80 research outputs found

    The Amplitude of Non-Equilibrium Quantum Interference in Metallic Mesoscopic Systems

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    We study the influence of a DC bias voltage V on quantum interference corrections to the measured differential conductance in metallic mesoscopic wires and rings. The amplitude of both universal conductance fluctuations (UCF) and Aharonov-Bohm effect (ABE) is enhanced several times for voltages larger than the Thouless energy. The enhancement persists even in the presence of inelastic electron-electron scattering up to V ~ 1 mV. For larger voltages electron-phonon collisions lead to the amplitude decaying as a power law for the UCF and exponentially for the ABE. We obtain good agreement of the experimental data with a model which takes into account the decrease of the electron phase-coherence length due to electron-electron and electron-phonon scattering.Comment: New title, refined analysis. 7 pages, 3 figures, to be published in Europhysics Letter

    Doubly connected minimal surfaces and extremal harmonic mappings

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    The concept of a conformal deformation has two natural extensions: quasiconformal and harmonic mappings. Both classes do not preserve the conformal type of the domain, however they cannot change it in an arbitrary way. Doubly connected domains are where one first observes nontrivial conformal invariants. Herbert Groetzsch and Johannes C. C. Nitsche addressed this issue for quasiconformal and harmonic mappings, respectively. Combining these concepts we obtain sharp estimates for quasiconformal harmonic mappings between doubly connected domains. We then apply our results to the Cauchy problem for minimal surfaces, also known as the Bjorling problem. Specifically, we obtain a sharp estimate of the modulus of a doubly connected minimal surface that evolves from its inner boundary with a given initial slope.Comment: 35 pages, 2 figures. Minor edits, references adde

    HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers

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    Amplification and oncogenic mutations of ERBB2, the gene encoding the HER2 receptor tyrosine kinase, promote receptor hyperactivation and tumor growth. Here we demonstrate that HER2 ubiquitination and internalization, rather than its overexpression, are key mechanisms underlying endocytosis and consequent efficacy of the anti-HER2 antibody-drug conjugates (ADCs) ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in lung cancer cell lines and patient-derived xenograft models. These data translated into a 51% response rate in a clinical trial of T-DM1 in 49 patients with ERBB2/HER2-amplified or mutant lung cancers. We show that co-treatment with irreversible pan-HER inhibitors enhances receptor ubiquitination and consequent ADC internalization and efficacy. We also demonstrate that ADC switching to T-DXd, which harbors a different cytotoxic payload, achieves durable responses in a patient with lung cancer and corresponding xenograft model developing resistance to T-DM1. Our findings may help guide future clinical trials and expand the field of ADC as cancer therapy

    Application of Fickian and non-Fickian diffusion models to study moisture diffusion in asphalt mastics

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    The objective of this study was to investigate certain aspects of asphalt mastic moisture diffusion characteristics in order to better understand the moisture damage phenomenon in asphalt mixtures. Moisture sorption experiments were conducted on four asphalt mastics using an environmental chamber capable of automatically controlling both relative humidity (85 %) and temperature (23 °C). The four mastics tested were identical in terms of bitumen type (40/60 pen), bitumen amount (25 % by of wt% total mix), mineral filler amount (25 % by wt%) and fine aggregate amount (50 % by wt%). The materials differed in terms of mineral filler type (granite or limestone) and fine aggregate type (granite or limestone). Preliminary data obtained during the early part of the study showed certain anomalous behavior of the materials including geometry (thickness)-dependent diffusion coefficient. It was therefore decided to investigate some aspects related to moisture diffusion in mastics by applying the Fickian and two non-Fickian (anomalous) diffusion models to the moisture sorption data. The two non-Fickian models included a two-phase Langmuir-type model and a two-parameter time-variable model. All three models predicted moisture diffusion in mastics extremely well (R 2 > 0.95). The observed variation of diffusion coefficient with thickness was attributed in part to microstructural changes (settlement of the denser fine aggregates near the bottom of the material) during the rather long-duration diffusion testing. This assertion was supported by X-ray computed tomography imaging of the mastic that showed significant accumulation of aggregate particles near the bottom of the sample with time. The results from the Langmuir-type model support a two-phase (free and bound) model for moisture absorbed by asphalt mastic and suggests about 80 % of absorbed water in the free phase remain bound within the mastic. The results also suggest that moisture diffusion in asphalt mastic may be time-dependent with diffusion decreasing by about four times during a typical diffusion test lasting up to 500 h. The study concludes that both geometry and time-dependent physical characteristics of mastic are important factors to consider with respect to moisture diffusion in asphalt mastics

    Activation of Estrogen Receptor-α by E2 or EGF Induces Temporally Distinct Patterns of Large-Scale Chromatin Modification and mRNA Transcription

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    Estrogen receptor-α (ER) transcription function is regulated in a ligand-dependent (e.g., estradiol, E2) or ligand-independent (e.g., growth factors) manner. Our laboratory seeks to understand these two modes of action. Using a cell line that contains a visible prolactin enhancer/promoter array (PRL-HeLa) regulated by ER, we analyzed ER response to E2 and EGF by quantifying image-based results. Data show differential recruitment of GFP-ER to the array, with the AF1 domain playing a vital role in EGF-mediated responsiveness. Temporal analyses of large-scale chromatin dynamics, and accumulation of array-localized reporter mRNA over 24 hours showed that the EGF response consists of a single pulse of reporter mRNA accumulation concomitant with transient increase in array decondensation. Estradiol induced a novel cyclical pattern of mRNA accumulation with a sustained increase in array decondensation. Collectively, our work shows that there is a stimuli-specific pattern of large-scale chromatin modification and transcript levels by ER

    A Review on the Mechanical Modeling of Composite Manufacturing Processes

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    © 2016, The Author(s). The increased usage of fiber reinforced polymer composites in load bearing applications requires a detailed understanding of the process induced residual stresses and their effect on the shape distortions. This is utmost necessary in order to have more reliable composite manufacturing since the residual stresses alter the internal stress level of the composite part during the service life and the residual shape distortions may lead to not meeting the desired geometrical tolerances. The occurrence of residual stresses during the manufacturing process inherently contains diverse interactions between the involved physical phenomena mainly related to material flow, heat transfer and polymerization or crystallization. Development of numerical process models is required for virtual design and optimization of the composite manufacturing process which avoids the expensive trial-and-error based approaches. The process models as well as applications focusing on the prediction of residual stresses and shape distortions taking place in composite manufacturing are discussed in this study. The applications on both thermoset and thermoplastic based composites are reviewed in detail
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