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181.
Yang Chen Xianxiang Xin Jie Li Jianfeng Xu Xiaoxiang Yu Tianyu Li Zengnan Mo Yanling Hu 《PloS one》2013,8(11)
Prostate cancer (PCa) is a global disease causing large numbers of deaths every year. Recent studies have indicated the RTK/ERK pathway might be a key pathway in the development of PCa. However, the exact association and evolution-based mechanism remain unclear. This study was conducted by combining genotypic and phenotypic data from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa) with related databases such as the HapMap Project and Genevar. In this analysis, expression of quantitative trait loci (eQTLs) analysis, natural selection and gene-based pathway analysis were involved. The pathway analysis confirmed the positive relationship between PCa risk and several key genes. In addition, combined with the natural selection, it seems that 4 genes (EGFR, ERBB2, PTK2, and RAF1) with five SNPs (rs11238349, rs17172438, rs984654, rs11773818, and rs17172432) especially rs17172432, might be pivotal factors in the development of PCa. The results indicate that the RTK/ERK pathway under natural selection is a key link in PCa risk. The joint effect of the genes and loci with positive selection might be one reason for the development of PCa. Dealing with all the factors simultaneously might give insight into prevention and aid in predicting the success of potential therapies for PCa. 相似文献
182.
Andrew Buchanan Veronica Clementel Rob Woods Nicholas Harn Michael A Bowen Wenjun Mo Bojana Popovic Steven M. Bishop William Dall’Acqua Ralph Minter Lutz Jermutus Vahe Bedian 《MABS-AUSTIN》2013,5(2):255-262
Antibodies can undergo a variety of covalent and non-covalent degradation reactions that have adverse effects on efficacy, safety, manufacture and storage. We had identified an antibody to Angiopoietin 2 (Ang2 mAb) that neutralizes Ang2 binding to its receptor in vitro and inhibits tumor growth in vivo. Despite favorable pharmacological activity, the Ang2 mAb preparations were heterogeneous, aggregated rapidly and were poorly expressed. Here, we report the engineering of the antibody variable and constant domains to generate an antibody with reduced propensity to aggregate, enhanced homogeneity, 11°C elevated Tm, 26-fold improved level of expression and retained activity. The engineered molecule, MEDI-3617, is now compatible with the large scale material supply required for clinical trials and is currently being evaluated in Phase 1 in cancer patients. This is the first report to describe the stability engineering of a therapeutic antibody addressing non canonical cysteine residues and the design strategy reported here is generally applicable to other therapeutic antibodies and proteins. 相似文献
183.
Abstract We present a “force-biased” algorithm for generating the irregular close packing of hard spheres. The algorithm is partly based on Jodrey and Tory's ideas [9] and incorporates methods from Molecular Dynamics. Packings generated by means of the two algorithms are consistent up to final packing fraction of 0.65, which seems to be the limit density of Jodrey and Tory's method. Significantly higher densities (up to 0.71) can be achieved for small numbers of spheres by the force-biased algorithm. However the shape of the radial and angle distribution functions implies that a partial short-range ordering occurs in packings of those densities. 相似文献
184.
Degradation kinetics of biochar from pyrolysis and hydrothermal carbonization in temperate soils 总被引:2,自引:0,他引:2
Mo Bai Burkhard Wilske Franz Buegger Jürgen Esperschütz Claudia Irene Kammann Christian Eckhardt Martin Koestler Philipp Kraft Martin Bach Hans-Georg Frede Lutz Breuer 《Plant and Soil》2013,372(1-2):375-387
Background and Aims
Estimates of biochar residence times in soils range over three orders of magnitude. We present the first direct comparison between the biodegradation of a char from hydrothermal carbonization (htcBC) and pyrolysis (pyrBC) with high temporal resolution.Methods
Mineralization of the biochars and their shared Miscanthus feedstock in three soils was determined directly by the 13CO2 efflux using a novel method incorporating wavelength scanned cavity ring-down spectroscopy. Biochar half-life (t1/2) was estimated with three empirical models.Results
(1) The htcBC was readily biodegradable, whereas pyrBC was more recalcitrant. (2) Cumulative degradation of both biochars increased with soil organic carbon and nitrogen content. (3) The corrected Akaike information criterion (AICC) showed an overall preference for the double exponential model (DEM) reflecting a labile and a recalcitrant C-pool, over the first-order degradation model (FODM) and a logarithmic model. (4) The DEM resulted in t1/2 ranging from 19.7–44.5, 0.7–2.1 and 0.8–1.3 years for pyrBC, htcBC and feedstock, respectively.Conclusion
The degradation was rather similar between feedstock and htcBC but one order of magnitude slower for pyrBC. The AICC preferred FODM in two cases, where the DEM parameters indicated no distinction between a labile and recalcitrant carbon pool. 相似文献185.
