316,972 research outputs found

    Computational identification and analysis of protein short linear motifs

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    Short linear motifs (SLiMs) in proteins can act as targets for proteolytic cleavage, sites of post-translational modification, determinants of sub-cellular localization, and mediators of protein-protein interactions. Computational discovery of SLiMs involves assembling a group of proteins postulated to share a potential motif, masking out residues less likely to contain such a motif, down-weighting shared motifs arising through common evolutionary descent, and calculation of statistical probabilities allowing for the multiple testing of all possible motifs. Much of the challenge for motif discovery lies in the assembly and masking of datasets of proteins likely to share motifs, since the motifs are typically short (between 3 and 10 amino acids in length), so that potential signals can be easily swamped by the noise of stochastically recurring motifs. Focusing on disordered regions of proteins, where SLiMs are predominantly found, and masking out non-conserved residues can reduce the level of noise but more work is required to improve the quality of high-throughput experimental datasets (e.g. of physical protein interactions) as input for computational discovery

    About the Scythian Shields

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    Shields played major role in the armament system of the Scythians. Made from organic materials, they are poorly traced on the materials of archaeological excavations. Besides, scaly surface of shields was often perceived in practice as the remnants of the scaly armor. E. V. Chernenko was able to discern the difference between shields’ scaly plates and armor scales. The top edge of the scales was bent inwards, and shield plates had a wire fixation. These observations let significantly increase the number of shields, found in the burial complexes of the Scythians. The comparison of archaeological materials and the images of Scythian warriors allow distinguishing the main forms of Scythian shields. All shields are divided into fencing shields and cover shields. The fencing shields include round wooden shields, reinforced with bronze sheet, and round moon-shaped shields with a notch at the top, with a metal scaly surface. They came to the Scythians under the Greek influence and are known in the monuments of the 4th century BC. Oval shields with scaly surface (back cover shields) were used by the Scythian cavalry. They protected the rider in case of frontal attack, and moved back in case of maneuver or closein fighting. Scythian battle tactics were based on rapid approaching the enemy and throwing spears and further rapid withdrawal. Spears stuck in the shields of enemies, forcing them to drop the shields, uncover, and in this stage of the battle the archers attacked the disorganized ranks of the enemy. That was followed by the stage of close fight. Oval form of a wooden shield with leather covering was used by the Scythian infantry and spearmen. Rectangular shields, including wooden shields and the shields pleached from rods, represented a special category. The top of such shield was made of wood, and a pleached pad on leather basis was attached to it. This shield could be a reliable protection from arrows, but it could not protect against javelins. Rectangular wooden shields are allocated into a separate group. The lower edge of this shield was made oval. Wooden base of the shield had a thickness of 1 cm, and it was covered with cowhide. The shields covered with the leather of mountain goats, called Tarand in ancient sources, were of special value. The shield was held by means of two belt loops. One had passed through the forearm, and the other was held by the left hand. There are grounds to assume the presence of a pair of metal brackets on the back side of the shield used for holding the shield. The Scythians did not have centralized production of shields. This fact explains the diversity of forms

    Letter, 1934 Mar. 11, New York, N.Y., to Nilla Shields, Lafayette, Ga.

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    Letter, George Palmer Putnam to Nilla Shields, regarding Nilla and David’s sudden marriage, Sunday (postmarked envelope, March 11, 1934

    Comments on "A reconsideration of tax shield valuation" by Enrique R. Arzac and Lawrence R. Glosten

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    While Arzac and Glosten (2005) affirm that "the value of tax shields depends upon the nature of the equity stochastic process, which, in turn, depends upon the free cash flow process," I prove that the value of tax shields depends only upon the nature of the stochastic process of the net increase of debt. Arzac and Glosten (2005) formulate the constant leverage ratio assumption as Dt = L•Et. The assumption of Fernández (2004) is E{Dt}= L•E{Et}, where E{•} is the expected value operator, D the value of debt, E the equity value, and L a constant. The Arzac and Glosten (2005) assumption requires continuous debt rebalancing, while mine does not. Under both financial policies, the expected leverage ratio is constant, but the Arzac and Glosten (2005) assumption is too extreme.Value of tax shields; required return to equity; cost of capital; net increase of debt;

    Estimation and efficient computation of the true probability of recurrence of short linear protein sequence motifs in unrelated proteins.

