4,641 research outputs found

    BH3 mimetic ABT-737 sensitizes colorectal cancer cells to ixazomib through MCL-1 downregulation and autophagy inhibition.

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    The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines. Mcl-1, an anti-apoptotic Bcl-2 family protein, was markedly elevated after treating a colorectal cancer cell line with MLN2238. We proved that inhibiting Mcl-1 expression enhances MLN2238 induced apoptosis and negatively regulates autophagy. Co-administration of BH3 mimetic ABT-737 with MLN2238 synergistically kills colorectal cancer cells through MCL-1 neutralization and autophagy inhibition. Furthermore, the synergistic killing effect of the combination therapy is correlated with P53 status in colorectal cancer. These data highlight that the combination of ABT-737 with MLN9708 is a promising therapeutic strategy for human colorectal cancer

    The Study of Scene Classification in the Multisensor Remote Sensing Image Fusion

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    We propose a scene classification method for speeding up the multisensor remote sensing image fusion by using the singular value decomposition of quaternion matrix and the kernel principal component analysis (KPCA) to extract features. At first, images are segmented to patches by a regular grid, and for each patch, we extract color features by using quaternion singular value decomposition (QSVD) method, and the grey features are extracted by Gabor filter and then by using orientation histogram to describe the grey information. After that, we combine the color features and the orientation histogram together with the same weight to obtain the descriptor for each patch. All the patch descriptors are clustered to get visual words for each category. Then we apply KPCA to the visual words to get the subspaces of the category. The descriptors of a test image then are projected to the subspaces of all categories to get the projection length to all categories for the test image. Finally, support vector machine (SVM) with linear kernel function is used to get the scene classification performance. We experiment with three classification situations on OT8 dataset and compare our method with the typical scene classification method, probabilistic latent semantic analysis (pLSA), and the results confirm the feasibility of our method

    Dimethyl 3,3′-diphenyl-2,2′-[(S)-thio­phene-2,5-diylbis(carbonyl­aza­nedi­yl)]dipropano­ate tetra­hydro­furan monosolvate

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    The title compound, C26H26N2O6S·C4H8O, a solvated bis-amide derivative, is also a chiral amino acid ester with l-phenyl­alanine methyl ester groups as amine substituents. The thio­phene-2,5-dicarboxamide core approximates C 2 point symmetry. The tetra­hydro­furan solvent mol­ecule is linked to the main mol­ecule through an inter­molecular N—H⋯O hydrogen bond. The central ring makes dihedral angles of 90.0 (2) and 76.5 (2)° with the pendant rings

    Simultaneous amplification and non-symmetric amplitude damping of two-mode Gaussian state

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    The evolution of two-mode Gaussian state under symmetric amplification, non-symmetric damping and thermal noise is studied. The time dependent solution of the state characteristic function is obtained. The separability criterions are given for the final state of weak amplification as well as strong amplification.Comment: 6 pages, 2 figure

    Facilitation of synaptic transmission and pain responses by CGRP in the amygdala of normal rats

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    Calcitonin gene-related peptide (CGRP) plays an important role in peripheral and central sensitization. CGRP also is a key molecule in the spino-parabrachial-amygdaloid pain pathway. Blockade of CGRP1 receptors in the spinal cord or in the amygdala has antinociceptive effects in different pain models. Here we studied the electrophysiological mechanisms of behavioral effects of CGRP in the amygdala in normal animals without tissue injury

    Thrusting and exhumation of the southern Mongolian Plateau: Joint thermochronological constraints from the Langshan Mountains, western Inner Mongolia, China

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    The Mongolian Plateau has undergone multi-stage denudation since the Late Triassic, and the NE-trending Langshan Mountains in the southern margin of the Mongolian Plateau is crucial to unraveling the Meso-Cenozoic cooling and exhumation history of the Mongolian Plateau. The Langshan Mountains are dominated by Precambrian gneiss and Permian–Middle Triassic granitic plutons crosscut by a set of NE-striking thrust faults. A joint thermochronological study was conducted on 31 granitic and gneissic samples along the HQ and CU transects across the Langshan Mountains and other two samples from the BQ in the north of the Langshan Mountains. Four biotite/muscovite and three K-feldspar 40Ar/39Ar plateau ages range from 205 ± 1 to 161 ± 1 and 167 ± 1 to 131 ± 1 Ma, respectively. Thirty-three apatite fission track (AFT) ages are between 184 ± 11 and 79 ± 4 Ma, with mean track lengths from 11.1 ± 1.8 to 13.1 ± 1.4 μm of mostly unimodal distributions. Thirty-one single-grain raw AHe ages are in a range of 134 ± 8 to 21 ± 1 Ma. The AFT ages decrease monotonously from NW to SE until thrust faults along the two transects, with an age-jump across thrust F35. Joint thermal history modelling shows a three-stage cooling history as a result of denudation, especially with spatial differentiation in the first stage. Relative slow cooling at c. 0.6–1.0 °C/Ma occurred in the BQ and the northern part of the HQ transect during 220–100 Ma and the northern part of the CU transect during 160–100 Ma, respectively, with an amount of c. 2–3 km denudation between 160 and 100 Ma, implying little movement along the thrusts F13 and F33. In the middle and southern parts of the HQ transect and the southern part of the CU transect, rapid cooling at c. 4.0–7.0 °C/Ma, with c. 6–9 km denudation during 170–130 or 160–100 Ma, respectively, is probably influenced by thrusting of F35, F38 and F42 and the resultant tilting. A combination of thrusting, tilting, and denudation led to the youngering trends towards thrusts in different parts. However, there was no significant denudation across the Langshan Mountains in the second stage from c. 100 or 80 Ma until the last stage of rapid denudation (c. 2 km) since 20–10 Ma, which is simultaneous with the rapid uplift of the northern part of the Tibetan Plateau at c. 15 Ma. A youngering trend of AFT ages from the inner to the peripherals of the Mongolian Plateau implies the outward propagation of the Mongolian Plateau since the Mesozoic
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