148,605 research outputs found
Hemiasterlin derivative (R)(S)(S)-BF65 and Akt inhibitor MK-2206 synergistically inhibit SKOV3 ovarian cancer cell growth
No full textWe reported previously that a hemiasterlin derivative BF65 is a potent anticancer agent that can inhibit microtubule assembly. Here we show that a more potent stereospecific diastereomer (R)(S)(S)-BF65 can synergize with an allosteric Akt inhibitor MK-2206 to suppress the growth of SKOV3 ovarian cancer cells with constitutively active Akt. (R)(S)(S)-BF65 induced mitotic arrest and MK-2206 caused G0/G1 arrest, while the combination of both induced simultaneous G0/G1 and G2/M cell cycle arrest. (R)(S)(S)-BF65 induced phosphorylation and inactivation of Bcl-2, and downregulated Mcl-1, consequently may lead to apoptosis. (R)(S)(S)-BF65 inhibited mitogen-activated protein kinases (MAPKs), which may stimulate cell proliferation upon activation. (R)(S)(S)-BF65 also induced DNA damage after long-term treatment. MK-2206 is known to inhibit phosphorylation and activation of Akt and suppress cancer cell growth. The combination of (R)(S)(S)-BF65 and MK-2206 also inhibited the Akt pathway. Interestingly, MK-2206 upregulated Bcl-2 and induced activation of MAPKs in SKOV3 cells; however, when combined with (R)(S)(S)-BF65, these prosurvival effects were reversed. The combination also more significantly decreased Mcl-1 protein, increased PARP cleavage, and induced gamma-H2AX, a DNA damage marker. Remarkably, MK-2206 enhanced the microtubule depolymerization effect of (R)(S)(S)-BF65. The combination of (R)(S)(S)-BF65 and MK-2206 also markedly inhibited cell migration. Thus, MK-2206 synergizes with (R)(S)(S)-BF65 to inhibit SKOV3 cell growth via downregulating the Akt signaling pathway, and enhancing the microtubule disruption effect of (R)(S)(S)-BF65. (R)(S)(S)-BF65 in turn suppresses Bcl-2 and MAPKs induced by MK-2206. (R)(S)(S)-BF65 and MK-2206 compensate each other leading to increased apoptosis and enhanced cytotoxicity, and may also suppress cancer cell invasion. (C) 2016 Elsevier Inc. All rights reserved
Mammalian LIN-7 PDZ proteins associate with beta-catenin at the cell junctions of epithelia and neurons
No full textThe heterotrimeric PDZ complex containing LIN-2, LIN-7 and LIN-10 is known to be involved in the organization of epithelial and neuronal junctions in Caenorhabditis elegans and mammals. We report here that mammalian LIN-7 PDZ proteins form a complex with cadherin and β-catenin in epithelia and neurons. The association of LIN-7 with cadherin and β-catenin is Ca2+ dependent and is mediated by the direct binding of LIN-7 to the C-terminal PDZ target sequence of β-catenin, as demonstrated by means of co-immunoprecipitation experiments and in vitro binding assays with the recombinant glutathione S-transferase:LIN-7A. The presence of β-catenin at the junction is required in order to relocate LIN-7 from the cytosol to cadherin-mediated adhesions, thus indicating that LIN-7 junctional recruitment is β-catenin dependent and that one functional role of the binding is to localize LIN-7. Moreover, when LIN-7 is present at the β-catenin-containing junctions, it determines the accumulation of binding partners, thus suggesting the mechanism by which β-catenin mediates the organization of the junctional domai
Spatial Chow-Lin Methods for Data Completion in Econometric Flow Models
Get PDFFlow data across regions can be modeled by spatial econometric models, see LeSage and Pace (2009). Recently, regional studies became interested in the aggregation and disaggregation of flow models, because trade data cannot be obtained at a disaggregated level but data are published on an aggregate level. Furthermore, missing data in disaggregated flow models occur quite often since detailed measurements are often not possible at all observation points in time and space. In this paper we develop classical and Bayesian methods to complete flow data. The Chow and Lin (1971) method was developed for completing disaggregated incomplete time series data. We will extend this method in a general framework to spatially correlated flow data using the cross-sectional Chow-Lin method of Polasek et al. (2009). The missing disaggregated data can be obtained either by feasible GLS prediction or by a Bayesian (posterior) predictive density.Missing values in spatial econometrics, MCMC, non-spatial Chow-Lin (CL) and spatial Chow-Lin (SCL) methods, spatial internal flow (SIF) models, origin and destination (OD) data
Sampling the structure of the noncanonical lin-4:lin-14 microRNA:mRNA complex by molecular dynamics simulations.
