<p>Telomeres are the ends of chromosomes which are composed of repetitive DNA sequence and telomere associated proteins. In C. elegans, the protein F39H2.5 was found to associate with the telomere, regulating both telomere length and genomic integrity. F39H2.5 is a member of the β-CASP family of proteins that are known to possess nuclease activity on DNA substrates. I thus sought to address whether any of the human β-CASP family proteins associated with telomeres. Here I show that hSnm1B localized to the telomere indirectly, via interaction with the double-stranded telomere binding protein TRF2. The terminal 37 amino acids of hSnm1B are necessary and sufficient for binding TRF2, and moreover that binding to TRF2 stabilized hSnm1B protein by preventing ubiquitination. In the absence of exogenous TRF2 this domain acted as a degron, promoting protein instability. I thus termed the domain the Protection And INstability (PAIN) domain. I hypothesize that TRF2 binding ensures that hSnm1B will only accumulate at telomeres by preventing the degradation of hSnm1B. However, hSnm1B stability appears to be further regulated, as telomere specific DNA damage stabilized hSnm1B independent of the PAIN domain. Thus, it appears that the telomere associated protein, hSnm1B, is regulated by protein stability in a manner that is both dependent and independent of the PAIN domain.</p> / Dissertation

<p>Transforming growth factor–β (TGF–β) signaling regulates a range of processes in a variety of cell types. Consequently, TGF–β plays a complex role in the progression of several types of cancers; it acts as a tumor suppressor in normal cells and early in tumor progression, yet it can promote tumor progression in later stages of cancer.</p><p>Among the cancers that TGF–β has been implicated in is glioblastoma multiforme (GBM), the most common primary brain neoplasm and one of the most lethal types of cancer. Because of its high mortality rate and the lack of effective treatments, discovering the molecular mechanisms that underlie GBM formation and growth is of great clinical interest. To this end, we investigated the function of a TGF–β target gene — the putative tumor suppressor N‐Myc downstream‐regulated gene 4 (NDRG4) — in GBM cell viability, proliferation and tumor formation. Contrary to the established roles of other NDRG family members, we found that NDRG4 expression is elevated in GBM and that NDRG4 is required for the survival of established GBM cell lines and primary GBM xenograft cells enriched for highly tumorigenic GBM cancer stem cells. Knockdown of NDRG4 expression results in G₁ cell cycle arrest followed by apoptosis that is associated with a decrease in the expression of XIAP and survivin. Finally, knockdown of NDRG4 expression in established GBM cell lines and GBM cancer stem cells results in decreased tumorigenicity following intracranial implantation of these cells into immunocompromised mice. Collectively, these data indicate that NDRG4 does not function as a tumor suppressor like other NDRG family members, but rather it is essential for GBM tumorigenicity and may represent a potential therapeutic target for this devastating disease.</p><p>In the second portion of this dissertation, we examine the TGF–β cytostatic signaling pathway in B lymphocytes. TGF–β–induced growth inhibition is the most extensively studied biological response to a TGF–β signal. Although in most cell types this response is mediated by Smad3– dependent regulation of c–Myc, p15<super>Ink4B</super>, and p21<super>Cip1</super> transcription, studies from Smad3 null mice suggest that TGF–β–induced growth inhibition in B lymphocytes occurs regardless of Smad3 status. We prove that this response does indeed occur independently of Smad3 in purified primary B lymphocytes and WEHI–231 cells. Consistent with this, p15<super>Ink4B</super> and p21<super>Cip1</super> are not noticeably induced by TGF–β in these cells, whereas Id3 and cyclin G2 are induced in a Smad3–independent manner. Finally, unlike the MAPK pathways we tested, the BMP–specific Smads 1 and 5 are activated in response to TGF–β in these cells, and this activation is dependent on ALK5 kinase activity. Collectively, these data indicate that TGF–β induces growth inhibition in B lymphocytes through a novel signaling pathway, and Smads 1 and 5 may help mediate this response.</p> / Dissertation

3-(o-(Methylthio)phenyl)-1-phenylprop-2-en-1-one (48) ¡B1-(o-(methylthio)-phenyl)-3-phenylprop-2-en-1-one (49) and 1-(o-(methylthio)phenyl)-3-phenylprop-2-yn-1-one (50) had been studied by means of pyrolysis and photolysis. Under pyrolytic conditions, compound 48 gave phenanthrene (2) as the major product. Both compounds 49 and 50 gave thioflavone (53) as the major product. Under photolytic conditions, compounds 48-50 gave the expected products 2-benzoylbenzo[b]thiophene (51)¡B 2-benzylidenebenzo[b]thiophen-3-one (52) and thioflavone (53), respectively.

