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Many naturally occurring biological molecules, such as nucleic acids or proteins, are evolutionary related, having evolved from a common ancestor via a process of sequence mutation. Mutations undergo a process of selection, with combinations of mutations that preserve or improve a molecule's fitness having a higher probability of being maintained. Mutations that modify structure are expected to particularly impact fitness, and often detectably influence observed patterns of mutations. Nucleotide coevolution is one such example, whereby pairs of nucleotides within biologically functional nucleic acid secondary structures exhibit evidence of coevolution that is consistent with the maintenance of canonical base-pairing. PINNACLE, the first of two models developed in this dissertation, is a sequence evolution model that assesses the rates of mutation associated with base-paired sites in alignments of DNA or RNA sequences. PINNACLE is able to fully account for an unknown secondary structure, and in doing so can be used to predict a secondary structure shared amongst an alignment of sequences. PINNACLE was used to infer rates of coevolution associated with GC, AU (AT in DNA), and GU (GT in DNA) dinucleotides in non-coding RNA alignments, and single-stranded RNA and DNA virus alignments. Strong evidence was found for GU dinucleotides being selectively favoured at base-paired sites in non-coding RNA and RNA virus alignments, with slight evidence for GT dinucleotides being selectively favoured at base-paired sites in DNA virus alignments. The strength of coevolution at base-paired sites in a SHAPE-MaP-determined HIV-1 NL4-3 RNA secondary structure and a corresponding alignment containing large numbers of HIV group 1M sequences was also measured, finding statistically significant correlations between the experimentally-determined SHAPE-MaP pairing scores and the inferred degrees of coevolution. The second model developed in this dissertation, ETDBN, differs from typical evolutionary models in that it models the structural evolution of proteins in addition to their sequence evolution. ETDBN uses a dihedral angle representation of protein structure, and models the evolutionary trajectory between a pair of protein structures using an angular diffusion process on the two-dimensional torus. ETDBN is trained on a large database of proteins, and is parameterised such that it can learn the dependencies between sequence and structural evolution. The model has interpretable parameters, and is comparatively more realistic than previous stochastic models of protein structure evolution. Using the trained model, we were able to identify apparent sequence-structure evolutionary motifs present in numerous homologous protein pairs. The generative nature of our model enabled us to evaluate its validity and to infer various quantities, such as protein structures or alignments from sequences of amino acids, dihedral angles, secondary structure labels, or any combination thereof.

Chronic pain sufferers can find themselves on the margins of evangelical culture in the United States. Evangelicals are largely guided by a paradigm of power, an ethos that finds little room for the hurting and disabled. Pain sufferers do not fit into such a paradigm; their physical limitations can prevent them from contributing to the evangelical church’s efforts to extend their influence. It is not that pain sufferers are ignored by evangelicals; many churches have some type of ministry function to assist them. The issue is that they are not valued in their current state of suffering. Spiritual formation for many evangelicals is centered around community activities that can be challenging for people with chronic pain to participate in. An over-emphasis on communal expressions rather than personal devotion places spiritually formative experiences outside the reach of some chronic pain sufferers. This dissertation considers various solutions within the church to meet the spiritual and emotional needs of chronic pain sufferers. Section One states the problem. Section Two looks at the current cultural/theological landscape within evangelicalism and how its paradigm of power excludes chronic pain sufferers. I then extract some ideas from Job’s account of personal suffering. I also look at the solutions offered by the contemporary signs and wonders movement among some Pentecostal churches, and finish with some of the thinking within contemporary Eastern Orthodoxy. Section Three is my thesis, that chronic pain sufferers embrace their thorn in the flesh as Paul does in 2 Corinthians 12. Section Four describes the artifact, a book entitled Spiritual Help for Chronic Pain: Three Phases of Spiritual Transformation. Section Five describes the specifications for the artifact through a book proposal. Section Six is the summation of what I have learned through my dissertation process.

Incorporated slightly more than a year ago, this company appears to have experienced tremendous "growing pangs" on a minute amount of invested capital. The company has been engaged in several operations, but the primary effort has been on construction excavating, grading, paving, and other work related to commercial and residential real estate development projects. Other (considerably smaller) income sources have included engineering and demolition projects, real estate commissions, and a small amount of hauling work.

