Using Glycosylated Hemoglobin to Define the Metabolic Syndrome in United States Adults

OBJECTIVE- To compare the use of GHb and fasting plasma glucose (FPG) to define the metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS- Data from the U.S. National Health and Nutrition Examination Survey 1999-2006 were used. MetS was defined using the consensus criteria in 2009. Raised blood glucose was defined as either FPG ≥100 mg/dl (5.6 mmol/l) or GHb ≥5.7%. RESULTS- In 2003-2006, there was 91.3% agreement between GHb and FPG when either was used to define MetS. The agreement was good irrespective of age, sex, race/ethnicity, BMI, and diabetes status (≥87.4%). Similar results were found in 1999-2002. Among subjects without diabetes, only the use of GHb alone, but not FPG, resulted in significant association with cardiovascular diseases (odds ratio 1.45, P = 0.005). CONCLUSIONS- Using GHb instead of FPG to define MetS is feasible. It also identifies individuals with increased cardiovascular risk. © 2010 by the American Diabetes Association.published_or_final_versionThe 5th International Symposium on Healthy Aging: Is Aging a Disease?, Hong Kong, 6-7 March, 2010. In Diabetes Care, 2010, v. 33 n. 8, p. 1856-185

Determination of absorption coefficients in AlInP lattice matched to GaAs

The absorption properties of Al0.52In0.48P have been investigated near the fundamental absorption edge by measuring the photocurrent as a function of wavelength in a series of PIN and NIP diodes. Modelling of the photocurrent in these structures enables the absorption coefficients to be determined accurately over a wide dynamic range, which allows the direct and indirect band-gap to be determined

Mitochondrial Electron Transport Is the Cellular Target of the Oncology Drug Elesclomol

Elesclomol is a first-in-class investigational drug currently undergoing clinical evaluation as a novel cancer therapeutic. The potent antitumor activity of the compound results from the elevation of reactive oxygen species (ROS) and oxidative stress to levels incompatible with cellular survival. However, the molecular target(s) and mechanism by which elesclomol generates ROS and subsequent cell death were previously undefined. The cellular cytotoxicity of elesclomol in the yeast S. cerevisiae appears to occur by a mechanism similar, if not identical, to that in cancer cells. Accordingly, here we used a powerful and validated technology only available in yeast that provides critical insights into the mechanism of action, targets and processes that are disrupted by drug treatment. Using this approach we show that elesclomol does not work through a specific cellular protein target. Instead, it targets a biologically coherent set of processes occurring in the mitochondrion. Specifically, the results indicate that elesclomol, driven by its redox chemistry, interacts with the electron transport chain (ETC) to generate high levels of ROS within the organelle and consequently cell death. Additional experiments in melanoma cells involving drug treatments or cells lacking ETC function confirm that the drug works similarly in human cancer cells. This deeper understanding of elesclomol's mode of action has important implications for the therapeutic application of the drug, including providing a rationale for biomarker-based stratification of patients likely to respond in the clinical setting