Since Taiwan government allowed resident of China visiting Taiwan from July 2008, they have been made over one hundred billion NT dollars profit. The tourism industries also invested over one hundred and sixty billion NT dollars, including travel industry, hotel industry and entertainment industry. The main purpose of foreigners visiting Taiwan is shifting from business to travel as well, and it count up to 58% in 2011. In the meanwhile, B&Bs (bed and breakfast) industry plays an crucial role in the impetus of local cultural development. Different from typical hotel industry, B&Bs give tourists more than just a place to stay, instead, they provide a place which full of local cultural and characteristics to enjoy. The first B&Bs in the world can be traced back to world war two, and the industry in Taiwan has grown rapidly in recent years due to economic growth and society development. The number of legal B&Bs raised from 109 in 2003 to 3261 in 2011. Aside from their own unique characteristics, the reason of their survival in this kind of competitive environment is the chief objective of this thesis. The study attempts to discover the main success factors of these leading specific B&Bs in Taiwan. Through deeply semi-structural interviews with these B&B hosts, this study obtained authentic information. Based on interview outline and recording file recorded in interviews, researcher typed down the scripts of interviews. Thereat, in the basis of research outcomes, researcher acquired the conclusion of this study. Furthermore, researcher addressed research suggestions related to future studies.

Treatment of 1-(methylsulfinyl)-2-(phenylethynyl)benzene with 10 mol % of mercury dichloride and 1 equivalent of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in refluxing benzene gave benzo[b]thiophene in good yields. This method tolerated various functional groups in phenylethynyl moiety, including electron donating groups and electron withdrawing groups. Useing 1-(benzylsulfinyl)-2-(phenylethynyl)benzene as reaction substrate increased the yields of benzo[b]thiophene derivatives. Isotope effect showed that this cyclization reaction belong to Pummerer type cyclization reaction.

¤@. Photolysis of 2-azido-1-(2- pyridyl)ethanone (68),2-azido-1-(3-pyridyl)ethanone) (69),2-azido-1-(1-methyl-2-pyrryl)ethanone (53) and 2-azido-1-(1-methyl-3-indo yl)ethanone gave Norrish products (71, 7 3-76), (84-86, 89), (92-94) and (93, 95-98). ¤G. Pyrolysis of 2-(azidomethyl)pyridine (9) and 4-(azidomethyl)pyr idine (10) gave the expected products 1,3,5-tri-2-pyridyl-2,4-diaza-1,4-pentadiene (13) and 1,3,5-tri-4-pyridyl-2,4-diaza-1,4-pentadiene (21). ¤T. Pyrolysis of 2-cyclohexeno[b]furylmethyl benzoate (31) gave 2-methylbenzo[b]- furan (40) and benzene products.

Corals are marine animals from the class Anthozoa and are widely distributed in tropical and subtropical seawaters. They are considered as an important source of lead compounds for drug discovery. For evaluating the medicinal activities of briarane-type diterpenoids (BrDs) from marine coral Briareum excavatum, the regulation of a group of briarane-type diterpenoids (BrDs) on dendritic cell (DC) function, TPA-induced dermatitis and type 1 diabetes was investigated. The results show that the BrD excavatolide K (BrD2) remarkably suppressed the activation of human DCs, especially the expression of IL-12 p40. This inhibitory effect was mediated apparently by interference with the rictor-mTOR/Akt-mediated signaling network, resulting in persistent-phase activation of NF-kB and Erk1/2 signalings. In addition, the 8,17-epoxide of BrDs was observed to play a crucial role in inhibition of IL-12 p40 expression. Replacement of the C-12 hydroxyl group with longer esters in BrDs gradually decreased this inhibitory activity in human DCs. BrD excavatolide B (BrD1) effectively suppressed the capacity of mouse bone marrow-derived DCs to induce an antigen-specific Th1, response via the inhibition of IL-12 expression. Moreover, excavatolide B prevented the onset of autoreactive T cell-mediated diabetes in NOD/SCID mice. Furthermore, excavatolide B remarkably suppressed TPA-induced vascular permeability and edema in test skin tissues. At the biochemical level, excavatolide B inhibited TPA-induced expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase-9, the key indicators of cutaneous inflammation. This inhibition is apparently mediated by interference with the Akt/NF-kB-mediated signaling network. Together, these studies demonstrate that BrDs from specific marine corals can effectively regulate defined molecular and cellular functions of dendritic cells, suppress TPA-induced dermatitis, and prevent type 1 diabetes in murine models suggesting that BrDs may warrant further investigation as natural immunomodulatory agents or therapeutics.

¤@¡BPyrolysis of 2-azido-1-(4-methoxyphenyl)ethanone (69) and 2-(2-azidoethyl)furan (85) gave nitrene intermediate to study. There is 2-(4-methoxybenzoyl)-4-(4- methoxyphenyl)imidazole (81) ¡B2-(4-methoxybenzoyl)-5-(4-methoxyphenyl) imidazole] (81¡¦)¡B2,3-di(4-methoxybenzoyl)-5-(4-methoxyphenyl) pyrazine] (82) and 3,5-di(2-furyl) pyridine (92) for pyrolysis products. ¤G¡BPyrolysis of3-methyl-2-cyclohexen[b] furylmethyl benzoate) (50) gave carbene intermediate to study. There is 2,3-dimethylene cyclohexen[b]furan (59) for pyrolysis products.

This study focuses on the design, fabrication, test and application of in-plane rotary electromagnetic micro-generator to obtain a high power output. The micro-generator comprises multilayer planar low temperature co-fired ceramics (LTCC) Ag micro-coil and multipole hard magnet of Nd/Fe/B. Finite element simulations have been carried out to observe electromagnetic information. The study also establishes analytical solutions for the micro-generator to predict the induced voltage. Three different configurations of planar micro-coils investigated, which are sector-shaped, circle-shaped, and square-shaped micro-coils. A prototype of the micro-generator is as small as 9¡Ñ9¡Ñ1 mm3 in volume size. The experimental results show that the micro-generator with sector-shaped micro-coil has the highest power output of 1.89 mW, and the effective value of the induced voltage of 205.7 mV at 13,325 rpm is achieved. In application, this study designed and fabricated a planar rotary electromagnetic energy harvester with a low rotary speed for use in bicycle dynamos. Finite element analysis and the Taguchi method were used to design this dynamo system. LTCC technology was applied to fabricate Ag planar multilayer coils with 20 layers. A 28-pole magnet Nd/Fe/B with an outer diameter of 50 mm and a thickness of 2 mm was also sintered and magnetized. This harvester system was approximately 50¡Ñ50¡Ñ3 mm3 in volume. The experimentally induced voltages for 20-layer coils were 1.539 V at the rotary speeds of 300 rpm. The power output was 0.788 mW with an external resistance load of 740 £[, and the efficiency was 26.62%. This harvester is capable of powering a minimum of 200 light emitted diodes (LEDs) (forward voltage (VF) <2.2 V and 20 mA) using a rotary speed of 250 rpm, and can be used for bicycle dynamo lighting.

In the recent years, researchers have discovered a multitude of applications using nanofibers in fields like composites, biotechnology, environmental engineering, defense, optics and electronics. This increase in nanofiber applications needs a higher rate of nanofiber production. Electrospinning has proven to be the best nanofiber manufacturing process because of simplicity and material compatibility. Study of effects of various electrospinning parameters is important to improve the rate of nanofiber processing. In addition, several applications demand well-oriented nanofibers. Researchers have experimentally tried to control the nanofibers using secondary external electric field. In the first study, the electrospinning process is modeled and the bending instability of a viscoelastic jet is simulated. For this, the existing discrete bead model is modified and the results are compared, qualitatively, with previous works in literature. In this study, an attempt is also made to simulate the effect of secondary electric field on electrospinning process and whipping instability. It is observed that the external secondary field unwinds the jet spirals, reduces the whipping instability and increases the tension in the fiber. Lattice Boltzmann method (LBM) has gained popularity in the past decade as the method is easy implement and can also be parallelized. In the second part of this thesis, a hybrid numerical scheme which couples lattice Boltzmann method with finite difference method for a Oldroyd-B viscoelastic solution is proposed. In this scheme, the polymer viscoelastic stress tensor is included in the equilibrium distribution function and the distribution function is updated using SRT-LBE model. Then, the local velocities from the distribution function are evaluated. These local velocities are used to evaluate local velocity gradients using a central difference method in space. Next, a forward difference scheme in time is used on the Maxwell Upper Convected model and the viscoelastic stress tensor is updated. Finally, using the proposed numerical method start-up Couette flow problem for Re = 0.5 and We = 1.1, is simulated. The velocity and stress results from these simulations agree very well with the analytical solutions.