Molecular dynamics simulations and QM/MM calculations can provide insights into the structure and function of enzymes as well as changes due to mutations of the protein sequence.

Developmental dysplasia of the hip (DDH) is a common newborn condition where the femoral head is not located in its natural position in the acetabulum (hip socket). Several treatment methods are being implemented worldwide to treat this abnormal condition. One of the most effective methods of treatment is the use of Pavlik Harness, which directs the femoral head toward the natural position inside the acetabulum. This dissertation presents a developed method for identifying the least energy path that the femoral head would follow during reduction. This is achieved by utilizing a validated computational biomechanical model that allows the determination of the potential energy, and then implementing the principle of stationary potential energy. The potential energy stems from strain energy stored in the muscles and gravitational potential energy of four rigid-body components of lower limb bones. Five muscles are identified and modeled because of their effect on DDH reduction. Clinical observations indicate that reduction with the Pavlik Harness occurs passively in deep sleep under the combined effects of gravity and the constraints of the Pavlik Harness. A non-linear constitutive equation, describing the passive muscle response, is used in the potential energy computation. Different DDH abnormalities with various flexion, abduction, and hip rotation angles are considered, and least energy paths are identified. Several constraints, such as geometry and harness configuration, are considered to closely simulate real cases of DDH. Results confirm the clinical observations of two different pathways for closed reduction. The path of least energy closely approximated the modified Hoffman-Daimler method. Release of the pectineus muscle favored a more direct pathway over the posterior rim of the acetabulum. The direct path over the posterior rim of the acetabulum requires more energy. This model supports the observation that Grade IV dislocations may require manual reduction by the direct path. However, the indirect path requires less energy and may be an alternative to direct manual reduction of Grade IV infantile hip dislocations. Of great importance, as a result of this work, identifying the minimum energy path that the femoral head would travel would provide a non-surgical tool that effectively aids the surgeon in treating DDH.

No description available.

The assessment of the direct and indirect requirements for energy is known as embodied energy analysis. For buildings, the direct energy includes that used primarily on site, while the indirect energy includes primarily the energy required for the manufacture of building materials. This thesis is concerned with the completeness and reliability of embodied energy analysis methods. Previous methods tend to address either one of these issues, but not both at the same time. Industry-based methods are incomplete. National statistical methods, while comprehensive, are a ‘black box’ and are subject to errors. A new hybrid embodied energy analysis method is derived to optimise the benefits of previous methods while minimising their flaws. In industry-based studies, known as ‘process analyses’, the energy embodied in a product is traced laboriously upstream by examining the inputs to each preceding process towards raw materials. Process analyses can be significantly incomplete, due to increasing complexity. The other major embodied energy analysis method, ‘input-output analysis’, comprises the use of national statistics. While the input-output framework is comprehensive, many inherent assumptions make the results unreliable. Hybrid analysis methods involve the combination of the two major embodied energy analysis methods discussed above, either based on process analysis or input-output analysis. The intention in both hybrid analysis methods is to reduce errors associated with the two major methods on which they are based. However, the problems inherent to each of the original methods tend to remain, to some degree, in the associated hybrid versions. Process-based hybrid analyses tend to be incomplete, due to the exclusions associated with the process analysis framework. However, input-output-based hybrid analyses tend to be unreliable because the substitution of process analysis data into the input-output framework causes unwanted indirect effects. A key deficiency in previous input-output-based hybrid analysis methods is that the input-output model is a ‘black box’, since important flows of goods and services with respect to the embodied energy of a sector cannot be readily identified. A new input-output-based hybrid analysis method was therefore developed, requiring the decomposition of the input-output model into mutually exclusive components (ie, ‘direct energy paths’). A direct energy path represents a discrete energy requirement, possibly occurring one or more transactions upstream from the process under consideration. For example, the energy required directly to manufacture the steel used in the construction of a building would represent a direct energy path of one non-energy transaction in length. A direct energy path comprises a ‘product quantity’ (for example, the total tonnes of cement used) and a ‘direct energy intensity’ (for example, the energy required directly for cement manufacture, per tonne). The input-output model was decomposed into direct energy paths for the ‘residential building construction’ sector. It was shown that 592 direct energy paths were required to describe 90% of the overall total energy intensity for ‘residential building construction’. By extracting direct energy paths using yet smaller threshold values, they were shown to be mutually exclusive. Consequently, the modification of direct energy paths using process analysis data does not cause unwanted indirect effects. A non-standard individual residential building was then selected to demonstrate the benefits of the new input-output-based hybrid analysis method in cases where the products of a sector may not be similar. Particular direct energy paths were modified with case specific process analysis data. Product quantities and direct energy intensities were derived and used to modify some of the direct energy paths. The intention of this demonstration was to determine whether 90% of the total embodied energy calculated for the building could comprise the process analysis data normally collected for the building. However, it was found that only 51% of the total comprised normally collected process analysis. The integration of process analysis data with 90% of the direct energy paths by value was unsuccessful because: • typically only one of the direct energy path components was modified using process analysis data (ie, either the product quantity or the direct energy intensity); • of the complexity of the paths derived for ‘residential building construction’; and • of the lack of reliable and consistent process analysis data from industry, for both product quantities and direct energy intensities. While the input-output model used was the best available for Australia, many errors were likely to be carried through to the direct energy paths for ‘residential building construction’. Consequently, both the value and relative importance of the direct energy paths for ‘residential building construction’ were generally found to be a poor model for the demonstration building. This was expected. Nevertheless, in the absence of better data from industry, the input-output data is likely to remain the most appropriate for completing the framework of embodied energy analyses of many types of products—even in non-standard cases. ‘Residential building construction’ was one of the 22 most complex Australian economic sectors (ie, comprising those requiring between 592 and 3215 direct energy paths to describe 90% of their total energy intensities). Consequently, for the other 87 non-energy sectors of the Australian economy, the input-output-based hybrid analysis method is likely to produce more reliable results than those calculated for the demonstration building using the direct energy paths for ‘residential building construction’. For more complex sectors than ‘residential building construction’, the new input-output-based hybrid analysis method derived here allows available process analysis data to be integrated with the input-output data in a comprehensive framework. The proportion of the result comprising the more reliable process analysis data can be calculated and used as a measure of the reliability of the result for that product or part of the product being analysed (for example, a building material or component). To ensure that future applications of the new input-output-based hybrid analysis method produce reliable results, new sources of process analysis data are required, including for such processes as services (for example, ‘banking’) and processes involving the transformation of basic materials into complex products (for example, steel and copper into an electric motor). However, even considering the limitations of the demonstration described above, the new input-output-based hybrid analysis method developed achieved the aim of the thesis: to develop a new embodied energy analysis method that allows reliable process analysis data to be integrated into the comprehensive, yet unreliable, input-output framework. Plain language summary Embodied energy analysis comprises the assessment of the direct and indirect energy requirements associated with a process. For example, the construction of a building requires the manufacture of steel structural members, and thus indirectly requires the energy used directly and indirectly in their manufacture. Embodied energy is an important measure of ecological sustainability because energy is used in virtually every human activity and many of these activities are interrelated. This thesis is concerned with the relationship between the completeness of embodied energy analysis methods and their reliability. However, previous industry-based methods, while reliable, are incomplete. Previous national statistical methods, while comprehensive, are a ‘black box’ subject to errors. A new method is derived, involving the decomposition of the comprehensive national statistical model into components that can be modified discretely using the more reliable industry data, and is demonstrated for an individual building. The demonstration failed to integrate enough industry data into the national statistical model, due to the unexpected complexity of the national statistical data and the lack of available industry data regarding energy and non-energy product requirements. These unique findings highlight the flaws in previous methods. Reliable process analysis and input-output data are required, particularly for those processes that were unable to be examined in the demonstration of the new embodied energy analysis method. This includes the energy requirements of services sectors, such as banking, and processes involving the transformation of basic materials into complex products, such as refrigerators. The application of the new method to less complex products, such as individual building materials or components, is likely to be more successful than to the residential building demonstration.

