3,842 research outputs found

    The Rényi Redundancy of Generalized Huffman Codes

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    Huffman's algorithm gives optimal codes, as measured by average codeword length, and the redundancy can be measured as the difference between the average codeword length and Shannon's entropy. If the objective function is replaced by an exponentially weighted average, then a simple modification of Huffman's algorithm gives optimal codes. The redundancy can now be measured as the difference between this new average and A. Renyi's (1961) generalization of Shannon's entropy. By decreasing some of the codeword lengths in a Shannon code, the upper bound on the redundancy given in the standard proof of the noiseless source coding theorem is improved. The lower bound is improved by randomizing between codeword lengths, allowing linear programming techniques to be used on an integer programming problem. These bounds are shown to be asymptotically equal. The results are generalized to the Renyi case and are related to R.G. Gallager's (1978) bound on the redundancy of Huffman codes

    Simulation of spontaneous G protein activation reveals a new intermediate driving GDP unbinding

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    Activation of heterotrimeric G proteins is a key step in many signaling cascades. However, a complete mechanism for this process, which requires allosteric communication between binding sites that are ~30 Å apart, remains elusive. We construct an atomically detailed model of G protein activation by combining three powerful computational methods: metadynamics, Markov state models (MSMs), and CARDS analysis of correlated motions. We uncover a mechanism that is consistent with a wide variety of structural and biochemical data. Surprisingly, the rate-limiting step for GDP release correlates with tilting rather than translation of the GPCR-binding helix 5. β-Strands 1 - 3 and helix 1 emerge as hubs in the allosteric network that links conformational changes in the GPCR-binding site to disordering of the distal nucleotide-binding site and consequent GDP release. Our approach and insights provide foundations for understanding disease-implicated G protein mutants, illuminating slow events in allosteric networks, and examining unbinding processes with slow off-rates

    The West Falmouth oil spill

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    A spill of 650,000 to 700,000 1iters of #2 fuel oil in Buzzards Bay, Mass., USA, on September 16, 1969, has severely polluted the coastal waters, the marshes, the offshore sediments and the shell fish resources of Falmouth and of Bourne, Mass. In preliminary publications and reports we have discussed the chemical and biological data available during the first few months after the accident. The present report documents the continuation of our analytical effort; we include analyses of stations that had not previously been covered and present the data that were available by October, 1971. Three distinct, though partly overlapping, series of events followed the spill. First, within the first few hours or days after the accident, there was a very heavy kill of those organisms which came into contact with the oil. It extended over all phyla and over benthic and intertidal organisms. Next, within weeks or months after the spill, the oil pollution spread to areas that had not been immediately affected; and the kill extended, though in some cases more slowly than the spread of the oil, to outlying areas. Oil entered the marine food web and made the shellfish resources of our area unacceptable to human nutrition. The oil showed an unexpected persistence in the sediments and in marine life, especially in view of its relatively low boiling range and of earlier assertions that fuel oil pollution was transitory in nature and without long term consequences. For considerable time after the spill, the oil pollution of the sediments prevented the resettlement by the original fauna. Now, degradation of the oil has become evident. Biochemical and physical processes lead to a gradual reduction of the oil content of the polluted sediments. Concurrent with the degradation, there has been a gradual reduction in the immediate toxicity of the oil in the sediments. This has permitted resettlement of the polluted region first by the most resistant opportunists and later by a more varied and more normal fauna. However, oil-derived hydrocarbons have remained at all stations during the entire two year span for which data are now available, and it appears that the life span of pollution, even by a low boiling fuel oil must be measured in terms of many years. The eventual aim of this study is the documentation of the effects, the persistence and the eventual disappearance of pollutant hydrocarbons from a relatively small spill in a limited and previously clean coastal area. Of necessity, most of our analytical effort in the past was aimed at a survey of the extent of the oiling of the sediments and of some of the commercially important animals. As the degradation proceeds, we expect to devote a greater effort to a more detailed chemical analysis of the hydrocarbons remaining in the environment in order to define and understand the modes of degradation and to correlate chemical analyses with biological data. Parallel investigations on the weathering of different oils under other ecological and climatic circumstances are under way here and should, in combination with the West Falmouth study, give a more realistic assessment of the environmental hazard and persistence of crude oil than has been available until now.Prepared for the Office of Naval Researoh under Contract N00014-66-C0241; NR 083-0043 The. Environmental Protection Administration (Contract 18050 EBN) and the National Science Foundation (GA-19472)

    Functional expression of the yeast alpha-factor receptor in Xenopus oocytes

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    The STE2 gene of the yeast Saccharomyces cerevisiae encodes a 431- residue polypeptide that has been shown by chemical cross-linking and genetic studies to be a component of the receptor for the peptide mating pheromone, alpha-factor. To demonstrate directly that the ligand binding site of the alpha-factor receptor is comprised solely of the STE2 gene product, the STE2 protein was expressed in Xenopus oocytes. Oocytes microinjected with synthetic STE2 mRNA displayed specific surface binding for 35S-labeled alpha-factor (up to 40 sites/micron2/ng RNA). Oocytes injected with either STE2 antisense RNA or heterologous receptor mRNA (nicotinic acetylcholine receptor alpha, beta, gamma, and delta subunit mRNAs) showed no binding activity (indistinguishable from uninjected control oocytes). The apparent KD (7 nM) of the alpha-factor binding sites expressed on the oocyte surface, determined by competition binding studies, agreed with the values reported for intact yeast cells and yeast plasma membrane fractions. These findings demonstrate that the STE2 gene product is the only yeast polypeptide required for biogenesis of a functional alpha-factor receptor. Electrophysiological measurements indicated that the membrane conductance of oocytes injected with STE2 mRNA, or with both STE2 and GPA1 (encoding a yeast G protein alpha-subunit) mRNAs, did not change and was not affected by pheromone binding. Thus, the alpha-factor receptor, like mammalian G protein-coupled receptors, apparently lacks activity as an intrinsic or ligand-gated ion channel. This report is the first instance in which a membrane-bound receptor from a unicellular eukaryote has been expressed in a vertebrate cell

