博士
國立臺灣大學
生物化學暨分子生物學研究所
91
During the past years, non-viral gene delivery vector was emerging as a new modality as well as a technology in laboratory and in medical practice. A promising area of ...research is the design of targeted lipid-DNA complexes. It is clear that the physicochemical properties of lipid-DNA complexes are very important in the design of the ideal lipidic vector. The requirements for such an ideal vector can be summarized as follows: (1) the particles should be small enough to be taken up by organs and surface protected by polyethylene glycol (PEG), to avoid protein interaction in the serum and thus extend their circulation life time into the blood; (2) furthermore, the addition of a targeting ligand is necessary to allow specific recognition by target cells, and (3) the DNA should be condensed and protected from nuclease degradation; (4) finally, DNA should be sufficiently inert to the immune cells to avoid a high level of cytokine production. The results in this report demonstrate the feasibility of improvement in target-specific gene delivery to HER-2-overexpressing cells by insertion of lipid-modified anti-HER-2-Fab’ into the preformed liposomes; in another hand, the large polyethylenimine (PEI) could synergistically increase the transfection efficiency when combined with the cationic liposomes.
博士
國防醫學院
醫學科學研究所
98
Head and neck cancer is the sixth most common type of cancer. Most head and neck cancers are squamous cell carcinomas (SCCHN) that develop in the upper aerodigestive epithelium ...after exposure to carcinogens such as tobacco and alcohol. Recent studies have revealed that a plethora of genetic events leading to the inactivation of tumor-suppressor genes or activation of proto-oncogenes, or both, govern the development of SCCHN. Epidermal growth factor receptor (EGFR) protein is overexpressed in more than 90% of SCCHN relative to normal tissue, and high expression is associated with poor disease control. Surgery and radiotherapy have long been the major treatment approaches. Recently, a new class of agents, the EGFR inhibitors, has shown clinical benefit in this disease. Presently, no established biomarker and no chemopreventive agent are of proven benefit in SCCHN.
Beta-catenin is involved in two apparently independent processes, cell-cell adhesion and Wnt signal transduction. The Wnt/Beta-catenin pathway plays important roles in tumor formation. In the absence of Wnt, cytoplasmic Beta-catenin protein is constantly degraded by the action of the Axin complex, which is composed of the scaffolding protein Axin, the tumor suppressor APC, CK1, and GSK-3β. Therefore, Beta-catenin should not translocate to the nucleus and thus its target genes are not activated. The Wnt/Beta-catenin pathway is activated when a Wnt ligand binds to Frizzled (Fz or Fzd) receptor and thereby to the stabilization of Beta-catenin, which accumulates and travels to the nucleus to form complexes with T cell factor/lymphoid enhancer factor (TCF/LEF) and activates Wnt target genes, such as c-myc and cyclin D1 expression. Tumor genetics revealed that mutations in members of the Wnt/Beta-catenin pathway, such as APC and Beta-catenin, and mutations that activate the Wnt/Beta-catenin pathway promote stabilization of Beta-catenin and induce its nuclear accumulation. However, for some cancers, Beta-catenin accumulates in the nucleus even though mutation of Beta-catenin or APC is rare. Therefore, it is possible that mechanisms other than mutation are involved in the aberrant Beta-catenin expression observed in tumors.
Previously, we and others reported that aberrant expression of Beta-catenin was common in SCCHN and this change correlated with the malignancy index and patient prognosis. In the literature to date, no evidence of APC and Beta-catenin mutation has been available for SCCHN. Thus, in SCCHN, molecular events other than mutations in Beta-catenin and APC may be responsible for the activation of the Wnt/Beta-catenin signaling pathway and the cytoplasmic/nuclear expression of Beta-catenin. However, the molecular mechanisms that lead to aberrant expression of Beta-catenin in SCCHN are unclear and the mechanisms by which Beta-catenin promotes activation of target genes are also not well understood.
We used two types of SCCHN cell models to dissect critical events that regulate Beta-catenin stability and location, from Wnt antagonists (SFRPs) to the EGFR signaling, and nuclear machinery that mediates Beta-catenin-dependent transcription. In addition, we studied the clinicopathological and prognostic significance of Wnt antagonists (SFRPs), EGFR, Beta-catenin, and target genes regulation.
Part one – In the cell model of mucoepidermoid carcinoma in salivary gland, we investigated the possible involvement of Wnt antagonist (SFRP1) methylation and expression in the aberrant distribution of Beta-catenin.
Part two – In the cell model of oral cancer, we examined the effect of EGFR signaling on the nuclear accumulation of Beta-catenin and the mechanisms by which Beta-catenin promotes activation of target genes.
碩士
國立交通大學
電子研究所
81
In this thesis, efficient pipelined, high throughput rate
architectures for CORDIC algorithm are presented. Since the
CORDIC operation is dependent on the sign of remaining ...rotation
or the component of Y-axis, the computation time of the CORDIC
algorithm is limited by its inherently sequential relationship.
However, in CORDIC algorithm, the remaining rotation angle or
Y- component are always required to approach to zero. The key
idea of our approach is to separate the sign detection
operation of remaining rotation angle or the component of Y-
axis evaluation from the rotation operation. By taking the
absolute values of these variables, the angle or Y-component
iteration are fixed to subtraction operation. Therefore, we can
successively subtract the residues without knowing the signs of
preceding remaining rotation angle or the component of Y-axis,
while their signs can be detected parallely, independently and
in a pipelined fashion. Doing this way the sequential
relationship of CORDIC algorithm between the computation of
angle calculated and rotation operation is eliminated, and the
time for the CORDIC operations can be greatly reduced. The
corresponding CORDIC processor we proposed consists of regular
pipelined slices. Each pipeline slice contains only one or two
signed-digit adder and one digit level absoluter. Therefore,
the duration of a clock cycle is very short, that is about two
or three signed-digit adder delays. And iteration is completed
within two or three clock cycles. Since the pipeline slice is
regular, the CORDIC processor is well suited for VLSI
implementation. The sequential architecture for rotation mode
of CORDIC algorithm is realized by 0.8um CMOS technology to
verify our design. The chip, which has 32-bit operand
wordlength, is 6.2mm*5.3mm in area. It can operate at 10MHz
clock frequency.
