<p>The thesis contains two directions in the simulations of biomolecular systems. The first part (Chapter 2 - Chapter 4) mainly focuses on the simulations of electron transfer processes in condensed phase; the second part (Chapter 5 - Chapter 6) investigates the conformational sampling of polysaccharides and proteins. Electron transfer (ET) reaction is one of the most fundamental processes in chemistry and biology. Because of the quantum nature of the processes and the complicated roles of the solvent, calculating the accurate kinetic and dynamic properties of ET reactions is challenging but extremely useful. Based on the Marcus theory for thermal ET in weak coupling limit, we combined the rigorous ab initio quantum mechanical (QM) method and well-established molecular mechanical (MM) force field and developed an approach to directly calculate a key factor that affects the ET kinetics: the redox free energy. A novel reaction order parameter fractional number of electrons (FNE) was used to characterize the ET progress and to drive the QM/MMMD sampling of the nonadiabatic free energy surface. This method was used for two aqueous metal cations, iron and ruthenium in solution, and generated satisfactory results compared to experiments. In order to further reduce the computational cost, a QM/MM-minimum free energy path (MFEP) method is implemented and combined with the FNE in the calculation of redox free energies. The calculation results using QM/MM-MFEP+FNE generated identical results as the direct QM/MM-MD method for the two metal cations, demonstrating the consistency of the two different sampling strategy. Furthermore, this new method was applied to the calculation of organic molecules and enhanced the computational efficiency 15-30 times than the direct QM/MM-MD method, while maintaining high accuracy. Finally, I successfully extended the QM/MM-MFEP+FNE method to a series of redox proteins, azurin and its mutants, and obtained very accurate redox free energy differences with relative error less than 0.1 eV. The new method demonstrated its excellent transferability, reliability and accuracy among various conditions from aqueous solutions to complex protein systems. Therefore, it shows great promises for applications of the studies on redox reactions in biochemistry. In the studies of force-induced conformational transitions of biomolecules, the large time-scale difference from experiments presents the challenge of obtaining convergent sampling for molecular dynamics simulations. To circumvent this fundamental problem, an approach combining the replica-exchange method and umbrella sampling (REM-US) is developed to simulate mechanical stretching of biomolecules under equilibrium conditions. Equilibrium properties of conformational transitions can be obtained directly from simulations without further assumptions. To test the performance, we carried out REM-US simulations of atomic force microscope (AFM) stretching and relaxing measurements on the polysaccharide pustulan, a (1&rarr;6)-&beta;-D-glucan, which undergoes well-characterized rotameric transitions in the backbone bonds. With significantly enhanced sampling convergence and efficiency, the REMUS approach closely reproduced the equilibrium force-extension curves measured in AFM experiments. Consistent with the reversibility in the AFM measurements, the new approach generated identical force-extension curves in both stretching and relaxing simulations, an outcome not reported in previous studies, proving that equilibrium conditions were achieved in the simulations. In addition, simulations of nine different polysaccharides were performed and the conformational transitions were reexamined using the REM-US approach. The new approach demonstrated consistent and reliable performance among various systems. With fully converged samplings and minimized statistical errors, both the agreement and the deviations between the simulation results and the AFM data were clearly presented. REM-US may provide a robust approach to modeling of mechanical stretching on polysaccharides and even nucleic acids. However, the performance of the REM-US in protein systems, especially with explicit solvent model, is limited by the large system size and the complex interactions. Therefore, a Go-like model is employed to simulate the protein folding/unfolding processes controlled by AFM. The simulations exquisitely reproduced the experimental unfolding and refolding force extension relationships and led to the full reconstruction of the vectorial folding pathway of a large polypeptide, the 253-residue consensus ankyrin repeat protein, NI6C. The trajectories obtained in the simulation captured the critical conformational transitions and the rate-limiting nucleation event. Together with the AFM experiments, the coarse-grained simulations revealed the protein folding and unfolding pathways under the mechanical tension.</p> / Dissertation

