The frozen phonon technique is introduced as a means of including the effects of thermal vibrations in multislice calculations of CBED patterns. This technique produces a thermal diffuse background, Kikuchi bands and a Debye-Waller factor, all of which are neglected in the standard multislice calculation. The frozen phonon calculations match experimental silicon (100) CBED patterns for specimen 0108-7673/91/030267-12503.00© 1991 International Union of Crystallography THERMAL VIBRATIONS IN CONVERGENT-BEAM ELECTRON DIFFRACTIONthicknesses of up to at least 550 A. The best-fit silicon r.m.s, vibration amplitude at near room temperature was determined to be 0.085(5)/~. As an independent check of validity, a comparison of calculated CBED, experimental CBED and electron energy loss spectroscopy (EELS) data was also performed. The frozen phonon technique provides an improved theoretical basis for the simulation of CBED and therefore annular dark field scanning transmission electron microscope imaging.( 1) IntroductionConvergent-beam electron diffraction (CBED) is widely used for microcharacterization (Steeds, 1983; Eades, 1988). The most common application is to identify known structures and their orientations, but CBED has also been used to determine accurate unit-cell dimensions (Jones, Rackham & Steeds, 1977), structure symmetries (Goodman, 1975;Tanaka, Saito & Sekii, 1983) and even atomic positions (Vincent, Bird & Steeds, 1984). Strain fields around defects (Fung, 1985;Carpenter & Spence, 1982), specimen thicknesses (Kelly, Jostsons, Blake & Napier, 1975;Kirkland, Loane, Xu & Silcox, 1989), ionicity (Zuo, Spence & O'Keeffe, 1988) and the phase of complex atomic structure factors (Zuo, Spence & H¢ier, 1989;Bird, James & Preston, 1987) have also been determined. The sum of the large-angle scattering in the CBED pattern produces the annular dark field (ADF) scanning transmission electron microscope (STEM) image (Langmore, Wall & Isaacson, 1973), which has recently proven capable of resolving atomic structures with Z contrast (Pennycook, 1989;Pennycook, Jesson & Chisholm, 1990) at better than 2,~ resolution (Xu, Kirkland, Silcox & Keyse, 1990; Shin, Kirkland & Silcox, 1989). Three major features of the large-angle scattering are Kikuchi bands (Kikuchi, 1928;Kainuma, 1955;Takagi, 1958), a thermal diffuse scattering (TDS) background (Hall & Hirsch, 1965) and a higher-order Laue zone (HOLZ) ring (Hirsch, Howie, Nicholson, Pashley & Whelan, 1977). Thermal vibrations generate the first two features and reduce the intensity of the third by a Debye-Waller factor (Debye, 1914). Since the intensity in the HOLZ ring may be a significant fraction of the ADF STEM signal (Spence, Zuo & Lynch, 1989), the signal may be sensitive to thermal vibration. There are suggestions that thermal vibrations can change the relative contrast of different elements in the ADF STEM signal (Wang & Cowley, 1989), which differs from the suggestion that the signal is simply related to the atomic cross sections . Accordingly, understanding the ...

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Effective therapeutic strategies to treat CKD-induced muscle atrophy are urgently needed. Lowfrequency electrical stimulation (LFES) may be effective in preventing muscle atrophy, because LFES is an acupuncture technique that mimics resistance exercise by inducing muscle contraction. To test this hypothesis, we treated 5/6-nephrectomized mice (CKD mice) and control mice with LFES for 15 days. LFES prevented soleus and extensor digitorum longus muscle weight loss and loss of hind-limb muscle grip in CKD mice. LFES countered the CKD-induced decline in the IGF-1 signaling pathway and led to increases in markers of protein synthesis and myogenesis and improvement in muscle protein metabolism. In control mice, we observed an acute response phase immediately after LFES, during which the expression of inflammatory cytokines (IFN-g and IL-6) increased. Expression of the M1 macrophage marker IL-1b also increased acutely, but expression of the M2 marker arginase-1 increased 2 days after initiation of LFES, paralleling the change in IGF-1. In muscle cross-sections of LFES-treated mice, arginase-1 colocalized with IGF-1. Additionally, expression of microRNA-1 and -206, which inhibits IGF-1 translation, decreased in the acute response phase after LFES and increased at a later phase. We conclude that LFES ameliorates CKDinduced skeletal muscle atrophy by upregulation of the IGF-1 signaling pathway, which improves protein metabolism and promotes myogenesis. The upregulation of IGF-1 may be mediated by decreased expression of microRNA-1 and -206 and/or activation of M2 macrophages.

