Im Rahmen der vorliegenden Arbeit konnten Einflüsse magnetischer Felder, insbesondere mit hohen Gradienten der magnetischen Flussdichte, auf Korrosionsprozesse am Beispiel Eisen quantifiziert und deren Wirkungsmechanismus erklärt werden. Als ein besonders in technisch relevanten gering konzentrierten sauren wässrigen Lösungen bedeutsamer Effekt wurde eine sekundäre Wirkung der Feldgradientenkraft über den Mechanismus der Wahrung der Ladungsneutralität auf den pH-Wert an der Elektrodenoberfläche identifiziert. Somit konnte ein signifikanter Magnetfeldeinfluss auf die formal ladungstransferkontrollierte Korrosionsreaktion nachgewiesen werden. Um die komplexen Korrosionsvorgänge an mehrphasigen NdFeB-Magneten mit paramagnetischer intergranularer Nd-reicher Phase aufklären zu können, war zunächst eine vertiefte Analyse der freien und anodischen Korrosionsreaktionen des Neodyms notwendig. Die dabei gewonnenen Erkenntnisse erlauben den Magnetfeldeinfluss bei der Korrosion aufmagnetisierter NdFeB-Magnete zu verstehen.

Introduction. The aim of this thesis is to examine how Swedish private archival institutions perceive the possibility of being included in the Archival Law. At present the Archival Law of 1990 only applies to official documents from the public sector. Recently however a proposal to change the legislation so that it in part also applies to private archives has been made in the newly published Archival Inquiry commissioned by the government. A more far-reaching proposal to include the private archives in the law has also been made by the Swedish National Archives. Method. We conducted a qualitative research study using semi-structured interviews with 10 informants from 8 different private archival institutions in Sweden. Analysis. By presenting what has been said regarding legislation for private archives in previous archival inquiries, government propositions and other official reports we frame the idea of legislation for private archives by putting it in its culturalpolitical context. An important concept that permeates this thesis is the concept of cultural heritage and how it relates to private archives. The transcriptions from the interviews were analysed by the use of force-field analysis which has its roots in Karl Lewin’s field theory. Results. By collecting the informants thoughts concerning a new legislation for private archives and analysing them as forces working for (driving forces) and against (restraining forces) change we show the complexities surrounding this issue. Conclusion. In many cases uncertainty of what the consequences of the new legislation will be for the private archival institutions prevents them from supporting the change. Our informants also feel that the Swedish National Archives has a top-down perspective which prevents them from listening to and learn from the private sectors experiences. Collaboration between the public and the private sector seems to be the way forward. This is a two years master’s thesis in Archival Science

No description available.

Despite more than a decade-long process to transition aircraft maintenance practices from paper-to electronic-based systems, some organizations remain unable to complete this transition. Researchers have indicated that while organizations have invested resources in technology improvements, there remains a limited understanding of the factors that contribute to effectively managing technology-enabled change. The purpose of this case study was to identify and explore socio-technical (ST) factors that inhibit an effective transition from a paper-based system to an electronic-based system for aircraft maintenance. A conceptual model applying theories of change management, technology acceptance, systems thinking, and ST theory informed the research. Thirteen participants provided data via semistructured interviews, field observations, follow-up interviews, other documentation, and a questionnaire. Data were analyzed with open and axial coding techniques to identify themes, which were then crosschecked and triangulated with observation and follow-up interview data. Findings revealed communication issues, a fundamental misconception in training, and a false assumption that all personnel easily acquire computer literacy. Benefits gained from this study should assist maintenance, repair, and overall (MRO) organizations within the Department of Defense to improve current and future technology implementation as the research underscores real-life issues from a comparable organization. The implications for positive social change provide a greater understanding of technology-enabled change and contribute to the development of best practices for technology initiatives that address common ST issues in the MRO workplace.

No description available.

Conformational dynamics are important to the function of biological molecules. While many experimental techniques (e.g. X-ray crystallography and NMR spectroscopy) have been developed for providing the structure of functional conformations, it is exceptionally challenging to understand conformational dynamics from experimental characterization. Molecular dynamics (MD) simulations is a powerful tool for probing conformational dynamics. The timescale resolution of MD simulations enables people to investigate intermediate conformations and transition pathways in atomic detail. Recent advancements in computer hardware have increased the timescales accessible to MD simulations. Meanwhile, more accurate and specific force fields have been developed to accurately model a variety biological system of different sizes. My graduate research has been focused on using MD simulations to study the conformational dynamics of proteins. Markov State Model (MSM) based approaches are extensively applied to investigate a variety of folding and/or binding mechanisms in atomic detail. Another focus of my work has been developing a Bayesian inference-based approach called BICePs to reconcile experimental measurements with simulation data to determine conformational ensembles and to validate force fields. / Chemistry

