397 research outputs found

    Evidence for a Type-II band alignment between cubic and hexagonal phases of GaN

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    The study of photoluminescence spectra of a series of thin, undoped, hexagonal GaN films containing cubic GaN inclusions grown by molecular-beam epitaxy on 6H-SiC was presented. It was shown that an emission peak at ∼3.17 eV in thin, hexagonal GaN films exhibits behaviors typical of a spatially indirect transition. The values of the band offsets extracted from the data were in good agreement with theoretical predictions.published_or_final_versio

    Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

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    DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

    Cross-Platform Comparison of Microarray-Based Multiple-Class Prediction

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    High-throughput microarray technology has been widely applied in biological and medical decision-making research during the past decade. However, the diversity of platforms has made it a challenge to re-use and/or integrate datasets generated in different experiments or labs for constructing array-based diagnostic models. Using large toxicogenomics datasets generated using both Affymetrix and Agilent microarray platforms, we carried out a benchmark evaluation of cross-platform consistency in multiple-class prediction using three widely-used machine learning algorithms. After an initial assessment of model performance on different platforms, we evaluated whether predictive signature features selected in one platform could be directly used to train a model in the other platform and whether predictive models trained using data from one platform could predict datasets profiled using the other platform with comparable performance. Our results established that it is possible to successfully apply multiple-class prediction models across different commercial microarray platforms, offering a number of important benefits such as accelerating the possible translation of biomarkers identified with microarrays to clinically-validated assays. However, this investigation focuses on a technical platform comparison and is actually only the beginning of exploring cross-platform consistency. Further studies are needed to confirm the feasibility of microarray-based cross-platform prediction, especially using independent datasets

    Linking magmatism with collision in an accretionary orogen

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    A compilation of U-Pb age, geochemical and isotopic data for granitoid plutons in the southern Central Asian Orogenic Belt (CAOB), enables evaluation of the interaction between magmatism and orogenesis in the context of Paleo-Asian oceanic closure and continental amalgamation. These constraints, in conjunction with other geological evidence, indicate that following consumption of the ocean, collision-related calc-alkaline granitoid and mafic magmatism occurred from 255 ± 2 Ma to 251 ± 2 Ma along the Solonker-Xar Moron suture zone. The linear or belt distribution of end-Permian magmatism is interpreted to have taken place in a setting of final orogenic contraction and weak crustal thickening, probably as a result of slab break-off. Crustal anatexis slightly post-dated the early phase of collision, producing adakite-like granitoids with some S-type granites during the Early-Middle Triassic (ca. 251-245 Ma). Between 235 and 220 Ma, the local tectonic regime switched from compression to extension, most likely caused by regional lithospheric extension and orogenic collapse. Collision-related magmatism from the southern CAOB is thus a prime example of the minor, yet tell-tale linking of magmatism with orogenic contraction and collision in an archipelago-type accretionary orogen

    Does Applicability Domain Exist in Microarray-Based Genomic Research?

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    Constructing an accurate predictive model for clinical decision-making on the basis of a relatively small number of tumor samples with high-dimensional microarray data remains a very challenging problem. The validity of such models has been seriously questioned due to their failure in clinical validation using independent samples. Besides the statistical issues such as selection bias, some studies further implied the probable reason was improper sample selection that did not resemble the genomic space defined by the training population. Assuming that predictions would be more reliable for interpolation than extrapolation, we set to investigate the impact of applicability domain (AD) on model performance in microarray-based genomic research by evaluating and comparing model performance for samples with different extrapolation degrees. We found that the issue of applicability domain may not exist in microarray-based genomic research for clinical applications. Therefore, it is not practicable to improve model validity based on applicability domain

    Bioconjugates of Glucose Oxidase and Gold Nanorods Based on Electrostatic Interaction with Enhanced Thermostability

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    Bioconjugates made up of an enzyme and gold nanorods (GNRs) were fabricated by electrostatic interactions (layer-by-layer method, LBL) between anionic glucose oxidase (GOD) and positively charged GNRs. The assembled processes were monitored by UV–Vis spectra, zeta potential measurements, and transmission electron microscopy. The enzyme activity assays of the obtained bioconjugates display a relatively enhanced thermostability behavior in contrast with that of free enzyme. Free GOD in solution only retains about 22% of its relative activity at 90 °C. Unexpectedly, the immobilized GOD on GNRs still retains about 39.3% activity after the same treatment. This work will be of significance for the biologic enhancement using other kinds of anisotropic nanostructure and suggests a new way of enhancing enzyme thermostability using anisotropic metal nanomaterials

    Neuronal circuitry for pain processing in the dorsal horn

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    Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

    Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma

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    <p>Abstract</p> <p>Background</p> <p>Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of <it>Cimicifuga dahurica </it>showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of <it>C. dahurica </it>and therefore might eventually be useful in the prevention or treatment of Hepatoma.</p> <p>Methods</p> <p>The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H<sub>22 </sub>hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA <it>in vivo</it>.</p> <p>Results</p> <p>The IC<sub>50 </sub>values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 μg/ml, respectively. TGA induced G<sub>0</sub>/G<sub>1 </sub>cell cycle arrest at lower concentration (25 μg/ml), and triggered G<sub>2</sub>/M arrest and apoptosis at higher concentrations (50 and 100 μg/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H<sub>22 </sub>tumor in a dose-dependent manner.</p> <p>Conclusion</p> <p>TGA may potentially find use as a new therapy for the treatment of hepatoma.</p
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