This dissertation describes instability as a problem with a variety of sources and explains Publius' contribution to understanding the importance of these problems for politics and political theory. Using the Federalist and Publius' reading in political theory, history, and politics to ground my analysis, I explain the concept of instability as a multi-faceted problem that requires different solutions. I show that instability arises from one or a combination of four distinct notions: stasis or factional conflict, corruption, the mutability of the laws, and changing global conditions. My dissertation suggests that one of the primary goals of ancient and modern democracies was to solve the political challenges posed by instability. I further argue that the sources of instability remain relevant because they allow us to describe the problem of instability in a way that is theoretically and practically useful for understanding the role that democracy plays in addressing them. Finally, I suggest that describing and addressing the patterns of instability were central to Publius' interpretation of history and political theory and that recognizing and tackling these patterns are a part of the scope of modern political science and are central to the study of democratic politics. / Dissertation

<p>A mitotically dividing cell regularly experiences DNA damage including double-stranded DNA breaks (DSBs). Homologous mitotic recombination is an important mechanism for the repair of DSBs, but inappropriate repair of DNA breaks can lead to genome instability. Despite more than 70 years of research, the mechanism of mitotic recombination is still not understood. By genetic and physical studies in the yeast Saccharomyces cerevisiae, I investigated the mechanism of reciprocal mitotic crossovers. Since spontaneous mitotic recombination events are very infrequent, I used a diploid strain that allowed for selection of cells that had the recombinant chromosomes expected for a reciprocal crossover (RCO). The diploid was also heterozygous for many single-nucleotide polymorphisms, allowing the accurate mapping of the recombination events.</p> <p>I mapped spontaneous crossovers to a resolution of about 4 kb in a 120 kb region of chromosome V. This analysis is the first large-scale mapping of mitotic events performed in any organism. One region of elevated recombination was detected (a "hotspot") and the region near the centromere of chromosome V had low levels of recombination ("coldspot"). This analysis also demonstrated the crossovers were often associated with the non-reciprocal transfer of information between homologous chromosomes; such events are termed "gene conversions" and have been characterized in detail in the products of meiotic recombination. The amount of DNA transferred during mitotic gene conversion events was much greater than that observed for meiotic conversions, 12 kb and 2 kb, respectively. In addition, about 40% of the conversion events had patterns of marker segregation that are most simply explained as reflecting the repair of a chromosome that was broken in G1 of the cell cycle.</p> <p>To confirm this unexpected conclusion, I examined the crossovers and gene conversion events induced by gamma irradiation in G1- and G2-arrested diploid yeast cells. The gene conversion patterns of G1-irradiated cells (but not G2-irradiated cells) mimic the conversion events associated with spontaneous reciprocal crossovers (RCOs), confirming my hypothesis that many spontaneous crossovers are initiated by a DSB on an unreplicated chromosome. In conclusion, my results have resulted in a new understanding of the properties of mitotic recombination within the context of cell cycle.</p> / Dissertation

The primary purpose of this investigation was to experimentally determine the effect of operational parameters on the onset of flow instability (OFI) in narrow, uniformly heated, vertical, rectangular channels. The geometry investigated was a 9.0 cm long rectangular channel with a 1.0mm by 1.3cm cross section. This geometry closely matches the coolant channel geometry in an accelerator target. Nitrogen-saturated subcooled water was used as the coolant, with mass fluxes ranging from 250 to 1336 kg/m^2 s, and an inlet temperature of 26ºC for the OFI experiments. The exit pressures investigated ranged from 275kPa to 620kPa, while the heat flux ranged from 0.729 to 2.236 MW/m^2. The primary data collected from these experiments were used to develop two correlations for the heat flux and mass flux at OFI. Wall temperature data were also collected in order to develop a Nusselt number correlation for the single-phase regime. This correlation is valid for the Reynolds number range of 6x103 to 1.7x104. The data obtained in this investigation will aid designers of high-power-density systems establish design limits to prevent over heating and possible damage due to the onset of flow instability. The data obtained in this investigation will aid designers of high-power-density systems establish design limits to prevent over heating and possible damage due to the onset of flow instability.