Abstract In this globalized era, most industries will not be able to survive by simply optimizing internal structures and infrastructures based upon business strategy. The most successful manufacturers seem to be those that have carefully linked their internal processes to external suppliers and customers in unique supply chains. Quality management represents company-wide activities to improve the quality level of products and works through customer orientation, continuous quality improvement, employees¡¦ involvement, etc. to establish and sustain a competitive advantage. From a perspective of competitive strategy, quality is often seen as a source of differentiation. Quality improvement is an important issue influencing long-term viability of any business enterprise, especially manufacturing companies producing physical goods. A number of researchers suggest that better performance can be achieved by consolidating customer and supplier bases, removing unnecessary steps in the chain, speeding up information and material flows, and creating long-term partnerships with major customers and suppliers to leverage the capabilities of several companies in the chain. Recent years have seen growth in the importance of integration suppliers, manufacturers and customers. Effective integration of suppliers into supply chains serves as a key factor for some companies to gain competitive advantage. Supply chain integration refers to a formation of network encompassing elements of supply chain, which are the suppliers, customers and the company. This paper presents results of an empirical study on effect of quality management practices upon supply chain integration in Aerospace Industry manufacturing companies. Analysis of variance (ANOVA) and regression analysis were conducted to test hypothesizes. This paper used six scales to measure different aspects of quality management including top management leadership for quality , small group problem solving , processes management, supplier involvement, information and feedback and customer forcus upon supply chain integration. Regression results indicated two external factors including supplier involvement, customer forcus have significant impact on supply chain integration, also will increase company competitive performance if all resourses have been adopted properly. For those four internal factors,such as management leadership for quality , small group problem solving , processes management, information and feedback doesn¡¦t have significant impact on supply chain integration.

Electronic business covers the enterprise purchase and sale activities, collaboration between customers and partners, and inter-organizational electronic transactions. In the 21st century, the enterprise take Information Technology deeply to embed in each process (the Process Step), with the Internet technique that has become the indispensable kernel of competition in the business operations. After a number of semiconductor manufacturers participating in ¡§RosettaNet For Semiconductor Contract Manufacturing B2B Integration Project¡¨, it has been a necessary condition whether semiconductor manufacturers can provide customers with B2B information services now. However,the semiconductor manufacturers should be thinking how to meet the customers changing needs of B2B information service, how to integrate information, and how to synchronize induction environmental change. This research is based on ¡§the Impact of the QM practices on MC the capability mode¡¨. The B2B team members provide all of the ad hoc group for B2B project members' empirical perception to do the quality of B2B information services empirical analysis during implementation project. The objective aims to understand the impact of service quality for customer satisfaction. The result clearly indicates that the five dimensions will be a significant impact in B2B service quality for the enterprise information services, namely, small group problem solving, top management leadership for quality, information and feedback, supplier involvement and Process management. But if each dimension is to be analyzed individually, customer focus would impact on B2B information service quality. Generally speaking, the B2B team wants to enhance service quality, and then they should start with these five dimensions to proceed, and thereby to raise customer satisfaction. From the investing funds scale, they want to pursue efficiency, and almost each of semiconductor company has set up a similar B2B team to dominate the B2B project for customer service. Furthermore, this research used variables in the different conditions of demographic variables to summarize the diversity of satisfactions, and these analyses acquire the managerial implications that will be managers an important basis for improving the quality of B2B information services.

Researches on bone defects are focused on the use of composites due to the composite and well-organized hierarchical structure of the bone. In this study, it is aimed to develop Polycaprolactone based implants with different organic &amp / #8211 / DBM, HYA- and/or inorganic &amp / #8211 / bioglass, calcium sulfate- compositions for augmenting bone healing. Bioactivity of the discs was evaluated by scanning electron microscopy and EDS analysis after incubation in SBF for 1, 7 and 14 days. All bioglass containing groups showed apatite molecules at different incubation times. Degradation studies demonstrated that only PCL/BG/HYA discs had fast degradation upon incubations in PBS (4 and 6 weeks). Initial mechanical properties of composites were found to be directly related to the composition. However, decreases in disc mechanical properties were also obtained in the same order with the amount of water uptake at composite groups. According to biocompatibility studies investigated with cytotoxicity tests on Saos-2 cells, all groups, except the HYA involving one were found as biocompatible. After in vivo application of discs to critical size defects on rabbit humeri (for 7 weeks), their efficacy on healing was studied with computerized tomography, SEM and biomechanical tests. The results revealed that bone-implant interface formation has started for all groups with high bone densities at the interface of implant groups compared to empty defect sites of negative controls. Also the healing was suggested to be gradual from bone to implant site as microhardness values increased at regions closer to bone. However, regeneration was found to not reach to healthy bone levels.