    The Effects of CEO Compensation Structure on Reported Earnings and Shareholder Wealth

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    Corporate executives are paid at extremely high levels compared to lower-level employees, especially in the United States, and their level of compensation usually does not change based on company performance with respect to competitors, but rather with changes in their company\u27s stock price. It is well known that executive compensation among U.S. corporations is comprised mostly of stock options, sometimes up to 90% of overall compensation (Edgar 2002). These stock options allow executives, namely chief executive officers (CEOs), to cash in big bucks during good times and risk zero losses during bad times

    Uveal melanoma cells use ameboid and mesenchymal mechanisms of cell motility crossing the endothelium

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    Uveal melanomas (UMs) are malignant cancers arising from the pigmented layers of the eye. UM cells spread through the bloodstream, and circulating UM cells are detectable in patients before metastases appear. Extravasation of UM cells is necessary for formation of metastases, and transendothelial migration (TEM) is a key step in extravasation. UM cells execute TEM via a stepwise process involving the actin-based processes of ameboid blebbing and mesenchymal lamellipodial protrusion. UM cancers are driven by oncogenic mutations that activate Gαq/11, and this activates TRIO, a guanine nucleotide exchange factor for RhoA and Rac1. We found that pharmacologic inhibition of Gαq/11 in UM cells reduced TEM. Inhibition of the RhoA pathway blocked amoeboid motility but led to enhanced TEM; in contrast, inhibition of the Rac1 pathway decreased mesenchymal motility and reduced TEM. Inhibition of Arp2/3 complex allowed cells to transmigrate without intercalation, a direct mechanism similar to the one often displayed by immune cells. BAP1-deficient (+/-) UM subclones displayed motility behavior and increased levels of TEM, similar to the effects of RhoA inhibitors. We conclude that RhoA and Rac1 signaling pathways, downstream of oncogenic Gαq/11, combine with pathways regulated by BAP1 to control the motility and transmigration of UM cells

    Avaliação genética de seleções e híbridos de limões cravo, Volkameriano e Rugoso como porta-enxertos para laranjeiras Valência na presença da morte súbita dos citros.

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    Este estudo teve como objetivo realizar a avaliação genética da produção de frutos, eficiência produtiva e altura de laranjeiras Valência (Citrus sinensis) enxertadas em seleções e híbridos dos limões Cravo (C. limonia), Volkameriano (C. volkameriana) e Rugoso (C. jambhiri), em área endêmica para morte súbita dos citros (MSC). Foram avaliados 36 genótipos desses porta-enxertos, representados por cinco plantas cada, avaliados em cinco safras, do terceiro ao sétimo ano após o plantio. Sete dos genótipos avaliados apresentaram plantas com sintomas de MSC até o sétimo ano: Rangpur Otaheite orange 12901 (859), Rangpur Red Lime D.33.30 (866), Limão-Cravo EEL (871), Rangpur Borneo red (874), Citrus kokhai (1649), Limão-Rugoso 58329 (1655) e Limão- Cravo x Swingle B (1695). Para os genótipos que não manifestaram sintomas da doença, foram estimados parâmetros genéticos e fenotípicos e realizada a predição de valores genéticos dos indivíduos, visando à seleção e ao melhoramento genético para as características citadas, empregando-se o método REML/BLUP (máxima verossimilhança restrita/melhor predição linear não viciada). A análise de produção de frutos de cinco safras mostrou acurácia seletiva de 84,59%, tornando-se desnecessária a avaliação de maior número de safras. A seleção dos sete melhores genótipos proporcionou ganhos genéticos de 11,5% na produção de frutos, enquanto a do melhor genótipo conferiu ganho genético de 16,3%. As maiores médias genéticas preditas (>70,0 kg.pl-1) para produção de frutos foram obtidas pelos genótipos Limão-Cravo- Ipanema (1522), Santa- Bárbara-Red- Lime (884), Limão- Cravo- Limeira (863), Limão- Cravo- Taquaritinga (869), Limão- Rugoso- do -Cabo (1643), Rangpur- Rose Lime (868) e Limão- Cravo- da- Califórnia (1467). Já a acurácia seletiva da eficiência produtiva, para quatro colheitas, foi 77,4%. Para este caráter, as maiores médias genéticas (>8,0 kg.m-3) foram dos genótipos Rangpur- Lime x Trifoliata 3810 (1648), Rangpur- Lime x Trifoliata 5320 (1644), Limão- Cravo x Citrange- Carrizo (1524), Citrus pennivesiculata (880), Limão- Cravo x Trifoliata- Swingle A (1707), Rangpur- Rose- Lemon 124684 (864), Rangpur- Red -Lime D33.47 (867) e Limão- Cravo -Ipanema (1522). Dentre os 10 melhores genótipos para produção de frutos e para eficiência produtiva, apenas três são coincidentes: Rangpur- Rose -Lime (868), Citrus pennivesiculata (880) e Limão- Cravo-Ipanema (1522)
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