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DNA i-motif is an intercalated quadruplex structure formed by association of hemi- protonated C•CH+ pairs. The fact that i-motif folding sequences are widely present in oncogenic regions and human telomeric DNA suggests that the formation of i-motif may be associated with the regulation of oncogene expression. Due to the paramount significance of those regions to the gene transcription and cell apoptosis, i-motif has become an attractive drug target for cancer chemotherapy and gene transcription modulation. On the other hand, the i-motif sequences can be reversibly and rapidly oscillated from a stable quadruplex structure to a random coil by adjusting the pH. This renders i-motif a great potential as nanomolecular devices in the development of biosensors. Although the aforesaid significances in biology and nanotechnology have been investigated, some challenges still remain to be drilled. For example, due to the fast dissociation and association process, the mechanism of i-motif folding and unfolding between two different states is still unclear. Besides, the effects of i-motif structural changes and folding properties induced by various chemical modifications remain ambiguous. Furthermore, although a lot of i-motif based nanomachines, logic gates, nanoclusters have been developed, applications of i-motif to biosensing and bioimaging haven’t been well explored. In chapter 1, the discovery, definition and topology of i-motif has been reviewed. Current progresses in the folding dynamics, biological role and the applications of i-motif in nanotechnology have been briefly introduced. At last, remaining challenges in the i-motif research were discussed. In chapter 2, the effect of epigenetic nucleobases, methylcytosine (mC) and hydroxymethylcytosine (hmC) on the i-motif stability was studied. Methylcytosine can stabilize i-motif while hmC destabilizes i-motif structure. The factors of causing such effects on i-motif were discussed. In chapter 3, a fluorescent exciplex formed by single thiazole orange (TO) conjugated DNA using i-motif as the assembly scaffold was reported. Upon excitation with visible light, the single TO molecule emits orange-color exciplex fluorescence in i-motif structure and green emission as monomer in duplex DNA. The exciplex was used to monitor the formation and dissociation of i-motif. In chapter 4, single thiazole orange was covalently incorporated into the loop or termini of i-motif forming sequence to investigate the intramolecular i-motif folding and unfolding process. We successfully observed the existence of stable intermediate either near melting temperature of i-motif at pH 5 or under proton deficient conditions at room temperature. A folding and unfolding pathway of intramolecular i-motif was proposed based on the experiment data. In chapter 5, we designed an i-motif and Q-quadruplex based probe for detecting Let-7 miRNA. Under slightly acidic buffer (pH 6.3), the probe exhibited fluorescence enhancement after introducing target, although the signal amplification efficiency is not ideal. Two methods were proposed to improve the performance of the probe. Before joining in Dr. Shao’s lab in February, 2011, I had been doing the synthesis of abnormal N-heterocyclic carbine precursors and corresponding palladium complexes and the synthetic methodology of direct aromatic amide synthesis from alcohols and amines under the supervision of Dr. Hong Soon Hyeok since August in 2009. The appendix is the summary of my work on the syntheses of abnormal N-heterocyclic carbine precursors, their coordination with palladium salts and catalytic application in Suzuki-Miyaura coupling reactions. ​Doctor of Philosophy (SPMS)

In order to gain a true signal from the signal polluted by time-variant correlative noises, an adaptive noise canceler (ANC) is proposed. We develop an observation model using the ARMA process. The time-variant parameter vector of the ARMA model is described by using a generalized random walk model. Under the conditions that input and output noises are jointly normal white noises, we deduce the adaptive Kalman filter (AKF) of the parameter vector and the maximum a posterior (MAP) estimator of the noise statistics. The ANC consists of the AKF and the MAP estimator. Simulation results are obtained by using a conventional smooth signal with sinusoidal components as well as the "non-smooth" signal of recorded oil well colour spectrum data with time-variant correlative noise.

In this paper, a new second order recursive learning algorithm to multilayer feedforward network is proposed. This algorithm makes not only each layer's errors but also second order derivative information factors backpropagate. And it is proved that it is equivalent to Newton iterative algorithm and has second order convergent speed. New algorithm achieves the recurrence calculation of Newton search directions and the inverse of Hessian matrices. Its calculation complexity corresponds to that of common recursive least squares algorithm. It is stated clearly that this new algorithm is superior to Karayiannis' second order algorithm (1994) according to analysis of their properties.