23 research outputs found

    Correcting pervasive errors in RNA crystallography through enumerative structure prediction

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    Three-dimensional RNA models fitted into crystallographic density maps exhibit pervasive conformational ambiguities, geometric errors and steric clashes. To address these problems, we present enumerative real-space refinement assisted by electron density under Rosetta (ERRASER), coupled to Python-based hierarchical environment for integrated 'xtallography' (PHENIX) diffraction-based refinement. On 24 data sets, ERRASER automatically corrects the majority of MolProbity-assessed errors, improves the average Rfree factor, resolves functionally important discrepancies in noncanonical structure and refines low-resolution models to better match higher-resolution models

    Predicting new venture survival and growth: does the fog lift?

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    This paper investigates whether new venture performance becomes easier to predict as the venture ages: does the fog lift? To address this question we primarily draw upon a theoretical framework, initially formulated in a managerial context by Levinthal (Adm Sci Q 36(3):397–420, 1991) that sees new venture sales as a random walk but survival being determined by the stock of available resources (proxied by size). We derive theoretical predictions that are tested with a 10-year cohort of 6579 UK new ventures in the UK. We observe that our ability to predict firm growth deteriorates in the years after entry—in terms of the selection environment, the ‘fog’ seems to thicken. However, our survival predictions improve with time—implying that the ‘fog’ does lift

    Prospect theory and the effects of bankruptcy laws on entrepreneurial aspirations

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    We apply prospect theory to explain how personal and corporate bankruptcy laws affect risk perceptions of entrepreneurs at time of entry and therefore their growth ambitions. Previous theories have reached ambiguous conclusions as to whether countries with more debtor-friendly bankruptcy laws (i.e. laws that are more forgiving towards debtors in bankruptcy proceedings) are likely to have more entrepreneurs, or whether, creditorfriendly regimes have positive effects on new ventures via enhanced incentives for the supply of credit to entrepreneurs. Responding to this ambiguity, we apply prospect theory to propose that entrepreneurs do not attach the same significance to different elements of bankruptcy codes—and to explain which aspects of debtor-friendly bankruptcy laws matter more to entrepreneurs. Based on this, we derive and confirm hypotheses about the impact of aspects of bankruptcy codes on entrepreneurial activity using the Global Entrepreneurship Monitor combined with data on both personal and corporate bankruptcyregulations for 15 developed OECD countries. We use multilevel random coefficient logistic regressions to take account of the hierarchical nature of the data (country and individual levels). Because entrepreneurs and creditors are sensitive to different elements of the codes, there is scope for optimisation of the legal design of bankruptcy law to achieve both an adequate supply of credit and to encourage high-ambition entrepreneurship

    Structure of a mitochondrial fission dynamin in the closed conformation

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    Dynamin 1-like proteins (DNM1-L) are mechanochemical GTPases that induce membrane fission in mitochondria and peroxisomes. Their mechanism depends on conformational changes driven by nucleotide and lipid cycling. Here we show the crystal structure of a mitochondrial fission dynamin (CmDnm1) from the algae Cyanidioschyzon merolae. Unlike other eukaryotic dynamin structures, CmDnm1 is in a hinge 1 closed conformation, with the GTPase domain compacted against the stalk. Within the crystal, CmDnm1 packs as a diamond-shaped tetramer that is consistent with an inactive off-membrane state. Crosslinking, photoinduced electron transfer assays, and electron microscopy verify these structures. In vitro, CmDnm1 forms concentration-dependent rings and protein–lipid tubes reminiscent of DNM1-L and classical dynamin with hinge 1 open. Our data provides a mechanism for filament collapse and membrane release that may extend to other dynamin family members. Additionally, hinge 1 closing may represent a key conformational change that contributes to membrane fission
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