Description: Photoresponse of bimetallic Au-Ag nanoparticle embedded soda glass (Au-Ag@SG) substrate is reported for surface plasmon assisted optical switching using 808 nm excitation. Au-Ag@SG system is made by an ion beam technique where Ag + is introduced first in the soda glass matrix by ion exchange technique. Subsequently, 400 keV Au + is implanted in the sample for different fluences, which is followed by an ion beam annealing process using 1 MeV Si + at a fixed fluence of 2 × 10 16 ions·cm −2 . Characteristic surface plasmon resonance (SPR) peaks around 400 and 550 nm provided evidence for the presence of Au and Ag nanoparticles. An optical switching in the Au-Ag@SG system with 808 nm, which is away from the characteristic SPR peaks of Ag and Au nanoparticles, suggests the possible role of two photon absorption (TPA) owing to the presence of interacting electric dipole in these systems. The role of surface plasmon polariton is emphasized for the propagation of electronic carrier belonging to the conduction electron of Au-Ag system in understanding the observed photoresponse. Unique excitation dependent photoresponse measurements confirm the possible role of TPA process. A competitive interband and intraband transitions in the bimetallic system of Au and Ag, which may be primarily responsible for the observation, are validated qualitatively using finite difference time domain calculations where inter-particle separation of Au and Ag plays an important role. Thus, a smart way of optical switching can be envisaged in noble bimetallic nanocluster system where long wavelength with higher skin depth can be used for communication purpose.

Description: An increased risk of second primary malignancy after 131 I therapy has been reported. The objective of this study was to determine the risk of breast cancer in patients with thyroid cancer receiving or not receiving radioiodine treatment in Taiwan. Methods: This nationwide population-based cohort study was conducted using data obtained from the Taiwan National Health Insurance Database from 2000 to 2011. A total of 10,361 female patients with thyroid cancer (3,292 did not receive 131 I treatment and 7,069 received 131 I treatment) were enrolled, and 41,444 female controls were frequency-matched to the thyroid cancer patients in a 1:4 ratio by age (5-y age group). A Cox proportional hazards model was applied to estimate the risk of breast cancer in thyroid cancer patients receiving or not receiving 131 I treatment in terms of hazard ratios and 95% and 98% confidence intervals. Results: The incidence rates of breast cancer in patients with thyroid cancer receiving 131 I therapy, those not receiving 131 I therapy, and controls were 18.9, 17.7, and 13.1 per 10,000 person-years, respectively. Compared with patients with thyroid cancer treated with a cumulative 131 I dose of 4.44 GBq or less, the risk of breast cancer was not significantly increased in those treated with a cumulative 131 I dose of more than 4.44 GBq (adjusted hazard ratio, 0.78; 95% confidence interval, 0.50–1.21, P = 0.26; 98% confidence interval, 0.45–1.33, P 〉 0.02). Conclusion: The greatest increased risk of breast cancer in patients with thyroid cancer is associated with the fact that the patient has thyroid cancer regardless of 131 I administration. However, 131 I further increased that risk but not as much as just having thyroid cancer.

Description: Purpose: Non–small cell lung cancers (NSCLCs) harboring ALK gene rearrangements (ALK + ) typically become resistant to the first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) crizotinib through development of secondary resistance mutations in ALK or disease progression in the brain. Mutations that confer resistance to second-generation ALK TKIs ceritinib and alectinib have also been identified. Here, we report the structure and first comprehensive preclinical evaluation of the next-generation ALK TKI brigatinib. Experimental Design: A kinase screen was performed to evaluate the selectivity profile of brigatinib. The cellular and in vivo activities of ALK TKIs were compared using engineered and cancer-derived cell lines. The brigatinib–ALK co-structure was determined. Results: Brigatinib potently inhibits ALK and ROS1, with a high degree of selectivity over more than 250 kinases. Across a panel of ALK + cell lines, brigatinib inhibited native ALK (IC 50 , 10 nmol/L) with 12-fold greater potency than crizotinib. Superior efficacy of brigatinib was also observed in mice with ALK + tumors implanted subcutaneously or intracranially. Brigatinib maintained substantial activity against all 17 secondary ALK mutants tested in cellular assays and exhibited a superior inhibitory profile compared with crizotinib, ceritinib, and alectinib at clinically achievable concentrations. Brigatinib was the only TKI to maintain substantial activity against the most recalcitrant ALK resistance mutation, G1202R. The unique, potent, and pan-ALK mutant activity of brigatinib could be rationalized by structural analyses. Conclusions: Brigatinib is a highly potent and selective ALK inhibitor. These findings provide the molecular basis for the promising activity being observed in ALK + , crizotinib-resistant patients with NSCLC being treated with brigatinib in clinical trials. Clin Cancer Res; 22(22); 5527–38. ©2016 AACR .

Description: We introduce the Clouds Above the United States and Errors at the Surface (CAUSES) project with its aim of better understanding the physical processes leading to warm screen-temperature biases over the American Midwest in many numerical models. In this first of four companion papers, 11 different models, from 9 institutes, perform a series of 5-day hindcasts, each initialised from reanalyses. After describing the common experimental protocol and detailing each model configuration, a gridded temperature data set is derived from observations and used to show that all the models have a warm bias over parts of the Midwest. Additionally, a strong diurnal cycle in the screen-temperature bias is found in most models. In some models the bias is largest around midday, while in others it is largest during the night. At the Department of Energy Atmospheric Radiation Measurement Southern Great Plains (SGP) site, the model biases are shown to extend several kilometers into the atmosphere. Finally, to provide context for the companion papers, in which observations from the SGP site are used to evaluate the different processes contributing to errors there, it is shown that there are numerous locations across the Midwest where the diurnal cycle of the error is highly correlated with the diurnal cycle of the error at SGP. This suggests that conclusions drawn from detailed evaluation of models using instruments located at SGP will be representative of errors that are prevalent over a larger spatial scale.