124 research outputs found

    Roles of Free Electrons and H2O2 in the Optical Breakdown-Induced Photochemical Reduction of Aqueous [AuCl4]-

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    Free electrons and H2O2 formed in an optical breakdown plasma are found to directly control the kinetics of [AuCl4]− reduction to form Au nanoparticles (AuNPs) during femtosecond laser-assisted synthesis of AuNPs. The formation rates of both free electrons and H2O2 strongly depend on the energy and duration of the 800 nm laser pulses over the ranges of 10−2400 μJ and 30−1500 fs. By monitoring the conversion of [AuCl4]− to AuNPs using in situ UV−vis spectroscopy during laser irradiation, the first- and second-order rate constants in the autocatalytic rate law, k1 and k2, were extracted and compared to the computed free electron densities and experimentally measured H2O2 formation rates. For laser pulse energies of 600 μJ and lower at all pulse durations, the first-order rate constant, k1, was found to be directly proportional to the theoretically calculated plasma volume, in which the electron density exceeds the threshold value of 1.8 × 1020 cm−3. The second-order rate constant, k2, was found to correlate with the measured H2O2 formation rate at all pulse energies and durations, resulting in the empirical relationship k2 ≈ H2O20.5. We have demonstrated that the relative composition of free electrons and H2O2 in the optical breakdown plasma may be controlled by changing the pulse energy and duration, which may make it possible to tune the size and dispersity of AuNPs and other metal nanoparticle products synthesized with femtosecond laser-based methods

    The Common Factors of Grit, Hope, and Optimism Differentially Influence Suicide Resilience

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    No study to date has simultaneously examined the commonalities and unique aspects of positive psychological factors and whether these factors uniquely account for a reduction in suicide risk. Using a factor analytic approach, the current study examined the relationships between grit, hope, optimism, and their unique and overlapping relationships in predicting suicide ideation. Results of principle axis factor analysis demonstrated close relationships between these variables at both the construct and item level. Item-level analyses supported a five-factor solution (Stick-to-Itiveness, Poor Future, Consistency of Interest, Positive Future, and Poor Pathways). Four of the five factors (excluding Stick-to-Itiveness) were associated with suicide ideation. Additionally, results of a multiple regression analysis indicated that two of the five factors (Consistency of Interest and Positive Future) negatively predicted suicide ideation while Poor Future positively predicted suicide ideation. Implications regarding the interrelationships between grit, hope, and optimism with suicide ideation are discussed

    Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

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    Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance
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