Dan H. Barouch Kathryn E. Stephenson Erica N. Borducchi Kaitlin Smith Kelly Stanley Anna G. McNally Jinyan Liu Peter Abbink Lori F. Maxfield Michael S. Seaman Anne-Sophie Dugast Galit Alter Melissa Ferguson Wenjun Li Patricia L. Earl Bernard Moss Elena E. Giorgi James J. Szinger Leigh Anne Eller Erik A. Billings Mangala Rao Sodsai Tovanabutra Eric Sanders-Buell Mo Weijtens Maria G. Pau Hanneke Schuitemaker Merlin L. Robb Jerome H. Kim Bette T. Korber Nelson L. Michael 《Cell》2013
186.
Background
As a serine/threonine protein kinase, p70S6K plays an important role in tumor cells. Evidence has revealed overexpression of p70S6K and phosphorylated p70S6K (p-p70S6K) in various tumor tissues, with these proteins identified as independent prognostic markers in non-small cell lung cancer (NSCLC). In this study, we explored the role of the p70S6K specific inhibitor PF-4708671 in NSCLC.Methods
Three NSCLC cell lines (A549, SK-MES-1, and NCI-H460) were treated with PF-4708671 at five different concentrations, including 0.1μM, 0.3μM, 1μM, 3μM and 10μM, and protein levels were determined by Western-blot. Then, PF-4708671’s effects were assessed both in vitro (cell proliferation, apoptosis, cell cycle distribution, and invasion) and in vivo.Results
The expression levels of p-p70S6K and the downstream effector S6 were significantly reduced by PF-4708671. Diametrically opposite, the downstream protein levels of BAD, Caspase3 and ERK had increased after treatment with PF-4708671. In addition, PF-4708671 drastically inhibited cell proliferation and invasion ability in A549, SK-MES-1 and NCI-H460 cells in vitro, causing cell cycle arrest in G0-G1 phase. Limited effects of PF-4708671 were observed on apoptosis in the three NSCLC cell lines assessed. Importantly, PF-4708671 could inhibit tumorigenesis in nude mice in vivo.Conclusion
These findings demonstrated that the p70S6K specific inhibitor PF-4708671 has inhibitory effects on NSCLC tumorigenesis in vitro and in vivo. Therefore, P70S6K should be considered a new potential therapeutic target, and PF-470867 may be used as targeted drug for cancer treatment. 相似文献187.
188.
189.
Heavy metals, that is Cu(II), are harmful to the environment. There is an increasing demand to develop inexpensive detection methods for heavy metals. Here, we developed a yeast biosensor with reduced-noise and improved signal output for potential on-site copper ion detection. The copper-sensing circuit was achieved by employing a secondary genetic layer to control the galactose-inducible (GAL) system in Saccharomyces cerevisiae. The reciprocal control of the Gal4 activator and Gal80 repressor under copper-responsive promoters resulted in a low-noise and sensitive yeast biosensor for copper ion detection. Furthermore, we developed a betaxanthin-based colorimetric assay, as well as 2-phenylethanol and styrene-based olfactory outputs for the copper ion detection. Notably, our engineered yeast sensor confers a narrow range switch-like behaviour, which can give a ‘yes/no’ response when coupled with a betaxanthin-based visual phenotype. Taken together, we envision that the design principle established here might be applicable to develop other sensing systems for various chemical detections. 相似文献
190.
Zhu Jing Zeng Zhaofu Xiong Mengqing Mo Huaheng Jin Meng Hu Ke 《Sleep and biological rhythms》2022,20(3):421-429
Sleep and Biological Rhythms - The relationship between plasma orexin A (OXA) levels and cognitive function in patients with obstructive sleep apnea (OSA) remains unclear. This study aimed to... 相似文献