1,721,054 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Adenovirus-mediated gene transfer of an IL-6 antagonist
No full textIL-6 is a pleiotropic cytokine and plays a major role in inflammation and in the immune response. Altered serum levels of IL-6 have been described in several pathologies such as myeloma, EBV-lymphoma and chronic autoimmune disease. Here we report data on the utilization of a hIL-6 receptor superantagonist with a gene therapy approach. The superantagonist used in this work possesses very high affinity for the hIL-6 receptor, and is therefore an excellent candidate for the treatment of IL-6-dependent diseases. To obtain an efficient in vivo delivery method, we constructed a recombinant adenovirus expressing the IL-6 receptor superantagonist by inserting the cDNA, controlled by the RSV promoter, into a first generation replication-incompetent adenoviral vector. Recombinant virus allowed correct expression of the transgene in vitro. Supernatants of infected cells specifically inhibited IL-6-induced transcriptional activation in hepatoma cells and blocked the IL-6-dependent proliferation of human myeloma cells. After intravenous injection of the recombinant virus into mice, nanomolar amounts of antagonist were produced in the serum, and these were able completely to inhibit IL-6 bioactivity. Gene transfer of such an antagonist offers a practical means of imposing long-term blockade of IL-6 activity in vivo for investigational and therapeutic purposes
Effect of adenosylhomocysteine and other analog thioethers on a prokaryotic tRNA (guanine-7)-methyltransferase
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
The promise of anti-ErbB3 monoclonals as new cancer therapeutics
No full textIn the last 3-5 years strong evidence has been gathered demonstrating ErbB3 as a key node for the progression of several cancer types. From the mechanistic standpoint the intracellular region of this receptor is rich of tyrosine residues that, upon phosphorylation, become high affinity binding sites for PI3K and other proteins involved in signal transduction. The involvement of ErbB3 occurs at different levels, most likely as a consequence of its promiscuity in the interaction with other RTKs of the same or other families. Several efforts are therefore being put in the development of antibodies that target this receptor either singly or in combination with other synergizing receptors. Some of these compounds have already entered clinical development. Although clinical proof-of-concept has not yet been achieved, this is likely to occur soon and will further accelerate the inclusion of anti-ErbB3 monoclonals in the repertoire of anticancer agents for more effective combination therapy. In this paper we review the wealth of anti-ErbB3 antibodies under development and compare their properties and potential to become marketed drugs
Synergistic Transactivation of the Human C-reactive Protein Promoter By Transcription Factor Hnf-1 Binding At 2 Distinct Sites
No full textThe promoter region of the human C-reactive protein (CPR) gene comprises two distinct regions (APREs, for Acute Phase Responsive Elements) each one containing information necessary and sufficient for liver specific and IL-6 inducible expression in human hepatoma Hep3B cells. In this paper we show that both APREs contain a low affinity binding site for the liver specific transcription factor HNF-1/LF-B1. The two sites are separated by approximately 80 bp. Mutations in either of the two sites abolish inducible expression. The same effect is specifically obtained in cotransfection competition experiments when the human albumin HNF-1 site is used as competitor. However, HNF-1 is not the intranuclear mediator of IL-6 because synthetic promoters formed by multimerized copies of different HNF-1 binding sites are not transcriptionally activated by this cytokine. An expression vector encoding full length HNF-1 is capable of trans-activating transcription from the wild-type CPR promoter but not from mutants which have lost the ability to bind HNF-1. Moreover, the level of trans-activation observed with the natural promoter containing both HNF-1 binding sites is far greater than the level of mutated variants containing only one of the two sites. This result strongly suggests that two HNF-1 molecules bound simultaneously to sites distant from each other can act synergistically to activate gene expression
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
A Bipartite Activation Domain Is Responsible For the Activity of Transcription Factor Hnf1/lfb1 In Cells of Hepatic and Nonhepatic Origin
No full textHNF1/LFB1 is a transcription factor that controls the expression of several liver-specific genes. Previous in vitro experiments allowed us to identify two different regions in the carboxy-terminal portion of the protein responsible for most of the transcription activation potential: the first, ADI, between amino acids 546 and 628 and the second, ADII, between amino acids 281 and 318. To characterize the molecular anatomy of HNF1/LFB1 better, we have analyzed its trans-activating properties in vivo. Several HNF1/LFB1 deletion mutants were tested for their ability to induce transcription from HNF1/LFB1-dependent synthetic promoters in cells of hepatic and nonhepatic origin. These last recipient cells provide an HNF1/LFB1-deficient environment that is useful for a precise quantification of the recombinant protein. Our results confirm the importance of ADI and indicate that no activating property can be assigned to ADII in vivo. Moreover, a novel glutamine/proline-rich activation domain (ADIII) has been identified between amino acids 440 and 506. These findings are confirmed by domain-swapping experiments, carried out with the heterologous GAL4 DNA-binding domain, which also show that the activity of each individual activation domain is influenced by combining adjacent HNF1/LFB1 sequences. The data presented indicate that HNF1/LFB1 transcription activating potential relies on a complex structure and also provide important clues to understanding the different fucntions exerted by transcription factors of this family
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