Atomistic modeling and simulation methods enable a modern molecular approach to bio-medical research. Issues addressed range from structure-function relationships to structure-based drug design. The ability of these methods to address biologically relevant problems is largely determined by their accurate treatment of electrostatic interactions in the target biomolecular structure. In practical molecular simulations, the electrostatic charge density of molecules is approximated by an arrangement of fractional "point charges" throughout the molecule. While chemically intuitive and straightforward in technical implementation, models based exclusively on atom-centered charge placement, a major workhorse of the biomolecular simulations, do not necessarily provide a sufficiently detailed description of the molecular electrostatic potentials for small systems, and can become prohibitively expensive for large systems with thousands to millions of atoms. In this work, we propose a rigorous and generally applicable approach, Optimal Point Charge Approximation (OPCA), for approximating electrostatic charge distributions of biomolecules with a small number of point charges to best represent the underlying electrostatic potential, regardless of the distance to the charge distribution. OPCA places a given number of point charges so that the lowest order multipole moments of the reference charge distribution are optimally reproduced. We provide a general framework for calculating OPCAs to any order, and introduce closed-form analytical expressions for the 1-charge, 2-charge and 3-charge OPCA. We demonstrate the advantage of OPCA by applying it to a wide range of biomolecules of varied sizes. We use the concept of OPCA to develop a different, novel approach of constructing accurate and simple point charge water models. The proposed approach permits a virtually exhaustive search for optimal model parameters in the sub-space most relevant to electrostatic properties of the water molecule in liquid phase. A novel rigid 4-point Optimal Point Charge (OPC) water model constructed based on the new approach is substantially more accurate than commonly used models in terms of bulk water properties, and delivers critical accuracy improvement in practical atomistic simulations, such as RNA simulations, protein folding, protein-ligand binding and small molecule hydration. We also apply our new approach to construct a 3-point version of the Optimal Point Charge water model, referred to as OPC3. OPCA can be employed to represent large charge distributions with only a few point charges. We use this capability of OPCA to develop a multi-scale, yet fully atomistic, generalized Born approach (GB-HCPO) that can deliver up to 2 orders of magnitude speedup compared to the reference MD simulation. As a practical demonstration, we exploit the new multi-scale approach to gain insight into the structure of million-atom 30-nm chromatin fiber. Our results suggest important structural details consistent with experiment: the linker DNA fills the core region and the H3 histone tails interact with the linker DNA. OPC, OPC3 and GB-HCPO are implemented in AMBER molecular dynamics software package. / Ph. D.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Zellen enthalten zahlreiche Enzyme, deren Reaktionen von molekularem Sauerstoff abhängen. Oft sind deren aktive Zentren tief im inneren des Proteins verborgen, was die Frage nach spezifischen Zugangskanälen, die den Sauerstoff gezielt zum Ort der Katalyse leiten, aufwirft. In der vorliegenden Arbeit wird dies am Beispiel der 12/15-Lipoxygenase, als ein typisches Beipiel Sauerstoff verbrauchender Enzyme, untersucht. Die Sauerstoffverteilung innerhalb des Proteins wurde bestimmt und mögliche Routen für den Sauerstoffzugang definiert. Zu diesem Zweck wurden theoretische Untersuchungen eng mit Experimenten verzahnt. Zuerst wurden Molekulardynamik Simulationen des Proteins in Lösung durchgeführt. Aus den Trajektorien konnte die dreidimensionale Verteilung der Freien Enthalpie für Sauerstoff berechnet werden. Die Analyse der günstigsten Pfade in dieser Energielandschaft führte zur Identifikation von vier Sauerstoffkanälen im Protein. Alle Kanäle verbinden die Proteinoberfläche mit einem Gebiet hoher Sauerstoffaffinität am aktiven Zentrum. Diese Region liegt bezüglich des Substrats gegenüber dem Eisenzentrum, wodurch eine strukturelle Erklärung für die Reaktionsspezifität des Enzyms gegeben ist. Der katalytisch bedeutsamste Weg des Sauerstoffs kann durch L367F Austauschmutation blockiert werden, was zu einer stark erhöhten Michaelis-Konstante für Sauerstoff führt. Diese experimentell nachgewiesene Blockade konnte, mit Hilfe entsprechender Molekulardynamik Simulationen, durch eine Umordnung eines Wasserstoffbrücken-Netzwerks von Wassermolekülen innerhalb des Protein im Detail erklärt werden. Die Ergebnisse ermöglichen den Schluss, dass die Hauptroute für Sauerstoff zum aktiven Zentrum des Enzyms einem Kanal folgt, der aus vorübergehend verbundenen Hohlräumen besteht. Hierbei unterliegt das Öffnen und Schließen des Kanals der Dynamik der Proteinseitenketten. / Cells contain numerous enzymes utilizing molecular oxygen for their reactions. Often, their active sites are buried deeply inside the protein which raises the question whether there are specific access channels guiding oxygen to the site of catalysis. In the present thesis this question is investigated choosing 12/15-lipoxygenase as a typical example for such oxygen dependent enzymes. The oxygen distribution within the protein was determined and potential routes for oxygen access were defined. For this purpose an integrated strategy of structural modeling, molecular dynamics simulations, site directed mutagenesis, and kinetic measurements has been applied. First, molecular dynamics simulations of the protein in solution were performed. From the trajectories, the 3-dimensional free-energy distribution for oxygen could be computed. Analyzing energetically favorable paths in the free-energy map led to identification of four oxygen channels in the protein. All channels connect the protein surface with a zone of high oxygen affinity at the active site. This region is localized opposite to the non-heme iron providing a structural explanation for the reaction specificity of this lipoxygenase isoform. The catalytically most relevant path can be obstructed by L367F exchange which leads to a strongly increased Michaelis constant for oxygen. This experimetally proven blocking mechanism can, by virtue of molecular dynamics studies, be explained in detail through a reordering of the hydrogen bonding network of water molecules. As a conclusion, the results provide strong evidence that the main route for oxygen access to the active site of the enzyme follows a channel formed by transiently interconnected cavities whereby the opening and closure is governed by sidechain dynamics.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal