SINGLE STAGE LED DRIVER TECHNOLOGY WITH LOW FREQUENCY RIPPLE CANCELLATION

Because of high efficacy, long lifespan, and environment-friendly operation, LED lighting devices become more and more popular in every part of our life, such as ornament/interior lighting, outdoor lightings and flood lighting. The LED driver is the most critical part of the LED lighting fixture. It heavily affects the purchasing cost, operation cost as well as the light quality. Design a high efficiency, low component cost and flicker-free LED driver is the goal. The conventional single-stage LED driver can achieve low cost and high efficiency. However, it inevitably produces significant twice-line-frequency lighting flicker, which adversely affects our health. The conventional two-stage LED driver can achieve flicker-free LED driving at the expenses of significantly adding component cost, design complexity and low the efficiency. The basic ripple cancellation LED driving method has been proposed in chapter three. It achieves a high efficiency and a low component cost as the single-stage LED driver while also obtaining flicker-free LED driving performance. The basic ripple cancellation LED driver is the foundation of the entire thesis. As the research evolving, another two ripple cancellation LED drivers has been developed to improve different aspects of the basic ripple cancellation LED driver design. The primary side controlled ripple cancellation LED driver has been proposed in chapter four to further reduce cost on the control circuit. It eliminates secondary side compensation circuit and an opto-coupler in design while at the same time maintaining flicker-free LED driving. A potential integrated primary side controller can be designed based on the proposed LED driving method. The energy channeling ripple cancellation LED driver has been proposed in chapter five to further reduce cost on the power stage circuit. In previous two ripple cancellation LED drivers, an additional DC-DC converter is needed to achieve ripple cancellation. A power transistor has been used in the energy channeling ripple cancellation LED driving design to successfully replace a separate DC-DC converter and therefore achieved lower cost. The detailed analysis supports the theory of the proposed ripple cancellation LED drivers. Simulation and experiment have also been included to verify the proposed ripple cancellation LED drivers.

Characterization of ALDH1A1 as a novel tumorigenic target mediating TAZ-induced lung tumorigenesis and stem cell phenotypes

Recent studies suggest that lung cancer stem cells (CSCs) may play major roles in lung cancer development, metastasis and drug resistance. Therefore, identification of lung CSC drivers may provide promising targets for lung cancer. TAZ (transcriptional co-activator with PDZ-binding motif) is a transcriptional co-activator and key downstream effector of the Hippo pathway, which plays critical roles in various biological processes. TAZ has been shown to be overexpressed in non-small cell lung cancer (NSCLC) and involved in tumorigenicity of lung epithelial cells. However, whether TAZ is a driver for lung CSCs and tumor formation in vivo is unknown. In addition, the molecular mechanism underlying TAZ-induced lung tumorigenesis remains to be determined. In this study, we provided evidence that constitutively active TAZ (TAZ-S89A) is a driver for lung tumorigenesis in vivo in mice and formation of lung CSC. Oncogenes upregulated in TAZ-overexpressing cells were identified with further validation. The most dramatically activated gene, Aldh1a1 (Aldehyde dehydrogenase 1 family member a1), a well-established CSC marker, showed that TAZ induces Aldh1a1 transcription by activating its promoter activity through interaction with the transcription factor TEA domain (TEAD) family member. Most significantly, inhibition of ALDH1A1 with its inhibitor A37 or CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) gene knockout in lung cancer cells suppressed lung tumorigenic and CSC phenotypes in vitro, and tumor formation in mice in vivo. In conclusion, this study identified TAZ as a novel inducer of lung CSCs and the first transcriptional activator of the stem cell marker ALDH1A1. Most significantly, we identified ALDH1A1 as a critical meditator of TAZ-induced tumorigenic and CSC phenotypes in lung cancer. Our studies provided preclinical data for targeting of TAZ-TEAD-ALDH1A1 signaling to inhibit CSC-induced lung tumorigenesis and drug resistance in the future.