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Choi, Dooho,Liu, Xuan,Schelling, Patrick K.,Coffey, Kevin R.,Barmak, Katayun American Institute of Physics 2014 Journal of Applied Physics Vol.115 No.10
<P>The impact of electron scattering at surfaces and grain boundaries in nanometric polycrystalline tungsten (W) films was studied. A series of polycrystalline W films ranging in thickness from 10 to 310 nm and lateral grain size from 74 to 133 nm were prepared on thermally oxidized Si. The Fuchs-Sondheimer surface-scattering model and Mayadas-Shatzkes grain-boundary scattering model were employed for quantitative analyses. Predictions from the theoretical models were found to deviate systematically from the experimental data. Possible reasons for the failure of the theoretical models to describe the experimental data are explored. Finally, a discussion of the crucial features lacking from existing models is presented, along with possible avenues for improving the models to result in better agreement with experimental data. (C) 2014 AIP Publishing LLC.</P>
Kang, Ju-Hee,Mollenhauer, Brit,Coffey, Christopher S.,Toledo, Jon B.,Weintraub, Daniel,Galasko, Douglas R.,Irwin, David J.,Van Deerlin, Vivianna,Chen-Plotkin, Alice S.,Caspell-Garcia, Chelsea,Walig&oa Springer-Verlag 2016 Acta neuropathologica Vol.131 No.6
<P>The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-na < ve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (alpha-syn), amyloid-beta1-42 (A beta(1-42)), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF alpha-syn, t-tau and p-tau levels, but not A beta(1-42), were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of alpha-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest A beta(1-42), or highest t-tau/A beta(1-42) and t-tau/alpha-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower alpha-syn was significantly associated with worse cognitive test performance. APOE epsilon 4 genotype was associated with lower levels of A beta(1-42), but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance.</P>
Ménétrier’s Disease: Its Mimickers and Pathogenesis
Won Jae Huh,Robert J. Coffey,Mary Kay Washington 대한병리학회 2016 Journal of Pathology and Translational Medicine Vol.50 No.1
Ménétrier’s disease is a rare protein-losing hypertrophic gastropathy. Histologically, it can be mistaken for other disorders showing hypertrophic gastropathy. The pathogenesis of Ménétrier’s disease is not fully understood; however, it appears that the epidermal growth factor receptor (EGFR) ligand, transforming growth factor alpha, contributes to the pathogenesis of this disorder. In this review, we will discuss disease entities that can mimic Ménétrier’s disease and the role of EGFR signaling in Ménétrier’s disease.
Yu, Sungsook,Yang, Mijeong,Lim, Kyung-Min,Cho, Yejin,Kim, Hyunji,Lee, Keunwook,Jeong, Sang-Ho,Coffey, Robert J.,Goldenring, James R.,Nam, Ki Taek Elsevier 2018 The American journal of pathology Vol.188 No.12
<P>Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a transmembrane protein that antagonizes epidermal growth factor receptor signaling in epithelial tissues. LRIG1 is down-regulated in various epithelial cancers, including bladder, breast, and colorectal cancer, suggesting that it functions as a tumor suppressor. However, its role in gastric carcinogenesis is not well understood. Here, we investigated the changes in LRIG1 expression during the stages of gastric cancer. We used a DMP-777–induced spasmolytic polypeptide-expressing metaplasia mouse model and a tissue array of human gastric cancer lesions. The effects of LRIG1 knockdown were also assessed using the human gastric cancer cell line SNU638 in a xenograft model. LRIG1 expression varied over the course of gastric carcinogenesis, increasing in spasmolytic polypeptide-expressing metaplasia lesions but disappearing in intestinal metaplasia and cancer lesions, and the increase was concurrent with the up-regulation of epidermal growth factor receptor. In addition, LRIG1 knockdown promoted the tumorigenic potential <I>in vitro</I>, which was manifested as increased proliferation, invasiveness, and migration as well as increased tumor size <I>in vivo</I> in the xenograft model. Furthermore, LRIG1 expression was determined to be a positive prognostic biomarker for the survival of gastric cancer patients. Collectively, our findings indicate that LRIG1 expression is closely related wto gastric carcinogenesis and may play a vital role as a tumor suppressor through the modulation of epidermal growth factor receptor activity.</P>
Silva, M.,Daheron, L.,Hurley, H.,Bure, K.,Barker, R.,Carr, Andrew J.,Williams, D.,Kim, H.W.,French, A.,Coffey, Pete J.,Cooper-White, Justin J.,Reeve, B.,Rao, M.,Snyder, Evan Y.,Ng, Kelvin S.,Mead, Ben Cell Press 2015 Cell stem cell Vol.16 No.1
Induced pluripotent stem cells (iPSCs) have the potential to transform drug discovery and healthcare in the 21<SUP>st</SUP> century. However, successful commercialization will require standardized manufacturing platforms. Here we highlight the need to define standardized practices for iPSC generation and processing and discuss current challenges to the robust manufacture of iPSC products.