612 research outputs found
Inhibition of EGFR-AKT axis results in the suppression of ovarian tumors in vitro and in preclinical mouse model
No full textOvarian cancer is the leading cause of cancer related deaths in women. Genetic alterations including overexpression of EGFR play a crucial role in ovarian carcinogenesis. Here we evaluated the effect of phenethyl isothiocyanate (PEITC) in ovarian tumor cells in vitro and in vivo. Oral administration of 12 μmol PEITC resulted in drastically suppressing ovarian tumor growth in a preclinical mouse model. Our in vitro studies demonstrated that PEITC suppress the growth of SKOV-3, OVCAR-3 and TOV-21G human ovarian cancer cells by inducing apoptosis in a concentration-dependent manner. Growth inhibitory effects of PEITC were mediated by inhibition of EGFR and AKT, which are known to be overexpressed in ovarian tumors. PEITC treatment caused significant down regulation of constitutive protein levels as well as phosphorylation of EGFR at Tyr1068 in various ovarian cancer cells. In addition, PEITC treatment drastically reduced the phosphorylation of AKT which is downstream to EGFR and disrupted mTOR signaling. PEITC treatment also inhibited the kinase activity of AKT as observed by the down regulation of p-GSK in OVCAR-3 and TOV-21G cells. AKT overexpression or TGF treatment blocked PEITC induced apoptosis in ovarian cancer cells. These results suggest that PEITC targets EGFR/AKT pathway in our model. In conclusion, our study suggests that PEITC could be used alone or in combination with other therapeutic agents to treat ovarian cancer. © 2012 Loganathan et al
A study on the propagation of aero and wind uncertainties and their effect on the dynamic loads of a wind turbine
No full textThis work is concerned with the quantification of uncertainties associated with wind turbines. A part form the understanding of the Effects of uncertainties per se, the efficient propagation of uncertainties is necessary for the implementation of robust design optimization methods, which is one of our future goals. Among all possible sources of uncertainties, here uncertainties related to the incoming wind and to the aerodynamic characteristics of the blades are propagated throughout a high-fidelity multibody aeroservoelastic tool. Different techniques, which could all be used for propagating uncertainties other than the ones considered here, are tested and compared. These include different formulations from the family of Non-Intrusive Polynomial Chaos Expansion, as well as Ordinary and Universal Kriging. By running a reduced subset of standard design load cases, a comparison among the various methods is drawn in terms of accuracy and computational efficiency with respect to a standard Monte Carlo approach. It is concluded that, for the uncertain- ties considered here, all approaches lead to a significantly higher performance compared to Monte Carlo, with Universal Kriging slightly standing out. It is also observed that the output parameters exhibit significant variations, and this highlights the importance of a comprehensive framework for the quantification and propagation of uncertainties in wind energy systems
Empirical Bayes methods for the transformed Gaussian random field model with additive measurement errors
No full textIf geostatistical observations are continuous but can not be modeled by the Gaussian distribution, a more appropriate model for these data may be the transformed Gaussian model. In transformed Gaussian models it is assumed that the random field of interest is a nonlinear transformation of a Gaussian random field (GRF). For example, [9] propose the Bayesian transformed Gaussian model where they use the Box-Cox family of power transformation [3] on the observations and show that prediction for unobserved random fields can be done through posterior predictive distribution where uncertainty about the transformation parameter is taken into account. More recently, [5] consider maximum likelihood estimation of the parameters and a “plug-in” method of prediction for transformed Gaussian model with Box-Cox family of transformations. Both [9] and [5] consider spatial prediction of rainfall to illustrate their model and method of analysis. A review of the Bayesian transformed Gaussian random fields model is given in [8]. See also [6] who discusses several issues regarding the formulation and interpretation of transformed Gaussian random field models, including the approximate nature of the model for positive data based on Box-Cox family of transformations, and the interpretation of the model parameters.This is a manuscript of a chapter from Vivekananda Roy, Evangelos Evangelou, and Zhengyuan Zhu (2015), Empirical Bayes methods for Transformed Gaussian Random Fields Model with Additive Measurement Errors. In D. K. Dey, U. Singh and A. Loganathan (eds.), Current Trends in Bayesian Methodology with Applications, Chapman & Hall/CRC Press. Posted with permission.</p
A Linear Programming Method for Synthesizing Origin-Destination (O-D) Trip Tables from Traffic Counts for Inconsistent Systems