Hydrocarbons, in particular polycyclic aromatic hydrocarbons (PAHs), have been long discussed to be carriers of interstellar infrared (IR) emission and ultraviolet (UV) absorption features. Yet, their origin in dense phases of the interstellar medium (ISM), such as molecular clouds, remains unclear. In this work, growth mechanisms based on ion-molecule reactions between cationic PAHs/hydrocarbons and methyne (CH) were investigated. The reaction type and the precursor were derived and selected from known chemical and physical properties of the ISM. These chemical reactions were characterised by calculating branching ratios (based on cross sections) and capture rate coefficients, minimum reaction paths, reaction enthalpies, thermal equilibrium constants, and microcanonic isomerisation and radiative deactivation rate coefficients. In order to cope with the variety of reaction parameters, a hierarchic workflow scheme was set up. First, the reaction potential energy surface was sampled by molecular dynamics simulations. Then, minimum energy paths of the most probable reaction channels were investigated. Finally, molecular and kinetic properties of stationary points were calculated. The quantum chemical level of theory was increased at each step from DFTB (tight-binding density-functional), to DFT, and finally to post-Hartree-Fock methods. Results on CH based hydrocarbon growth showed the transition from non-cyclic hydrocarbons to cyclic and aromatic structures and from cyclic to polycyclic aromatic hydrocarbons. Additionally, the reactive collisions between hydrocarbons and CH were found to produce sufficient energy for isomerisation and fragmentation processes even at ultra low temperatures. In all, the results indicate that methyne might be a proper precursor for the formation of large interstellar PAHs. / Kohlenwasserstoffe, insbesondere polyzyklische Kohlenwasserstoffe (engl. PAHs), werden seit einigen Jahren als Mitverursacher interstellar IR-Emissions- und UV-Absorptionsbanden angesehen und diskutiert. Dabei ist die Herkunft dieser Moleküle in den dichten Phasen des interstellaren Mediums (ISM) aber noch nicht aufgeklärt. In dieser Arbeit wurden daher die Bildungsmechanismen, welche auf Ion-Molekül-Reaktionen zwischen kationischen PAHs und Kohlenwasserstoffen und dem Molekül CH beruhen, untersucht. Sowohl der Reaktionstyp als auch der Präkursor wurden anhand von bekannten physikalischen und chemischen Eigenschaften des ISM abgeleitet und ausgewählt. Die Analyse der chemischen Reaktionen basierte auf Berechnungen zur Produktzusammensetzung und Einfangsratenkoeffizienten (welche wiederum aus berechneten Reaktionsquerschnitten hervorgingen) Minimumenergiepfade (MEP), Reaktionsenthalpien, thermische Gleichgewichtskonstanten und mikrokanonische Isomerisierungs- und Strahlungsdeaktivierungs-Ratenkoeffizienten. Um der Vielzahl an Reaktionsparameter gerecht zu werden, wurden die Berechnungsmethoden entsprechend eines hierarischen Fließschemas kombiniert. Hierzu wurden zuerst durch Molekulardynamik-Simulationen die Reaktionspotentialenergieflächen abgerastert. Auf der nächsten Stufe wurden statistisch bedeutsame Reaktionskanäle bezüglich ihrer Minimumenergiepfade untersucht. Den Abschluss bildete die Berechnung molekularer und kinetischer Charakteristika stationärer Punkte auf einem MEP. Entsprechend dieses Schemas wurde die quantenchemische Genauigkeit auf jeder Stufe von approximativer DFT über DFT zu post-Hartree-Fock verändert. Die Ergebnisse des CH-basierten Kohlenwasserstoffwachstums zeigten einen Übergang von nichtzyklischen zu zyklischen and aromatischen Strukturen, sowie von zyklischen zu polyzyklischen Kohlenwasserstoffen. Außerdem zeigte sich, dass reaktive Kollisionen zwischen Kohlenwasserstoffen und CH auch bei Tiefsttemperaturen immer ausreichend Energie für Isomerisierungs- und Fragmentationsprozesse liefert. Die Ergebnisse dieser Arbeit lassen den Schluss zu, dass CH ein geeigneter Präkursor für die Bildung großer interstellarer PAH ist.

