Computational chemists have successfully simulated many systems by applying the principles of quantum mechanics, while approximate molecular mechanical models have seen great utility in problems of biochemical interest. In recent years, a number of methods have been developed to combine the advantages of both techniques. In this study the so-called QM/MM method is developed and applied to the determination of the free energy of a simple Menshutkin S_N2 chemical reaction. This is an extremely demanding process, well beyond the computational capacity of an average workstation, and thus a Beowulf-class Linux cluster is constructed to perform the calculations, and tested for a variety of computational chemistry applications. A number of methods for improving the QM/MM approach are considered in this work. The Fluctuating Charge, or FlucQ, polarizable molecular mechanics force field is implemented in a flexible manner within the CHARMM package and tested for a variety of systems, including the S_N2 test case. Several drawbacks of the original method are addressed and overcome. Both molecular dynamics and Monte Carlo techniques are used within the QM/MM framework to investigate the S_N2 reaction, and the two methods are compared. Techniques are developed and tested to increase the efficiency of QM/MC calculations to the point where they become competitive with QM/MD. Extremely expensive QM treatments are shown to be required to obtain accurate energies for the Menshutkin reaction. A method is developed and tested, and compared with the traditional ONIOM technique, for dramatically reducing the computational time required to use these treatments for QM/MC simulations, paving the way for fully ab initio high basis set QM/MM simulation.

AN ABSTRACT OF THE DISSERTATION OF CANDACE A. DAVIS, for the Doctor of Philosophy Degree in ANTHROPOLOGY, presented on March 31, 2011, at Southern Illinois University at Carbondale. TITLE: BILATERAL ASYMMETRY IN INCISORS: IMPLICATIONS FOR MIOCENE HOMINOID SPECIES DIAGNOSIS MAJOR PROFESSOR: Dr. Robert S. Corruccini The primary purpose of this dissertation is to show how knowledge of variation and asymmetry in incisor antimeric pairs of living great ape genera can be utilized as a "yardstick" for pairwise comparisons of isolated Miocene ape incisors from the two genera Kenyapithecus and Equatorius . The research was designed to help determine whether these fossil teeth could be reliably sorted into one or more than one genera. Both metric and morphological data for each class of incisor were recorded for Kenyapithecus and Equatorius , and resampling was performed to determine the significance of variation (p<.05) for each of 12 traits. Intraindividual antimeric differences in three genera of extant great apes were compared with interspecimen differences between Equatorius and Kenyapithecus. Pairwise comparisons using resampling sorted out which traits showed intraindividual significant variation and which could be used to discriminate between the two fossil genera under consideration. Based on these results, one can cautiously conclude the two fossil species within these genera are not different enough to justify placing them in two different genera.

The dissertation consists of a series of experiments conducted to study developmental stability of various genetic stocks at different stages in the life cycle. The primary measures of stability were type and degree of asymmetry of bilateral traits and heterosis. Higher relative asymmetry (RA), which was defined as (|L-R| / [(L+R)/2]) x 100, was observed in lines of White Leghorns selected 23 generations for high or low antibody response to sheep red blood cells than in their F1 crosses. The bilateral traits were 39-day shank length and length and weight of the first primary wing feather. Shank length was again measured on day 49 while body, heart, shank, and lung weights and ceca lengths were obtained on day 56. Heterosis was positive for organ sizes and negative for degree of RA. Shank length and diameter, weight and length of the first primary wing feather, and distance between the junction of maxilla and mandibles and auditory canal (face length) were used to classify bilateral types and measure RA in six genetic stocks. The stocks were the S23 generation of White Leghorn lines selected for high or low antibody response to SRBC, sublines where selection had been relaxed for eight generations, and reciprocal crosses of the selected lines. Differences were found among all stocks for the traits measured. Rankings among traits for RA in descending order were face length, shank diameter, feather weight, and shank and feather lengths. The RA of shank and feather lengths did not differ from each other. The mean RA of the five traits was higher for the two selected lines than the crosses between them. The RAs of the two lines where selection had been relaxed was similar to that of selected lines. In a line of White Rocks selected 39 generations for low eight-week body weight, bilateral traits measured were shank length and diameter, face length, and weight and length of the first primary wing feather of females at 240 days of age. The RAs of individuals that had not commenced egg production by 245 days of age were similar to those that had entered lay. In both cases, these RAs were higher than those of a subline in which selection had been relaxed for four generations. Broiler sire lines had higher RA than dam lines for lung weight at hatch. Heterosis of RAs suggested superior homeostasis in F1 crosses than in the sire lines. Based on populations studied, it may be concluded that RAs were trait specific with the RA of shank length being lower (0 < RA < 2%) than lung weight which was 10% or higher regardless of genetic background. The types of bilateral asymmetry exhibited although less consistent, still had consistency such that feather weight and ceca weight exhibited antisymmetry across different stocks. Length and width of shank and weight of lung, were generally of fluctuating asymmetry. Heart:lung ratios differed among genetic stocks. In White Leghorns, lungs from late embryonic development to 25 days after hatch were heavier in a line which had heavier juvenile body weight than in one with lower juvenile body weight. In commercial broilers, heart:lung ratios at hatch were lower and thus inferior in parental lines than in their F1 crosses. / Ph. D.

