14,723 research outputs found

    Fishes of the Eleven Point River Within Arkansas

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    A survey of the fishes of the Eleven Point River and its tributaries was made between 31 January 1976 and 13 February 1977. Sixty-three collections, literature records and personal communications revealed 90 species distributed among 19 families. This study revealed 31 species previously not reported for this river system. The Eleven Point River is a clear, predominantly springfed Ozark stream which is located in western Randolph County. From the Arkansas-Missouri state line, the Eleven Point River flows south for approximately 64 km before joining the Spring River. Terrain in the Arkansas portion of this river is rugged as the river meanders through the Salem Plateau of the Ozark Mountains

    What is the Value of Public Goods Generated by a National Football League Team: A CVM Approach

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    Using the Contingent Valuation Method, this paper estimates the value of public goods the National Football League’s Jaguars produce for Jacksonville, Florida, including the value of elevating Jacksonville to major league status. It also estimates the incremental value of public goods potentially produced by a National Basketball Association team in Jacksonville. The present value of public goods created by the Jaguars is 25millionorless,farbelowsubsidiesprovidedtoattracttheJaguars.Forabasketballteam,thefigureislessthan25 million or less, far below subsidies provided to attract the Jaguars. For a basketball team, the figure is less than 12.7 million. Sports public goods probably cannot justify the large public expenditures on stadiums and arenas.

    Multiple interfaces between a serine recombinase and an enhancer control site-specific DNA inversion.

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    Serine recombinases are often tightly controlled by elaborate, topologically-defined, nucleoprotein complexes. Hin is a member of the DNA invertase subclass of serine recombinases that are regulated by a remote recombinational enhancer element containing two binding sites for the protein Fis. Two Hin dimers bound to specific recombination sites associate with the Fis-bound enhancer by DNA looping where they are remodeled into a synaptic tetramer competent for DNA chemistry and exchange. Here we show that the flexible beta-hairpin arms of the Fis dimers contact the DNA binding domain of one subunit of each Hin dimer. These contacts sandwich the Hin dimers to promote remodeling into the tetramer. A basic region on the Hin catalytic domain then contacts enhancer DNA to complete assembly of the active Hin tetramer. Our results reveal how the enhancer generates the recombination complex that specifies DNA inversion and regulates DNA exchange by the subunit rotation mechanism. DOI:http://dx.doi.org/10.7554/eLife.01211.001

    A Framework to Manage the Complex Organisation of Collaborating: Its Application to Autonomous Systems

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    In this paper we present an analysis of the complexities of large group collaboration and its application to develop detailed requirements for collaboration schema for Autonomous Systems (AS). These requirements flow from our development of a framework for collaboration that provides a basis for designing, supporting and managing complex collaborative systems that can be applied and tested in various real world settings. We present the concepts of "collaborative flow" and "working as one" as descriptive expressions of what good collaborative teamwork can be in such scenarios. The paper considers the application of the framework within different scenarios and discuses the utility of the framework in modelling and supporting collaboration in complex organisational structures

    Selectivity by Small-Molecule Inhibitors of Protein Interactions Can Be Driven by Protein Surface Fluctuations

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    Small-molecules that inhibit interactions between specific pairs of proteins have long represented a promising avenue for therapeutic intervention in a variety of settings. Structural studies have shown that in many cases, the inhibitor-bound protein adopts a conformation that is distinct from its unbound and its protein-bound conformations. This plasticity of the protein surface presents a major challenge in predicting which members of a protein family will be inhibited by a given ligand. Here, we use biased simulations of Bcl-2-family proteins to generate ensembles of low-energy conformations that contain surface pockets suitable for small molecule binding. We find that the resulting conformational ensembles include surface pockets that mimic those observed in inhibitor-bound crystal structures. Next, we find that the ensembles generated using different members of this protein family are overlapping but distinct, and that the activity of a given compound against a particular family member (ligand selectivity) can be predicted from whether the corresponding ensemble samples a complementary surface pocket. Finally, we find that each ensemble includes certain surface pockets that are not shared by any other family member: while no inhibitors have yet been identified to take advantage of these pockets, we expect that chemical scaffolds complementing these “distinct” pockets will prove highly selective for their targets. The opportunity to achieve target selectivity within a protein family by exploiting differences in surface fluctuations represents a new paradigm that may facilitate design of family-selective small-molecule inhibitors of protein-protein interactions.This work was supported by a grant from the National Institute of General Medical Sciences of the National Institutes of Health (R01GM099959), the National Science Foundation through XSEDE allocation MCB130049, and the Alfred P. Sloan Fellowship (JK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Forest Planning on the National Forests Under Ecosystem Management

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    17 pages. Contains 2 pages of references

    Druggable Protein Interaction Sites Are More Predisposed to Surface Pocket Formation than the Rest of the Protein Surface

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    Despite intense interest and considerable effort via high-throughput screening, there are few examples of small molecules that directly inhibit protein-protein interactions. This suggests that many protein interaction surfaces may not be intrinsically “druggable” by small molecules, and elevates in importance the few successful examples as model systems for improving our fundamental understanding of druggability. Here we describe an approach for exploring protein fluctuations enriched in conformations containing surface pockets suitable for small molecule binding. Starting from a set of seven unbound protein structures, we find that the presence of low-energy pocket-containing conformations is indeed a signature of druggable protein interaction sites and that analogous surface pockets are not formed elsewhere on the protein. We further find that ensembles of conformations generated with this biased approach structurally resemble known inhibitor-bound structures more closely than equivalent ensembles of unbiased conformations. Collectively these results suggest that “druggability” is a property encoded on a protein surface through its propensity to form pockets, and inspire a model in which the crude features of the predisposed pocket(s) restrict the range of complementary ligands; additional smaller conformational changes then respond to details of a particular ligand. We anticipate that the insights described here will prove useful in selecting protein targets for therapeutic intervention.This work was supported by grants from the National Center for Research Resources (5P30RR030926) and the National Institute of General Medical Sciences (1R01GM099959 and 8P30GM103495) of the National Institutes of Health, and the Alfred P. Sloan Fellowship (JK)

    Forest Planning on the National Forests Under Ecosystem Management

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    17 pages. Contains 2 pages of references

    Harnessing Natural Resource Wealth for Development: The case of Ghana

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    Ghana’s economy depends largely on foreign aid and has performed well in recent years in terms of GDP growth after the launch of the economic recovery programme in 1983. In spite of this there has been minimal impact on poverty reduction with rural folks bearing the major brunt of poverty. Ghana on the other hand is endowed with rich natural resources that can prudently be managed to ensure sustainable economic growth, high standards of living and a prosperous new Ghana. The scary thing however, about windfall wealth is that they can be a blessing creating economic prosperity or a curse spawning war, corruption and deindustrialization. The recent discovery of oil and current discussion by government on the concept to adopt in managing oil revenues have also added to the hopes of many Ghanaians for a better life as they wait patiently on ‘Petro-dollars’ to help improve the performance of the economy. Irrespective of which strategy government adopts, engineering a new Ghanaian economy demands policies that uses natural resource revenues to diversify and produce a robust self reliant economy capable of sustaining itself against external shock necessary to avoid the resource curse or Dutch-Disease. Keywords: National Resources, Diversification, Value Addition, Development, Ghan

    Assembly of a Tightly Interwound DNA Recombination Complex Poised for Deletion

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    In a recent issue of Molecular Cell, Mouw et al. (2008) report a crystal structure of a serine recombinase bound to a regulatory DNA site in an unexpected synaptic complex configuration, which forms the framework for a new model of the entire 12 subunit, 186 bp deletion complex
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