Probing the origin of VHE emission from M 87 with MWL observations in 2010

The large majority of extragalactic very high energy (VHE; E>100 GeV) sources belongs to the class of active galactic nuclei (AGN), in particular the BL Lac sub-class. AGNs are characterized by an extremely bright and compact emission region, powered by a super-massive black hole (SMBH) and an accretion disk, and relativistic outflows (jets) detected all across the electro-magnetic spectrum. In BL Lac sources the jet axis is oriented close to the line of sight, giving rise to a relativistic boosting of the emission. In radio galaxies, on the other hand, the jet makes a larger angle to the line of sight allowing to resolve the central core and the jet in great details. The giant radio galaxy M 87 with its proximity (1 6Mpc) and its very massive black hole ((3-6) x 10^9 M_solar) provides a unique laboratory to investigate VHE emission in such objects and thereby probe particle acceleration to relativistic energies near SMBH and in jets. M 87 has been established as a VHE emitter since 2005. The VHE emission displays strong variability on time-scales as short as a day. It has been subject of a large joint VHE and multi-wavelength (MWL) monitoring campaign in 2008, where a rise in the 43 GHz VLBA radio emission of the innermost region (core) was found to coincide with a flaring activity at VHE. This had been interpreted as a strong indication that the VHE emission is produced in the direct vicinity of the SMBH black hole. In 2010 again a flare at VHE was detected triggering further MWL observations with the VLBA, Chandra, and other instruments. At the same time M 87 was also observed with the Fermi-LAT telescope at GeV energies and the European VLBI Network (EVN). In this contribution preliminary results from the campaign will be presented.Comment: 5 pages, 2 figures, in the proceedings of the "International Workshop on Beamed and Unbeamed Gamma-Rays from Galaxies" 11-15 April 2011, Lapland Hotel Olos, Muonio, Finland, Journal of Physics: Conference Series Volume 355, 201

Evaluation of the combined use of adiponectin and C-reactive protein levels as biomarkers for predicting the deterioration in glycaemia after a median of 5.4 years

Aims/hypothesis: Hypoadiponectinaemia and raised C-reactive protein (CRP) level are obesity-related biomarkers associated with glucose dysregulation. We evaluated the combined use of these two biomarkers in predicting the deterioration of glycaemia in a prospective study after a median of 5.4 years. Methods: In total 1,288 non-diabetic participants from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2, with high-sensitivity CRP (hsCRP) and total adiponectin levels measured were included. OGTT was performed in all participants. Two hundred and six participants had deterioration of glycaemia at follow-up, whereas 1,082 participants did not. Results: Baseline age, hsCRP and adiponectin levels were significant independent predictors of the deterioration of glycaemia in a Cox regression analysis after adjusting for baseline age, sex, BMI, hypertension, triacylglycerols, 2 h post-OGTT glucose and homeostasis model assessment of insulin resistance index (all p < 0.01). The introduction of hsCRP or adiponectin level to a regression model including the other biomarker improved the prediction of glycaemic progression significantly in all participants, especially in women (all p < 0.01). The combined inclusion of the two biomarkers resulted in a modest improvement in model discrimination, compared with the inclusion of either one alone. Among participants with impaired fasting glucose/impaired glucose tolerance (IFG/IGT) at baseline, hsCRP and adiponectin levels were not predictive of progression or improvement of glycaemic status. Conclusions/interpretation: Adiponectin and hsCRP levels are independent factors in predicting the deterioration of glycaemia, supporting the role of adiposity-related inflammation in the development of type 2 diabetes. Their combined use as predictive biomarkers is especially useful in women, but not in participants with IFG/IGT. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure

The KCNJ11 E23K Polymorphism and Progression of Glycaemia in Southern Chinese: A Long-Term Prospective Study

Context: The KCNJ11 E23K variant is associated with type 2 diabetes mellitus (T2DM) in cross-sectional studies, but conflicting findings have been reported from prospective studies. Objective: This study aimed to evaluate whether the E23K variant could predict glycaemic progression in a Southern Chinese population. Methods/Principal Findings: We performed a long-term prospective study on 1912 subjects from the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISPS). The KCNJ11 E23K variant was associated with the progression to prediabetes after a median interval of 12 years on multinomial logistic regression analysis, even after adjustment for traditional risk factors (OR 1.29, P age, sex, BMI and fasting plasma glucose [FPG] adjusted = 0.02). Based on Cox proportional hazard regression analysis, the E23K variant also predicted incident prediabetes (HR 1.18, P age, sex, BMI and FPG adjusted = 0.021). However, E23K was not associated with the progression to T2DM in either multinomial or Cox regression analysis, and the association of E23K with glycaemic progression to either prediabetes or T2DM was significant only in unadjusted Cox regression analysis (P = 0.039). In a meta-analysis of eight prospective studies including our own, involving 15680 subjects, the E23K variant was associated with incident T2DM (fixed effect: OR 1.10, P = 4×10 -3; random effect: OR 1.11, P = 0.035). Conclusions: Our study has provided supporting evidence for the role of the E23K variant in glycaemic progression in Chinese, with its effect being more evident in the early stage of T2DM, as the subjects progressed from normal glucose tolerance to prediabetes. © 2011 Cheung et al.published_or_final_versio

