Background: Mutations of the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients predict the patients who will respond to EGFR tyrosine kinase inhibitor (TKI) ...treatment. A recent study has suggested that 33% of NSCLC showed primary tumor/metastasis discordance of EGFR expression by immunohistochemistry analysis. We intended to find out whether the EGFR mutations of primary lung cancers are concordant to that of corresponding metastatic tumors. Materials and methods: We analyzed EGFR exons 18–21 from paired primary and metastatic tumors in 67 lung cancer patients who had not received TKI before tissues were sampled. Results: Using the direct sequencing method, 9 of 18 (50%) patients with EGFR mutation-positive primary lung tumors had lost the mutations in metastases. For 26 patients who were EGFR mutation positive in the metastatic tumors, 17 (65%) were negative in the primary tumors. We analyzed these paired tissues with discrepant EGFR mutations by the Scorpion Amplified Refractory Mutation System assay. Finally, the discordant rate reached 27% (18 of 67 cases). Conclusion: EGFR mutations in primary lung tumors do not always reflect the same situation in metastases. Analysis of EGFR mutations in the primary lung tumor would be inadequate for planning the use of TKI for advanced NSCLC.
Summary Introduction Matrix metalloproteinases and ‘aggrecanase’ ADAMTSs are well established to play key roles in osteoarthritis (OA) through degradation of extracellular matrix type II collagen and ...aggrecan, and are thus potential targets for development of OA therapies. Objective This paper aims to provide a comprehensive review of the expression and potential roles of other, lesser-known ADAMTSs and related adamalysins (or ADAMs) in cartilage, with a view to identifying potentially protective or homeostatic metalloproteinases in the joint and informing consequent selective inhibitor design. Design A comprehensive literature search was performed using PubMed terms ‘osteoarthritis’ and ‘ADAMTS’ or ‘ADAM’. Results Several ADAMTSs and ADAMs were identified as having reportedly increased expression in OA. These include enzymes likely to play roles in cartilage matrix anabolism (e. g. the procollagen N-proteinases ADAMTS-2, ADAMTS-3 and ADAMTS-14), chondrocyte differentiation and proliferation (e. g. ADAM9, ADAM10, ADAM12), as well as enzymes contributing to cartilage catabolism (e. g. COMP-degrading ADAMTS-7 and ADAMTS-12). Conclusions In addition to the well-characterised MMPs, ADAMTS-4 and ADAMTS-5, many other ADAMTSs and ADAMs are expressed in cartilage and several show significantly altered expression in OA. Studies aimed at elucidating the pathophysiological roles of these enzymes in cartilage will contribute to our understanding of OA pathogenesis and enable design of targeted inhibitors that effectively target metalloproteinase-mediated cartilage degradation while sparing cartilage repair pathways.
In conventional solid-state photovoltaics, electron-hole pairs are created by light absorption in a semiconductor and separated by the electric field spaning a micrometre-thick depletion region. The ...maximum voltage these devices can produce is equal to the semiconductor electronic bandgap. Here, we report the discovery of a fundamentally different mechanism for photovoltaic charge separation, which operates over a distance of 1-2 nm and produces voltages that are significantly higher than the bandgap. The separation happens at previously unobserved nanoscale steps of the electrostatic potential that naturally occur at ferroelectric domain walls in the complex oxide BiFeO(3). Electric-field control over domain structure allows the photovoltaic effect to be reversed in polarity or turned off. This new degree of control, and the high voltages produced, may find application in optoelectronic devices.
Malignant pleural effusions (MPEs) are often observed in lung cancer, especially adenocarcinoma. Epidermal growth factor receptor (EGFR) gene mutations are usually detected in lung adenocarcinoma. ...The purpose of the present study was to investigate the EGFR mutation rate in MPEs of lung adenocarcinoma. Between June 2005 and December 2006, 136 MPEs from lung adenocarcinoma were collected for EGFR mutation detection. In addition, between April 2001 and November 2004, 91 surgically resected specimens of lung adenocarcinoma from patients without MPEs were assessed for EGFR mutation. The EGFR mutation rate was significantly higher in the patients with MPEs than in the patients without (68.4% versus 50.5%). The EGFR mutation rate in patients with MPEs was not associated with sex, smoking history, age or cancer stage. By multivariate analysis, an age of <65 yrs, never smoking, Eastern Cooperative Oncology Group performance status 0-1, and EGFR mutation were significantly associated with a longer overall survival for lung adenocarcinoma patients with MPEs. The patients with malignant pleural effusions related to lung adenocarcinoma had a higher epidermal growth factor receptor gene mutation rate than the patients from whom surgically resected specimens were taken. Epidermal growth factor receptor tyrosine kinase inhibitors may be the treatment of choice for lung adenocarcinoma with malignant pleural effusions in east Asia.