BackgroundThere is growing evidence that Bit1 exerts different roles in the development and progression of human cancers. Although Bit1 was highly exhibited in ESCC tissues in our previous study, its roles and molecular mechanisms implicated in development and progression of ESCC remain unknown.MethodsBit1 protein expression in ESCC cell lines and normal esophageal epithelial cell was detected by Western blotting. Bit1 protein expression mediated by Bit1 shRNA was investigated by Western blotting. MTT, migration assay, invasion experiment, ELISA and Flow cytometry were utilized to determine the effects of Bit1 knockdown on cell proliferation, migration, invasion and apoptosis, respectively. A xenograft model was used to examine in vivo tumourigenicity, and immunohistochemistry and TUNEL were utilized to evaluate the related protein expression and apoptosis. Gene microarray was determined by Agilent SurePrint G3 Human GE 8 × 60 K Microarray, the interaction of Bit1 and FAK proteins were detected by Immunoprecipitation and the key protein expressions of FAK-paxillin pathway were detected by Western blotting.ResultsWe found Bit1 expression in all human ESCC cell lines tested was significantly higher than that in normal esophageal epithelial cell Het-1A (P < 0.05), in which EC9706 presented the highest Bit1 level. Bit1 protein level was significantly downregulated at day 1 after transfection with specific shRNA against Bit1 (P < 0.05). At days 2 and 3, Bit1 level reached the lowest value after transfection with Bit1 shRNA. Moreover, Bit1 depletion contributed to growth inhibition in vitro and in vivo, reduced cell migration and invasion abilities, and induced cell apoptosis in EC9706 and TE1 cells. More importantly, Bit1 downregulation significantly lowered Bcl-2 and MMP-2 levels in EC9706 xenografted tumor tissues, meanwhile triggered apoptosis after treatment with different doses of Bit1 shRNA. Further gene microarray revealed that 23 genes in Bit1-RNAi group were markedly downregulated, whereas 16 genes were obviously upregulated. Notably, Bit1 intrinsically interacted with FAK protein in EC9706 cells. Moreover, paxillin was downregulated at mRNA and protein levels in Bit1 shRNA group, coupled with the decreases of FAK mRNA and protein expressions.ConclusionBit1 may be an important regulator in cell growth, apoptosis, migration and invasion of ESCC via targeting FAK-paxillin pathway, and thereby combinative manipulation of Bit1 and FAK-paxillin pathway may be the novel and promising therapeutic targets for the patients with ESCC.

Abstract. Previous studies have demonstrated that Notch1 signaling pathway plays a major role in maintaining the balance of cell proliferation, differentiation and apoptosis, and is closely associated with tumorigenesis. However, roles of Notch1 signaling pathway in esophageal squamous cell carcinoma (ESCC), which is a common cause of mortality in China, remain poorly understood. Therefore, a novel strategy for seeking a rational molecular therapeutic target for ESCC is urgently needed. The purpose of this study is to examine the effect of the active Notch1 signaling pathway on the proliferation and apoptosis of ESCC cells and to investigate the underlying molecular mechanisms in carcinogenesis of the esophagus. The results revealed that a constitutively activated Notch1 signaling pathway was observed in ESCC cell line EC9706, through a pcNICD vector mediated expression system. Clearly, the activated Notch1 signaling pathway gave rise to proliferation suppression of the cells, accompanied with a cell cycle inhibition at the G 0 /G 1 phase and apoptosis. In contrast to the expression of CDK2, cyclin D1 and cyclin E observed in EC9706 cells untreated and transfected with pcDNA3.1, there was a markedly decrease in the cells stably expressing Notch1 NICD. Up-and down-regulations of GSK3ß and ß-catenin, respectively, indicated that Notch1 inhibited proliferation and induced apoptosis of EC9706 cells through Wnt-mediated signaling pathway. These findings suggest that Notch1 signaling pathway may participate in carcinogenesis of the esophagus.