The effects of gravity modulation on the instability of double-diffusive convections in a horizontal tank with aspect ratio (width/height) of 11 have been investigated by experiments and numerical simulations. The stably stratified fluid layer is set up with ethanol-water solution of 0.0 and 2.0% (by weight). The tank is fixed on a platform that can oscillate in the vertical direction. A constant temperature difference is maintained across the tank at thermal Rayleigh number . The fluid layer becomes unstable as the initially stable solute gradient slowly decreases due to the non-diffusive boundary conditions. The experiments determine that the instability onset under steady gravity is at with onset vortices of wavelength and oscillatory frequency . When the tank is oscillated at modulation frequency and amplitude , the fluid layer is destabilized slightly with a critical and onset vortices of and . A two-dimensional numerical simulation has accurately reproduced the experimental results of steady gravity, and demonstrated that the slight destability effect of gravity modulation is contributed by the asymmetry of the actual gravity modulation.Further simulations have yielded following results: (1) Under steady gravity, the kinetic energy and mechanical work components oscillate synchronously with . Under modulated gravity, they only oscillate synchronously with when is low, whereas not only synchronously with locally but also synchronously with globally when is high; (2) The resonance phenomenon predicted by Chen (2001) also exists under the present lab conditions. Such instability is in the sub-harmonic mode and the destability effect increases as increases. (3) The double-diffusive fluid layer may experience density-mode instability before the double-diffusive instability onset at certain and . Such density-mode instability is generally in the sub-harmonic mode, although it may be in the synchronous mode when is low and is large. This instability accelerates the mixing of the density gradient across the fluid layer and thus affects the succeeding double-diffusive instability; (4) When the background gravity is absent, the purely modulated gravity destabilizes the fluid layer when is low. On the contrary, it stabilizes the fluid layer when is high and the instability onset is in the synchronous mode.

Internal friction has been known to be a cause of whirl instability in built-up rotors since the early 1900's. This internal damping tends to make the rotor whirl at shaft speeds greater than a critical speed, the whirl speed usually being equal to the critical speed. Over the years of research, though models have been developed to explain instabilities due to internal friction, its complex and unpredictable nature has made it extremely difficult to come up with a set of equations or rules that can be used to predict instabilities accurate enough for design. This thesis deals with suggesting improved methods for predicting the effects of shrink fits on threshold speeds of instability. A supporting objective is to quantify the internal friction in the system by measurements. Experimental methods of determining the internal damping with non-rotating tests are investigated, and the results are correlated with appropriate mathematical models for the system. Rotating experiments were carried out and suggest that subsynchronous vibration in rotating machinery can have numerous sources or causes. Also, subsynchronous whirl due to internal friction is not a highly repeatable phenomenon.

The tube hydroforming process has gained increasing attention in recent years. Coordination of the internal pressurization and axial feeding curves is critical in the tube hydroforming process to generate successful parts without fracture or wrinkling failure. The stress state at a given time and location varies with the process history and the design and control of the load paths. A new process parameter, counter-pressure, is introduced to achieve a favorable tri-axial stress state during the deformation process. The new process is referred to as dual hydroforming. The benefits offered by dual hydroforming will be characterized based upon the amount of wall thinning, plastic instability limit and final bulged configuration. An analytical model is developed to analyze the stress and strain state in the part (tube) during the dual hydroforming process. The stress-strain condition analyzed will be used to evaluate and compare thinning for tube hydroforming and dual hydroforming. The effect of applying counter-pressure on the plastic instability of thin-walled tubes with only internal pressure and combination of internal pressure and independent axial loading is considered. Finite element analysis is used to quantify the merits of dual hydroforming in terms of final bulged configuration. A parametric study has been conducted to investigate the effectiveness of dual hydroforming based on the various material properties and process conditions. Dual hydroforming results in different stress and strain states compared to tube hydroforming. The counter-pressure enabled favorable tri-axial stress state during deformation that resulted in different thickness and percentage thinning. Finite element analysis showed that for a particular amount of wall thinning there is an increase of around 8% in bulge height for dual hydroforming. Dual hydroforming delays the onset of plastic instability. This increase in the value of effective strain to failure results in an increase of around 12% in bulge height for dual hydroforming as shown by finite element simulations. Results of this study indicate that dual hydroforming can increase expansion i.e. more difficult parts can be designed and manufactured. Also, for a given part geometry, higher strength and less formable materials can be used.