The objective of this research is the development of an alternative method for transient analysis of dynamical systems. The proposed method consists of the traditional single frequency analysis ...method to capture the steady state operation of the system and a wavelet-based transient analysis which captures the disturbance. The total solution is obtained from the superposition of the periodic steady state solution and the wavelet-based disturbance solution. This thesis focuses on the second part of the solution. We have named this approach WBTA (Wavelet-Based Transient Analysis). The WBTA method is based on equivalent wavelet companion circuits of system components, such as resistors, inductors, and capacitors. This method can be implemented using any set of orthogonal wavelets. In this thesis, an implementation with Daubechies wavelets is presented. To augment the modeling of system components, the numerical integration technique and the finite difference approximation method are utilized as a means to approximate the integral and derivative of wavelet base functions. The equivalent wavelet companion circuits are developed by applying wavelet series analysis on the integro-differential equations for each element. The procedure results in a set of algebraic equations for the entire network. The solution is in terms of the wavelet coefficients of the voltages at the nodes of the network. The actual voltages can be reconstructed via wavelet series reconstruction. The results obtained using the proposed approach are compared and verified with a numerical time-domain analysis method. The advantages of the proposed method are: (1) providing trade-off between solution accuracy and computational speed, and (2) providing possible numerical stability for stiff systems.
A novel online hybrid direct/indirect adaptive Petri fuzzy neural network (PFNN) controller with stare observer for a class of multi-input multi-output (MIMO) uncertain nonlinear systems is developed ...in the paper. By using the Lyapunov synthesis approach, the online observer-based tracking control law and the weight-update law of the adaptive hybrid intelligent controller are derived. According to the importance and viability of plant knowledge and control knowledge, a weighting factor is utilized to sum together the direct and indirect adaptive PFNN controllers. In this paper, we prove that the proposed online observer-based hybrid PFNN controller can guarantee that all signals involved are bounded and that the system outputs of the closed-loop system can track asymptotically the desired output trajectories. An example including four cases is illustrated to show the effectiveness of this approach.
성인에서 진단된 PFAPA증후군 김상옥; Sang Ock Kim; 형건덕 ...
The Korean journal of medicine,
12/2009, Letnik:
77, Številka:
7
Journal Article
Recenzirano
PFAPA증후군은 주기적인 발열을 특징으로 하는 질환군으로 면역학적 조절이상이 그 원인으로 생각되어지고 있고, 소아에서 주로 보고되고 있으나 성인에서도 원인을 알 수 없는 주기적인 발열소견이 보일 때 의심해 보아야 할 질환이다. 이에 저저들은 성인에서 발생한 PFAPA증후군을 진단하고 치료에 반응을 보인 1예를 경험하였기에 문헌고찰과 함께 보고하는 ...바이다.
In 1987, Marshall et al. described a new periodic fever that was later named periodic fever, aphthous ulcers, pharyngitis, and cervical adenitis (PFAPA) syndrome. Other periodic fever diseases, such as recurrent tonsillitis, a number of infectious diseases, juvenile idiopathic arthritis, Behcet`s disease, cyclic neutropenia, familial Mediterranean fever (FMF), familial Hibernian fever (FHF), and hyperglobulinema D syndrome must be excluded as diagnoses. The diagnostic criteria were proposed in 1989 and modified 10 years later. Adult onset PFAPA syndrome has rarely been reported and has not been reported in Korea. We diagnosed PFAPA syndrome with characteristic clinical findings in a 50-year-old man, who showed good response to steroid therapy. (Korean J Med 77:S1332-S1336, 2009)
Symptomatic gastro-intestinal metastasis in lung cancer is extremely rare and only a few case reports have been published. Here, we report a case with lung adenocarcinoma that presented with acute ...abdominal pain, nausea and vomiting due to duodenum, jejunum, and colon obstruction by the gastro-intestinal metastasis. The patient underwent colonoscopy and the pathologic report was adenocarcinoma. When there are similar histologic findings in both colon and pulmonary lesion, the question is whether both lesions are primary cancer or the colon lesions are metastases from lung cancer. Microscopic examination of a conventional pathologic section was not sufficient to make this determination. Immunohistochemistry was positive for thyroid transcription factor-1 (TTF-1) and cytokeratin 7 (CK7), and negative for cytokeratin 20 (CK20) and caudal-related homeobox transcription factor-2 (CDX-2) on colon mucosa specimen. Accordingly, we used immunohistochemical marker for differential diagnosis of primary adenocarcinoma of the lung with gastro-intestinal metastasis.
This study investigates the fabrication characteristics of a femtosecond fiber laser on a fused-silica-based optical waveguide. The wavelength and repetition rate of the femtosecond fiber laser are ...532 nm and 1 MHz, respectively. We selected three main fabrication parameters for systematic adjustment: laser power (E), scanning speed (ν s ) and focus depth (d = 0 at the surface of substrate). We succeeded in fabricating a waveguide layer inside the silica subtracts. By analyzing the light translation path and the net fluence in the waveguide, the range of fabrication energy of the waveguide on the fused silica was kept within 0.973 - 1.438 KJ/cm 2 .