No description available.

Free energy calculations for the transfer of a water molecule from the pure liquid to an interior cavity site in a protein are presented. Three different protein cavities, in bovine pancreatic trypsin inhibitor (BPTI), the I106A mutant of lysozyme, and in the I76A mutant of barnase, represent very different environments for the water molecule, one which is polar, forming four water-protein hydrogen bonds, and two which are more hydrophobic, only forming one or two water-protein hydrogen bonds. The calculations give very different free energies for the different cavities, with only the polar BPTI cavity predicted to be hydrated. The corresponding entropies for the transfer to the interior cavities are calculated as well and show that the transfer to the polar cavity is significantly entropically unfavorable while the transfer to the non-polar cavity is entropically favorable. For all proteins an analysis of the fluctuations in the positions of the protein atoms shows that the addition of a water molecule makes the protein more flexible. This increased flexibility appears to be due to an increase length and weakened strength of protein-protein hydrogen bonds near the cavity. Similar free energy studies are performed on the three proteins at high pressure, 3 kbar. As in the 1 atm studies BPTI is the only protein that should be hydrated at 3 kbar, however the protein free energy changes appear to be not strongly dependent on the number of hydrogen bonds available. Changes in protein structure and flexibility are analyzed in an attempt to more fully understand the changes proteins undergo prior to pressure induced denaturation. These changes can help understand the forces at work in the last stages of protein folding. The role of interior water in this process is also analyzed. Changes to the fluctuating charge algorithm that handles polarizability in molecular dynamics simulations were performed to allow for longer time steps. The fluctuating charge model treats partial charges as variables which are propagated using Lagrangian dynamics. A coordinate transform to normal mode charge variables is applied to the TIP4P-FQ model of water to decrease the coupling between the atomic and charge degrees of freedom.

