This master thesis project is about easier commuting in a more eco-friendly way thus a new foldable pedelec - pedal electric cycle was created. The idea is that the commuters are able to fold their bicycle to a convenient size and store it under the desk in the office, in a trunk of a car, or even brought on a bus if used as a connecting transport. It incorporates the latest ergonomic, safety, display and drivetrain features in combination with a sleek single-fork design. This enables the pedelec to be folded more conveniently and save additional space. To appeal to a wider range of users they are given the opportunity to choose their own colour codes and personalize their own foldable pedelec.

In this thesis, we study foldings of orthogonal polygons into orthogonal polyhedra. The particular problem examined here is whether a paper cutout of an orthogonal polygon with fold lines indicated folds up into a simple orthogonal polyhedron. The folds are orthogonal and the direction of the fold (upward or downward) is also given. We present a polynomial time algorithm to solve this problem. Next we consider the same problem with the exception that the direction of the folds are not given. We prove that this problem is NP-complete. Once it has been determined that a polygon does fold into a polyhedron, we consider some restrictions on the actual folding process, modelling the case when the polyhedron is constructed from a stiff material such as sheet metal. We show an example of a polygon that cannot be folded into a polyhedron if folds can only be executed one at a time. Removing this restriction, we show another polygon that cannot be folded into a polyhedron using rigid material.

<p>Understanding the interconversion between the thermodynamically distinguishable states present in a protein folding pathway provides not only the kinetics and energetics of protein folding but also insights into the functional roles of these states in biological systems. The protein component of bacterial RNase P holoenzyme from Bacillus subtilis (P protein) was used as a model system to elucidate the general folding/unfolding of an intrinsically unstructured protein (IUP) both in the absence and presence of ligands.</p><p>P protein was previously characterized as an intrinsically unstructured protein, and it is predominantly unfolded in the absence of ligands. Addition of small anions can induce the protein to fold. Therefore, the folding and binding are tightly coupled. Trimethylamine-N oxide (TMAO), an osmolyte that stabilizes the unliganded folded form of the protein, enabled us to study the folding process of P protein in the absence of ligand. Transient stopped-flow kinetic time courses at various final TMAO concentrations showed multiphase kinetics. Equilibrium "cotitration" experiments were performed using both TMAO and urea to obtain a TMAO-urea titration surface of P protein. Both kinetic and equilibrium studies show evidence of an intermediate state in the P protein folding process. The intermediate state is significantly populated and the folding rate constants involved in the reaction are slow relative to similar size proteins. </p><p>NMR spectroscopy was used to characterize the structural properties of the folding intermediate of P protein. The results indicate that the N-terminal (residues 2-19) and C-terminal regions (residues 91-116, 118 is the last residue) are mostly unfolded. 1H-15N HSQC NMR spectra were collected at various pH values. The results suggest that His 22 may play a major role in the energetics of the equilibria between the unfolded, intermediate, and native states of P protein.</p><p>Ligand-induced folding kinetics were also investigated to elucidate the overall coupled folding and binding mechanism of P protein and the holoenzyme assembly process. Stopped flow fluorescence experiments were performed at various final ligand concentrations and the data were analyzed using a minimal complexity model that included three conformational states (unfolded, intermediate and folded) in each of three possible liganding states (0, 1 and 2 ligands). The kinetic and equilibrium model parameters that best fit the data were used to calculate the flux through each of the six possible folding/binding pathways. This novel flux-based analysis allows evaluation of the relative importance of pathways in which folding precedes binding or vice versa. The results indicate that the coupled folding and binding mechanism of P protein is strongly dependent on ligand concentration. This conclusion can be generalized to other protein systems for which ligand binding is coupled to conformational changes.</p> / Dissertation

A 2.5V 8-bit 100MSample/sec folding and interpolation analog to digital converter is described in this thesis. First, a cascoding folding amplifier is used for improve power consumption. The differential pairs of the folding amplifier are cascoded to reduce the numbers of reference current source, so the power consumption is reduced. In order to reduce more power consumption, we drop the power supply down to 2.5V. However, the power supply is not large enough to keep the folding amplifier working normally and it causes the output signal aberration. Hence, we propose a back-end amplifier to connect the folding amplifier to overcome the problem. Therefore, the power consumption of all circuit is reduced to 15.292mW. Moreover, the capacitive loading at the output of the cascoded differential pairs is smaller than that of conventional cascaded differential pairs, and we employ a distributed folding technique to reduce the folding factors of each folding amplifier. Therefore, we improve the frequency multiplication effect to increase the analog input signal bandwidth. Beside, in order to heave the input signal range of the voltage mode comparator, we employ an n-channel input stage. Because the input signal range of n-channel is higher than that of p-channel input stage. By using these techniques, the input signal bandwidth and the power consumption of overall circuit are improved greatly. The proposed analog to digital converter is designed by TSMC 0.35£gm 2P4M CMOS process, and it operates at 2.5V power supply voltage with 1V to 2.4V reference voltage. The simulation results show that the power consumption is 15.292mW, DNL is +/- 0.55LSB, and INL is 1.7LSB ~ -0.8LSB.