A consistent treatment for pion form factors in space-like and time-like regions

We write down some relevant matrix elements for the scattering and decay processes of the pion by considering a quark-meson vertex function. The pion charge and transition form factors $F_\pi$, $F_{\pi\gamma}$, and $F_{\pi\gamma^*}$ are extracted from these matrix elements using a relativistic quark model on the light-front. We found that, the form factors $F_\pi$ and $F_{\pi\gamma}$ in the space-like region agree well with experiment. Furthermore, the branching ratios of all observed decay modes of the neutral pion, that are related to the form factors $F_{\pi\gamma}$ and $F_{\pi\gamma^*}$ in the time-like region, are all consistent with the data as well. Additionally, $F_\pi$ in the time-like region, which deals with the nonvalence contribution, is also discussed.Comment: 24 pages, 6 figures, to appear in Phys. Rev.

A comprehensive platform for highly multiplexed mammalian functional genetic screens

<p>Abstract</p> <p>Background</p> <p>Genome-wide screening in human and mouse cells using RNA interference and open reading frame over-expression libraries is rapidly becoming a viable experimental approach for many research labs. There are a variety of gene expression modulation libraries commercially available, however, detailed and validated protocols as well as the reagents necessary for deconvolving genome-scale gene screens using these libraries are lacking. As a solution, we designed a comprehensive platform for highly multiplexed functional genetic screens in human, mouse and yeast cells using popular, commercially available gene modulation libraries. The Gene Modulation Array Platform (GMAP) is a single microarray-based detection solution for deconvolution of loss and gain-of-function pooled screens.</p> <p>Results</p> <p>Experiments with specially constructed lentiviral-based plasmid pools containing ~78,000 shRNAs demonstrated that the GMAP is capable of deconvolving genome-wide shRNA "dropout" screens. Further experiments with a larger, ~90,000 shRNA pool demonstrate that equivalent results are obtained from plasmid pools and from genomic DNA derived from lentivirus infected cells. Parallel testing of large shRNA pools using GMAP and next-generation sequencing methods revealed that the two methods provide valid and complementary approaches to deconvolution of genome-wide shRNA screens. Additional experiments demonstrated that GMAP is equivalent to similar microarray-based products when used for deconvolution of open reading frame over-expression screens.</p> <p>Conclusion</p> <p>Herein, we demonstrate four major applications for the GMAP resource, including deconvolution of pooled RNAi screens in cells with at least 90,000 distinct shRNAs. We also provide detailed methodologies for pooled shRNA screen readout using GMAP and compare next-generation sequencing to GMAP (i.e. microarray) based deconvolution methods.</p

VERITAS Upper Limit on the VHE Emission from the Radio Galaxy NGC 1275

The recent detection by the Fermi gamma-ray space telescope of high-energy gamma-rays from the radio galaxy NGC 1275 makes the observation of the very high energy (VHE: E > 100 GeV) part of its broadband spectrum particularly interesting, especially for the understanding of active galactic nuclei (AGN) with misaligned multi-structured jets. The radio galaxy NGC 1275 was recently observed by VERITAS at energies above 100 GeV for about 8 hours. No VHE gamma-ray emission was detected by VERITAS from NGC 1275. A 99% confidence level upper limit of 2.1% of the Crab Nebula flux level is obtained at the decorrelation energy of approximately 340 GeV, corresponding to 19% of the power-law extrapolation of the Fermi Large Area Telescope (LAT) result.Comment: Accepted for publication in ApJ Letter