The conformational preferences of several oligosaccharides are investigated herein using a combination of NMR spectroscopy and molecular dynamics (MD) simulations, focusing on the torsion angles associated with the glycosidic linkages. Strategies for obtaining usable J-HMBC spectra for carbons with an adjacent 13C label are described. By employing a selective pulse or a constant time modification, spectra free from interferences are obtained for site-specifically 13C labeled oligosaccharides. Intermolecular hydrogen bonding in sucrose is investigated using MD simulations performed at different concentrations. One of the most frequent intermolecular hydrogen bonds in the simulations, O3f∙∙∙HO3g, was detected using the HSQC-TOCSY NMR experiment. Based on MD simulations and NMR spectroscopy, the conformational ensemble for a trisaccharide segment of the LeaLex hexasaccharide is proposed to feature conformational exchange between conformations with positive and negative values for the ψ3 torsion angle in the β-D-GlcpNAc-(1→3)-β-D-Galp linkage. Using MD simulations, the conformation of the N-acetyl group is shown to influence the glycosidic conformation at a nearby linkage in two oligosaccharides. Short (1→6)-linked oligosaccharides are shown to exhibit conformational exchange at the ω and ψ torsion angles. Notably, the former torsion angle populates states with ψ ≈ ±90°. Conformationally sensitive homo- and heteronuclear coupling constants are determined using various NMR experiments. The experimental data, including effective distances from NOESY obtained for two of the compounds, is used to improve the representation of the ω torsion angle in the CHARMM36 force field. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Manuscript. Paper 5: Accepted. Paper 6: Manuscript.</p>

Thesis (Ph. D.)--University of Hawaii at Manoa, 2004. / Includes bibliographical references (leaves 220-229). / Also available by subscription via World Wide Web / vi, 229 leaves, bound 29 cm

Thesis (Ph.D.)--George Mason University, 2009. / Vita: p. 152. Thesis director: Thomas E. Jordan. Thesis director: Donald P. Kelso. Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Environmental Science and Public Policy. Title from PDF t.p. (viewed June 10, 2009). Includes bibliographical references (p. 140-151). Also issued in print.

Thesis (M.S.)--Pennsylvania State University, 2008. / Mode of access: World Wide Web. Thesis advisor: Rick Lane Day.

Class of 2012 Abstract / Specific Aims: To assess the accuracy of the presenting signs and symptoms, diagnostic procedures, and treatments presented in the last twelve episodes of season five of the popular medical drama, House, MD. Methods: A descriptive retrospective evaluation of the accuracy and inaccuracies of episodes 13 to 24 in season five of the television series House, MD. The accuracy of the presenting signs and symptoms, diagnostic procedures, and treatment in each episode was rated on a scale of one to four. A rating of one described a correct and usual representation. A rating of two described a correct but somewhat unusual representation. A rating of three described a correct but extremely unusual representation. A rating of four described an incorrect representation. Each researcher independently rated the episodes, and then a collaborative rating was agreed upon by both researchers. Main Results: Results of the ANOVA test demonstrated a statistically significant difference between the three dependent variables (p=0.002). The Tukey HSD post-hoc test confirmed a significant difference between the accuracy of treatment when compared with signs and symptoms (p=0.012), and with diagnostic procedures (p=0.002). The average rating for the treatment variable was 1.58 (0.9), whereas the average ratings for the signs and symptoms and diagnosis variables were 2.75 ( 0.754), and 3 (1.128), respectively. Conclusions: The treatments presented in the last twelve episode of season five of House, MD were more accurate than both the presenting signs and symptoms and the diagnosis.

Mechanical injuries to the cell often lead to disruptions of the cell’s phospholipid bilayer membrane and potential detrimental effects including cell death. Understanding the mechanical states required to disrupt the phospholipid bilayer would result in better multiscale constitutive models and further knowledge of cell injury. The objectives of this research were to perform biaxial deformations of the phospholipid bilayer to quantify phospholipid bilayer disruption and to identify potential parameters that can be used in multiscale constitutive equations. We show that the von Mises stress, 26.6-61.1, increases linearly with the von Mises strain rate, 1.7e8-6.7e8, and that the strain at failure is dependent on the stress state with non- and equibiaxial being the most detrimental when failing at <.73 von Mises strain. Understanding the effects of nanoscale mechanical trauma to the cell provides a better understanding of cell injury and may provide insight regarding initiation and progression of cell damage.

Current researchers have looked to nature to learn how self-assembly processes occur. By understanding the self-assembly process, designers can begin to build strong structural materials that are extremely light weight. The discrete element modeling method was used to gain a better understanding of the directed self-assembly of M13 bacteriophage. This model was parameterized from molecular dynamics simulations at the nanometer scale. Three types of functionalized bacteriophage were studied: Wild-type, 4E, and CLP8. Results showed that Wild-type phage are attracted in a head-to-tail orientation, but repelled in head-to-head orientation. The 4E bacteriophage behaved similarly with a stronger bond in the head-to-tail orientation, and CLP8 showed to physically repel in either orientation. The overall finding was that the electrostatic physics dominated as the controlling forces of the phage interactions.

