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This thesis describes a software tool used to study the biomechanics of elbow extension. The tool is an integrated computer program for data processing and graphing, and is used in the development of an EMG driven muscle model for dynamic ballistic muscle movement. The software is designed to manipulate data from a series of isometric and dynamic elbow extension experiments. Inputs include recordings from a torque sensor, load cell, and potentiometer as well as EMG from triceps and biceps muscles. Calculations are made to determine the effect of gravity, the Moment of Inertia, as well as the force-EMG, force-length and force-velocity relationships. Additionally, fatigue tests and postactivation potentials are analyzed. Modeling parameters are derived from isometric controls and verified by applying them to data from dynamic experiments. The principal design requirements for this software tool were adaptability, user control, and data processing protocol verification. The majority of data processing parameters can be controlled and adjusted by the user. Care was taken during software coding so that it would be easy to modify each step of the protocol and if necessary, add additional processing. Data is displayed on interactive graphs to provide control feedback to the user. / Thesis / Master of Engineering (MEngr)

Thermoelectric semiconductors can convert temperature differences into electricity or electricity into temperature differences. This offers great potential for the use of wasted heat or cooling. These materials can be used in a variety of fields, from healthcare to space exploration. The effectiveness of the materials is evaluated by their thermoelectric properties such as the Seebeck coefficient, electrical conductivity, and thermal conductivity. The aim of this PhD thesis is to investigate the electronic structure using first-principle methods for potential thermoelectric applications. Materials of interest include Copper and Tin based ternary /quaternary compounds, and monolayers of SnS2, SnSe2 and Janus SnSSe. Density functional theory, ab initio molecular dynamics and Boltzmann transport theory are used to study the electronic and phonon transport properties. In the first part of the thesis, electronic structure calculations were performed on both monoclinic and disordered cubic forms of Cu2SnS3(CTS). The impact of structural disorder on thermoelectric properties was examined through these simulations. The results, obtained through first-principle calculations, revealed the existence of band tails in the electronic density of states for the disordered structure, and low-lying optical modes in the disordered cubic structure. This was found to be caused by a significant variation in Sn bonding, leading to strong anharmonicity as measured by the Grüneisen parameter. The findings from the first principle calculations were supported by Nuclear inelastic scattering experiments. Furthermore, the effect of grain size on Cu2SnS3 was studied using first-principles calculations on various ordered and disordered surfaces. The density of states (DOS) revealed that the surface of CTS is conductive due to the presence of dangling bonds. Furthermore, calculations of the formation energy showed that the stoichiometric CTS, Cu-vacant and Cu-rich systems are energetically more favourable, while the formation of Sn-vacant and Sn-rich systems is less likely. In the subsequent study, the impact of Ag substitution at the Sn site at various concentrations was investigated. The Fermi level for Ag-substituted systems was found to lie deep within the valence band, with the shift of the Fermi level inside the valence band increasing with substitution increasing the carrier concentration. The incorporation of Ag into the system decreases the root mean squared displacement of the other cations and anions, which reduces the scattering of phonons and thereby increases the lattice thermal conductivity. A comparative study of various polymorphs of CTS, Cu2ZnSnS4 and Cu2ZnSnSe4 was done. Ab-initio molecular dynamics was performed on CTS, CZTS and CZTSe. The root mean squared displacement value for the disordered polymorph was higher than for the ordered phase, indicating increased static disorder. This corresponds to the static (temperature-independent) distortion of the crystalline lattice due to the disorder of the cations and is associated with higher anharmonicity and bond inhomogeneity in the disordered phase, which is then directly responsible for the ultra-low thermal conductivity. In the final part of the thesis, thermoelectric properties of dichalcogenide monolayer of SnS2, SnSe2 and Janus SnSSe was performed. Density functional theoretical calculations points out the hexagonal Janus SnSSe monolayer as a potential high-performing thermoelectric material. Results for the Janus SnSSe monolayer show an ultra-low thermal conductivity originating from the low group velocity of the low-lying optical modes, leading to superior zT values of 0.5 and 3 at 300 K and 700 K for the p-type doping, respectively. The successful calculation of properties for materials shows that the computational work done in this thesis can be used for further research into thermoelectricity.

