The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins

ErbB2 and EGFR are attractive oncology therapeutic targets as their overexpression in tumors predicts a poorer clinical outcome in a variety of epithelial malignancies. However, clinical results with therapeutic compounds targeting these receptors have been mixed. Therefore, there is a need for improved predictive biomarkers for these targeted therapeutics. In this study we analysed tissue microarrays of patients treated with combination chemotherapy and Herceptin for expression or phosphorylation of signalling proteins associated with erbB receptors to identify protein biomarkers that are predictive of breast cancer patient response. A comparison of expression or phosphorylation of these markers with patient outcome revealed that response to Herceptin depended not only on expression levels of erbB2 but also on expression of EGFR, expression of erbB ligands, expression of other receptors and phosphorylation of downstream proteins. Elucidating the biological effects of EGFR/erbB2 targeted therapeutics will enable patient tumor profiling to identify likely responders and the determination of biologically effective doses that allows chronic administration of these agents in order to maximise efficacy

Asymptotic iteration method for eigenvalue problems

An asymptotic interation method for solving second-order homogeneous linear differential equations of the form y'' = lambda(x) y' + s(x) y is introduced, where lambda(x) \neq 0 and s(x) are C-infinity functions. Applications to Schroedinger type problems, including some with highly singular potentials, are presented.Comment: 14 page

Effective Operator Treatment of the Anharmonic Oscillator

We analyse the one dimensional quartic oscillator using the effective operator methodology of Lee and Suzuki. We reproduce known results for low lying energy eigenvalues.Comment: 9 Pages, Extended version with new references. To appear in Phys.ReV.

A Guide to Precision Calculations in Dyson's Hierarchical Scalar Field Theory

The goal of this article is to provide a practical method to calculate, in a scalar theory, accurate numerical values of the renormalized quantities which could be used to test any kind of approximate calculation. We use finite truncations of the Fourier transform of the recursion formula for Dyson's hierarchical model in the symmetric phase to perform high-precision calculations of the unsubtracted Green's functions at zero momentum in dimension 3, 4, and 5. We use the well-known correspondence between statistical mechanics and field theory in which the large cut-off limit is obtained by letting beta reach a critical value beta_c (with up to 16 significant digits in our actual calculations). We show that the round-off errors on the magnetic susceptibility grow like (beta_c -beta)^{-1} near criticality. We show that the systematic errors (finite truncations and volume) can be controlled with an exponential precision and reduced to a level lower than the numerical errors. We justify the use of the truncation for calculations of the high-temperature expansion. We calculate the dimensionless renormalized coupling constant corresponding to the 4-point function and show that when beta -> beta_c, this quantity tends to a fixed value which can be determined accurately when D=3 (hyperscaling holds), and goes to zero like (Ln(beta_c -beta))^{-1} when D=4.Comment: Uses revtex with psfig, 31 pages including 15 figure

Arbitrarily Accurate Eigenvalues for General Anharmonic Potentials

We show that the Riccati form of the Schrodinger equation can be reformulated in terms of two linear equations depending on an arbitrary function G. When $G$ and the potential are polynomials, the solutions of these two equations are entire functions (L and K) and the zeroes of K are identical to those of the wave function. Requiring such a zero at a large but finite value of the argument yields the low energy eigenstates with exponentially small errors. Judicious choice of G can improve dramatically the numerical treatment. The method yields many significant digits with modest computer means.Comment: 10 pages, 8 figures, uses revtex; new section added, references adde

Clusters and networks as enablers of product and process innovation

One of the strategies adopted in the Philippines to facilitate a more consistent supply of good quality vegetables from smallholder farmers is the clustering approach, whereby a small group or cluster of smallholder farmers is organized to deliver a pre-determined amount of produce to a focal customer (CRS-Philippines, 2007). Developed from the CIAT Territorial Approach, the CRS Eight Step Clustering Approach for Agro-enterprise Development employs a participatory action learning process, where the cluster members proactively plan their production to meet the specifc quality and delivery requirements of their focal customer. The clustering approach is a strategy which allows smallholder farmers to access higher value chains. Evidence is provided to demonstrate how several of the clusters facilitated have utilised the skills and knowledge acquired in servicing their focal customer to develop new products for new markets, to adopt alternative low cost systems of production to reduce their reliance on external inputs, to reduce postharvest losses and product deterioration through improved packaging, to improve access to low cost community-based loans and to take advantage of local and national government grants that provide production inputs and support the development of community-based infrastructure projects

Operator Method for Nonperturbative Calculation of the Thermodynamic Values in Quantum Statistics. Diatomic Molecular Gas

