Urokinase receptor and resistance to targeted anticancer agents

The urokinase receptor/uPAR is a GPI-anchored membrane protein, which regulates protease activity at the cell surface and, in collaboration with a system of co-receptors, triggers cell-signaling and regulates gene expression within the cell. In normal tissues, uPAR gene expression is limited; however, in cancer, uPAR is frequently over-expressed and the gene may be amplified. Hypoxia, which often develops in tumors, further increases uPAR expression by cancer cells. uPAR-initiated cell-signaling promotes cancer cell migration, invasion, metastasis, epithelial-mesenchymal transition, stem cell-like properties, survival, and release from states of dormancy. Newly emerging data suggest that the pro-survival cell-signaling activity of uPAR may allow cancer cells to escape from the cytotoxic effects of targeted anticancer drugs. Herein, we review the molecular properties of uPAR that are responsible for its activity in cancer cells and its ability to counteract the activity of anticancer drugs

Using the ROC Curve to Measure Association and Evaluate Prediction Accuracy for a Binary Outcome

This review article addresses the ROC curve and its advantage over the odds ratio to measure the association between a continuous variable and a binary outcome. A simple parametric model under the normality assumption and the method of Box-Cox transformation for non-normal data are discussed. Applications of the binormal model and the Box-Cox transformation under both univariate and multivariate inference are illustrated by a comprehensive data analysis tutorial. Finally, a summary and recommendations are given as to the usage of the binormal ROC curve

Nutrition Regulation of Male Accessory Gland Growth and Maturation in \u3cem\u3eTribolium castaneum\u3c/em\u3e

Insulin/IGF-1 signaling (IIS) pathway is known to control growth, development and reproduction. Insulin-like peptide mediated body size plasticity in Drosophila melanogaster has been reported. Here, our studies showed that IIS pathway and nutrition regulate growth and maturation of the male accessory gland (MAG) in the red flour beetle, Tribolium castaneum. The size of MAG increased from day 1 to day 5 post-adult emergence (PAE). This increase in the size of MAG is contributed by an increase in cell size, but not cell number. The growth of MAG was impaired after double-stranded RNA (dsRNA)-mediated knockdown in the expression of genes coding for ILP3, InR, Chico, PI3k, AKT, and GATA1 involved in IIS pathway. Interestingly, starvation showed similar effects on the growth and maturation of MAG. The phenotypes observed in animals where IIS signaling pathway genes were knocked down are similar to the phenotypes observed after starving beetles for 5 days PAE. These data suggest that nutrition signals working through IIS pathway regulate maturation of MAG by promoting the growth of MAG cells

Monitoring Mechanisms, Managerial Incentives, Investment Distortion Costs, and Derivatives Usage

We relate derivatives usage to the level of corporate governance/monitoring mechanisms, managerial incentives and investment decisions of UK firms. We find evidence to suggest that the monitoring environment, e.g., board size, influences the use of both currency and interest rate derivatives usage. Managerial compensation also influences derivatives usage. Investment decisions are affected by the governance and managerial compensation of firms, which in turn impact on derivatives usage. We find a strong tendency for UK firms to reduce derivatives usage in situations where derivatives usage should be increased. There is limited evidence that firms use hedging substitutes to avoid monitoring from external capital markets

Correction of Verication Bias using Log-Linear Models for a Single Binaryscale Diagnostic Tests

In diagnostic medicine, the test that determines the true disease status without an error is referred to as the gold standard. Even when a gold standard exists, it is extremely difficult to verify each patient due to the issues of costeffectiveness and invasive nature of the procedures. In practice some of the patients with test results are not selected for verification of the disease status which results in verification bias for diagnostic tests. The ability of the diagnostic test to correctly identify the patients with and without the disease can be evaluated by measures such as sensitivity, specificity and predictive values. However, these measures can give biased estimates if we only consider the patients with test results who also underwent the gold standard procedure. The emphasis of this paper is to apply the log-linear model approach to compute the maximum likelihood estimates for sensitivity, specificity and predictive values. We also compare the estimates with Zhou’s results and apply this approach to analyze Hepatic Scintigraph data under the assumption of ignorable as well as non-ignorable missing data mechanisms. We demonstrated the efficiency of the estimators by using simulation studies

Contrasting xylem vessel constraints on hydraulic conductivity between native and non-native woody understory species

We examined the hydraulic properties of 82 native and non-native woody species common to forests of Eastern North America, including several congeneric groups, representing a range of anatomical wood types. We observed smaller conduit diameters with greater frequency in non-native species, corresponding to lower calculated potential vulnerability to cavitation index. Non-native species exhibited higher vessel-grouping in metaxylem compared with native species, however, solitary vessels were more prevalent in secondary xylem. Higher frequency of solitary vessels in secondary xylem was related to a lower potential vulnerability index. We found no relationship between anatomical characteristics of xylem, origin of species and hydraulic conductivity, indicating that non-native species did not exhibit advantageous hydraulic efficiency over native species. Our results confer anatomical advantages for non-native species under the potential for cavitation due to freezing, perhaps permitting extended growing seasons

A Finite Element Mesh Aggregating Approach to Multiple-Source Reconstruction in Bioluminescence Tomography

A finite element mesh aggregating approach is presented to reconstruct images of multiple internal bioluminescence sources. Rather than assuming independence between mesh nodes, the proposed reconstruction strategy exploits spatial structure of nodes and aggregation feature of density distribution on the finite element mesh to adaptively determine the number of sources and to improve the quality of reconstructed images. With the proposed strategy integrated in the regularization-based reconstruction process, reconstruction algorithms need no a priori knowledge of source number; even more importantly, they can automatically reconstruct multiple sources that differ greatly in density or power

Measurement and interpretation of electrocardiographic QT intervals in murine hearts.

Alterations in ECG QT intervals correlate with the risk of potentially fatal arrhythmias, for which transgenic murine hearts are becoming increasingly useful experimental models. However, QT intervals are poorly defined in murine ECGs. As a consequence, several different techniques have been used to measure murine QT intervals. The present work develops a consistent measure of the murine QT interval that correlates with changes in the duration of ventricular myocyte action potentials (APs). Volume-conducted ECGs were compared with simultaneously recorded APs, obtained using floating intracellular microelectrodes in Langendorff-perfused mouse hearts. QT intervals were measured from the onset of the QRS complex. The interval, Q-APR90, measured to the time at 90% AP recovery, was compared with two measures of the QT interval. QT1 was measured to the recovery of the ECG trace to the isoelectric baseline for entirely positive T-waves or to the trough of any negative T-wave undershoot. QT2-used extensively in previous studies-was measured to the return of any ECG trough to the isoelectric baseline. QT1, but not QT2, closely correlated with changes in Q-APR90. These findings were confirmed over a range of pacing rates, in low K(+) concentration solutions, and in Scn5a+/ΔKPQ hearts used to model human long QT syndrome. Application of this method in whole anesthetized mice similarly demonstrated a prolonged corrected QT (QTc) in Scn5a+/ΔKPQ hearts. We therefore describe a robust method for the determination of QT and QTc intervals that correlate with the duration of ventricular myocyte APs in murine hearts.This is the final published version. It has been published by the American Physiological Society in the American Journal of Physiology Heart and Circulatory Physiology here: http://ajpheart.physiology.org/content/306/11/H1553