Study of STAT3 interactions with DNA as a target for anticancer drug discovery

STAT3 is a transcription factor involved in the regulation of many cellular functions including proliferation, differentiation, apoptosis, migration and immune response. It has great biological value in understanding the regulation system from genes to cellular activities. STAT3, is one transcriptional activator, but is involved in multiple cellular activities in different cells. It is regarded as an important anti-cancer drug target and a biomarker for tumour growth. Understanding the detailed biological activity of STAT3 can lead to the discovery of mechanisms of regulation of different cellular functions. In this thesis, we reveal more detailed biological activities of STAT3 with three different in vitro methods: protein electrophoresis mobility shift assay (PEMSA), fluorescent polarization (FP) and fluorescent resonance energy transfer (FRET). The development of in vitro methods not only provide more direct visualization of STAT3 biological functions such as DNA binding activity, dimerization, and aggregation, but also can be easily developed into inhibitor screening methods. We successfully created and purified different STAT3 mutations that provide different STAT3 functional domains to detect detailed STAT3 domain functions. Both PEMSA assay and FP assay suggest that STAT3 binds to dsDNA without a requirement for the SH2 domain, which emphasis the possibility of STAT3 binding to dsDNA as a monomer. The PEMSA assay provided an intuitive and orthogonal method to detect STAT3 DNA binding activity while the FP assay is very highthroughput. The developed FRET assay can not only be used to study the DNA binding activity of STAT3 but also be used to detect STAT3 dimerization

Experts in the Loop: Conditional Variable Selection for Accelerating Post-Silicon Analysis Based on Deep Learning

Post-silicon validation is one of the most critical processes in modern semiconductor manufacturing. Specifically, correct and deep understanding in test cases of manufactured devices is key to enable post-silicon tuning and debugging. This analysis is typically performed by experienced human experts. However, with the fast development in semiconductor industry, test cases can contain hundreds of variables. The resulting high-dimensionality poses enormous challenges to experts. Thereby, some recent prior works have introduced data-driven variable selection algorithms to tackle these problems and achieved notable success. Nevertheless, for these methods, experts are not involved in training and inference phases, which may lead to bias and inaccuracy due to the lack of prior knowledge. Hence, this work for the first time aims to design a novel conditional variable selection approach while keeping experts in the loop. In this way, we expect that our algorithm can be more efficiently and effectively trained to identify the most critical variables under certain expert knowledge. Extensive experiments on both synthetic and real-world datasets from industry have been conducted and shown the effectiveness of our method

Probing Triple-W Production and Anomalous WWWW Coupling at the CERN LHC and future 100TeV proton-proton collider

Triple gauge boson production at the LHC can be used to test the robustness of the Standard Model and provide useful information for VBF di-boson scattering measurement. Especially, any derivations from SM prediction will indicate possible new physics. In this paper we present a detailed Monte Carlo study on measuring WWW production in pure leptonic and semileptonic decays, and probing anomalous quartic gauge WWWW couplings at the CERN LHC and future hadron collider, with parton shower and detector simulation effects taken into account. Apart from cut-based method, multivariate boosted decision tree method has been exploited for possible improvement. For the leptonic decay channel, our results show that at the sqrt{s}=8(14)[100] TeV pp collider with integrated luminosity of 20(100)[3000] fb-1, one can reach a significance of 0.4(1.2)[10]sigma to observe the SM WWW production. For the semileptonic decay channel, one can have 0.5(2)[14]sigma to observe the SM WWW production. We also give constraints on relevant Dim-8 anomalous WWWW coupling parameters.Comment: Accepted version by JHE

Development of high resolution arrayed waveguide grating spectrometers for astronomical applications: first results

Astrophotonics is the next-generation approach that provides the means to miniaturize near-infrared (NIR) spectrometers for upcoming large telescopes and make them more robust and inexpensive. The target requirements for our spectrograph are: a resolving power of about 3000, wide spectral range (J and H bands), free spectral range of about 30 nm, high on-chip throughput of about 80% (-1dB) and low crosstalk (high contrast ratio) between adjacent on-chip wavelength channels of less than 1% (-20dB). A promising photonic technology to achieve these requirements is Arrayed Waveguide Gratings (AWGs). We have developed our first generation of AWG devices using a silica-on-silicon substrate with a very thin layer of silicon-nitride in the core of our waveguides. The waveguide bending losses are minimized by optimizing the geometry of the waveguides. Our first generation of AWG devices are designed for H band and have a resolving power of around 1500 and free spectral range of about 10 nm around a central wavelength of 1600 nm. The devices have a footprint of only 12 mm x 6 mm. They are broadband (1450-1650 nm), have a peak on-chip throughput of about 80% (-1 dB) and contrast ratio of about 1.5% (-18 dB). These results confirm the robustness of our design, fabrication and simulation methods. Currently, the devices are designed for Transverse Electric (TE) polarization and all the results are for TE mode. We are developing separate J- and H-band AWGs with higher resolving power, higher throughput and lower crosstalk over a wider free spectral range to make them better suited for astronomical applications.Comment: 12 pages, 13 figures, 3 tables. SPIE Astronomical Telescopes and Instrumentation, Edinburgh (26 June - 1 July, 2016

Experimental demonstrations of high-Q superconducting coplanar waveguide resonators

We designed and successfully fabricated an absorption-type of superconducting coplanar waveguide (CPW) resonators. The resonators are made from a Niobium film (about 160 nm thick) on a high-resistance Si substrate, and each resonator is fabricated as a meandered quarter-wavelength transmission line (one end shorts to the ground and another end is capacitively coupled to a through feedline). With a vector network analyzer we measured the transmissions of the applied microwave through the resonators at ultra-low temperature (e.g., at 20 mK), and found that their loaded quality factors are significantly high, i.e., up to 10^6. With the temperature increases slowly from the base temperature (i.e., 20 mK), we observed the resonance frequencies of the resonators are blue shifted and the quality factors are lowered slightly. In principle, this type of CPW-device can integrate a series of resonators with a common feedline, making it a promising candidate of either the data bus for coupling the distant solid-state qubits or the sensitive detector of single photons.Comment: Accepted by Chinese Science Bulleti