Operator method and cumulant expansion are used for nonperturbative calculation of the partition function and the free energy in quantum statistics. It is shown for Boltzmann diatomic molecular gas with some model intermolecular potentials that the zeroth order approximation of the proposed method interpolates the thermodynamic values with rather good accuracy in the entire range of both the Hamiltonian parameters and temperature. The systematic procedure for calculation of the corrections to the zeroth order approximation is also considered.Comment: 22 pages, 7 Postscript figures, accepted for publication in Journal of Physics

Conformal mappings versus other power series methods for solving ordinary differential equations: illustration on anharmonic oscillators

The simplicity and the efficiency of a quasi-analytical method for solving nonlinear ordinary differential equations (ODE), is illustrated on the study of anharmonic oscillators (AO) with a potential $V(x) =\beta x^{2}+x^{2m}$ ($m>0$). The method [Nucl. Phys. B801, 296 (2008)], applies a priori to any ODE with two-point boundaries (one being located at infinity), the solution of which has singularities in the complex plane of the independent variable $x$. A conformal mapping of a suitably chosen angular sector of the complex plane of $x$ upon the unit disc centered at the origin makes convergent the transformed Taylor series of the generic solution so that the boundary condition at infinity can be easily imposed. In principle, this constraint, when applied on the logarithmic-derivative of the wave function, determines the eigenvalues to an arbitrary level of accuracy. In practice, for $\beta \geq 0$ or slightly negative, the accuracy of the results obtained is astonishingly large with regards to the modest computing power used. It is explained why the efficiency of the method decreases as $\beta$ is more and more negative. Various aspects of the method and comparisons with some seemingly similar methods, based also on expressing the solution as a Taylor series, are shortly reviewed, presented and discussed.Comment: 32 pages, 7 figures, 8 table

Comparison of DNA histograms by standard flow cytometry and image cytometry on sections in Barrett's adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare DNA histograms obtained by standard flow cytometry (FC) and high fidelity image cytometry on sections (ICS) in normal gastrointestinal mucosa and Barrett's adenocarcinoma (BAC).</p> <p>Methods</p> <p>Archival formalin-fixed paraffin-embedded tissue blocks of 10 normal controls from 10 subjects and 42 BAC tissues from 17 patients were examined. DNA FC was performed using standard techniques and ICS was carried out by Automated Cellular Imaging System (ACIS). DNA ploidy histograms were classified into diploid with peak DNA index (DI) at 0.9–1.1, and aneuploid with peak DI > 1.1. DI values of aneuploid peaks were determined. Additionally, for DNA ICS, heterogeneity index (HI) representing DNA content heterogeneity, and histograms containing cells with DI > G2 were also identified.</p> <p>Results</p> <p>All control samples were diploid by both FC and ICS analyses. In BAC, FC showed diploid peaks in 29%, diploid peaks with additional aneuploid or tetraploid peaks in 57%, and 14% of the samples, respectively. In contrast, ICS showed aneuploid peaks in all the cases with peak DI > 1.25; 37 cases had peak DI between 1.25 and 2.25; and 5 cases had peak DI > 2.25. HI values (mean ± SD) were 11.3 ± 1.1 in controls and 32.4 ± 8.5 in BAC (p < 0.05). Controls had no G2 exceeding cells. However, 19/37 (51%) of the cases with primary peak DI < 2.25 had cells exceeding 9N.</p> <p>Conclusion</p> <p>ICS detects DNA aneuploidy in all BAC samples while FC missed the diagnosis of aneuploidy in 29%. In addition, ICS provides more information on HI and G2 exceeding rates.</p

The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers

The role of transcriptional factor FOXO1 in the mechanism of drug-resistance in ovarian cancer has not been elucidated. In ovarian cancer cell lines, FOXO1 expression and its correlation with paclitaxel treatment was investigated by cytotoxic assay and silencing experiment. Clinical ovarian cancer samples were also examined for FOXO1 expression by immunohistochemistry. FOXO1 expression was distinctively upregulated in paclitaxel-resistant cell line, and enhanced by exposure to paclitaxel. FOXO1 overexpression was frequently observed in tissue samples from chemoresistant patients compared to chemosensitive patients. FOXO1 silencing in paclitaxel-resistant cell line decreased its resistance. Modification of oxidative stress by co-treatment with pharmacologic modulators of reactive oxygen species attenuated cytotoxicity of paclitaxel. Downstream targets of FOXO1 involving oxidative stress were also attenuated in silencing experiment, suggesting its involvement in altered sensitivity to paclitaxel. These results indicate that FOXO1 links to cytotoxic stress induced by paclitaxel and contributes to the drug-resistance in ovarian cancers