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Biomolecular systems, in particular those involving proteins and their constituents, have been the focus of much research in the last century. The relationship between experiment, development of models and simulation has enabled vast improvements in our knowledge of subjects such as protein folding and the processes by which key biomolecules affect the human body. In particular, vital information can be obtained from understanding the building blocks of polypeptides and proteins involved in these processes. This work focuses on simulating two such building blocks; glutamate, the salt of the proteinogenic amino acid, glutamic acid, and glycine-proline-glutamate, or GPE, a related tripeptide. Both are important in neurotransmission processes in the brain. Glutamate is the most abundant neurotransmitter in the central nervous system and GPE is an important neuroprotective agent. This work aims to elucidate the key structural properties of aqueous solutions of glutamate and GPE, focusing on the solute-solute as well as the solute-solvent interactions. Both systems were considered with classical empirical potentials using the CHARMM22 force-fi eld. The glutamate system has also been studied using Car-Parrinello Molecular Dynamics and classical parallel tempering. In both the aqueous glutamate and GPE systems the molecules formed a large proportion of bifurcated bonding motifs with both carboxyl groups, but not with the amin (N-terminal) of the molecules. Bifurcated bonds form between solute molecules as well as in the solute-solvent interactions. The structure of the glutamate solution was found to be dependent on the initial con figuration and thus the parallel tempering simulations enabled better sampling of the conformational landscape. In addition, in the glutamate system single water molecules form a stable structure by bonding to both the amine (N-terminal) and C -carboxyl within the same glutamate molecule.

This diploma thesis confronts specific features of English language teaching in private language schools. The theoretical section of this study is concerned with the distinction between general purpose English (GPE) and English for specific purposes (ESP), types of courses, education and qualification structure of employees, management of this type of school, syllabi, and those who are responsible for making them. The practical section is focused on analysis of questionnaires and interviews I have conducted with the directors of private language schools. The research objective was to assess the specific factors affecting the process, quality control and English language instruction at this school.

<p>Deep brain stimulation (DBS) is used to treat the motor symptoms of advanced Parkinson's disease (PD). Although this therapy has been widely applied, the mechanisms of action underlying its effectiveness remain unclear. The goal of this dissertation was to investigate the mechanisms underlying the effectiveness of subthalamic nucleus (STN) DBS by quantifying changes in neuronal activity in the basal ganglia during both effective and ineffective DBS.</p><p>Two different approaches were adopted in this study. The first approach was the unilateral 6-hydroxydopamine (6-OHDA) lesioned rat model. Using this animal model, we developed behavioral tests that were used to quantify the effectiveness of DBS with various frequencies and temporal patterns. These changes in behavior were correlated with changes in the activity of multiple single neurons recorded from the globus pallidus externa (GPe) and substantia nigra reticulata (SNr). The second approach was a computational model of the basal ganglia-thalamic network. The output of the model was quantified using an error index that measured the fidelity of transmission of information in model thalamic neurons. We quantified changes in error index as well as neural activity within the model GPe and globus pallidus interna (GPi, equivalent to the SNr in rats).</p><p>Using these two approaches, we first quantified the effects of different frequencies of STN DBS. High frequency stimulation was more effective than low frequency stimulation at reducing motor symptoms in the rat, as well as improving the error index of the computational model. In both the GPe and SNr/GPi from the rat and computational model, pathological low frequency oscillations were present. These low frequency oscillations were suppressed during effective high frequency DBS but not low frequency DBS. Furthermore, effective high frequency DBS generated oscillations in neural firing at the same frequency of stimulation. Such changes in neuronal firing patterns were independent of changes in firing rates.</p><p>Next, we investigated the effects of different temporal patterns of high frequency stimulation. Stimulus trains with the same number of pulses per second but different coefficients of variation (CVs) were delivered to the PD rat as well as PD model. 130 Hz regular DBS was more effective than irregular DBS at alleviating motor symptoms of the PD rat and improving error index in the computational model. However, the most irregular stimulation pattern was still more effective than low frequency stimulation. All patterns of DBS were able to suppress the pathological low frequency oscillations present in the GPe and SNr/GPi, but only 130 Hz stimulation increased high frequency 130 Hz oscillations. Therefore, the suppression of pathological low frequency neural oscillations was necessary but not sufficient to produce the maximum benefits of DBS.</p><p>The effectiveness of regular high frequency STN DBS was associated with a decrease in pathological low frequency oscillations and an increase in high frequency oscillations. These observations indicate that the effects of DBS are not only mediated by changes in firing rate, but also involve changes in neuronal firing patterns within the basal ganglia. The shift in neural oscillations from low to high frequency during effective STN DBS suggests that high frequency regular DBS suppresses pathological firing by entraining neurons to the stimulus pulses. </p><p>Therefore, results from this dissertation support the hypothesis that the underlying mechanism of effective DBS is its ability to entrain and regularize neuronal firing, therefore disrupting pathological patterns of activity within the basal ganglia.</p> / Dissertation

This project studied two different ways of imposing boundary conditions weakly with the finite difference summation-by-parts (SBP) operators. These operators were combined with the boundary handling methods of simultaneous-approximation-terms (SAT) and the Projection to impose homogeneous Neumann and Dirichlet boundary conditions. The convergence rate of both methods was analyzed for different boundary conditions for the one-dimensional (1D) Schrödinger equation, without potential, which resulted in both methods performing similarly. A multi-block discretization was then implemented and different combinations of SBP-SAT and SBP-Projection were applied to impose inner boundary conditions of continuity between the blocks. A convergence study of the different methods of imposing the inner BC:s was conducted for the 1D Schrödinger equation without potential. The resulting convergence was the same for all methods and it was concluded that they performed similarly. Methods involving SBP-Projection had the slight advantage of faster computation time. Finally, the 1D Gross-Pitaevskii equation (GPE) and the 1D Schrödinger equation were analyzed with a step potential. The waves propagating towards the potential barrier were in both cases partially transmitted and partially reflected. The waves simulated with the Schrödinger equation dispersed, while the solitons simulated with the GPE kept their shape due to the equations reinforcing non-linear term. The bright soliton was partly transmitted and partly reflected. The dark soliton was either totally reflected or totally transmitted.