with invertebrates inhabiting leaf litter on the forest floor and those dispersing aerially throughout the study area. At the higher taxonomic resolution (i.e., Order or Class), community composition within the tree holes was highly variable, and there was no strong distinction between invertebrates from tree holes, leaf litter or Malaise traps. Moreover, although some beetle species emerging from tree holes were found exclusively in tree holes, most of these were represented by a single individual. Consequently, only minor differences in species composition were detected between beetle assemblages from tree holes, leaf-litter and those aerially dispersing throughout the forest. In contrast, the aquatic invertebrate assemblage within water-filled tree holes was highly distinctive from that in ground-based freshwater ecosystems, with only six aquatic taxa in common between all freshwater habitats. Using experimental water-filled tree-hole microcosms, I found that species richness and community composition within these microcosms were primarily driven by resource concentration, although habitat quality (i.e., water chemistry parameters) was also an important determinant of the identity and composition of colonising species. Overall, my study has shown that tree holes are common in the study area, and are likely to be more abundant in New Zealand’s indigenous forests than previously thought. Moreover, these generally small, discrete forest ecosystems support a diverse array of terrestrial invertebrates as well as a distinctive aquatic invertebrate community that is primarily structured by organic matter resource availability. These findings not only represent an important advance in our knowledge of New Zealand’s freshwater invertebrate biodiversity, but also highlight the need for further investigation into these unique forest canopy habitats which may well be at risk from deforestation and land use change.

No description available.

No description available.

No description available.

Class size has long been recognized as a factor affecting achievement in face-to-face contexts. However, few studies have examined the effects of class size in online courses, or the effects of dividing an online class into smaller discussion groups. The current study examined the relationship between class size and the use of grouping strategies on note reading, note writing, and collaborative discussions in online graduate-level courses. This mixed-methods study analyzed tracking logs from 25 graduate-level online courses using Web Knowledge Forum (25 instructors and 341 students) and interviews from 10 instructors and 12 graduate students with diverse backgrounds. The quantitative and qualitative data analyses were designed to complement each other. Findings suggested 13 to 15 as an optimal class size and four to five as an ideal subgroup size. Not surprisingly, the results revealed that, as class size increased, the total notes that participants read increased significantly. However, as class size increased, the percentage of course notes that students read decreased significantly (i.e., students were reading a smaller proportion of the course notes). In larger classes, participants were more likely to experience information overload and students were more selective in the notes that they read. A significant positive correlation was found between class size and total notes written. Students’ note size and grade-level score were negatively correlated with class size. The data also suggest that the overload effects of large classes can be minimized by dividing students into small groups for discussion purposes. Interviewees felt that the use of small groups in large classes benefited their collaborative discussions. The preceding results underscore the importance of using small discussion groups when class sizes are large. The research concludes with a list of pedagogical recommendations and suggests new software features that may help enhance learning in online courses.