Apis mellifera é uma espécie de abelha bastante estudada sob diferentes perspectivas, tanto em pesquisas básicas como aplicadas. Possui uma natureza singular associada não só a interesses econômicos como produção de cera, mel, própolis, geléia real, pólen, mas também, por seu potencial agrícola como polinizador. Esta espécie tem sido alvo de muitos estudos morfométricos, principalmente pela sua importância ecológica, pela sua grande capacidade de adaptação, sua ampla distribuição e por serem capazes de se estabelecer eficientemente em diversos ambientes. A morfometria geométrica permite uma análise rigorosa da variação da forma de uma determinada estrutura em organismos de diversos tamanhos, principalmente utilizando métodos de estatística multivariada, além de ser capaz de avaliar a instabilidade no desenvolvimento de um organismo. O presente trabalho teve como objetivo estudar as variações da forma e tamanho em asas e corbículas de operárias de Apis mellifera, provenientes das 5 regiões geográficas do Brasil, utilizando análises morfogeométricas. A existência de padrões de variação de forma e tamanho das abelhas africanizadas no Brasil obtidos há 16 anos em estudo clássico realizado por Diniz-Filho e Malaspina, possibilitou uma análise espaço-temporal comparativa com os resultados obtidos utilizando recursos tecnológicos atuais para a avaliação de dados morfométricos, bem como, verificar por meio das análises de assimetria flutuante a plasticidade fenotípica no tamanho e forma da asa e corbícula dessa espécie, possibilitou ainda, avaliar se condições adversas relacionadas às ações antrópicas influenciam no aumento de desvios na simetria bilateral desses caracteres morfológicos. Foi realizada uma amostragem abrangendo as 5 regiões geográficas do Brasil, pela forma das asa e análises multivariadas verificou-se que existe um padrão geográfico entre as populações de Apis mellifera no Brasil (P < 0,001). Essas variações geográficas podem ser devidas à grande extensão territorial, além da possível associação das diferenças entre ecorregiões. Verificou-se, também, a presença de assimetria flutuante na forma das asas e das corbículas de Apis mellifera em todas as populações estudadas, porém, na análise multivariada e assimetria do tamanho não obteve significância em algumas populações, constatando-se que para estudo de assimetria e distribuição populacional a forma da asa e das corbículas é a análise mais indicada e que apresenta maior precisão. / Apis mellifera is bee specie very studied under different perspectives, as for basic studies to applied ones. They have a singular nature, not only associated to economic issues as wax, honey, propolis, royal jelly and pollen production, but also for their agricultural potential as pollinators. This specie has been long aimed for morphometric studies, because of its ecological importance, easy capacity of adaptation, large distribution and for being able of efficient establishment in diverse environments. The geometric morphometric allows rigorous analyses in shape variation of a given structure in organism of diverse sizes, especially when using multivariate statistics methods, enabling the evaluation of instability in the development of an organism. The present study aim the variations of shape and size in wings and pollen basket from workers of Apis mellifera, acquired at 5 geographic regions of Brazil, using morphogeometric analyses. The existence of variation patters in shape and size of Africanized bees in Brazil, obtained 16 years ago in classic study made by Diniz-Filho and Malaspina, made possible a comparative spatialtemporal analyses with the results obtained in this study, using updated technology resources for evaluation of morphometric data, as well as the phenotypic plasticity exam of size and shape in wings and pollen basket of this specie, using fluctuating asymmetric analysis, and evaluate if diverse conditions made by anthropomorphic actions has influence on the deviation increase among bilateral symmetry of this morphological characters. The sample was made including 5 geographic regions of Brazil. By the wings size shape and multivariate analyses, it was verified the existence of a geographic pattern among Brazilian Apis mellifera populations (P< 0,001). Those geographical variations may be caused due to the big territorial expansion, alongside with the possible association of different ecoregions. It was also verified floating asymmetric in the shape of wings and pollen basket from Apis mellifera in all studied populations, however, in the multivariate analyses the asymmetry in shape was not significant in some populations, showing that, for studies of asymmetry and populational distribution, the shape of wings and pollen basket is the most indicated and precise analyses.

Analysing variation of skull shape in wild populations can give us an insight into evolutionary processes. By looking into patterns of morphological variation within populations, we can extrapolate and make assumptions on the patterns of variation on higher taxonomic levels. In this thesis, I collected data on skull shape of a wild population of Soay sheep using geometric morphometrics methods. I applied a multitude of quantitative genetics and geometric morphometrics methods to explore the factors behind the evolution of skull shape. I analysed several aspects of skull shape, including integration and modularity, predicted response to hypothetical selection, estimates of natural selection, presence of heterochrony, and fluctuating asymmetry (FA) in an ecological and genetic point of view. I found low levels of integration in the Soay sheep skull, along with the presence of two modules: face and neurocranium. Both the levels of integration and the pattern of modularity were found across different origins of variation, individual, genetic and developmental (FA), indicating a strong correspondence between levels. Although genetic integration is not strong, I found that most of hypothetical selection regimes result in as much correlated selection as direct selection responses. But the nose region has shown to be quite independent from the rest of the skull, with a retraction of the nose causing almost no correlated changes. Selection on skull shape is comparatively strong in the Soay sheep. The skull shape selected for in males differs from the shape selected in females. Males are selected to have wider nasal bones along with longer, flatter braincase, whereas females are selected towards narrower nasal bones, along with smaller braincases. But selection is not the only factor influencing changes in skull shape. Changes in temperature along the past 30 years are causing a change in developmental timing in Soay sheep, causing a decrease in overall body size in the population. And I found that skull shape is also being affected, thus indicating that this population might be undergoing heterochronic processes. Finally, I found that factors such as vegetation quality, parasite load and breeding success are related to FA levels, whereas population density and climate are not. I also found no significant heritability nor dominance in FA of skull shape. Overall, this thesis certainly contributes to the understanding of evolution of skull shape in natural populations. By successfully combining quantitative genetics and geometric morphometrics methods, I was able to tackle questions about the evolution of complex shapes, and give valuable insights into this still underexplored field.