In this thesis, the learning of probabilistic relationships between stimulus-action pairs is investigated under the probability learning paradigm. The effect of reward is investigated in the first three experiments. Additionally, the effect of context and uncertainty is investigated in the second and third experiments, respectively. The fourth experiment is the replication of the second experiment with a group of Parkinson patients where the effect of dopamine medication on probability learning is studied. In Experiment 1, we replicate the classical probability learning task by comparing monetary and non-monetary reward feedback. Probability learning behavior is observed in both monetary and non-monetary rewarding feedback conditions. However, no significant difference between the monetary and non-monetary feedback conditions is observed. In Experiment 2, a variation of the probability learning task which includes irrelevant contextual information is applied. Probability learning behavior is observed, and a significant effect is found between monetary and non-monetary feedback conditions. In Experiment 3 / a probability learning task similar to that in Experiment 2 is applied, however, in this experiment, stimulus included relevant contextual information. As expected, due to the utilization of the relevant contextual information from the start of the experiment, no significant effect is found for probability learning behavior. The effect of uncertainty observed in this experiment is a replication of the reports in literature. Experiment 4 is identical to Experiment 2 / except that the subject population is a group of dopamine medicated Parkinson patients and a group of age matched controls. This experiment is introduced to test the suggestions in the literature regarding the enhancement effect of dopamine medication in probability learning based on positive feedback conditions. In Experiment 4, probability learning behavior is observed in both groups, but the difference in learning performance between Parkinson patients and controls was not significant, probably due to the low number of subject recruited in the experiment. In addition to these investigations, learning mechanisms are also examined in Experiments 1 and 4. Our results indicate that subjects initially search for patterns which lead to probability learning. At the end of Experiments 1 and 4, upon learning the winning frequencies, subjects change their behavior and demonstrate maximization behavior, which makes them prefer continuously one option over the other.

Obstructive Sleep Apnea Syndrome (OSAS) is defined as a sleep related breathing disorder that causes the body to stop breathing for about 10 seconds and mostly ends with a loud sound due to the opening of the airway. OSAS is traditionally diagnosed using polysomnography, which requires a whole night stay at the sleep laboratory of a hospital, with multiple electrodes attached to the patient&#039 / s body. Snoring is a symptom which may indicate presence of OSAS / thus investigation of snoring sounds, which can be recorded in the patient&#039 / s own sleeping environment, has become popular in recent years to diagnose OSAS. In this study, we aim to develop a new method to detect post-apnea snoring episodes with the goal of diagnosing apnea or creating a new criteria similar to apnea / hypopnea index. In this method, first segmentation is done to eliminate the silence parts and only deal with active. Then these episodes are represented by distinctive features / some of these features are available in literature but some of them are novel. Finally, these episodes are classified using supervised and unsupervised methods. We are especially interested in detecting post apnea episodes, hence the apnea periods. False alarm rates are reduced by adding additional constraints into the detection algorithm. These methods are applied to snoring sound signals of OSAS patients, recorded in Gulhane Military Medical Academy, to verify the success of our algorithms.

This dissertation presents three experiments to investigate the general distribution of hand preference across a reachable working space, as well as the effect of sensory information about the reaching hand, and if this distribution is affected by long term practice. In addition, the underlying mechanisms of hand preference behavior were investigated with the obtained kinematic data. Experiment 1 explored the distribution of hand preferences across the workspace among non-athlete right-handed participants, as well as the role that visual feedback might play in this distribution. Experiment 2 tested the hypothesis, if occlusion of visual feedback influences hand preference, accordingly interlimb differences. The third final experiment examined the effect of long term practice on hand preference among right-handed elite fencers. The first study showed that the choice of arms is related to the energetic cost and dynamic efficiency of the movements. The results of the second experiment displayed that the choice of hands changes under no visual feedback condition, demonstrating that the choice is active and not habitual, depending on sensorimotor performance asymmetries. The final experiment demonstrated that elite athletes have different patterns of limb selection than non- athletes. Athletes, specifically fencers, show improved coordination in their non-dominant arms, which apparently increases the selection of this arm for reaching. Overall, it was concluded that hand preference depends on sensorimotor performance asymmetries and influenced by the long term practice.