The evolution of prostate cancer from normal epithelium via the preneoplastic lesion of high-grade prostatic intraepithelial neoplasia to invasive carcinoma is characterised by a number of particular genomic abnormalities that are predominantly generated in the preneoplastic phase. Whilst there are numerous candidates for the cause of these alterations, telomere dysfunction is thought to be a major contributor. Telomeres are the terminal ends of human chromosomes, and when dysfunctional can lead to break-fusion-bridge cycles and multi-polar mitoses that generate numerical and structural chromosomal instability. The results presented reinforce the association of telomere dysfunction with the generation of certain markers of genomic instability such as abnormalities of the arms of chromosome 8. Furthermore, this work clarifies that the TMPRSSS2-ERG aberrations are not telomere related phenomena and are associated with a genomic deletion in a proportion of cases. Similarly, the PTEN microdeletions did not appear to have an association with telomere attrition. A previously unrecognised association between the telomere length in various types of prostatic epithelia and adjacent stroma is defined, suggesting evidence of a micro-environmental field effect in the generation of prostatic neoplasia. Finally, when examined retrospectively, it appears that telomere attrition, both in the HPIN epithelium and the stroma has independent prognostic value in the diagnosis of prostate cancer after a previous diagnosis of HPIN. Taken together, the research presented suggests important avenues for further research to determine the nature of barriers to the evolution of prostatic carcinogenesis such as oncogene- and telomere-induced senescence that may be exploited for therapeutic gain. These understandings may also help tailor management for prostate cancer such as risk stratification for men with HPIN and the use of targeted agents such as AKT inhibitors and telomerase inhibitors. In more advanced disease, translational application of this work has enabled a clinical trial of cytarabine in the treatment of metastatic hormone refractory prostate cancer.

The evolution of prostate cancer from normal epithelium via the preneoplastic lesion of high-grade prostatic intraepithelial neoplasia to invasive carcinoma is characterised by a number of particular genomic abnormalities that are predominantly generated in the preneoplastic phase. Whilst there are numerous candidates for the cause of these alterations, telomere dysfunction is thought to be a major contributor. Telomeres are the terminal ends of human chromosomes, and when dysfunctional can lead to break-fusion-bridge cycles and multi-polar mitoses that generate numerical and structural chromosomal instability. The results presented reinforce the association of telomere dysfunction with the generation of certain markers of genomic instability such as abnormalities of the arms of chromosome 8. Furthermore, this work clarifies that the TMPRSSS2-ERG aberrations are not telomere related phenomena and are associated with a genomic deletion in a proportion of cases. Similarly, the PTEN microdeletions did not appear to have an association with telomere attrition. A previously unrecognised association between the telomere length in various types of prostatic epithelia and adjacent stroma is defined, suggesting evidence of a micro-environmental field effect in the generation of prostatic neoplasia. Finally, when examined retrospectively, it appears that telomere attrition, both in the HPIN epithelium and the stroma has independent prognostic value in the diagnosis of prostate cancer after a previous diagnosis of HPIN. Taken together, the research presented suggests important avenues for further research to determine the nature of barriers to the evolution of prostatic carcinogenesis such as oncogene- and telomere-induced senescence that may be exploited for therapeutic gain. These understandings may also help tailor management for prostate cancer such as risk stratification for men with HPIN and the use of targeted agents such as AKT inhibitors and telomerase inhibitors. In more advanced disease, translational application of this work has enabled a clinical trial of cytarabine in the treatment of metastatic hormone refractory prostate cancer.