Cobalt-60 (Co-60) units played an integral role in radiation therapy from the mid-1950s to the 1970s. Although they continue to be used to treat cancer in some parts of the world, their role has been significantly reduced due to the invention of medical linear accelerators. A number of groups have indicated a strong potential for Co-60 units in modern radiation therapy. The Medical Physics group at the Cancer Center of the Southeastern Ontario and Queen’s University has shown the feasibility of Intensity Modulated Radiation Therapy (IMRT) via simple conformal treatment planning and dose delivery using a Co-60 unit. In this thesis, initial Co-60 tomotherapy planning investigations on simple uniform phantoms are extended to actual clinical cases based on patient CT data. The planning is based on radiation dose data from a clinical Co-60 unit fitted with a multileaf collimator (MLC) and modeled in the EGSnrc Monte Carlo system. An in house treatment planning program is used to calculate IMRT dose distributions. Conformal delivery in a single slice on a uniform phantom based on sequentially delivered pencil beams is verified by Gafchromic film. Volumetric dose distributions for Co-60 serial tomotherapy are then generated for typical clinical sites that had been treated at our clinic by conventional 6MV IMRT using Varian Eclipse treatment plans. The Co-60 treatment plans are compared with the clinical IMRT plans using conventional matrices such as dose volume histograms (DVH). Dose delivery based on simultaneously opened MLC leaves is also explored and a novel MLC segmentation method is proposed. In order to increase efficiency of dose calculations, a novel convolution based fluence model for treatment planning is also proposed. The ion chamber measurements showed that the Monte Carlo modeling of the beam data under the MIMiC MLC is accurate. The film measurements from the uniform phantom irradiations confirm that IMRT plans from our in-house treatment planning system are deliverable. Comparing the Co-60 dose distributions and DVHs to the IMRT plans from the clinic indicates that Co-60 is able to provide similar dose conformality to targets and dose sparing to critical organs. The results of the novel MLC segmentation algorithm and the photon fluence model proposed in this work compared well with the Monte Carlo calculations. In summary, the investigations presented in this thesis confirm that Co-60 tomotherapy is indeed capable of providing state-of-the-art conformal dose delivery. We have shown that the perceived beam limitations often identified with Co 60 (e.g., lower penetration, source size artifacts under small field collimation, and larger penumbra) are negligible when using intensity modulated techniques. / Thesis (Ph.D, Physics, Engineering Physics and Astronomy) -- Queen's University, 2013-08-22 11:34:14.861

Cobalt-60 (Co-60) units played an integral role in radiation therapy from the mid-1950s to the 1970s. Although they continue to be used to treat cancer in some parts of the world, their role has been significantly reduced due to the invention of medical linear accelerators. A number of groups have indicated a strong potential for Co-60 units in modern radiation therapy. The Medical Physics group at the Cancer Center of the Southeastern Ontario and Queen’s University has shown the feasibility of Intensity Modulated Radiation Therapy (IMRT) via simple conformal treatment planning and dose delivery using a Co-60 unit. In this thesis, initial Co-60 tomotherapy planning investigations on simple uniform phantoms are extended to actual clinical cases based on patient CT data. The planning is based on radiation dose data from a clinical Co-60 unit fitted with a multileaf collimator (MLC) and modeled in the EGSnrc Monte Carlo system. An in house treatment planning program is used to calculate IMRT dose distributions. Conformal delivery in a single slice on a uniform phantom based on sequentially delivered pencil beams is verified by Gafchromic film. Volumetric dose distributions for Co-60 serial tomotherapy are then generated for typical clinical sites that had been treated at our clinic by conventional 6MV IMRT using Varian Eclipse treatment plans. The Co-60 treatment plans are compared with the clinical IMRT plans using conventional matrices such as dose volume histograms (DVH). Dose delivery based on simultaneously opened MLC leaves is also explored and a novel MLC segmentation method is proposed. In order to increase efficiency of dose calculations, a novel convolution based fluence model for treatment planning is also proposed. The ion chamber measurements showed that the Monte Carlo modeling of the beam data under the MIMiC MLC is accurate. The film measurements from the uniform phantom irradiations confirm that IMRT plans from our in-house treatment planning system are deliverable. Comparing the Co-60 dose distributions and DVHs to the IMRT plans from the clinic indicates that Co-60 is able to provide similar dose conformality to targets and dose sparing to critical organs. The results of the novel MLC segmentation algorithm and the photon fluence model proposed in this work compared well with the Monte Carlo calculations. In summary, the investigations presented in this thesis confirm that Co-60 tomotherapy is indeed capable of providing state-of-the-art conformal dose delivery. We have shown that the perceived beam limitations often identified with Co 60 (e.g., lower penetration, source size artifacts under small field collimation, and larger penumbra) are negligible when using intensity modulated techniques. / Thesis (Ph.D, Physics, Engineering Physics and Astronomy) -- Queen's University, 2013-08-22 11:34:14.861