Meniscus is a fibrocartilaginous tissue which plays an important role in joint stability, lubrication, and load bearing and transmission. Meniscal tears are commonly encountered in sports activities, or caused by degeneration of the cartilage with ageing. They lead to pain, loss of work, disturbed biomechanics of the knee and inability to walk or even move the legs. As the meniscal tissue is avascular in the inner portion, injury to this part does not heal by itself, and therefore treatments are needed. In some cases when complex tears occur, the tissue cannot be successfully treated with the conventional methods. Tissue engineering appears to be a promising alternative to treat such complex tears. It includes the application of cells on scaffolds (or cell carriers), and provision of bioactive agents to the site of injury in order to regenerate the damaged tissue. The cells and the bioactive agents are involved in the synthesis of the new tissue, while the scaffold acts as a support to guide the cells until the new tissue is formed, and it is slowly absorbed by the body leaving the new tissue behind. Thus, a natural tissue is generated at the end. Few studies have been reported on the tissue engineering of meniscus, but neither of them was able to completely mimic the meniscus structure, nor could they succeed in constructing scaffolds with sufficiently high tensile properties. In the current in vitro study, a novel 3D construct was proposed, in which the natural tissue is perfectly mimicked. The 3D construct consisted of aligned collagen fibers embedded within a foam network which stabilizes the structure. The foam was prepared by freezing a polymer solution with a certain concentration, and lyophilizing it. Aligned fibers were aimed to improve the tensile properties. The construct was impregnated in alginate gel, which was then crosslinked, to improve the compressive properties. The foam was prepared from (poly(L-lactic acid)/poly(lactic-co-glycolic acid) (PLLA/PLGA) solutions of various concentrations (2%, 2.5%, 3%, and 4% w/v) and at different freezing temperatures (-20oC or -80oC) to select the best preparation condition. After analysis of the microstructure and mechanical properties, foams prepared from 3% polymer solution frozen at -20oC were found to be the most appropriate for use as scaffold for the 3D construct, since they had large pores, high and interconnected porosity, as well as high mechanical strength. The 3D constructs were seeded with human meniscus cells and incubated for 21 days. Cell behavior on the constructs was examined. Cell attachment and proliferation was found to be better with the constructs not coated with alginate. However, the constructs coated with alginate demonstrated higher compressive strength. It was also found that incorporation of collagen fibers significantly improved the tensile properties. All the constructs were shown to lead to the production of extracellular components specific for fibrocartilages, and thus it was concluded that they were promising for use in meniscal replacement.

The purpose of this study was to investigate the effects of Swiss ball training on (1) knee joint reposition sense (knee proprioception), (2) core muscle strength and (3) dynamic balance in sedentary collegiate students. In this thesis, two different participant groups and two different training methods were used. In order to evaluate the effect of Swiss ball training on knee proprioception and core strength, 3 days per week training was conducted throughout 10 weeks (Study 1). In order to evaluate the effect of Swiss ball training on dynamic balance, 2 days per week training was conducted throughout 10 weeks (Study 2). 60 sedentary university students participated in Study 1. 47 sedentary university students participated in Study 2. The results of the study indicated that Swiss ball training has significant effect on knee proprioception and core muscle strength. For dynamic balance, at the end of the 10-week Swiss ball training, in both groups (Swiss ball and control), dynamic balance scores were improved significantly. Therefore, effect of the Swiss ball training on dynamic balance could not be determined. As a conclusion, an instability training program using Swiss balls with body weight as resistance can provide prolonged improvements in joint proprioception and core strength which would contribute to general health and performance.

Probability learning is the ability to establish a relationship between stimulus and outcomes based on occurrence probabilities using repetitive feedbacks. Participants learn the task according to the cue-outcome relationship, and try to gain in depth understanding of this relationship throughout the experiment. While learning is at the highest level, people rely on their working memory. In this study 20 participants were presented a probability learning task, and their prefrontal cortex activity was measured with functional Near-Infrared Spectroscopy. It was hypothesized that as participants gain more knowledge of the probabilities they will learn cue-outcome relationships and therefore rely less on their working memory. Therefore as learning precedes a drop in the fNIRS signal is expected. We obtained results confirming our hypothesis: Significant negative correlation between dorsolateral prefrontal cortex activity and learning was found. Similarly, response time also decreased through the task, indicating that as learning precedes participants made decisions faster. Participants used either the frequency matching or the maximization strategy in order to solve the task in which they had to decide whether the blue or the red color was winning. When they use the frequency matching strategy they chose blue at the rate of winning for the blue choice. When they use the maximization strategy they chosed blue almost always. Our task was designed such that the frequency for blue to win was 80%. We had hypothesized that the people in frequency matching and maximization groups would show working memory differences which could be observed from the fNIRS signal. However, we were unable to detect this type of behavioral difference in the fNIRS signal. Overall, our study showed the relationship between probability learning and working memory as depicted by brain activity in the dorsolateral prefrontal cortex which widely known as the central executive component of working memory.