A combination of in situ sampling and numerical modeling was used to investigate the effects of mesoscale (<50 km) circulation patterns and stratification on the evolution of hypoxia on the Louisiana Shelf. Temperature, salinity, and dissolved oxygen concentrations records reveal the presence of an alongshelf meander, which is manifested vertically and horizontally as a wave-like distribution of the properties in the water column. The observations suggest the meander is a ubiquitous characteristic of the shelf with alongshore spatial scale approximately 50 km and less, which is consistent with the locations of sandy shoals along the coast and the local deformation radius. Twelve numerical experiments using an idealized three-dimensional shelf circulation model were performed to evaluate the relative importance of the variable bottom topography and freshwater forcing on the development, evolution, and scales of the dynamic instabilities. The inclusion of the shoals into the bottom topography showed the development of the dynamic instabilities as the flow passed over the shoals and downstream. Introduction of fresh water onto the shelf resulted in greater salinity differences, and, as a consequence in the formation of the dynamically unstable salinity fronts along the plume edge. The combination of the freshwater forcing and shoaling topography produced competing and complex interactions. Six numerical experiments were analyzed in order to investigate the effect of dynamic instabilities on spatial and temporal patterns of dissolved oxygen concentrations along the shelf. Although a linear relationship between Brunt-Väisälä frequency and dissolved oxygen deficit was expected, a nonlinear loop-like relationship was discovered that reflects the response of biochemical properties to the alongshelf variability of the density field. Comparison of the numerical modeling runs to observations of density and dissolved oxygen concentrations on the Louisiana Shelf reinforces the importance of physical processes such as topographic steering and/or freshwater forcing on the alongshore distribution of physical and biochemical properties. It suggests that the time scales of respiration (~3 days) and buoyancy transfer processes (~5-7 days), associated with the physical processes that are responsible for water column stability and ventilation, are similar to the time scales associated with the benthic respiration rates.

An eddy-permitting 2-1/2-layer Reduced Gravity Ocean (RGO) model is developed. Compared with the conventional 2-1/2-layer RGO models, the new model has improvements in subsurface thermodynamics, vertical mixing scheme and open boundary conditions. Using this new 2-1/2-layer RGO model as a dynamical tool, a systematic investigation of the role of oceanic processes in controlling tropical Atlantic sea-surface temperature (SST) response to Atlantic Meridional Overturning Circulation (AMOC) changes is carried out by varying the strength of northward mass transport at the open boundaries. It is found that the North Brazil Undercurrent (NBUC) reverses its direction in response to a shut-down of the AMOC. Such circulation change allows warm waters of the northern subtropical gyre enter the equatorial zone, giving rise to a prominent warming in the Gulf of Guinea and off the coast of Africa. Sensitivity experiments further show that the SST response behaves nonlinearly to AMOC changes. The rate of SST changes increases dramatically when the AMOC strength is below a threshold value. This nonlinear threshold behavior depends on the position of subsurface temperature gradient. The new RGO is coupled to an atmosphere general circulation model (AGCM) (CCM3.6). The coupled model is capable of capturing major features of tropical Atlantic variability. With the aid of this coupled model, a series of experiments with different combinations of oceanic and atmospheric processes are carried out to elucidate the relative importance of the oceanic processes and atmospheric processes in AMOC-induced tropical Atlantic variability/change. It is found that the oceanic processes are a primary factor contributing to the warming at and south of the equator and the precipitation increase over the Gulf of Guinea, while atmospheric processes are responsible for the surface cooling of the tropical north Atlantic and southward displacement of ITCZ. The sensitivity of the coupled system to different strength of the AMOC is further investigated. It is found that equatorial SST and precipitation response also behaves nonlinearly to AMOC changes. The impact of AMOC changes on Tropical Instability Waves (TIWs) is assessed. It is found that the activity of TIWs is reduced in response to the AMOC-induced equatorial SST warming. Correlation analysis suggests that AMOC may affect TIW activities by modifying SST gradient north of the equator.

The effect of single mode initial conditions at the interface of Rayleigh-Taylor(RT) mixing are experimentally examined utilizing the low Atwood number water channel facility at Texas A&M. The water channel convects two separated stratified flows and unifies them at the end of a splitter plate. The RT instability is attained by convecting a cold stream above a warmer stream. Average density calculations are based on long time average optical measurements. The water channel was modifified with a flapper fin like device at the end of the splitter plate which was actuated by a computer controlled servo motor. Other modifications to the experiment were implemented resulting in reduced uncertainty. The experiment examined five different modes in addition to the baseline: 2 cm, 3 cm, 4 cm, 6 cm, and 8 cm wavelengths. The mixing width growth rates were shown to be dependent on initial conditions. Additionally, it appears that the growth rates commence with terminal velocity and are observed to line up with the baseline case.