The forces of interaction were measured between the siderophore azotobactin and the minerals goethite (FeOOH) and diaspore (AlOOH) in solution using force microscopy. Azotobactin was covalently linked to a hydrazide terminated atomic force microscope tip using a standard protein coupling technique. Upon contact with each mineral surface, the adhesion force between azotobactin and goethite was two to three times the value observed for the isostructural Al-equivalent diaspore. The affinity for the solid iron oxide surface reflected in the force measurements correlates with the specificity of azotobactin for aqueous ferric iron. Further, the adhesion force between azotobactin and goethite significantly decreases when small amounts of soluble iron are added to the system suggesting a significant specific interaction between the azotobactin and the mineral surface. Changes in the force signature with pH and ionic strength were fairly predictable when considering mineral solubility, the charge character of the mineral surfaces, the molecular structure of azotobactin, and the intervening solution. Molecular and quantum mechanical calculations which were completed to further investigate the interaction between azotobactin and iron/aluminum oxide surfaces, and to more fully understand the force measurements, also showed an increased force affinity for Fe over Al. Ab initio calculations on siderophore fragment analogs suggest the iron affinity can be attributed to increased electron density associated with the Fe-O bond compared to the Al-O bond; an observation that correlates with iron's larger electronegativity compared to aluminum. Attachment of the ligand to each surface was directed by steric forces within the molecule and coulombic interactions between the siderophore oxygens and the metals in the mineral. Chelating ligand pairs coordinated with neighboring metal atoms in a bidentate, binuclear geometry. Upon simulated retraction of azotobactin from each surface, the Fe-O(siderophore) bonds persisted into a higher force regime than Al-O(siderophore) bonds, and surface metals were removed from both minerals. Extrapolation of the model to more realistic hydrated conditions using a PCM model in the quantum mechanical calculations and water clusters in the molecular mechanical model demonstrated that the presence of water energetically favors and enhances metal extraction, making this a real possibility in a natural system. / Ph. D.

Alzheimer's disease is the leading cause of senile dementia in the elderly, and as life expectancy increases across the globe, incidence of the disease is continually increasing. Current estimates place the number of cases at 25-30 million worldwide, with more than 5.4 million of these occurring in the United States. While the exact cause of the disease remains a mystery, it has become clear that the amyloid β-peptide (Aβ) is central to disease pathogenesis. The aggregation and deposition of this peptide in the brain is known to give rise to the hallmark lesions associated with Alzheimer's disease, but its exact mechanism of toxicity remains largely uncharacterized. Molecular dynamics (MD) simulations have achieved great success in exploring molecular events with atomic resolution, predicting and explaining phenomena that are otherwise obscured from even the most sensitive experimental techniques. Due to the difficulty of obtaining high-quality structural data of Aβ and its toxic assemblies, MD simulations can be an especially useful tool in understanding the progression of Alzheimer's disease on a molecular level. The work contained herein describes the interactions of Aβ monomers and oligomers with lipid bilayers to understand the mechanism by which Aβ exerts its toxicity. Also explored is the mechanism by which flavonoid antioxidants may prevent Aβ self-association and destabilize toxic aggregates, providing insight into the chemical features that give rise to this therapeutic effect. / Ph. D.

No / Budesonide is a mixture of 22R and 22S epimers. The epimeric content of budesonide was reported in both British and European pharmacopoeias to be within the range of 60-49/40-51 for R and S epimers, respectively. In this work, contribution of the two epimers to the overall infrared spectrum of budesonide has been investigated by quantum chemical calculations.

No / Violacein is a bisindole pigment occurring as a biosynthetic product of Chromobacterium violaceum and Janthinobacterium lividum. It has some structural similarities to the cyanobacterial UV-protective pigment scytonemin, which has been the subject of comprehensive spectroscopic and structural studies. A detailed experimental Raman spectroscopic study with visible and near-infrared excitation of violacein produced by C. violaceum has been undertaken and supported using theoretical DFT calculations. Raman spectra with 514 and 785 nm excitation of cultivated cells as well as extracts and Gaussian (B3LYP/6-311++G(d,p)) calculations with proposed molecular vibrational assignments are reported here.

Yes / Three equations of state with a group contribution model for binary interaction parameters were employed to calculate the vapor-liquid equilibria of synthetic and real natural gas mixtures with heavy fractions. In order to estimate the binary interaction parameters, critical temperatures, critical pressures and acentric factors of binary constituents of the mixture are required. The binary interaction parameter model also accounts for temperature. To perform phase equilibrium calculations, the heavy fractions were first discretized into 12 Single Carbon Numbers (SCN) using generalized molecular weights. Then, using the generalized molecular weights and specific gravities, the SCN were characterized. Afterwards, phase equilibrium calculations were performed employing a set of (nc + 1) equations where nc stands for the number of known components plus 12 SCN. The equations were solved iteratively using Newton's method. Predictions indicate that the use of binary interaction parameters for highly sour natural gas mixtures is quite important and must not be avoided. For sweet natural gas mixtures, the use of binary interaction parameters is less remarkable, however.

