4,158 research outputs found

    Altering the stability of the Cdc8 overlap region modulates the ability of this tropomyosin to bind cooperatively to actin and regulate myosin.

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    Tropomyosin (Tm) is an evolutionarily conserved ?-helical coiled-coil protein, dimers of which form end-to-end polymers capable of associating with and stabilising actin-filaments and regulate myosin function. The fission yeast, Schizosaccharomyces pombe, possesses a single essential Tm, Cdc8, which can be acetylated on its amino terminal methionine to increase its affinity for actin and enhance its ability to regulate myosin function. We have designed and generated a number of novel Cdc8 mutant proteins with amino terminal substitutions to explore how stability of the Cdc8-polymer overlap region affects the regulatory function of this Tm. By correlating the stability of each protein, its propensity to form stable polymers, its ability to associate with actin and to regulate myosin, we have shown the stability of the amino terminal of the Cdc8 ?-helix is crucial for Tm function. In addition we have identified a novel Cdc8 mutant with increased amino-terminal stability, dimers of which are capable of forming Tm-polymers significantly longer than the wild-type protein. This protein had a reduced affinity for actin with respect to wild type, and was unable to regulate actomyosin interactions. The data presented here are consistent with acetylation providing a mechanism for modulating the formation and stability of Cdc8 polymers within the fission yeast cell. The data also provide evidence for a mechanism in which Tm dimers form end-to-end polymers on the actin-filament, consistent with a cooperative model for Tm binding to actin

    Survival and Reproduction of Wild Turkeys in the Northern Black Hills of South Dakota

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    In South Dakota, wild turkeys are a high-interest species for both consumptive and non-consumptive uses.  Harvest records indicate that the population segment residing in the northern Black Hills may be declining.  Although data on hen survival, nesting survival, and early poult survival were collected for the southern Black Hills in the early 2000s, there is currently a paucity of demographic data for the northern Black Hills.  We seek to inform wild turkey management by characterizing demography specifically for the northern Black Hills.  We radio-tracked 80 turkey hens (40 adults/40 juveniles) in 2016 to estimate rates of hen survival, nesting, nesting success, and early poult survival; this two-year study will continue in 2017.  Based on preliminary data, rates of nesting by adult hens are lower in the northern Black Hills than the southern Black Hills (77.5% vs. 98%), as are rates of renesting by adult hens (33% vs. 75%).  We are in the process of estimating hen survival, but preliminary results indicate that annual survival is approximately 50%.  Poult survival to 4 weeks is comparable in the northern and southern Black Hills, but lower than in other portions of the range of Merriam’s wild turkey.  Although the northern and southern Black Hills are in close proximity, the substantial climatic differences likely explain the reduced productivity of the turkey population in the northern Black Hills.  Limiting fall harvest of wild turkey hens in the northern Black Hills may be required to sustainably manage this important game species

    Discovering the Elite Hypervolume by Leveraging Interspecies Correlation

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    Evolution has produced an astonishing diversity of species, each filling a different niche. Algorithms like MAP-Elites mimic this divergent evolutionary process to find a set of behaviorally diverse but high-performing solutions, called the elites. Our key insight is that species in nature often share a surprisingly large part of their genome, in spite of occupying very different niches; similarly, the elites are likely to be concentrated in a specific "elite hypervolume" whose shape is defined by their common features. In this paper, we first introduce the elite hypervolume concept and propose two metrics to characterize it: the genotypic spread and the genotypic similarity. We then introduce a new variation operator, called "directional variation", that exploits interspecies (or inter-elites) correlations to accelerate the MAP-Elites algorithm. We demonstrate the effectiveness of this operator in three problems (a toy function, a redundant robotic arm, and a hexapod robot).Comment: In GECCO 201

    Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression

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    background: There is an acute need to uncover biomarkers that reflect the molecular pathologies, underpinning prostate cancer progression and poor patient outcome. We have previously demonstrated that in prostate cancer cell lines PDE4D7 is downregulated in advanced cases of the disease. To investigate further the prognostic power of PDE4D7 expression during prostate cancer progression and assess how downregulation of this PDE isoform may affect disease outcome, we have examined PDE4D7 expression in physiologically relevant primary human samples. methods: About 1405 patient samples across 8 publically available qPCR, Affymetrix Exon 1.0 ST arrays and RNA sequencing data sets were screened for PDE4D7 expression. The TMPRSS2-ERG gene rearrangement status of patient samples was determined by transformation of the exon array and RNA seq expression data to robust z-scores followed by the application of a threshold >3 to define a positive TMPRSS2-ERG gene fusion event in a tumour sample. results: We demonstrate that PDE4D7 expression positively correlates with primary tumour development. We also show a positive association with the highly prostate cancer-specific gene rearrangement between TMPRSS2 and the ETS transcription factor family member ERG. In addition, we find that in primary TMPRSS2-ERG-positive tumours PDE4D7 expression is significantly positively correlated with low-grade disease and a reduced likelihood of progression after primary treatment. Conversely, PDE4D7 transcript levels become significantly decreased in castration resistant prostate cancer (CRPC). conclusions: We further characterise and add physiological relevance to PDE4D7 as a novel marker that is associated with the development and progression of prostate tumours. We propose that the assessment of PDE4D7 levels may provide a novel, independent predictor of post-surgical disease progression

    The neutron halo of 6^6He in a microscopic model

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    The two--neutron separation energy of 6^6He has been reproduced for the first time in a realistic parameter--free microscopic multicluster model comprising the α+n+n\alpha +n+n and t+tt+t clusterizations, with α\alpha cluster breathing excitations included. The contribution of the t+tt+t channel is substantial. A very thick (0.85 fm) neutron halo has been found in full agreement with the results of the latest phenomenological analysis.Comment: Submitted to Phys. Rev. C, 8 pages, Latex with Revtex, 2 figures (not included) available on request, 08-03-9

    On Hilberg's Law and Its Links with Guiraud's Law

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    Hilberg (1990) supposed that finite-order excess entropy of a random human text is proportional to the square root of the text length. Assuming that Hilberg's hypothesis is true, we derive Guiraud's law, which states that the number of word types in a text is greater than proportional to the square root of the text length. Our derivation is based on some mathematical conjecture in coding theory and on several experiments suggesting that words can be defined approximately as the nonterminals of the shortest context-free grammar for the text. Such operational definition of words can be applied even to texts deprived of spaces, which do not allow for Mandelbrot's ``intermittent silence'' explanation of Zipf's and Guiraud's laws. In contrast to Mandelbrot's, our model assumes some probabilistic long-memory effects in human narration and might be capable of explaining Menzerath's law.Comment: To appear in Journal of Quantitative Linguistic

    Wear Minimization for Cuckoo Hashing: How Not to Throw a Lot of Eggs into One Basket

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    We study wear-leveling techniques for cuckoo hashing, showing that it is possible to achieve a memory wear bound of loglogn+O(1)\log\log n+O(1) after the insertion of nn items into a table of size CnCn for a suitable constant CC using cuckoo hashing. Moreover, we study our cuckoo hashing method empirically, showing that it significantly improves on the memory wear performance for classic cuckoo hashing and linear probing in practice.Comment: 13 pages, 1 table, 7 figures; to appear at the 13th Symposium on Experimental Algorithms (SEA 2014

    Hybridization and Postprocessing Techniques for Mixed Eigenfunctions

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    We introduce hybridization and postprocessing techniques for the Raviart–Thomas approximation of second-order elliptic eigenvalue problems. Hybridization reduces the Raviart–Thomas approximation to a condensed eigenproblem. The condensed eigenproblem is nonlinear, but smaller than the original mixed approximation. We derive multiple iterative algorithms for solving the condensed eigenproblem and examine their interrelationships and convergence rates. An element-by-element postprocessing technique to improve accuracy of computed eigenfunctions is also presented. We prove that a projection of the error in the eigenspace approximation by the mixed method (of any order) superconverges and that the postprocessed eigenfunction approximations converge faster for smooth eigenfunctions. Numerical experiments using a square and an L-shaped domain illustrate the theoretical results
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