Genomic instability is commonly seen in breast cancers. To date, various chromosomal or segmental loss or amplification regions have been detected in primary tumors and cell lines. Hence, an intensive search for potent tumor suppressors or oncogenes located in these regions continues. MicroRNAs (miRNAs) are ~18-24 nt long non-coding RNAs that regulate protein expression either by target mRNA cleavage or translational repression. We hypothesized that miRNAs located in genomic instability regions in breast cancer cells may contribute to the initiation or maintenance of breast tumors. Here, we investigated genomic levels of miRNAs on frequent loss or gain regions of breast cancer cells. First, using bioinformatics resources we mapped known miRNAs and candidate miRNAs to reported genomic instability regions. Our extensive searches resulted with more than 30 known miRNAs and 35 candidate miRNAs. To further confirm loss or amplification of miRNA genes on these chromosomal regions in breast cancer cells, we designed specific primers for the known pre-miRNA DNA regions and performed semi-quantitative PCR in 20 breast cancer cell lines, 2 immortalized mammary cell lines, and 2 control samples. Densitometry results suggested that a striking 61 % (22/36) of selected miRNAs showed either loss or amplification in at least 3 different breast cancer cell lines. Interestingly most of these alterations were found to be amplifications even in regions reported to harbor losses in breast tumors. Genomic fold change results of these microRNAs provide a biologically relevant starting point for further expression and functional experiments of microRNAs in breast cancer studies. Genomic fold change analysis followed expression analysis of two significant microRNAs (hsa-miR-21 and hsa-miR-383) was done by qRT-PCR method. Our data provide a wide screen of genomic instability of 36 microRNA genes in 20 breast cancer cells and normal samples detected by semi-quantitative duplex PCR method as well as expression analysis of two microRNAs. To this date, such an extensive data on genomic status of microRNA genes in breast cancer cells did not exist. Therefore, our results are the first comprehensive investigation of many microRNA genes on genomic instability regions in breast cancers and provide further clues to the potential involvement of these microRNAs in breast tumorigenesis MicroRNA genomic instability may affect their expression and therefore their targets&rsquo / expressions. Understanding how these microRNAs regulate their targets and contribute to the neoplastic events will also contribute to the field by using this information for future diagnostic and threaupetical applications.

ABSTRACT The objective of this study is to establish the Forming Limit Diagram (FLD) of tubes. An experimental system of tube hydroforming, the electrical chemical etching method and the image process system are used to carry out the sheet metal forming test and the hydraulic bulge-forming test of annealed aluminum alloy tubes. Furthermore, Hill¡¦s new yield criterion is also used to predict the Forming Limit Curves of sheets. The predicted forming limit diagrams are compared with experimental data. The forming limit diagrams of tubes are coincident with those of sheets. Also, the predicted forming limit curves by Hill¡¦s new yield criterion agree quite well with those by experiments. Therefore, Hill¡¦s new yield criterion can be used to establish the forming limit curves of sheets or tubes.

A new closed-loop frequency-domain model is developed to incorporate the water hammer effect with pump rotordynamics, in order to investigate the sub-synchronous instability problem observed in a field pump. Seal flow-rate perturbations due to eccentricity are calculated from Soulas and San Andres's seal code. A complete transfer function matrix between rotor motion and reaction force due to pressure perturbation is developed in detail. Stability analysis with transfer-function'add-in' modules is conducted in XLTRC2. Seal clearances and the reaction force angle are found to be important in shifting natural frequencies and damping. The sub-synchronous instability observed in field is duplicated successfully with double-clearance seals.

In the study, vibrations of small elastic cylinders mounted in the shear flow of an air jet are investigated experimentally. In such cases, the amplitude of the cylinder oscillation changed along with the variation of the jet velocity gradient is due to the influence of fluid elastic instability. The experiment is based on the method of the magnetic field induction to measure the motion of the small cylinder, and it involves measurements of the varying velocity in a jet through the hot- wire anemometer. We focus on the fluid-elastic instability of a circular cylinder in shear flow. The vibration behaviors of the cylinder above the critical condition are be examined with different velocity gradients, mass ratios and damping factors. The vibration amplitude of the cylinder is also larger as velocity gradient is larger. With lower mass ratios and damping factor, moreover, the orbit of cylinder is larger. When the velocity gradient is increasing, the frequency of cylinder vibration becomes higher.