350 research outputs found

    Diverse Levels of Sequence Selectivity and Catalytic Efficiency of Protein-Tyrosine Phosphatases

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    The sequence selectivity of 14 classical protein-tyrosine phosphatases (PTPs) (PTPRA, PTPRB, PTPRC, PTPRD, PTPRO, PTP1B, SHP-1, SHP-2, HePTP, PTP-PEST, TCPTP, PTPH1, PTPD1, and PTPD2) was systematically profiled by screening their catalytic domains against combinatorial peptide libraries. All of the PTPs exhibit similar preference for pY peptides rich in acidic amino acids and disfavor positively charged sequences, but differ vastly in their degrees of preference/disfavor. Some PTPs (PTP-PEST, SHP-1, and SHP-2) are highly selective for acidic over basic (or neutral) peptides (by >105-fold), whereas others (PTPRA and PTPRD) show no to little sequence selectivity. PTPs also have diverse intrinsic catalytic efficiencies (kcat/KM values against optimal substrates), which differ by >105-fold due to different kcat and/or KM values. Moreover, PTPs show little positional preference for the acidic residues relative to the pY residue. Mutation of Arg47 of PTP1B, which is located near the pY-1 and pY-2 residues of a bound substrate, decreased the enzymatic activity by 3–18-fold toward all pY substrates containing acidic residues anywhere within the pY-6 to pY+5 region. Similarly, mutation of Arg24, which is situated near the C-terminus of a bound substrate, adversely affected the kinetic activity of all acidic substrates. A co-crystal structure of PTP1B bound with a nephrin pY1193 peptide suggests that Arg24 engages in electrostatic interactions with acidic residues at the pY+1, pY+2, and likely other positions. These results suggest that long-range electrostatic interactions between positively charged residues near the PTP active site and acidic residues on pY substrates allow a PTP to bind acidic substrates with similar affinities and the varying levels of preference for acidic sequences by different PTPs are likely caused by the different electrostatic potentials near their active sites. The implications of the varying sequence selectivity and intrinsic catalytic activities with respect to PTP in vivo substrate specificity and biological functions are discussed

    Spatial differences in corneal electroretinogram potentials measured in rat with a contact lens electrode array

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    PURPOSE: It has been known for several decades that the magnitude of the corneal electroretinogram (ERG) varies with position on the eye surface, especially in the presence of focal or asymmetric stimuli or retinal lesions. However, this phenomenon has not been well-characterized using simultaneous measurements at multiple locations on the cornea. This work provides the first characterization of spatial differences in the ERG across the rat cornea. METHODS: A contact lens electrode array was employed to record ERG potentials at 25 corneal locations simultaneously following brief full-field flash stimuli in normally sighted Long-Evans rats. These multi-electrode electroretinogram (meERG) responses were analyzed for spatial differences in a-wave and b-wave amplitudes and implicit times. RESULTS: Spatially distinct ERG potentials could be recorded reliably. Comparing relative amplitudes across the corneal locations suggested a slight non-uniform distribution when using full-field, near-saturating stimuli. Amplitudes of a- and b-waves were approximately 3 % lower in the inferior quadrant than in the superior quadrant of the cornea. CONCLUSIONS: The present results comprise the start of the first normative meERG database for rat eyes and provide a basis for comparison of results from eyes with functional deficit. Robust measures of spatial differences in corneal potentials will also support optimization and validation of computational source models of the ERG. To fully utilize the information contained in the meERG data, a detailed understanding of the roles of the many determinants of local corneal potentials will eventually be required

    European Starlings Fly Before They Fledge

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    Aircraft bird strikes are increasing globally. Bird strikes constitute a major human health and safety risk and result in millions of dollars in economic impacts. Invasive avian species, such as the European starling (Sturnus vulgaris; starlings), have been implicated in bird strikes in North America. Because this species is highly adaptive and has been successful at establishing in new areas, such as airports, it is essential that managers better understand the potential risks and how to mitigate them. Herein we present a case study regarding a novel observation of unique starling nesting behavior that may pose a risk to airport operations and aircraft

    The suicide of Mayakovsky: Jakobson, Russian Formalism and On the generation that spent its poets

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    This paper presents a bibliographical review of the literary criticism movement known as Russian Formalism (1915-1916) and one of its most prominent theorists, Roman Jakobson (1896-1982). After a brief historical and biographical survey, we analyzed the work On the Generation that Spent its Poets (1931), written by Jakobson after the suicide of his friend, the poet Vladimir Mayakovsky (1893-1930). The analysis aimed to verify how Jakobson, in his comments about the poems of Mayakovsky, brought to his interpretation biographical matters of the poet, especially his suicide. Taking into account that the first phase of Russian Formalism did not allow the practice of biographism, we understand that Jakobson broke with some methodological paradigms of the movement, leading it to a new phase.O presente artigo traz uma revisão bibliográfica a respeito do movimento de crítica literária conhecido como Formalismo Russo (1915-1916) e um de seus teóricos mais proeminentes, Roman Jakobson (1896-1982). Após breve apanhado histórico e biográfico, analisou-se a obra A Geração que Esbanjou seus Poetas (1931), escrita por Jakobson após o suicídio de seu amigo, o poeta Vladimir Maiakóvski (1893-1930). A análise teve por objetivo verificar como Jakobson, em seus comentários sobre os poemas de Maiakóvski, trouxe para sua interpretação questões biográficas do poeta, em especial seu suicídio. Levando em consideração que a primeira fase do Formalismo Russo não admitia a prática do biografismo, entende-se que Jakobson rompeu com alguns paradigmas metodológicos do movimento, conduzindo-o para uma nova fase