No full textOrigin-Destination (O-D) trip tables represent the demand-supply information of each directed zonal-pair in a given region during a given period of time. The effort of this research is to develop a linear programming methodology for estimating O-D trip tables based on observed link volumes. In order to emphasize the nature of uncertainty in the data and in the problem, the developed model permits the user's knowledge of path travel time to vary within a band-width of values, and accordingly modifies the user-optimality principle. The data on the observed flows might also not be complete and need not be perfectly matched. In addition, a prior trip table could also be specified in order to guide the updating process via the model solution. To avoid excessive computational demands required by a total numeration of all possible paths between each O-D pair, a Column Generation Algorithm (CGA) is adopted to exploit the special structures of the model. Based on the known capacity of each link, a simple formula is suggested to calculate the cost for the links having unknown volumes. An indexed cost is introduced to avoid the consideration of unnecessary passing-through-zone paths, and an algorithm for solving the corresponding minimum-cost-path problem is developed. General principles on the design of an object-oriented code are presented, and some useful programming techniques are suggested for this special problem. Some test results on the related models are presented and compared, and different sensitivity analyses are performed based on different scenarios. Finally, several research topics are recommended for future research.Master of Scienc
Extracellular Matrix Dynamics in Biology, Bioengineering, and Pathology
No full textThis eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
PHASE-TRANSFER-CATALYZED D-GLUCOSYLATION - SYNTHESIS OF BENZOYLATED ARYL BETA-D-GLUCOPYRANOSIDES AND BETA-D-GLUCOPYRANOSYL-SUBSTITUTED CINNAMATES
No full textPhotoactivated chemotherapy (PACT) : the potential of excited-state d-block metals in medicine
No full textThe fields of phototherapy and of inorganic chemotherapy both have long histories. Inorganic photoactivated chemotherapy (PACT) offers both temporal and spatial control over drug activation and has remarkable potential for the treatment of cancer. Following photoexcitation, a number of different decay pathways (both photophysical and photochemical) are available to a metal complex. These pathways can result in radiative energy release, loss of ligands or transfer of energy to another species, such as triplet oxygen. We discuss the features which need to be considered when developing a metal-based anticancer drug, and the common mechanisms by which the current complexes are believed to operate. We then provide a comprehensive overview of PACT developments for complexes of the different d-block metals for the treatment of cancer, detailing the more established areas concerning Ti, V, Cr, Mn, Re, Fe, Ru, Os, Co, Rh, Pt, and Cu and also highlighting areas where there is potential for greater exploration. Nanoparticles (Ag, Au) and quantum dots (Cd) are also discussed for their photothermal destructive potential. We also discuss the potential held in particular by mixed-metal systems and Ru complexes
Determination of the pKa of Glucuronic Acid and Heparin's Carboxyl Groups by 13C NMR
No full textBiochemical Journal, 278, 689-695Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.As part of our continuing studies on heparin, the present paper uses 13C-n.m.r. spectroscopy to examine the acidity of heparin's uronic acid carboxylate groups. Heparin contains three different uronic acids. In porcine mucosal heparin these account for approx. 91, 7 and 2 mol% of the total uronic acid residues. These are alpha-L-idopyranosyluronic acid 2-sulphate, beta-D-glucopyranosyluronic acid and alpha-L-idopyranosyluronic acid. The pKa values of their carboxylate groups were determined as 3.13 (using heparin), 2.79 (using heparin) and 3.0 (predicted by using model compounds) respectively. 18C-n.m.r. spectroscopy, performed at various pH values, provided a convenient method of simultaneously determining the pKa of multiple carboxylate groups, of similar acidity, within heparin D-Glucopyranosyluronic acid and heparin-derived di-, tetra- and hexa-saccharides were used as model compounds to determine pKa values of the different carboxy groups. The results suggested that molecular size had an effect on pKa. Unambiguous assignment of carboxy carbon resonances were accomplished through the use of two-dimensional n.m.r. spectroscopy. Finally, application of this method to the simplest model compound, D-glucopyranosyluronic acid, permitted the determination of the pKa of both its alpha- and beta-anomers.https://login.libproxy.rpi.edu/login?url=https://doi.org/10.1042/bj2780689https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1151401
FISCAL ADJUSTMENT AND DYNAMIC ECONOMICS PERFORMANCE: THE CASE OF MALAYSIA
No full textThe main objective of this study is to identify the link between fiscal adjustment and dynamic economic performance in Malaysia using time series data for entire period of 1980-2009. To examine the long-run relationship between fiscal adjustment and economic performance, this has study employed the Gregory-Hansen cointegration approach to capture the endogenous structural breaks in long-run equilibrium relationship with three different specifications. The finding of this study indicates that there is long-run positive cointegration relationship between fiscal adjustment and economic performance in Malaysia. Therefore, the finding of this study clearly shows that the dynamic and continuous economics performance is a key element of the successful of the stability of Malaysia’s economic in Southeast Asian region, although have faced several economic crisis.Fiscal adjustment, Economic performance, Gregory-Hansen
- …