Pipelined microprocessors allow the simultaneous execution of several machine instructions at a time, increasing the total throughput of instructions. Because an instruction being executed by a pipelined microprocessor may depend on the results of another instruction that is being executed simultaneously, data and control hazards can reduce the efficiency of pipelined microprocessors. This dissertation examines data hazards caused by memory load instructions and branch hazards caused by conditional branch instructions. Load instructions can be particularly difficult to execute efficiently because computer memory systems are often significantly slower than contemporary microprocessors. The load target buffer is a microarchitectural feature that predicts the address that will be needed by a memory load instruction before the actual address is computed. Simulations of the SPEC89 benchmarks on single-issue in-order-execution pipelines determine that an effective load target buffer needs to include at least 1024 entries. When branch prediction is accurate, delaying the pipeline stage that performs ALU operations improves the ability of processors to tolerate a slow memory system. Branch instructions can reduce the ability of a processor to exploit instruction-level parallelism, even when the processor has accurate branch prediction. Predicated instructions are machine instructions with an extra operand that acts as a logical predicate to the execution of the instruction. Compilers can replace code that contains conditional branches with code that contains predicated instructions, reducing the number of branches. The dissertation describes DecisionScanner, a tool that instruments C source code and traces the decisions made by conditional branches as the instrumented program executes. Experiments on five of the SPEC92 C benchmarks, the UNIX word count utility, and an MPEG video player show significant performance improvement for machines that support out-of-order execution that can issue eight or more instructions per cycle. Machines that issue fewer instructions per cycle realize a moderate improvement in performance. Processors achieve most of the benefits of full predication when only conditional moves are available.

The primary objectives of this study were (1) to apply recently developed quantitative vegetation analysis procedures to the problem of describing the forest vegetation of the central portion of the Great Smoky Mountains National Park, (2) to group samples into forest types based on the importance of a large number of taxa and to compare the results with studies using types defined by relative density or basal area of canopy dominants, (3) to assess and further define the relationships of vegetation pattern with elevation and with topographic characteristics, (4) to examine possible relationships between soil characteristics and vegetation pattern, and (5) to examine the successful status of the forest types. Data were analyzed from 266 sample locations ranging from 759 to 1585 m elevation in the central portion of the Great Smoky Mountains National Park, in the vicinity of Mt. LeConte, Greenbrier Pinnacle, and Thomas Ridge. The 266 sample soils were tentatively classified as: Typic Dystrochrepts, 51%; Lithic Dystrochrepts, 14%; Typic Haplumberpts, 15%; Umbric Dystrochrepts, 10%; Lithic Histosols, 4%; Lithic Umbric Dystrochrepts 3%; Fragmental, 2%; and Lithic Umbrepts, 1%. Sample linear correlations among the soil, site and vegetation characteristics were computed. The highest number of significant vegetation-soil correlations occurred with clay content of the A and B horizons and with phw. Most of the general vegetation characteristics were significantly correlated with microtopographic position. Canopy sample plots were grouped into forest types based on taxa and importance values with the aid of the agglomerative minimum dispersion clustering procedure. The types were: Spruce-Yellow Birch, Yellow Birch-Hemlock, Hemlock-Buckeye, Basswood, Northern Red Oak, Red Maple-Sweet Birch, Red Maple-Northern Red Oak, Yellow Poplar, Chestnut Oak, Oak-Pine, Table-Mountain Pine-Pitch Pine and Table-Mountain Pine. The discreteness of the plot groups (types) was tested by canonical analysis. Vegetation, site and soil characteristics of the 17 forest types were described. Relative densities of tree taxa in the canopy, sapling and seedling strata were compared to judge the successional stability of the types. Types which had no evidence of past disturbance appeared to be relatively stable, although periodic reproduction apparently had occurred in some plots. Acer rubrum, Quercus prinus, Q. rubra and Oxydendrum arboreum were the most common tree taxa which had replaced American chestnut. A "topographic site gradient" was constructed based on combinations of potential solar irradiation classes (based on aspect and slope angle) and microtopographic slope positions. Each position along this gradient was assigned a number, termed the "site gradient index" (SGI), which increased toward mesic sites. The samples of each forest type were plotted on axes of elevation and SGI. A composite diagram was made portraying the pattern of most of the types on the SGI -elevation axes. Observable patterns were noted when Umbrepts, Umbric Dystrochrepts and Lithic Dystrochrepts were plotted on the site diagram. Other characteristics showing patterns on the diagram were: percent clay in the B horizon, total vascular taxa, percent shrub cover, tree sapling density, and canopy basal area. The combined vegetation-site summary contained in the composite site diagram suggests that the Mt. LeConte area departs significantly in detail (if not in basic outline) from the mosaic chart of Whittaker. This suggests that further local studies are needed in the Park to further verify or redefine its outline and / or details.