150 research outputs found

    Analog quantum simulator of the multistate Landau-Zener model

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    Superconducting qubits are one of the most promising candidates for near term quantum applications. In this work we established a subtractive method to build Josephson junctions, the centerpiece of almost all superconducting quantum circuits. Using this technique we built a quantum simulator of the multistate Landau-Zener model. In time-resolved measurements we studied the transient dynamics of this system for different initial states

    Development and application of novel NMR methodology for elucidation of protein structure and dynamics

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    The design of a novel drug is a creative act. The difference between a researcher and an artist, besides the pursuit of a particular goal, is that his/her creativity is based on scientific knowledge and technology. Until today, drug discovery was mainly dominated by trial and error, based on empirically derived rules. Today, the “trial and error” approach is being replaced by a conscious design based on improved predictions. These improvements in the prediction of the structure of a drug molecule are mainly based on the increasing knowledge about molecular mechanisms. [1] This increase of mechanistic knowledge is also caused by the progress of structure elucidation techniques like NMR-spectroscopy or X-ray crystallography. So far, our understanding of molecular mechanisms is based on the justified principle: Structure determines function. The number of deposited protein structures grows exponentially. Nevertheless, the ratio between solved and unsolved human protein structures is in the single-digit percentage range. [2] This relative number is even lower for proteins that are insoluble and at the same time amorphous in the solid-state, such as fibrils or membrane proteins. The structure of such proteins of great importance is not accessible by X-ray crystallography or liquid-state NMR-spectroscopy. In order to close this gap, a new NMR methodology has been developed over the last two decades, the proton-detected fast-magic-angle-spinning solid-state NMR-spectroscopy. This new method enables the structure-elucidation of such amorphous and insoluble proteins. In this context, Bernd Reif et al., Rasmus Linser et al., Guido Pintacuda et al., and others did the pioneering work. In this line, an important objective of this thesis was to contribute to the continuous development of this methodology. The key to well-resolved protein structure from NMR-spectroscopy is precise distance restraints. However, till date, solid state NMR-spectroscopy has only been able to provide qualitative restraints, grouping the internuclear distance as close, medium, or far. Opposed to the general picture, with the help of Suresh K. Vasa, Evgeny Nimerovsky, Himanshu Singh, Beat Vögeli, and others, I developed a user-friendly approach to determine accurate distance restraints in solid-state NMR. Hereby, all site-specific errors that occur during magnetization transfer are addressed by an integrated approach. The approximations to be made are carefully validated by numerical simulations. Further, in order to address challenging protein targets where the assignment might be ambiguous and incomplete, I have performed the first kinetic hydrogen-deuterium exchange measurements in solid-state NMR-spectroscopy in collaboration with Suresh K. Vasa, Himanshu Singh, and others. The method reports on the over-all positioning of exchangeable protons within the protein by information on the presence in the hydrophobic core or on the hydrophilic surface and on the presence and strength of structural hydrogen bonds. Therefore, this information can be used for assignment purposes and for structure determination. Hereby, it was crucial to be able to separate exchange hindrance due to hydrophobic shielding from the hindrance due to hydrogen bonding. Experimental site-specific information about hydrogen bond strength is valuable for determination of protein structure and dynamics simultaneously. In addition to a well-defined distance restraint, a hydrogen bond also reports on the rigidity of structural elements. In particular, the stabilization of functionally important loop tips by sidechain-to-backbone hydrogen bonds is investigated in this work. While the interplay of protein structure and function is well accepted and understood, the current state of understanding how local motion contribute to functional mechanisms leaves much to be discovered. In this context, NMR spectroscopy is one of the techniques of choice. Nowadays detailed information on directional protein motions is provided primarily by the theoretically based MD simulations. Another part of this work is dedicated to advance and apply NMR-spectroscopic methods, which have been developed to determine these directional dynamics and lead towards interpretations of the biological function. Along these lines, in liquid-state protein NMR, Vögeli et al. recently developed an approach that provides distance restraints with such accuracy that differences between distance restraints and average atomic positions are no longer associated with experimental error but with protein dynamics. With the help of Cornelia Hebrank, Snehal Patel, and Lars V. Schäfer, this method was applied to the protein binding domain SH3, yielding interesting mechanistic insights regarding ligand binding. For the first time, the novel method was evaluated using state-of-the-art MD simulations and further compared with the dynamics data using other NMR approaches. In addition to providing mechanistical insides for the protein SH3, the value of this new approach, which is the first experimental method for the determination of spatial dynamics, is emphasized. In general, the main objective of this work was to develop applicable methods for the benefit of other researchers and thus for the benefit of science and humanity

    The Microbiological Safety of Fresh Produce in Lebanon- A holistic “farm-to-fork chain” approach to evaluate food safety, compliance levels and underlying risk factors

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    The consumption of unsafe fresh vegetables has been linked to an increasing number of outbreaks of human infections. In Lebanon, although raw vegetables are major constituents of the national cuisine, studies on the safety of fresh produce are scant. This research employed a holistic approach to identify the different stages of the food chain that contribute to the microbiological risks on fresh produce and the spreading of hazards. A thorough analysis of the institutional and regulatory framework and the socio-political environment showed that the safety of local fresh produce in Lebanon is at risk due to largely unregulated practices and shortfalls in supporting the agricultural environment as influenced by the lack of a political commitment. Microbiological analysis showed that the faecal indicator levels ranged from <0.7 to 7 log CFU/g (Escherichia coli), 1.69-8.16 log CFU/g (total coliforms) and followed a significantly increasing trend from fields to the post-harvest washing area. At washing areas, Salmonella was detected on lettuce (6.7% of raw vegetables from post-harvest washing areas). This suggested that post-harvest cross-contamination occurs predominantly in the washing stage. At retails, a combination of observation and self-reported data provided an effective tool in assessing knowledge, attitudes and practices. It showed that the food safety knowledge and sanitation practices of food handlers were inadequate, even among the better trained in corporate-managed SMEs. Overall, the microbiological quality of fresh-cut salad vegetables in SMEs was unsatisfactory. The link between Staphylococcus aureus and microorganism levels on fresh salads vegetables and the overall inspection scores could not be established. On the other hand, inspection ratings on individual components, e.g., cleanliness and cross-contamination preventive measures showed significant correlation with Listeria spp. levels. Together, results confirmed that inspection ratings don’t necessary reflect the microbiological safety of fresh vegetables and that the application of control points of risk factors that likely to contribute to microbial contamination in the production environment are essential. The washing methods were limited in their effectiveness to reduce the contamination of parsley with Salmonella. In general, the pre-wash chopping and storing of parsley at 30ºC reduced the decontamination effect of all solutions, including sodium dichloroisocyanurate which was reduced by 1.3 log CFU/g on both intact and chopped leaves stored at 30ºC. In such conditions, the transfer rate of Salmonella from one contaminated parsley to subsequently chopped clean batches on the same cutting board(CB) recorded 60%-64%. Furthermore, the transmission of Salmonella persisted via washed CBs stored at 30°C for 24 h. It is recommended to keep parsley leaves unchopped and stored at 5ºC until wash for an optimum decontamination effect and to apply vigilant sanitation of CBs after use with fresh produce. This research presented important data for quantitative risk assessment for Salmonella in parsley and useful descriptive information to inform decision-makers and educators on microbial hazards associated with fresh produce in Lebanon. It also highlighted the risks areas that require urgent interventions to improve food safety. Considering the complex institutional and political challenges in Lebanon, there is an obvious need to direct development programs and support towards local agriculture production, effective education strategies and growing awareness of consumers and stakeholders on food safety related risks.Lebanese National Council for Scientific Research (CNRS) through American University of Beiru

    Multilevel inverters for renewable energy systems

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    Voltage source inverters have become widely used in the last decade primarily due to the fact that the dangers and limitations of relying on fossil fuel based power generation have been seen and the long term effects felt especially with regards to climate change. Policies and targets have been implemented such as from the United Nations climate change conference (COPxx) concerning human activities that contribute to global warming from individual countries. The most effective way of reducing these greenhouse gases is to turn to renewable energy sources such as the solar, wind etc instead of coal. Converters play the crucial role of converting the renewable source dc power to ac single phase or multiphase. The advancement in research in renewable energy sources and energy storage has made it possible to do things more efficiently than ever before. Regular or 2 level inverters are adequate for low power low voltage applications but have drawbacks when being used in high power high voltage applications as switching components have to be rated upwards and also switch between very high potential differences. To lessen the constraints on the switching components and to reduce the filtering requirements, multilevel inverters (MLI's) are preferred over two level voltage source inverters (VSI's). This thesis discusses the implementation of various types of MLI's and compares four different pulse width modulation (pwm) techniques that are often used in MLI under consideration: three, five, seven and nine level inverters. Harmonic content of the output voltage is recorded across a range of modulation indices for each of the three popular topologies in literature. Output from the inverter is filtered using an L only and an LC filter whose design techniques are presented. A generalized prediction algorithm using machine learning techniques to give the value of the expected THD as the modulation index is varied for a specific topology and PWM switching method is proposed in this study. Simulation and experimental results are produced in five level form to verify and validate the proposed algorithm

    ACCIDENT ANALYSIS, RISK AND RELIABILITY MODELING OF MARINE TRANSPORTATION SYSTEMS

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    Ph.DDOCTOR OF PHILOSOPH
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