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991.
Abstract A multilayer film of argon adsorbed on the basal plane of graphite at 103 K was simulated using isokinetic molecular dynamics. The local chemical potentials in the film were evaluated using three algorithms suggested in the literature: test particle insertion, real particle calculation and the ratio method, which relies on calculations of the local energy distribution functions for test and real particles. Although none of these was suitable for calculations involving the partially solidified first adsorbed layer, the test particle and the ratio method produced useful results for regions in the film corresponding to second and higher layers. The ratio method is shown to be the most realistic, giving constant local chemical potentials of reasonably high precision for all points other than in the first layer. 相似文献
992.
993.
Volkmar Weissig Sarathi V. Boddapati Shing-Ming Cheng Gerard G. M. D’souza 《Journal of liposome research》2013,23(3):249-264
Mitochondrial research is presently one of the fastest growing disciplines in biomedicine. Since the early 1990s, it has become increasingly evident that mitochondrial dysfunction contributes to a large variety of human disorders, ranging from neurodegenerative and neuromuscular diseases, obesity, and diabetes to ischemia-reperfusion injury and cancer. Most remarkably, mitochondria, the “power house” of the cell, have also become accepted as the “motor of cell death” reflecting their recognized key role during apoptosis. Based on these recent exciting developments in mitochondrial research, increasing pharmacological efforts have been made leading to the emergence of “Mitochondrial Medicine” as a whole new field of biomedical research. The identification of molecular mitochondrial drug targets in combination with the development of methods for selectively delivering biologically active molecules to the site of mitochondria will eventually launch a multitude of new therapies for the treatment of mitochondria-related diseases, which are based either on the selective protection, repair, or eradication of cells. Yet, while tremendous efforts are being undertaken to identify new mitochondrial drugs and drug targets, the development of mitochondria-specific drug carrier systems is lagging behind. To ensure a high efficiency of current and future mitochondrial therapeutics, colloidal vectors, i.e., delivery systems, need to be developed able to selectively transport biologically active molecules to and into mitochondria within living human cells. Here we review ongoing efforts in our laboratory directed toward the development of different phospholipid- and non-phospholipid-based mitochondriotropic drug carrier systems. 相似文献
994.
Alanna M. Gilmour Samar Abdulkhalek Timothy S.W. Cheng Farah Alghamdi Preethi Jayanth Leah K. O’Shea Olivia Geen Luis A. Arvizu Myron R. Szewczuk 《Cellular signalling》2013,25(12):2587-2603
Epidermal growth factor (EGF)-induced EGFR tyrosine kinase receptor activation in cancer cell survival responses has become a strategic molecular-targeting clinical therapeutic intent, but the failures of these targeted approaches in the clinical setting demand alternate strategies. Here, we uncover a novel neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP-9) cross-talk in alliance with GPCR neuromedin B, which is essential for EGF-induced receptor activation and cellular signaling. Neu1 and MMP-9 form a complex with EGFR on the cell surface. Tamiflu (oseltamivir phosphate), anti-Neu1 antibodies, broad range MMP inhibitor galardin (GM6001), neuromedin B GPCR specific antagonist BIM-23127, the selective inhibitor of whole heterotrimeric G-protein complex BIM-46174 and MMP-9 specific inhibitor dose-dependently inhibited Neu1 activity associated with EGF stimulated 3T3–hEGFR cells. Tamiflu, anti-Neu1 antibodies and MMP9i attenuated EGFR phosphorylation associated with EGF-stimulated cells. Preclinical data provide the proof-of-evidence for a therapeutic targeting of Neu1 with Tamiflu in impeding human pancreatic cancer growth and metastatic spread in heterotopic xenografts of eGFP-MiaPaCa-2 tumors growing in RAGxCγ double mutant mice. Tamiflu-treated cohort exhibited a reduction of phosphorylation of EGFR-Tyr1173, Stat1-Tyr701, Akt-Thr308, PDGFRα-Tyr754 and NFκBp65-Ser311 but an increase in phospho-Smad2-Ser465/467 and -VEGFR2-Tyr1175 in the tumor lysates from the xenografts of human eGFP-MiaPaCa-2 tumor-bearing mice. The findings identify a novel promising alternate therapeutic treatment of human pancreatic cancer. 相似文献
995.
996.