It is well known that the biological function of a protein depends on its 3D structure. Therefore, solving the problem of protein structures is one of the most important works for studying proteins. However, protein structure prediction is a very challenging task because there is still no clear feature about how a protein folds to its 3D structure yet. In this thesis, we propose a genetic algorithm (GA) based on the lattice model to predict the 3D structure of an unknown protein, target protein, whose primary sequence and secondary structure elements (SSEs) are assumed known. Hydrophobic-hydrophilic model (HP model) is one of the most simplified and popular protein folding models. These models consider the hydrophobic-hydrophobic interactions of protein structures, but the results of prediction are still not encouraged enough. Therefore, we suggest that some other features should be considered, such as SSEs, charges, and disulfide bonds. That is, the fitness function of GA in our method considers not only how many hydrophobic-hydrophobic pairs there are, but also what kind of SSEs these amino acids belong to. The lattice model is in fact used to help us get a rough folding of the target protein, since we have no idea how they fold at the very beginning. We show that these additional features do improve the prediction accuracy by comparing our prediction results with their real structures with RMSD.

Functional expression of a protein in life form is decided by its tertiary structure. In the past few decades, a significant number of studies have been made on this subject. However, the folding rules of a protein still stay unsolved. The challenge is to predict the three-dimensional tertiary structure of a protein from its primary amino acid sequence. We propose a hybrid method combining homology model and the folding approach to predict protein three-dimensional structure from amino acid sequence. The previous researches on folding problem mostly take the HP (Hydrophobic-Polar) model, which is not able to simulate the native structure of proteins. We use a more exquisite model, the sliced lattice model, to approximate the native forms. Another essential factor influencing protein structures is disulfide bonds, which are ignored in the HP model. We use the ant colony optimization algorithm to approximate the folding problem with the constrained disulfide bond on the sliced lattice HP model. We show that the prediction results are better than previous methods by the measurement of RMSD(Root Mean Square Deviation).

Properly folded proteins are necessary for all living organisms. Incorrectly folded proteins can lead to a variety of diseases such as Alzheimer’s Disease or Bovine Spongiform Encephalitis (Mad Cow Disease). Understanding the forces involved in protein folding is essential to the understanding and treatment of protein misfolding diseases. When proteins fold, a significant amount of surface area is buried in the protein interior. It has long been known that burial of hydrophobic surface area was important to the stability of the folded structure. However, the impact of burying polar surface area is not well understood. Theoretical results suggest that burying polar groups decreases the stability, but experimental evidence supports the belief that polar group burial increases the stability. Studies of tyrosine to phenylalanine mutations have shown the removal of the tyrosine OH group generally decreases stability. Through computational investigations into the effect of buried tyrosine on protein stability, favorable van der Waals interactions are shown to correlate with the change in stability caused by replacing the tyrosine with phenylalanine to remove the polar OH group. Two large-scale studies on nearly 1000 high-resolution x-ray structures are presented. The first investigates the electrostatic and van der Waals interactions, analyzing the energetics of burying various atom groups in the protein interior. The second large-scale study analyzes the packing differences in the interior of the protein and shows that hydrogen bonding increases packing, decreasing the volume of a hydrogen bonded backbone by about 1.5 Å3 per hydrogen bond. Finally, a structural comparison between RNase Sa and a variant in which five lysines replaced five acidic groups to reverse the net charge is presented. It is shown that these mutations have a marginal impact on the structure, with only small changes in some loop regions.

Recently, the stochastic approximation Monte Carlo algorithm has been proposed by Liang et al. (2005) as a general-purpose stochastic optimization and simulation algorithm. An annealing version of this algorithm was developed for real small protein folding problems. The numerical results indicate that it outperforms simulated annealing and conventional Monte Carlo algorithms as a stochastic optimization algorithm. We also propose one method for the use of secondary structures in protein folding. The predicted protein structures are rather close to the true structures. Phylogenetic trees have been used in biology for a long time to graphically represent evolutionary relationships among species and genes. An understanding of evolutionary relationships is critical to appropriate interpretation of bioinformatics results. The use of the sequential structure of phylogenetic trees in conjunction with stochastic approximation Monte Carlo was developed for phylogenetic tree reconstruction. The numerical results indicate that it has a capability of escaping from local traps and achieving a much faster convergence to the global likelihood maxima than other phylogenetic tree reconstruction methods, such as BAMBE and MrBayes.

Thesis (Ph.D. (Biochemistry, Microbiology & Biotechnology)) - Rhodes University, 2009.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 100-106).