    Não mais temas o calor do sol: a morte de si e a morte do outro em Mrs. Dalloway

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    Attitudes toward death differ according to time and space. The First World War, which ended in 1918, had an impact on those attitudes in populations of the whole world, mainly in the countries involved in the conflict. Virginia Woolf's novel Mrs. Dalloway, published in 1925, brings in its protagonists, Clarissa Dalloway and Septimus Warren Smith, samples of the attitudes toward death present in the English society of their time. The research aims to understand how the attitudes toward the death of oneself and of the other are represented in that novel, taking into account the socio-historical context in which it was produced. First, a bibliographic review is brought up regarding the socio-historical context in which the novel is situated, punctuating aspects regarding the current attitudes toward death at that time; then, the novel is analyzed based on its protagonists, verifying their reflections and attitudes regarding the death of themselves and of other people and their consonance with the context of the novel's production. It is noticed that the protagonists present similar views about death, but different attitudes. At the end of the novel, both unite the death of themselves and the death of the others in different ways, Septimus through suicide and Clarissa through a new beginning.As posturas diante da morte diferem de acordo com o tempo e o espaço. A Primeira Guerra Mundial, finalizada em 1918, trouxe impactos em relação a essas posturas nas populações do mundo todo, principalmente nos países envolvidos no conflito. O romance Mrs. Dalloway, de Virginia Woolf, publicado em 1925, traz em seus protagonistas, Clarissa Dalloway e Septimus Warren Smith, amostras das posturas diante da morte presentes na sociedade inglesa da época. A pesquisa tem como objetivo compreender como as posturas diante da morte de si e do outro são representadas nesse romance, levando em consideração o contexto sócio-histórico em que ele foi produzido. Primeiramente, traz-se uma revisão bibliográfica a respeito do contexto sócio-histórico em que o romance é situado, pontuando questões referentes às posturas diante da morte recorrentes na época; em seguida, a obra é analisada a partir de seus protagonistas, verificando suas reflexões e posturas a respeito da morte de si e do outro e a consonância destas com o contexto de produção do romance. Percebe-se que os protagonistas, acerca da morte, apresentam visões semelhantes, mas posturas diferentes. Ao final do romance, ambos unem a morte de si e a morte do outro de formas distintas, Septimus por meio do suicídio e Clarissa por meio de um recomeço

    Influence of Behavioral Leadership Strategies on Employee Engagement in Hospital Departments

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    Lack of employee engagement as a result of deficient behavioral leadership strategies has the potential for adverse business outcomes on productivity, business mission, and strategy. As a result of this qualitative single case study, hospital department managers who apply behavioral leadership strategies are more likely to promote an environment conducive to employee engagement. Grounded in the employee engagement theory, the purpose of this qualitative single case study was to explore behavioral leadership strategies hospital department managers use to promote an environment conducive to employee engagement. The participants were five hospital department managers who had been successful with employee engagement. Data were collected using semistructured interviews, a review of organization employee handbooks, and employee meeting notes. Through thematic analysis, three themes were identified: (a) increased employee engagement with open communication, (b) empowering employee decision making, and (c) relationship development. A key recommendation is for business leaders to acknowledge the needs of their employees and continue to improve their behavioral leadership strategies. The implications for positive social change include the potential to retain valued employees and support the local community workforce through workers giving back their time

    Método para análise de sistemas de conhecimento, inspirado no princípio da complementaridade de Niels Bohr

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    Tese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia de ProduçãoO presente trabalho situa-se na área de abrangência da Teoria Geral dos Sistemas, em sua dimensão de identificação (sobre o que caracteriza os sistemas) e mais especificamente no tema da emergência dos sistemas (sobre como surgem os sistemas). A partir de estatísticas que demonstram que os principais problemas encontrados nos sistemas de informações são originados nos processos de análise dos sistemas psico-sociais que os incorporam, o trabalho demonstra a importância das teorias na determinação da forma como os analistas percebem a existência e o surgimento dos sistemas. Em última análise, o scopus do trabalho consiste em identificar se a partir do princípio teórico da complementaridade podem ser desenvolvidos métodos de análise para sistemas de conhecimento mais eficazes que os derivados do mecanicismo clássico, baseado no princípio da causalidade. Para atingir esse propósito, é feita uma descrição do significado das teorias e, estrito senso, dos princípios da causalidade e da complementaridade, precedida de uma revisão da Teoria Geral dos Sistemas e dos seus desdobramentos mais recentes. Na seqüência são analisados aspectos de alguns dos métodos de análise de sistemas disponíveis, apresentando uma alternativa ao conceito de "problema", que lhes é inerente, a partir da própria perspectiva da Teoria Geral dos Sistemas. O método utilizado na verificação da plausibilidade dos argumentos apresentados no desenvolvimento da teoria consistiu da análise de estudos de casos feitos por alunos de Análise de Sistemas do Centro de Ciências Tecnológicas da Universidade do Estado de Santa Catarina, chegando-se à conclusão de que realmente o princípio teórico da complementaridade desvenda possibilidades relevantes no desenvolvimento de "um novo olhar" sobre os sistemas psico-sociais
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