Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near <i>PAX4</i>

Ma, R. C. W.,Hu, C.,Tam, C. H.,Zhang, R.,Kwan, P.,Leung, T. F.,Thomas, G. N.,Go, M. J.,Hara, K.,Sim, X.,Ho, J. S. K.,Wang, C.,Li, H.,Lu, L.,Wang, Y.,Li, J. W.,Wang, Y.,Lam, V. K. L.,Wang, J.,Yu, W.,Ki Springer-Verlag 2013 Diabetologia Vol.56 No.6

<P><B>Aims/hypothesis</B></P><P>Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.</P><P><B>Methods</B></P><P>We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.</P><P><B>Results</B></P><P>We identified <I>CDKN2A/B</I> and four novel type 2 diabetes association signals with <I>p</I> < 1 × 10<SUP>−5</SUP> from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (<I>p</I><SUB>meta</SUB> = 2.6 × 10<SUP>−8</SUP>; OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (<I>p</I><SUB>meta</SUB> = 2.3 × 10<SUP>−10</SUP>) and a population of European descent (<I>p</I> = 8.6 × 10<SUP>−3</SUP>). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians.</P><P><B>Conclusions/interpretation</B></P><P>Our study identifies rs10229583 near <I>PAX4</I> as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00125-013-2874-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users.</P>

COMPARISON OF DRYOUT POWER DATA BETWEENCANFLEX MK-V AND CANFLEX MK-IV BUNDLE STRINGSIN UNCREPT AND CREPT CHANNELS

전지수,L.K.H. LEUNG 한국원자력학회 2005 Nuclear Engineering and Technology Vol.37 No.6

Optimum LCVA for suppressing harmonic vibration of damped structures

Shum, K.M.,Xu, Y.L.,Leung, H.Y. Techno-Press 2017 Smart Structures and Systems, An International Jou Vol.20 No.4

Explicit design formulae of liquid column vibration absorber (LCVA) for suppressing harmonic vibration of structures with small inherent structural damping are developed in this study. The developed design formulae are also applicable to the design of a tuned mass damper (TMD) and a tuned liquid column damper (TLCD) for damped structures under harmonic force excitation. The optimum parameters of LCVA for suppressing harmonic vibration of undamped structures are first derived. Numerical searching of the optimum parameters of tuned vibration absorber system for suppressing harmonic vibration of damped structure is conducted. Explicit formulae for these optimum parameters are then obtained by a series of curve fitting techniques. The analytical result shows that the control performance of TLCD for reducing harmonic vibration of undamped structure is always better than that of non-uniform LCVA for same mass and length ratios. As for the effects of structural damping on the optimum parameters, it is found that the optimum tuning ratio decreases and the optimum damping ratio increases as the structural damping is increased. Furthermore, the optimum head loss coefficient is inversely proportional to the amplitude of excitation force and increases as the structural damping is increased. Numerical verification of the developed explicit design expressions is also conducted and the developed expressions are demonstrated to be reasonably accurate for design purposes.

The Role of Turmerones on Curcumin Transportation and P-Glycoprotein Activities in Intestinal Caco-2 Cells

Grace G.L. Yue,Sau-Wan Cheng,Hua Yu,Zi-Sheng Xu,Julia K.M. Lee,Po-Ming Hon,Mavis Y.H. Lee,Edward J. Kennelly,Gary Deng,Simon K. Yeung,Barrie R. Cassileth,Kwok-Pui Fung,Ping-Chung Leung,Clara B.S. Lau 한국식품영양과학회 2012 Journal of medicinal food Vol.15 No.3

The rhizome of Curcuma longa (turmeric) is often used in Asia as a spice and as a medicine. Its most wellstudied component, curcumin, has been shown to exhibit poor bioavailability in animal studies and clinical trials. We hypothesized that the presence of lipophilic components (e.g., turmerones) in turmeric extract would affect the absorption of curcumin. The effects of turmerones on curcumin transport were evaluated in human intestinal epithelial Caco-2 cells. The roles of turmerones on P-glycoprotein (P-gp) activities and mRNA expression were also evaluated. Results showed that in the presence of a- and aromatic turmerones, the amount of curcumin transported into the Caco-2 cells in 2 hours was significantly increased. a-Turmerone and verapamil (a P-gp inhibitor) significantly inhibited the efflux of rhodamine-123 and digoxin (i.e.,inhibited the activity of P-gp). It is interesting that aromatic turmerone significantly increased the rhodamine-123 efflux and Pgp (MDR1 gene) mRNA expression levels. The effects of a- and aromatic turmerones on curcumin transport as well as P-gp activities were shown here for the first time. The presence of turmerones did affect the absorption of curcumin in vitro. These findings suggest the potential use of turmeric extract (including curcumin and turmerones), rather than curcumin alone, for treating diseases.