Os estudos de modelagem molecular das interações entre ligantes baseado em oxindóis (isaepy, isapn, [Cu(isapn)]², isaenim e o SU9516) e as proteínas kinases dependentes de ciclina (CDK1 e CDK2) são apresentados neste trabalho. Uma inibição na atividade da CDK1 e CDK2, que catalisam a fosforilação de grupos específicos em proteínas, tem implicações na indução da apoptose celular. O objetivo é tentar determinar qual destes ligantes potencializa a inibição da síntese de ATP (adenosina trifosfato) em ADP (adenosina difosfato) no sítio ativo da CDK1 e CDK2 para, desta forma, induzir a apoptose de células cancerígenas. Os estudos realizados neste trabalho indicam que dentre os ligantes analisados, o isaepy e o isapn obtiveram melhores resultados de estabilidade e ligações de hidrogênio entre aminoácidos dentro do sítio. Analisamos a influência do íon Cu no aumento da eficácia do isapn na atividade inibitória (complexo [Cu(isapn)]²) e comparamos os resultados obtidos dos estudos do isapn e [Cu(isapn)]², quando inseridos no sítio de ligação do ATP da CDK1, com medidas de eletroforese em gel. Verificamos que os nossos resultados foram corroborados com as medidas de eletroforese. Também discutimos os resultados de cálculos de acoplamento hiperfino para o Cu no [Cu(isapn)]² em diferentes ambientes químicos e fizemos a comparação destes resultados com medidas de EPR. Desta forma, conseguimos verificar o ambiente químico do íon Cu e um aumento da estabilidade do isapn dentro do sítio estudado com a inserção do íon Cu. Este trabalho visa contribuir para a síntese de novos ligantes que aumentem a eficácia da inibição da síntese de ATP em ADP nas CDKs e também para a minimização dos custos através da diminuição da realização de experimentos que se baseiam em métodos de tentativa e erro. / Molecular modeling studies of the interaction of oxindol based ligands (isaepy, isapn [Cu(isapn)]²,isaenim and SU9516) with Cyclin Dependent Kinases proteins (CDK1 and CDK2) are presented here. CDK1 and CDK2 catalyze the phosphorylation of specific groups in proteins and inhibition of its activities implies in induction of cancer cells apoptosis. The goal is to determine which ligands increase the inhibition of ATP (adenosine triphosphate) into ADP (adenosine diphosphate) synthesis which occurs inside the CDK1 and CDK2 active site. We analyze the influence of the Cu ion on increasing the inhibitory activity in isapn ([Cu(isapn)]² metal complex). Comparisons between the results obtained from studies of the isapn and [Cu(isapn)]² inserted into the ATP binding site of CDK1 with measurements of gel electrophoresis were performed. The hyperfine coupling at Cu ion in [Cu(isapn)]² in different chemical environments are here obtained and the results are compared with EPR measurements. This work aims to contribute to the development of new ligands which increase the inhibition of the synthesis of ATP into ADP in the CDKs moreover we aim to assist in the reduction of the costs of measurements that are based on trial and error aproaches.

Os estudos de modelagem molecular das interações entre ligantes baseado em oxindóis (isaepy, isapn, [Cu(isapn)]², isaenim e o SU9516) e as proteínas kinases dependentes de ciclina (CDK1 e CDK2) são apresentados neste trabalho. Uma inibição na atividade da CDK1 e CDK2, que catalisam a fosforilação de grupos específicos em proteínas, tem implicações na indução da apoptose celular. O objetivo é tentar determinar qual destes ligantes potencializa a inibição da síntese de ATP (adenosina trifosfato) em ADP (adenosina difosfato) no sítio ativo da CDK1 e CDK2 para, desta forma, induzir a apoptose de células cancerígenas. Os estudos realizados neste trabalho indicam que dentre os ligantes analisados, o isaepy e o isapn obtiveram melhores resultados de estabilidade e ligações de hidrogênio entre aminoácidos dentro do sítio. Analisamos a influência do íon Cu no aumento da eficácia do isapn na atividade inibitória (complexo [Cu(isapn)]²) e comparamos os resultados obtidos dos estudos do isapn e [Cu(isapn)]², quando inseridos no sítio de ligação do ATP da CDK1, com medidas de eletroforese em gel. Verificamos que os nossos resultados foram corroborados com as medidas de eletroforese. Também discutimos os resultados de cálculos de acoplamento hiperfino para o Cu no [Cu(isapn)]² em diferentes ambientes químicos e fizemos a comparação destes resultados com medidas de EPR. Desta forma, conseguimos verificar o ambiente químico do íon Cu e um aumento da estabilidade do isapn dentro do sítio estudado com a inserção do íon Cu. Este trabalho visa contribuir para a síntese de novos ligantes que aumentem a eficácia da inibição da síntese de ATP em ADP nas CDKs e também para a minimização dos custos através da diminuição da realização de experimentos que se baseiam em métodos de tentativa e erro. / Molecular modeling studies of the interaction of oxindol based ligands (isaepy, isapn [Cu(isapn)]²,isaenim and SU9516) with Cyclin Dependent Kinases proteins (CDK1 and CDK2) are presented here. CDK1 and CDK2 catalyze the phosphorylation of specific groups in proteins and inhibition of its activities implies in induction of cancer cells apoptosis. The goal is to determine which ligands increase the inhibition of ATP (adenosine triphosphate) into ADP (adenosine diphosphate) synthesis which occurs inside the CDK1 and CDK2 active site. We analyze the influence of the Cu ion on increasing the inhibitory activity in isapn ([Cu(isapn)]² metal complex). Comparisons between the results obtained from studies of the isapn and [Cu(isapn)]² inserted into the ATP binding site of CDK1 with measurements of gel electrophoresis were performed. The hyperfine coupling at Cu ion in [Cu(isapn)]² in different chemical environments are here obtained and the results are compared with EPR measurements. This work aims to contribute to the development of new ligands which increase the inhibition of the synthesis of ATP into ADP in the CDKs moreover we aim to assist in the reduction of the costs of measurements that are based on trial and error aproaches.