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    An approach for de novo structure determination of dynamic molecular assemblies by electron cryomicroscopy.

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    SummarySingle-particle electron cryomicroscopy is a powerful method for three-dimensional (3D) structure determination of macromolecular assemblies. Here we address the challenge of determining a 3D structure in the absence of reference models. The 3D structures are determined by alignment and weighted averaging of densities obtained by native cryo random conical tilt (RCT) reconstructions including consideration of missing data. Our weighted averaging scheme (wRCT) offers advantages for potentially heterogeneous 3D densities of low signal-to-noise ratios. Sets of aligned RCT structures can also be analyzed by multivariate statistical analysis (MSA) to provide insights into snapshots of the assemblies. The approach is used to compute 3D structures of the Escherichia coli 70S ribosome and the human U4/U6.U5 tri-snRNP under vitrified unstained cryo conditions, and to visualize by 3D MSA the L7/L12 stalk of the 70S ribosome and states of tri-snRNP. The approach thus combines de novo 3D structure determination with an analysis of compositional and conformational heterogeneity

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Etiologic influence on chromosomal aberrations in European hepatocellular carcinoma identified by CGH

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    Previous studies suggest different pathways in the molecular development of hepatocellular carcinoma (HCC). We investigated the pattern of chromosomal imbalances in HCC depending on the type of underlying liver disease as detected by comparative genomic hybridization in 67 cases of primary HCC occurring in non-cirrhotic livers (n = 30), in liver cirrhosis (LC) related to alcohol intake (n = 9), cryptogenic or metabolic changes (n = 11), and chronic viral hepatitis B or C (n = 17). HCC were treated by liver resection in 48 patients and transplantation in 19 patients. The 10-year disease-free and overall survival rates were 51% and 68%, respectively. The copy number changes occurring in more than 10% of cases were gains at 8q (55%), 1q (49%), 7q (15%), 7p (13%), 6p (12%), and 20q (12%), as well as losses at 8p (55%), 4q (33%), 6q (33%), 13q (25%), 14q (24%), 17p (22%), 16q (19%),1p (18%), 18q (16%), 9p (13%), 10q (13%), 4p (12%), and 9q (12%). HCC arising in alcoholic LC showed a different pattern with significantly fewer net changes (p = 0.008), particularly fewer chromosomal gains (p = 0.008) and fewer breakpoints (p = 0.003) compared to the other investigated HCC subgroups. Future clinical studies should evaluate the prognostic relevance of these findings. (C) 2013 Elsevier GmbH. All rights reserved
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