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    Background: large datasets of protein interactions provide a rich resource for the discovery of Short Linear Motifs (SLiMs) that recur in unrelated proteins. However, existing methods for estimating the probability of motif recurrence may be biased by the size and composition of the search dataset, such that p-value estimates from different datasets, or from motifs containing different numbers of non-wildcard positions, are not strictly comparable. Here, we develop more exact methods and explore the potential biases of computationally efficient approximations. Results: a widely used heuristic for the calculation of motif over-representation approximates motif probability by assuming that all proteins have the same length and composition. We introduce pv, which calculates the probability exactly. Secondly, the recently introduced SLiMFinder statistic Sig, accounts for multiple testing (across all possible motifs) in motif discovery. However, it approximates the probability of all other possible motifs, occurring with a score of p or less, as being equal to p. Here, we show that the exhaustive calculation of the probability of all possible motif occurrences that are as rare or rarer than the motif of interest, Sig', may be carried out efficiently by grouping motifs of a common probability (i.e. those which have permuted orders of the same residues). Sig'v, which corrects both approximations, is shown to be uniformly distributed in a random dataset when searching for non-ambiguous motifs, indicating that it is a robust significance measure. Conclusions: a method is presented to compute exactly the true probability of a non-ambiguous short protein sequence motif, and the utility of an approximate approach for novel motif discovery across a large number of datasets is demonstrated

    On the Indo-European genitive suffix *-e/o

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    This brief paper presents data from Greek and Celtiberian to support the hypothesis presented in Shields 1991 that Indo-European possessed a genitive suffix in *-e/o. Conversely, the paper sheds new light on the etymology of some problematic genitive constructions in these dialects.Esta breve nota presenta datos del griego y el celtibérico en apoyo de la hipótesis, formulada en Shields 1991, de que el indoeuropeo tenía un sufijo de genitivo en *-e/o. Por otra parte, la nota arroja nueva luz sobre la etimología de algunas construcciones de genitivo problemáticas en esos dialectos

    The SLiMDisc server: short, linear motif discovery in proteins

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    Short, linear motifs (SLiMs) play a critical role in many biological processes, particularly in protein-protein interactions. Overrepresentation of convergent occurrences of motifs in proteins with a common attribute (such as similar subcellular location or a shared interaction partner) provides a feasible means to discover novel occurrences computationally. The SLiMDisc (Short, Linear Motif Discovery) web server corrects for common ancestry in describing shared motifs, concentrating on the convergently evolved motifs. The server returns a listing of the most interesting motifs found within unmasked regions, ranked according to an information content-based scoring scheme. It allows interactive input masking, according to various criteria. Scoring allows for evolutionary relationships in the data sets through treatment of BLAST local alignments. Alongside this ranked list, visualizations of the results improve understanding of the context of suggested motifs, helping to identify true motifs of interest. These visualizations include alignments of motif occurrences, alignments of motifs and their homologues and a visual schematic of the top-ranked motifs. Additional options for filtering and/or re-ranking motifs further permit the user to focus on motifs with desired attributes. Returned motifs can also be compared with known SLiMs from the literature. SLiMDisc is available at: http://bioware.ucd.ie/ approximately slimdisc/

    Postcard from Frederic Shields to Cecil Schott, September 2, 1881

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    1 leaf (double-sided)Handwritten postcard from Frederic Shields to "E" [Cecil Schott], postmarked September 2, 1881. Note from finding aid: Cecil Schott's other name was Edwin

    Postcard from Frederic Shields to Cecil Schott, September 2, 1881

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    1 leaf (double-sided)Handwritten postcard from Frederic Shields to "E" [Cecil Schott], postmarked September 2, 1881. Note from finding aid: Cecil Schott's other name was Edwin
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