Integration of disease-specific single nucleotide polymorphisms, expression quantitative trait loci and coexpression networks reveal novel candidate genes for type 2 diabetes.

Aims/hypothesisWhile genome-wide association studies (GWASs) have been successful in identifying novel variants associated with various diseases, it has been much more difficult to determine the biological mechanisms underlying these associations. Expression quantitative trait loci (eQTL) provide another dimension to these data by associating single nucleotide polymorphisms (SNPs) with gene expression. We hypothesised that integrating SNPs known to be associated with type 2 diabetes with eQTLs and coexpression networks would enable the discovery of novel candidate genes for type 2 diabetes.MethodsWe selected 32 SNPs associated with type 2 diabetes in two or more independent GWASs. We used previously described eQTLs mapped from genotype and gene expression data collected from 1,008 morbidly obese patients to find genes with expression associated with these SNPs. We linked these genes to coexpression modules, and ranked the other genes in these modules using an inverse sum score.ResultsWe found 62 genes with expression associated with type 2 diabetes SNPs. We validated our method by linking highly ranked genes in the coexpression modules back to SNPs through a combined eQTL dataset. We showed that the eQTLs highlighted by this method are significantly enriched for association with type 2 diabetes in data from the Wellcome Trust Case Control Consortium (WTCCC, p = 0.026) and the Gene Environment Association Studies (GENEVA, p = 0.042), validating our approach. Many of the highly ranked genes are also involved in the regulation or metabolism of insulin, glucose or lipids.Conclusions/interpretationWe have devised a novel method, involving the integration of datasets of different modalities, to discover novel candidate genes for type 2 diabetes

Advancement of the annual traffic census in Hong Kong

This paper summarises the process, findings and recommendations of a recently completed joint university consultancy project that reviewed the annual traffic census (ATC) in Hong Kong. The results of a survey that assessed the usefulness of the census report are presented, together with an overview of the existing traffic data collection process and traffic detection equipment. Areas for improvement are then identified, including the sampling strategies for the collection of vehicle classification and occupancy data, the procedure for the development of group scaling factors, the method for the selection of core and coverage stations, the approaches to developing growth factors and traffic flow estimation, the presentation method and database structure of the census framework, and the manpower requirements. Based on these identified areas, a new computer program is developed to integrate all of the tasks of the census report and to produce the results in CD-ROM format. Finally, concluding remarks are given together with recommendations for further study.published_or_final_versio

Asymmetric adiabatic couplers for fully-integrated broadband quantum-polarization state preparation

© 2017 The Author(s). Spontaneous parametric down-conversion (SPDC) is a widely used method to generate entangled photons, enabling a range of applications from secure communication to tests of quantum physics. Integrating SPDC on a chip provides interferometric stability, allows to reduce a physical footprint, and opens a pathway to true scalability. However, dealing with different photon polarizations and wavelengths on a chip presents a number of challenging problems. In this work, we demonstrate an on-chip polarization beam-splitter based on z-cut titanium-diffused lithium niobate asymmetric adiabatic couplers (AAC) designed for integration with a type-II SPDC source. Our experimental measurements reveal unique polarization beam-splitting regime with the ability to tune the splitting ratios based on wavelength. In particular, we measured a splitting ratio of 17 dB over broadband regions (>60 nm) for both H-and V-polarized lights and a specific 50%/50% splitting ratio for a cross-polarized photon pair from the AAC. The results show that such a system can be used for preparing different quantum polarization-path states that are controllable by changing the phase-matching conditions in the SPDC over a broad band. Furthermore, we propose a fully integrated electro-optically tunable type-II SPDC polarization-path-entangled state preparation circuit on a single lithium niobate photonic chip

ZNF750 is a lineage-specific tumour suppressor in squamous cell carcinoma.

ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotypes of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a long non-coding RNA (TINCR), which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions

On-chip adiabatic couplers for broadband quantum-polarization state preparation

© 2018 OSA. We present a unique wavelength-dependent polarization splitter based on asymmetric adiabatic couplers designed for integration with type-II spontaneous parametric-down-conversion sources. The system can be used for preparing different quantum polarization-path states over a broad band

Optical Waveplates Based on Birefringence of Anisotropic Two-Dimensional Layered Materials

Birefringence is an inherent optical property of anisotropic materials introduced by the anisotropic confinement in their crystal structures. It enables manipulation of light propagation properties (e.g., phase velocity, reflection, and refrac- tion) for various photonic and optoelectronic applications, including waveplates and liquid crystal displays. Two-dimensional (2D) layered materials with high anisotropy are currently gaining an increasing interest for polarization-integrated nano- device applications, which advances the research on birefringent materials. In this article, we investigate the optical birefrin- gence of three anisotropic 2D layered materials (black phosphorus (BP), rhenium disulfide (ReS2), and rhenium diselenide (ReSe2)). We demonstrate that the birefringence in BP (~0.245) is ~ 6 times larger than that of ReS2 (~0.037) and ReSe2 (~0.047) at 520 nm and is comparable to the current state of the art bulk materials (e.g., CaCO3). We use these 2D materials to fabricate atomically-thin optical waveplates and investigate their performance. In particular, for BP, we observe a polarization-plane rotation of ~0.05° per atomic layer at 520 nm. Our results show that the relatively large birefringence of anisotropic 2D layered materials can enable accurate manipulation of light polarization with atomically controlled device thickness for various applications where integrated, nanoscale polarization-controllers are required

LNK (SH2B3): paradoxical effects in ovarian cancer.

LNK (SH2B3) is an adaptor protein studied extensively in normal and malignant hematopoietic cells. In these cells, it downregulates activated tyrosine kinases at the cell surface resulting in an antiproliferative effect. To date, no studies have examined activities of LNK in solid tumors. In this study, we found by in silico analysis and staining tissue arrays that the levels of LNK expression were elevated in high-grade ovarian cancer. To test the functional importance of this observation, LNK was either overexpressed or silenced in several ovarian cancer cell lines. Remarkably, overexpression of LNK rendered the cells resistant to death induced by either serum starvation or nutrient deprivation, and generated larger tumors using a murine xenograft model. In contrast, silencing of LNK decreased ovarian cancer cell growth in vitro and in vivo. Western blot studies indicated that overexpression of LNK upregulated and extended the transduction of the mitogenic signal, whereas silencing of LNK produced the opposite effects. Furthermore, forced expression of LNK reduced cell size, inhibited cell migration and markedly enhanced cell adhesion. Liquid chromatography-mass spectroscopy identified 14-3-3 as one of the LNK-binding partners. Our results suggest that in contrast to the findings in hematologic malignancies, the adaptor protein LNK acts as a positive signal transduction modulator in ovarian cancers

Broadband on-chip polarization mode splitters in lithium niobate integrated adiabatic couplers

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement. We report, to the best of our knowledge, the first broadband polarization mode splitter (PMS) based on the adiabatic light passage mechanism in the lithium niobate (LiNbO3) waveguide platform. A broad bandwidth of ~140 nm spanning telecom S, C, and L bands at polarization-extinction ratios (PER) of >20 dB and >18 dB for the TE and TM polarization modes, respectively, is found in a five-waveguide adiabatic coupler scheme whose structure is optimized by an adiabaticity engineering process in titanium-diffused LiNbO3 waveguides. When the five-waveguide PMS is integrated with a three-waveguide “shortcut to adiabaticity” structure, we realize a broadband, high splitting-ratio (ηc) mode splitter for spatial separation of TE- (H-) polarized pump (700-850 nm for ηc>99%), TM- (V-) polarized signal (1510-1630 nm for ηc>97%), and TE- (H-) polarized idler (1480-1650 nm for ηc>97%) modes. Such a unique integrated-optical device is of potential for facilitating the on-chip implementation of a pump-filtered, broadband tunable entangled quantum-state generator

Broadband On-Chip Adiabatic-Coupling Polarization Mode Splitters in Lithium Niobate Waveguides

© 2019 The Author(s) 2019 OSA. We report the first broadband (>120 nm at >97% splitting efficiency for both polarization modes) polarization mode-splitter in LiNbO3 adiabatic light-passage configuration. This device can facilitate the on-chip implementation of pump-filtered, broadband tunable Bell-state generators