Jing-Jing Yang Hui Tao Cheng Huang Kai-hu Shi Tao-Tao Ma Er-Bao Bian Lei Zhang Li-Ping Liu Wei Hu Xiong-Wen Lv Jun Li 《Cellular signalling》2013,25(5):1202-1211
Hepatic stellate cell (HSC) activation plays an important role in liver fibrogenesis. Transdifferentiation of quiescent hepatic stellate cells into myofibroblastic-HSCs is a key event in liver fibrosis. The methyl-CpG-binding protein MeCP2 which promotes repressed chromatin structure is selectively detected in myofibroblasts of diseased liver. MeCP2 binds to methylated CpG dinucleotides, which are abundant in the promoters of many genes. Treatment of HSCs with DNA methylation inhibitor 5-aza-2′- deoxycytidine (5-azadC) prevented proliferation and activation. Treatment with 5-azadC prevented loss of Patched (PTCH1) expression that occurred during HSCs activation. In a search for underlying molecular medchanisms, we investigated whether the targeting of epigenetic silencing mechanisms could be useful in the treatment of PTCH1-associated fibrogenesis. It was indicated that hypermethylation of PTCH1 is associated with the perpetuation of fibroblast activation and fibrosis in the liver. siRNA knockdown of MeCP2 increased the expressions of PTCH1 mRNA and protein in hepatic myofibroblasts. These data suggest that DNA methylation and MeCP2 may provide molecular mechanisms for silencing of PTCH1. 相似文献
997.
Xiao‐Peng Zhang Tao Wu Jian Liu Jin‐Cheng Zhao Cheng‐Hui Li Xiao‐Zeng You 《Chirality》2013,25(7):384-392
Two couples of enantiomeric platinum(II) complexes: Pt(L1a)Cl ( 1a ), Pt(L1b)Cl ( 1b ) and Pt(L1a)(C ≡ C ? Ph) ( 2a ), Pt(L1b)(C ≡ C ? Ph) ( 2b ) (L1a = (+)‐1,3‐di‐(2‐(4,5‐pinene)pyridyl)benzene, L1b = (?)‐1,3‐di‐(2‐(4,5‐pinene)pyridyl)benzene) were synthesized and characterized. Their absolute configurations were determined by single crystal X‐ray diffraction and further verified by circular dichroism (CD) spectra (including electronic circular dichroism [ECD] and vibrational circular dichroism [VCD]). These complexes show interesting mechanoluminescence and/or vapoluminescence due to crystalline‐to‐amorphous transformation. The crystalline solids, grinding‐induced amorphous powders, and vapor‐induced amorphous powders of complexes 2a and 2b were comparatively investigated by solid‐state ECD and VCD spectra. The transformation from crystalline solids to amorphous powders was accompanied by significant variances of the spectral feature in both ECD and VCD spectra. Chirality 25:384–392, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
998.
999.
1000.
Cheng X. Li Xin Wei Lu Lu Jeremy L. Peirce Robert W. Williams 《Somatosensory & motor research》2013,30(3):141-150
We measured the combined area of posterior medial barrel subfield (PMBSF) and anterior lateral barrel subfield (ALBSF) areas in four common inbred strains (C3H/HeJ, A?/J, C57BL?/6J, DBA/2J), B6D2F1, and ten recombinant inbred (RI) strains generated from C57BL/6J and DBA/2J progenitors (BXD) as an initial attempt to examine the genetic influences underlying natural variation in barrel field size in adult mice. These two subfields are associated with the representation of the whisker pad and sinus hairs on the contralateral face. Using cytochrome oxidase labeling to visualize the barrel field, we measured the size of the combined subfields in each mouse strain. We also measured body weight and brain weight in each strain. We report that DBA/2J mice have a larger combined PMBSF/ALBSF area (6.15?±?0.10?mm2,?n?=?7) than C57BL?/6J (5.48?±?0.13?mm2,?n?=?10), C3H/HeJ (5.37?±?0.16?mm2,?n?=?10), and A/J mice (5.04?±?0.09?mm2,?n?=?15), despite the fact that DBA/2J mice have smaller average brain and body sizes. This finding may reflect dissociation between systems that control brain size with those that regulate barrel field area. In addition, BXD strains (average n?=?4) and parental strains showed considerable and continuous variation in PMBSF/ALBSF area, suggesting that this trait is polygenic. Furthermore, brain, body, and cortex weights have heritable differences between inbred strains and among BXD strains. PMBSF/ALBSF pattern appears similar among inbred and BXD strains, suggesting that somatosensory patterning reflects a common plan of organization. This data is an important first step in the quantitative genetic analysis of the parcellation of neocortex into diverse cytoarchitectonic zones that vary widely within and between species, and in identifying the genetic factors underlying barrel field size using quantitative trait locus (QTL) analyses. 相似文献