The transport physics of domain wall conductivity in La-doped bismuth ferrite (BiFeO3) has been probed using variable temperature conducting atomic force microscopy and piezoresponse force microscopy ...in samples with arrays of domain walls in the as-grown state. Nanoscale current measurements are investigated as a function of bias and temperature and are shown to be consistent with distinct electronic properties at the domain walls leading to changes in the observed local conductivity. Our observation is well described within a band picture of the observed electronic conduction. Finally, we demonstrate an additional degree of control of the wall conductivity through chemical doping with oxygen vacancies, thus influencing the local conductive state.
The control of material interfaces at the atomic level has led to novel interfacial properties and functionalities. In particular, the study of polar discontinuities at interfaces between complex ...oxides lies at the frontier of modern condensed matter research. Here we employ a combination of experimental measurements and theoretical calculations to demonstrate the control of a bulk property, namely ferroelectric polarization, of a heteroepitaxial bilayer by precise atomic-scale interface engineering. More specifically, the control is achieved by exploiting the interfacial valence mismatch to influence the electrostatic potential step across the interface, which manifests itself as the biased-voltage in ferroelectric hysteresis loops and determines the ferroelectric state. A broad study of diverse systems comprising different ferroelectrics and conducting perovskite underlayers extends the generality of this phenomenon.
Timely and accurate forecasts of tropical cyclones (TCs, i.e., hurricanes and typhoons) are of great importance for risk mitigation. Although in the past two decades there has been steady improvement ...in track prediction, improvement on intensity prediction is still highly challenging. Cooling of the upper ocean by TC‐induced mixing is an important process that impacts TC intensity. Based on detail in situ air‐deployed ocean and atmospheric measurement pairs collected during the Impact of Typhoons on the Ocean in the Pacific (ITOP) field campaign, we modify the widely used Sea Surface Temperature Potential Intensity (SST_PI) index by including information from the subsurface ocean temperature profile to form a new Ocean coupling Potential Intensity (OC_PI) index. Using OC_PI as a TC maximum intensity predictor and applied to a 14 year (1998–2011) western North Pacific TC archive, OC_PI reduces SST_PI‐based overestimation of archived maximum intensity by more than 50% and increases the correlation of maximum intensity estimation from r2 = 0.08 to 0.31. For slow‐moving TCs that cause the greatest cooling, r2 increases to 0.56 and the root‐mean square error in maximum intensity is 11 m s−1. As OC_PI can more realistically characterize the ocean contribution to TC intensity, it thus serves as an effective new index to improve estimation and prediction of TC maximum intensity.
Key Points
Current potential intensity index considers only ocean's surface contribution
Inclusion of ocean's subsurface information to improve estimation
Based on a valuable in situ data set from the ITOP field campaign
A Strain-Driven Morphotropic Phase Boundary in BiFeO3 Zeches, R. J.; Rossell, M. D.; Zhang, J. X. ...
Science (American Association for the Advancement of Science),
11/2009, Letnik:
326, Številka:
5955
Journal Article
Recenzirano
Odprti dostop
Piezoelectric materials, which convert mechanical to electrical energy and vice versa, are typically characterized by the intimate coexistence of two phases across a morphotropic phase boundary. ...Electrically switching one to the other yields large electromechanical coupling coefficients. Driven by global environmental concerns, there is currently a strong push to discover practical lead-free piezoelectrics for device engineering. Using a combination of epitaxial growth techniques in conjunction with theoretical approaches, we show the formation of a morphotropic phase boundary through epitaxial constraint in lead-free piezoelectric bismuth ferrite (BiFeO3) films. Electric field–dependent studies show that a tetragonal-like phase can be reversibly converted into a rhombohedral-like phase, accompanied by measurable displacements of the surface, making this new lead-free system of interest for probe-based data storage and actuator applications.
Quantum computers are expected to outperform conventional computers in several important applications, from molecular simulation to search algorithms, once they can be scaled up to large ...numbers-typically millions-of quantum bits (qubits)
. For most solid-state qubit technologies-for example, those using superconducting circuits or semiconductor spins-scaling poses a considerable challenge because every additional qubit increases the heat generated, whereas the cooling power of dilution refrigerators is severely limited at their operating temperature (less than 100 millikelvin)
. Here we demonstrate the operation of a scalable silicon quantum processor unit cell comprising two qubits confined to quantum dots at about 1.5 kelvin. We achieve this by isolating the quantum dots from the electron reservoir, and then initializing and reading the qubits solely via tunnelling of electrons between the two quantum dots
. We coherently control the qubits using electrically driven spin resonance
in isotopically enriched silicon
Si, attaining single-qubit gate fidelities of 98.6 per cent and a coherence time of 2 microseconds during 'hot' operation, comparable to those of spin qubits in natural silicon at millikelvin temperatures
. Furthermore, we show that the unit cell can be operated at magnetic fields as low as 0.1 tesla, corresponding to a qubit control frequency of 3.5 gigahertz, where the qubit energy is well below the thermal energy. The unit cell constitutes the core building block of a full-scale silicon quantum computer and satisfies layout constraints required by error-correction architectures
. Our work indicates that a spin-based quantum computer could be operated at increased temperatures in a simple pumped
He system (which provides cooling power orders of magnitude higher than that of dilution refrigerators), thus potentially enabling the integration of classical control electronics with the qubit array
.
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