Overview of methods to increase dryout power in CANDU fuel bundles

Groeneveld, D.C.,Leung, L.K.H.,Park, J.H. Elsevier 2015 Nuclear engineering and design Vol.287 No.-

<P><B>Abstract</B></P> <P>In CANDU reactors some degradation in the CCP (critical channel power, or power corresponding to the first occurrence of CHF in any fuel channel) will occur with time because of ageing effects such as pressure-tube diametral creep, increase in reactor inlet-header temperature, increased hydraulic resistance of feeders. To compensate for the ageing effects, various options for recovering the loss in CCP are described in this paper. They include: (i) increasing the bundle heated perimeter, (ii) optimizing the bundle configuration, (iii) optimizing core flow and flux distribution, (iv) reducing the bundle hydraulic resistance, (v) use of CHF-enhancing bundle appendages, (vi) more precise experimentation, and (vii) redefining CHF. The increase in CHF power has been quantified based on experiments on full-scale bundles and subchannel code predictions. The application of several of these CHF enhancement principles has been used in the development of the 43-rod CANFLEX bundle.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Small changes in bundle geometry can have noticeable effects on the bundle CHF. </LI> <LI> Rod spacing devices can results in increases of over 200% in CHF. </LI> <LI> CHF enhancement decays exponentially downstream from spacers. </LI> <LI> CHF-enhancing bundle appendages also increase the post-CHF heat transfer. </LI> </UL> </P>

COMPARISON OF DRYOUT POWER DATA BETWEEN CANFLEX MK-V AND CANFLEX MK-IV BUNDLE STRINGS IN UNCREPT AND CREPT CHANNELS

JUN JI SU,LEUNG L.K.H. Korean Nuclear Society 2005 Nuclear Engineering and Technology Vol.37 No.6

The CANFLEX Mk-V bundle is designed to improve upon the critical heat flux (CHF) characteristics of the CANFLEX Mk-IV bundle. The main difference between these two bundles is an increase in bearing pad height of about 0.3 mm in the CANFLEX Mk-IV bundle. This change in bearing pad height leads to an increase in gap flow at the bottom of the bundle, primarily eliminating the localized narrow-gap effect that limits the CHF of the CANFLEX Mk-IV bundle. The objective of this paper is to examine the effects of bearing pad height and pressure tube creep on the sheath-temperature distribution, dryout power, and dryout location, as observed ken full-scale bundle tests, between CANFLEX Mk-IV and Mk-V bundles In uncrept and crept channels. A comparison of surface-temperature differences between the top and bottom elements of the bundles showed that increasing the bearing pad height has led to a more homogeneous enthalpy distribution in subchannels of the bundle. Initial dryout locations of the CANFLEX Mk-V bundle were mainly observed at the mid-spacer plane of either the $10^{th}$ (about $80\%$) or $11^{th}$ ($20\%$) bundle in the 12-bundle string, as compared to the mid-spacer and downstream-button planes for the CANFLEX Mk-IV bundle. Dryout power and boiling-length-average (BLA) CHF values exhibit consistent trends and little scatter with varying flow conditions for both types of CANFLEX bundles in uncrept and crept channels. An increase in pressure tube creep has led to a reduction in dryout power (about $20\%$ far the $3.3\%$ crept channel and $27\%$ for the $5.1\%$ crept channel as compared to dryout powers for the uncrept channel). Increasing the bearing pad height of the CANFLEX bundle has led to an increase in the dryout power. Overall, the dryout power of the CANFLEX Mk-V bundle is 7 to $10\%$ higher than that of the CANFLEX Mk-IV bundle at the inlet temperature range of interest (i.e., between 243 and $290^{\circ}C$).

The General Post-CHF Heat Transfer Prediction Method for Tubes on the Base of the Look-up Table

A. D. Efanov,A. A. Ivashkevitch,P. L. Kirillov,V. V. Sergeev,I. P. Smogalev,V. N. Vinogradov,D. C. Groeneveld,L. K. H. Leung 대한기계학회 1998 Heat transter conference Vol.2 No.1