Two different models were used to obtain transport and kinetic parameters using nonlinear regression from experimental charge/discharge curves of a lithium-ion cell measured at 35°C under four rates, C/5, C/2, 1C, and 2C, where the C rate is 1.656A . The Levenberg-Marquardt method was used to estimate parameters in the models such as the diffusion of lithium ions in the positive electrode. A confidence interval for each parameter was also presented. The parameter values lie within their confidence intervals. The use of statistical weights to correct for the scatter in experimental data as well as to treat one set of data in preference to other is illustrated. An F-test was performed to discriminate between the goodness of fit obtained from the two models.
Purpose: Non-small cell lung cancer (NSCLC) with KRAS mutation may be resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). This study aims to evaluate a plasma-based KRAS mutation analysis and the clinical significance of plasma KRAS mutation as a predictive marker for tumor resistance to EGFR-TKIs in patients with NSCLC.Experimental Design: DNA extracted from plasma and matched tumor tissues were obtained from 273 patients with advanced stage NSCLC. Patients were followed up prospectively for treatment outcomes. KRAS mutations in codon 12 and 13 were detected using PCR-restriction fragment length polymorphism. Mutations in plasma and matched tumors were compared. Associations between KRAS mutation status and patients' clinical outcomes were analyzed.Results: KRAS mutation was found in 35 (12.8%) plasma samples and 30 (11.0%) matched tumor tissues. The consistency of KRAS mutations between plasma and tumors is 76.7% (23 of 30; κ = 0.668; P < 0.001). Among 120 patients who received EGFR-TKI treatment, the response rate was only 5.3% (1 of 19) for patients with plasma KRAS mutation compared with 29.7% for patients with no KRAS mutation in plasma DNA (P = 0.024). The median progression-free survival time of patients with plasma KRAS mutation was 2.5 months compared with 8.8 months for patients with wild-type KRAS (P < 0.001).Conclusions: KRAS mutation in plasma DNA correlates with the mutation status in the matched tumor tissues of patients with NSCLC. Plasma KRAS mutation status is associated with a poor tumor response to EGFR-TKIs in NSCLC patients and may be used as a predictive marker in selecting patients for such treatment. Clin Cancer Res; 16(4); 1324-30. ©2010 AACR.Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) such as gefitinib and erlotinib are selective TKIs that can block the intracellular receptor binding sites of ATP, thus inhibiting the downstream signaling transmission. Several EGFR-TKIs have been approved as second-or third-line agents for advanced non-small cell lung cancer (NSCLC) patients who failed in platinumbased chemotherapy (1, 2).The discovery that EGFR tyrosine kinase domain mutations were strongly associated with greater sensitivity of NSCLC to EGFR-TKIs in vitro and higher response rates in clinical studies provided rationale for using molecular markers to identify patients who are most likely to benefit from EGFR-TKI therapy. Subsequent prospective studies focusing on exploring the possibility of EGFR-TKIs as first-line therapy, such as IPASS (IRESSA Pan-Asia Study, a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced NSCLC in Asia) and the Spanish Lung Cancer Group trial (a multicenter prospective phase II trial of customized erlotinib for advanced NSCLC patients with EGFR mutations), have shown an outstanding survival benefit for patients with EGFR mutant tumors who received first-line EGFR-TKI therapy, which is superior to the outc...
A model for the simulation of the steady-state impedance response of a polymer electrolyte membrane fuel cell ͑PEMFC͒ cathode is presented. The catalyst layer of the electrode is assumed to consist of many flooded spherical agglomerate particles surrounded by a small volume fraction of gas pores. Stefan-Maxwell equations are used to describe the multicomponent gas-phase transport occurring in both the gas diffusion layer and the catalyst layer of the electrode. Liquid-phase diffusion of O 2 is assumed to take place in the flooded agglomerate particles. Newman's porous electrode theory is applied to determine over-potential distributions.
The validity of estimating the solid phase diffusion coefficient, D s , of a lithium intercalation electrode from impedance measurement by a modified electrochemical impedance spectroscopy ͑EIS͒ method is studied. A macroscopic porous electrode model and concentrated electrolyte theory are used to simulate the synthetic impedance data. The modified EIS method is applied for estimating D s . The influence of parameters such as the exchange current density, radius of active material particle, solid phase conductivity, porosity, volume fraction of inert material, and thickness of the porous carbon intercalation electrode, the solution phase diffusion coefficient, and transference number, on the validity of D s estimation, is evaluated. A simple dimensionless group is developed to correlate all the results. It shows that the accurate estimation of D s requires large particle size, small electrode thickness, large solution diffusion coefficient, and low active material loading. Finally, a ''full model'' method is developed for the cases where the modified EIS method does not work well.
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