Hydrocarbons, in particular polycyclic aromatic hydrocarbons (PAHs), have been long discussed to be carriers of interstellar infrared (IR) emission and ultraviolet (UV) absorption features. Yet, their origin in dense phases of the interstellar medium (ISM), such as molecular clouds, remains unclear. In this work, growth mechanisms based on ion-molecule reactions between cationic PAHs/hydrocarbons and methyne (CH) were investigated. The reaction type and the precursor were derived and selected from known chemical and physical properties of the ISM. These chemical reactions were characterised by calculating branching ratios (based on cross sections) and capture rate coefficients, minimum reaction paths, reaction enthalpies, thermal equilibrium constants, and microcanonic isomerisation and radiative deactivation rate coefficients. In order to cope with the variety of reaction parameters, a hierarchic workflow scheme was set up. First, the reaction potential energy surface was sampled by molecular dynamics simulations. Then, minimum energy paths of the most probable reaction channels were investigated. Finally, molecular and kinetic properties of stationary points were calculated. The quantum chemical level of theory was increased at each step from DFTB (tight-binding density-functional), to DFT, and finally to post-Hartree-Fock methods. Results on CH based hydrocarbon growth showed the transition from non-cyclic hydrocarbons to cyclic and aromatic structures and from cyclic to polycyclic aromatic hydrocarbons. Additionally, the reactive collisions between hydrocarbons and CH were found to produce sufficient energy for isomerisation and fragmentation processes even at ultra low temperatures. In all, the results indicate that methyne might be a proper precursor for the formation of large interstellar PAHs. / Kohlenwasserstoffe, insbesondere polyzyklische Kohlenwasserstoffe (engl. PAHs), werden seit einigen Jahren als Mitverursacher interstellar IR-Emissions- und UV-Absorptionsbanden angesehen und diskutiert. Dabei ist die Herkunft dieser Moleküle in den dichten Phasen des interstellaren Mediums (ISM) aber noch nicht aufgeklärt. In dieser Arbeit wurden daher die Bildungsmechanismen, welche auf Ion-Molekül-Reaktionen zwischen kationischen PAHs und Kohlenwasserstoffen und dem Molekül CH beruhen, untersucht. Sowohl der Reaktionstyp als auch der Präkursor wurden anhand von bekannten physikalischen und chemischen Eigenschaften des ISM abgeleitet und ausgewählt. Die Analyse der chemischen Reaktionen basierte auf Berechnungen zur Produktzusammensetzung und Einfangsratenkoeffizienten (welche wiederum aus berechneten Reaktionsquerschnitten hervorgingen) Minimumenergiepfade (MEP), Reaktionsenthalpien, thermische Gleichgewichtskonstanten und mikrokanonische Isomerisierungs- und Strahlungsdeaktivierungs-Ratenkoeffizienten. Um der Vielzahl an Reaktionsparameter gerecht zu werden, wurden die Berechnungsmethoden entsprechend eines hierarischen Fließschemas kombiniert. Hierzu wurden zuerst durch Molekulardynamik-Simulationen die Reaktionspotentialenergieflächen abgerastert. Auf der nächsten Stufe wurden statistisch bedeutsame Reaktionskanäle bezüglich ihrer Minimumenergiepfade untersucht. Den Abschluss bildete die Berechnung molekularer und kinetischer Charakteristika stationärer Punkte auf einem MEP. Entsprechend dieses Schemas wurde die quantenchemische Genauigkeit auf jeder Stufe von approximativer DFT über DFT zu post-Hartree-Fock verändert. Die Ergebnisse des CH-basierten Kohlenwasserstoffwachstums zeigten einen Übergang von nichtzyklischen zu zyklischen and aromatischen Strukturen, sowie von zyklischen zu polyzyklischen Kohlenwasserstoffen. Außerdem zeigte sich, dass reaktive Kollisionen zwischen Kohlenwasserstoffen und CH auch bei Tiefsttemperaturen immer ausreichend Energie für Isomerisierungs- und Fragmentationsprozesse liefert. Die Ergebnisse dieser Arbeit lassen den Schluss zu, dass CH ein geeigneter Präkursor für die Bildung großer interstellarer PAH ist.