No full textsiRNA and microRNA (miRNA) are two classes of noncoding RNAs that carry out post-transcriptional gene
regulation by interacting with the target mRNA. The structural features of siRNA/miRNA-mRNA complex
play a crucial role in gene silencing. Here we have used computer modeling and simulation approach to (i)
elucidate the possible structures of the partially complementary lin-4:lin-14 miRNA-mRNA complex and (ii)
compare the structural features with the fully complementary lin-4:lin-14 siRNA-mRNA complex. The fully
complementary siRNA complex maintains a canonical helical shape while the presence of mismatch base
pairs and bulge induce a kinked structure in the miRNA complex. Docking of the simulated duplex models
on to the argonaute protein gives a direct indication that in the siRNA-mRNA structure, the scissile phosphate
of the mRNA strand is more accessible to the catalytic site as compared to the miRNA-mRNA structures,
providing an explanation for the less prevalence of the cleavage in the later case
Model based defect characterization in composites
Get PDFWork is reported on model-based defect characterization in CFRP composites. The work utilizes computational models of the interaction of NDE probing energy fields (ultrasound and thermography), to determine 1) the measured signal dependence on material and defect properties (forward problem), and 2) an assessment of performance-critical defect properties from analysis of measured NDE signals (inverse problem). Work is reported on model implementation for inspection of CFRP laminates containing multi-ply impact-induced delamination, with application in this paper focusing on ultrasound. A companion paper in these proceedings summarizes corresponding activity in thermography. Inversion of ultrasound data is demonstrated showing the quantitative extraction of damage properties.This proceeding may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing.
This proceeding appeared in Roberts, R., and S. Holland. "Model based defect characterization in composites." In AIP Conference Proceedings, vol. 1806, no. 1, p. 090015. AIP Publishing LLC, 2017, and may be found at
DOI: 10.1063/1.4974659.
Copyright 2017 Author(s).
Posted with permission
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
Get PDFBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
SPATIAL CHOW-LIN METHODS: BAYESIAN AND ML FORECAST COMPARISONS
Get PDFCompleting data that are collected in disaggregated and heterogeneous spatial units is a quite frequent problem in spatial analyses of regional data. Chow and Lin (1971) (CL) were the rst to develop a uni ed framework for the three problems (interpolation, extrapolation and distribution) of predicting disaggregated times series by so-called indicator series. This paper develops a spatial CL procedure for disaggregating cross-sectional spatial data and compares the Maximum Likelihood and Bayesian spatial CL forecasts with the naive pro rata error distribution. We outline the error covariance structure in a spatial context, derive the BLUE for the ML estimator and the Bayesian estimation procedure by MCMC. Finally we
apply the procedure to European regional GDP data and discuss the disaggregation assumptions. For the evaluation of the spatial Chow-Lin procedure we assume that only NUTS 1 GDP is known and predict it at NUTS 2 by using employment and spatial information available at NUTS 2. The spatial neighborhood is de ned by the inverse travel time by car in minutes. Finally, we present the forecast accuracy criteria comparing the predicted values with the actual observations.
Liftings for noncomplete probability spaces
No full textThe current state of knowledge concerning liftings for noncomplete probability spaces is discussed. This is a somewhat expanded version of the author's talk given at the 1991 Summer Conference on General Topology and Applications in Honor of Mary Ellen Rudin and Her Work.PT: S; CR: BURKE MR, IN PRESS P AM MATH S BURKE MR, 1991, ISRAEL J MATH, V73, P33 BURKE MR, 1992, ISRAEL J MATH, V79, P289 CARLSON T, THEOREM LIFTING CHRISTENSEN JPR, 1974, TOPOLOGY BOREL STRUC FREMLIN DH, 1989, HDB BOOLEAN ALGEBRAS, P877 INOESCUTULCEA A, 1966, 5TH P BERK S MATH ST, V2 IONESCUTULCEA A, 1967, CONTRIBUTIONS PROB 1, P63 IONESCUTULCEA A, 1969, TOPICS THEORY LIFTIN JECH TJ, 1978, SET THEORY JOHNSON RA, 1980, P AM MATH SOC, V80, P234 JUST W, IN PRESS T AM MATH S KUPKA J, 1983, INDIANA U MATH J, V32, P717 LOSERT V, 1983, LNM, V1080, P95 MAHARAM D, 1958, P AM MATH SOC, V9, P987 SHELAH S, 1983, ISRAEL J MATH, V45, P90 TALAGRAND M, 1982, P AM MATH SOC, V84, P379 VONNEUMANN J, 1931, CRELLES J MATH, V165, P109; NR: 18; TC: 0; J9: ANN N Y ACAD SCI; PG: 4; GA: BZ86BSource type: Electronic(1
Support Vector Machines in R
Get PDFBeing among the most popular and efficient classification and regression methods currently available, implementations of support vector machines exist in almost every popular programming language. Currently four R packages contain SVM related software. The purpose of this paper is to present and compare these implementations. (author's abstract)Series: Research Report Series / Department of Statistics and Mathematic
On the low regularity of the Benney–Lin equation
No full textAbstractWe consider the low regularity of the Benney–Lin equation ut+uux+uxxx+β(uxx+uxxxx)+ηuxxxxx=0. We established the global well posedness for the initial value problem of Benney–Lin equation in the Sobolev spaces Hs(R) for 0⩾s>−2, improving the well-posedness result of Biagioni and Linares [H.A. Biaginoi, F. Linares, On the Benney–Lin and Kawahara equation, J. Math. Anal. Appl. 211 (1997) 131–152]. For s<−2 we also prove some ill-posedness issues
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