Studies were conducted on a population of tiger salamanders, Ambystoma tigrinum, at Henderson Island Wildlife Management Area in Jefferson County, TN. Tests were conducted to locate the nonbreeding habitat of the salamanders and to detect any difference in fluctuating asymmetry (FA) between larval populations in a large, permanent pond and an ephemeral wetland. Drift fences were installed with pitfall traps at selected locations around each pond to determine nonbreeding habitat use by adults. Most adult salamanders were found using a blackberry (Rubus sp.) dominated old-field, a grassy field, and a shrub-grass mix field, which were all adjacent to the ponds. No statistical difference in FA between the 2 ponds.

In this thesis, we investigate the ergodic capacity under several power adaption schemes, including optimal power and rate algorithm (OPRA), optimal rate algo rithm (ORA), channel inversion (CI), and truncated channel inversion (TCI), over fluctuating two-ray (FTR) fading channels and Fisher-Snedecor F fading channels. After some mathematical manipulations, the exact expressions for the EC under those power adaption schemes are derived. To simplify the expressions and also get some insights from the analysis, the corresponding asymptotic expressions for the EC are also derived in order to show the slope and power offset of the EC in the high signal-to-noise ratio (SNR) region. These two metrics, i.e., slope and power offset, govern the EC behaviour in the high SNR region. Specifically, from the derived asymptotic expressions, we find that the slope of the EC of OPRA and ORA over FTR fading channels is always unity with respect to the average SNR in the log-scale in high SNRs, while the asymptotic EC of the TCI method is not a line function in the log-scale. For the Fisher-Snedecor F fading channel, the slope of asymptotic EC under OPRA, ORA, and CI (m > 1) schemes is unity in the log-scale, where m is the fading parameter. The slope of the TCI method depends on m, i.e., unity for m > 1 and m for m > 1, while the asymptotic EC of TCI is not a line function for m = 1. Finally, Monte-Carlo simulations are used to demonstrate the correctness of the derived expressions.

Since the global budget system carried out by National Health Insurance Bureau in 2003, hospital autonomy management practiced in 2003 as well as reviews carried by specialized doctors system established, local hospitals have faced critical impacts. The fluctuating point reimbursement was applied, it not only restrains the reimbursement received by the hospitals, but also causes management difficulties for local hospital as the fluctuating points shrink year by year. The number of western medical hospitals is decreasing. The number in 2000 was 575, but now only 500 local hospitals operate in Taiwan. For survival, local hospitals have to establish sound financial system in order to deal with changing national health insurance policies. On the other hand, they are encouraged to use strategy management theories to promote the competitiveness for local hospitals to well control their expenditures and create their income. The study has analyzed the statistical data from Statistical Office, Department of Health and National Health Insurance Bureau and integrated related literatures to understand the management strategies and responses of local hospitals under national health insurance policies and the economic, demographic and political environment. Results of the study will be provided for reference. Beside statistic data and literatures, strategy management concepts and theories were also adopted to clarify current policies of health insurance, reimbursement system and the situation of local hospitals to probe into the difficulties and possible solutions. Local hospitals were chosen to be the study subjects, and through SWOT Analysis, Poter¡¦s Five Force Analysis, Blue Sea Strategy and the findings from literature review, we found that (1)the financial gap of health insurance has transferred to medical organizations, especially local hospitals; (2)under global budget system, local hospitals have to increase income and decrease expenditures by transformation, running pay business or joint outpatient service; ¡]3¡^cost management is critical for local hospitals to establish internal strength; (4) referring to blue sea strategy to develop distinguished business and differential products can create niche for local hospitals to break through the bottleneck.