The Canadian National Memorial Site, near Vimy, Artois, France, commemorates the WWI Battle of Vimy Ridge; where all four divisions of the young Canadian Corps fought together with the British Forces to liberate the French ridge. Today, trench systems and an extensive subterranean network of tunnels underlie the gentle landscape of the park, which is visited each year by hundreds of thousands of tourists. Failure within these excavations is expressed as local subsidence and is potentially hazardous to the public. The following research identifies the geologic factors that influence instability in the excavations and how these factors vary both with depth and lateral extent. The Artois region of northern France is underlain by Upper Cretaceous chalk with a thin veneer of Paleocene sediments. Structure is dominated by the northwest-southeast trending Weald-Boulonnais anticlinorium. Three principle geological controls govern failure within the excavations at the Vimy site; lithologic variations, structural geometry and carbonate dissolution. An extensive stratigraphic study identified variable horizons such as chalk marls, nodular chalks, hardgrounds and flint seams, which affect the strength, permeability and structure of the rockmass. Structural geometry in the chalk varies with depth and clay content. Orthogonal fracture patterns are typical in pure carbonate rockmasses whereas inclined conjugate sets occur in clay-rich chalk. Three failure mechanisms were observed in the Vimy excavations that vary with structure and lithology. Beam failure via block fall-out is observed in pure chalk with subhorizontal and subvertical structures. Ravelling, the upward propagation of roof failure, is typical of closely spaced inclined jointing, and is also observed in shallow clay-rich lithologies. Finally, dissolution pipes occur at the intersection lineations of conjugate joint sets, and are also typical of clay-rich lithologies. Dissolution by meteoric groundwater is identified as the third geologic control and results in a decrease of intact strength, weakening of joint surfaces and overall loss of confinement in the rockmass, thereby initiating the failure modes described previously. These extensive geologic studies pinpoint the origins and variability of instability in the rockmass at the Vimy site. / Thesis (Master, Geological Sciences & Geological Engineering) -- Queen's University, 2007-12-21 11:08:16.522

Cancer is a disease that involves genomic instability, to which c-Myc contributes during its initiation and progression. Over 70% of all human cancers show deregulated levels of c-Myc protein. The term genomic instability refers to genetic and/or epigenetic changes that alter the normal organization and function of genes and chromosomes. Genomic instability is a hallmark of cancer and often is associated with cancer. Deregulated c-Myc expression generates genomic instability by initiating intra- and extrachromosomally locus-specific gene amplification, gene rearrangements and karyotypic instability that includes translocations, fusions, insertions and deletions. Out of the several outlined pathways by which deregulated levels of c-Myc can lead to genomic instability, the work described in this thesis focuses on three with direct relevance to tumorigenesis; gene amplification (increase in gene copy number), remodeling of the chromosomal and telomeric structures in the interphase nucleus and comparing the effect of Myc to that of Epstein Bar virus (EBV) infection in remodeling the nuclear structure that may lead to genomic instability.

No description available.

Cancer is a disease that involves genomic instability, to which c-Myc contributes during its initiation and progression. Over 70% of all human cancers show deregulated levels of c-Myc protein. The term genomic instability refers to genetic and/or epigenetic changes that alter the normal organization and function of genes and chromosomes. Genomic instability is a hallmark of cancer and often is associated with cancer. Deregulated c-Myc expression generates genomic instability by initiating intra- and extrachromosomally locus-specific gene amplification, gene rearrangements and karyotypic instability that includes translocations, fusions, insertions and deletions. Out of the several outlined pathways by which deregulated levels of c-Myc can lead to genomic instability, the work described in this thesis focuses on three with direct relevance to tumorigenesis; gene amplification (increase in gene copy number), remodeling of the chromosomal and telomeric structures in the interphase nucleus and comparing the effect of Myc to that of Epstein Bar virus (EBV) infection in remodeling the nuclear structure that may lead to genomic instability.

The instability behaviour of detonation waves are studied using Fickett's model with a 2-step reaction model with separately controlled induction and reaction zones. This model acts as a simplified toy-model to the reactive Euler equations allowing for more clarity of the detonation phenomenon. We numerically simulate a 1D self-supported detonation and investigate the pulsating instability behaviour. We are able to clarify the governing mechanism behind the pulsations through a characteristic analysis describing the coupling that takes place between the amplification of the compressions waves and the alteration to the induction timing. We examine the acceleration phase of the pulsations and determine an analytical solution to describe the strength of the amplification. Fickett's model is as well shown to reproduce the same period doubling bifurcation with increasing sensitivity of the induction rate, and route to chaos as seen in the full reactive Euler equations.