A Phase I and Pharmacokinetic Study of OSI-7904L, a Liposomal Thymidylate Synthase Inhibitor in Combination with Oxaliplatin in Patients with Advanced Colorectal Cancer.

OSI-7904L is a liposomal formulation of a potent thymidylate synthase (TS) inhibitor. This phase I study evaluated the safety, tolerability and pharmacokinetics (PK) of OSI-7904L administered in combination with oxaliplatin every 21 days in patients with advanced colorectal carcinoma. METHOD: A 3+3 study design was utilized at predefined dose levels. Polymorphisms in the TS enhancer region and XPD enzyme were investigated as potential predictors of efficacy and toxicity. RESULTS: Fourteen patients received 76 cycles of treatment. At the highest dose level (OSI-7904L 9 mg/m(2), oxaliplatin 130 mg/m(2)) investigated, one of nine patients experienced dose-limiting toxicity of grade 3 oral mucositis with cycle 1 and five further patients required dose reductions. The toxicity profile of stomatitis, diarrhea, nausea, fatigue, sensory neuropathy and skin rash was consistent with that expected for a TS inhibitor/oxaliplatin combination regimen. PK analysis showed high interpatient variability with no detectable interaction between OSI-7904L and oxaliplatin. Partial radiological responses were documented in two patients. CONCLUSIONS: The recommended regimen for further investigation is OSI-7904L 9 mg/m(2) and oxaliplatin 130 mg/m(2).

Effective collision strengths for allowed transitions among the n

Aims.In this paper we report on calculations of collision strengths and effective collision strengths for allowed transitions among the $n \le$ 5 degenerate levels of Al XIII.
Methods.The Dirac atomic R-matrix code (DARC) has been adopted for these calculations.
Results.Collision strengths are reported over a wide energy range below 300 Ryd, and effective collision strengths are provided for electron temperatures of 4.4 $\le$ log $T_{\rm e} \le$ 6.8 K.

Reducing Drifts in the Inertial Measurements of Wrist and Elbow Positions

In this paper, we present an inertial-sensor-based monitoring system for measuring the movement of human upper limbs. Two wearable inertial sensors are placed near the wrist and elbow joints, respectively. The measurement drift in segment orientation is dramatically reduced after a Kalman filter is applied to estimate inclinations using accelerations and turning rates from gyroscopes. Using premeasured lengths of the upper and lower arms, we compute the position of the wrist and elbow joints via a proposed kinematic model. Experimental results demonstrate that this new motion capture system, in comparison to an optical motion tracker, possesses an RMS position error of less than 0.009 m, with a drift of less than 0.005 ms-1 in five daily activities. In addition, the RMS angle error is less than 3??. This indicates that the proposed approach has performed well in terms of accuracy and reliability.

Laser pulse compression and amplification via Raman backscattering in plasma

A simple theoretical model is proposed for the interaction between two counter-propagating laser pulses (a pump and a seed pulse) in unmagnetized plasma. Pulse compression and amplification are observed via numerical simulation. A one dimensional fluid model for stimulated Raman backscattering is proposed to investigate the pulse compression and pulse amplification mechanisms. To accomplish this, energy is transferred from the long pump pulse to a seed pulse, with a Langmuir plasma wave mediating the transfer. The study focuses on the intensity profile of the pump laser pulse. A Gaussian and a ring intensity profile are, separately, considered for the pump laser pulse.

CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: Implications for the pathogenesis of diabetic nephropathy

We describe the activation of Wnt signalling in mesangial cells by CCN2. CCN2 stimulates phosphorylation of LRP6 and GSK-3 beta resulting in accumulation and nuclear localisation of beta-catenin, TCF/LEF activity and expression of Wnt targets. This is coincident with decreased phosphorylation of beta-catenin on Ser 33/37 and increased phosphorylation on Tyr142. DKK-1 and LRP6 siRNA reversed CCN2's effects. Microarray analyses of diabetic patients identified differentially expressed Wnt components. beta-Catenin is increased in type 1 diabetic and UUO mice and in in vitro models of hyperglycaemia and hypertension. These findings suggest that Wnt/CCN2 signalling plays a role in the pathogenesis of diabetic nephropathy. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Metastatic testicular carcinoma from the colon with clinical, immunophenotypical, and molecular characterization: Report of a case

We report a case of testicular metastasis from a colonic adenocarcinoma. The presentation of testicular metastasis, diagnosis, management, and possible modes of spread are reported. In addition to conventional investigations and histopathologic techniques, a molecular study of the testicular metastasis and colon primary, using microsatellite analysis, was performed to confirm the primary origin. Its potential uses are discussed.

Effect of hydrophobic nanopatches within an ionic surface on the structure of liquids

The structures of liquid water and isopropanol have been studied as a function of the size of a hydrophobic patch present in a model hydrophilic surface via molecular dynamics simulations. A significant anisotropy extending into the first few solvent layers is found over the patch which suggests implications for many real-world systems in which nanoscale heterogeneity is found.

Attitudes towards women in politics: Gender, generation and party identification in Ireland

This article analyzes the effects of gender, generation and party support towards a greater inclusion of women in politics in the Republic of Ireland and Northern Ireland. It explores attitudes on this issue using the same question in the Irish National Election Study (INES) and the Northern Ireland Life and Times Survey (NILT). The article documents a consistent gender gap in both polities that persists across the generations, despite controls for socio-demographic factors. It also reveals an unexpected generational effect that we explain as the enduring legacy of politicization to women’s rights during the 1970s. Support among party identifiers for more women in politics follows predictable lines, yet gender and generational patterns persist. The gender gap and generational patterns found in the two polities on the island provide reason for concern among those committed to gender equality in representation.