Indiana University-Purdue University Indianapolis (IUPUI) / Bacterial endospores have been a topic of research interest over the last several decades given their high resistance to ultraviolet (UV) damage. Unlike vegetative bacterial cells, which form cyclobutane pyrimidine dimers (CPD) and pyrimidine 6-4 pyrimidone photoproducts (6-4PPs) as the major product upon UV irradiation, endospore bacteria form a spore photoproduct (5-(R-thyminyl)-5,6-dihydrothymine or SP) as the major product. Vegetative bacteria cells are subject to regular cell activities and processes such as division and deoxyribonucleic acid (DNA) replication, which are prone to damage from UV exposure. However, in endospores, which have a largely anhydrous inner environment, the DNA remains dormant when bound to spore-specific small acid-soluble proteins (SASP) and dipicolinic acid, making spores highly resistant to radiation, heat, desiccation, and chemical harm. During spore germination, SP lesions in DNA are repaired by a distinctive repair enzyme, spore photoproduct lyase (SPL). In this thesis, molecular dynamics (MD) simulations were carried out to (i) examine how the formation of the SP lesion in DNA affects the global and local structural properties of duplex DNA and (ii) study how this lesion is recognized and repaired in endospore. The first part of this work was focused on designing and developing a structurally and dynamically stable model for dinucleotide SP molecule (TpT), which was subsequently used as an SP patch incorporated into duplex DNA. Computationally, this requires modifications of the bond and nonbonded force field parameters. The stability of the patch and developed parameters was tested via solution-phase MD simulations for the SP lesion incorporated within the B-DNA dodecamer duplex (PDB 463B). The second part involved applying the new SP patch to simulate the crystallographic structure of the DNA oligomer containing SP lesions. Solution-phase MD simulations were performed for the SP-containing DNA oligomers (modeled based on PDB 4M94) and compared to the simulations of the native structure (PDB 4M95). Our analysis of the MD trajectories revealed a range of SP-induced structural and dynamical changes, including the weakened hydrogen bonds at the SP sites, increased DNA bending, and distinct conformational stability and distribution. In the third part of this thesis project, we carried out MD simulations of SP-containing DNA bound with SASPs to examine how the DNA interacts differently with SASP in the presence and absence of the SP lesion. The simulation results suggested decreased electrostatic and hydrogen bonding interactions between SASP and the damaged DNA at the SP site compared to the undamaged DNA-protein complex. In addition, decreased helicity percentage was observed in the SASPs that directly interact with the SP lesion. The last part of this this thesis work focused on the SP-dimer flipping mechanism, as the lesion is likely flipped out to its extrahelical state to be recognized and repaired by SPL. Using steered molecular dynamic (SMD) simulations and a pseudo-dihedral angle reaction coordinate, we obtained possible SP flipping pathways both in the presence and absence of SASP. Collectively, these simulation results lend new perspectives toward understanding the unique behavior of the SP lesion within the DNA duplex and the nucleoprotein complex. They also provide new insights into how the SP lesion is efficiently recognized and repaired during spore germination.

本研究透過文字探勘對美國企業2004年至2014年的MD&A資訊進行分析，並搭配財務資訊相互比較，分析美國企業所揭露的MD&A語調一致性，接著透過實證研究分析造成美國企業MD&A語調一致性結果的原因。MD&A非量化資訊運用Loughran and McDonald正負向詞典、TFIDF、K-Means等技術進行分析，並結合財務資訊分析，分析美國企業2004年至2014年的MD&A資訊；再利用企業績效變異度、企業規模與企業成立年數等變數，來分析影響公司MD&A揭露誇大與否的因素。 研究結果顯示，企業規模、企業風險程度、分析師追蹤人數與企業成立年 數皆會深深影響MD&A語調的一致性。除了主要實證分析結果外，另外搭配三組穩健性測試來測試模型的敏感性。本研究希望讓資訊使用者運用企業所揭露的MD&A資訊時，能做更多適當的調整，考慮公司MD&A的揭露是否有過度樂觀誇大或是過度悲觀的情勢，並且可以藉此做出正確的經濟決策。 / This study presented a way to analyze the MD&A information of US listed companies from 2004 to 2014 via text mining techniques such as Loughran and McDonald Word Count and TFIDF. Then I cross compare a company’s MD&A information with its financial information using K-Means and establish an index to capture the consistency between the two types of information. Finally, I develop empirical model with explanatory variables such as volatility of earnings, company scale, company’s age, etc. for the consistency index. According to the empirical results, company scale, company operating risks, analyst coverage, and company’s age are significantly related to the MD&A consistency. Three robustness checks demonstrate the similar results. The results suggest investors an additional way of using MD&A other than merely reading it. Investors should consider whether the MD&A is overstated or understated while using it in their investment decisions.

Thesis (Ph. D.)--University of Hawaii at Manoa, 2004. / Includes bibliographical references (leaves 220-229).