1,194 research outputs found
Tyrosine Residues in the C-Terminal Domain of the Insulin-Like Growth Factor-I Receptor Mediate Mitogenic and Tumorigenic Signals*
No full textWe investigated cellular proliferation, the transforming activity, and activation of known signal transduction pathways in NIH-3T3 cells stably expressing insulin-like growth factor-I receptors (IGF-IRs) with amino acid substitutions in the carboxy(C)-terminal domain. The mutant receptors contained substitutions of both tyrosines 1250 and 1251 with phenylalanine and histidine (amino acids present in the analogous positions in the insulin receptor), as well as phenylalanine 1310 replaced by tyrosine (IsY clones) to resemble the placement of tyrosine residues in the C-terminal domain of the insulin receptor. As a control for the IsY clones, a second mutant receptor was expressed with a substitution of phenylalanine 1310 with tyrosine only (DBY clones). Clones expressing IGF-IRs with the IsY substitutions had a significantly slower rate of growth compared with cells expressing an equivalent number of wild-type IGF-IRs (NWT). In contrast, the DBY clones showed relatively normal growth rates. Cells with wild-type IGF-IR demonstrated a transformed phenotype in softagar assays. The IsY clones lost the transforming ability of the wild type IGF-IR, whereas DBY clones formed colonies. IGF-I-stimulated autophosphorylation of the IGF-IR and tyrosine phosphorylation of IRS-1 and SHC, known substrates in the IGF-IR signal transduction pathway, were studied. Mutated IGF-IRs (IsY and DBY) did not alter the IGF-I-induced tyrosine phosphorylation of these proteins. Furthermore, the mutated IGF-IRs did not alter Grb2 association with phosphorylated IRS-I and SHC. IGF-I stimulation of Crk-II phosphorylation, a novel substrate of the IGF-LR, was similar in cells expressing mutated and wild-type IGF-IRs. IGF-I-induced activation of phosphatidylinositol (PI) 3'-kinase was equivalent in cells expressing either mutant or wild-type IGF-IRs. These data suggest that the IGF-IR mediates, at least in part, cellular proliferation and increased transforming ability through its C-terminal domain. The exact postreceptor signaling pathway(s) involved have yet to be fully elucidated
Ford, Derek / interviewed by Dr. Philip van Beynen Oral History: Derek Ford
No full textDr. Derek Ford, karst science authority and author, begins the interview discussing his childhood in and around the city of Bath, England and the beginnings of his interest in rock climbing, cave diving, and cave mapping. Special attention is given to his relationship to the transition from the physiographic approach to geography to a quantitative approach. He elaborates on his friendship with eminent geomorphologist Paul Williams and how they came to write their book together. The conversation continues with an in-depth discussion of Dr. Ford\u27s major scientific breakthroughs and notable publications with various research partners. He reflects on his career highs, specifically his love of teamwork and mentoring students. Dr. Ford shares stories of past students, their personalities, and where they are now in their lives. The interview concludes with Dr. Ford\u27s opinion on the future of karst research.
Interview conducted January 24, 2008 at the University of South Florida in Tampa, Florida
A critical edition of Derek Walcott's Omeros
No full textThe thesis is a Critical Edition of Derek Walcott’s Omeros, consisting of a Critical
Introduction and Annotations. The Critical Introduction analyses:
- Narrative
- Settings
- Metaphor and Paronomasia
- Symbolism
- Historiography
- Intertexts
- Dualism
- Autobiography
- Dialects
- Prosody.
The Annotations comment on more than 1000 references that may be obscure and on
specifics of narrative, language and prosody.
This study presents new conclusions about some aspects of Omeros:
- It challenges the prevailing view that the work is written substantially in a
variation of terza rima and shows that regular quatrains predominate.
- It demonstrates ways in which the metrics follow the sense of the narrative and
takes a more balanced position on the use of Caribbean as opposed to classical
metrics than that put forward previously.
- It identifies a paragraphic structure to the verse.
- It proposes a new prosodic structure for the significant Chapter XXX/iii.
- It extends Walcott’s recognised use of numerology into word counting the
names of characters.
- It develops the idea of Walcott’s dualism and his use of pairing and
contradiction as a dialectical method.
- It defines his wide use of paronomasia and shows that many of the puns have a
metaphorical aspect beyond mere word-play.
- It analyses some of Walcott’s symbolism.
- It identifies intertextual links to his earlier works and to some thirty other
writers, and suggests homage to Hemingway and possibly Heaney.
- It provides the first complete analysis of Walcott’s rhyme types in Omeros.
In its analysis of Omeros and in the Annotations it has included commentary from
across the critical literature, to provide some sense of other views on Walcott’s
writing, and has included as many as possible of Walcott’s own comments on Omeros
and on the writer’s task, as a background to understanding the poem
The literary impact of the Haitian Revolution
No full textThe Haitian Revolution (1 791-1804) reshaped the debates about slavery and
freedom in Europe, accelerated the abolitionist movement, precipitated
rebellions in neighbouring territories, and intensified both repression and antislavery
sentiment. Its long-term effects remain visible in the many
representations, recuperations, and invocations of the Revolution as an
exemplar of black agency. At the same time, the violence of the conflict led to
portrayals of Haiti as unregenerate and primitive, a prey to 'voodoo' and
lawlessness. Hence the recuperation of Haiti's political and cultural history, in
which the establishment of the first postcolonial nation must be accounted for
as a momentous event despite its ostensible failure, contests the tradition of
imperial denigration. The thesis addresses how the Haitian Revolution followed
by the establishment of a Black Republic, provided inspiration for writers,
artists and intellectuals throughout the Atlantic Diaspora in diverse cultural and
intellectual locations from the 1920s onwards. If public knowledge about
Haitian history has for some time now been limited in Europe and North
America, the Revolution has been a potent factor in black memory and it
remains an inspiration to Carib beans, Africans, African Americans, and Latin
Americans, as well as to radical intellectuals and artists worldwide. The thesis
studies the writings generated by the Revolution in the works of Aime Cesaire,
C. L. R. James, Rene Depestre, Langston Hughes, Edouard Glissant, Alejo
Carpentier, Derek Walcott, and Madison Smartt Bell, spanning French, English,
and Spanish, and including poetry, drama, history, biography, fiction, and
opera; while in the visual arts it considers the paintings of Kimathi Donkor and
commemorative postage stamps. My discussion addresses both critical
understandings and fictional reinventions of the Revolution's achievement and
tragic reversals. I examine the ideologies informing the analyses, and the
aesthetics of the imaginative writings, where a political stance in some cases
served to promote innovation and experimental style and in others was a
constraint
A graphical and computational modelling platform for biological pathways
No full textA major endeavor of systems biology is the construction of graphical and computational models of biological pathways as a means to better understand their structure and function. Here, we present a protocol for a biologist-friendly graphical modeling scheme that facilitates the construction of detailed network diagrams, summarizing the components of a biological pathway (such as proteins and biochemicals) and illustrating how they interact. These diagrams can then be used to simulate activity flow through a pathway, thereby modeling its dynamic behavior. The protocol is divided into four sections: (i) assembly of network diagrams using the modified Edinburgh Pathway Notation (mEPN) scheme and yEd network editing software with pathway information obtained from published literature and databases of molecular interaction data; (ii) parameterization of the pathway model within yEd through the placement of 'tokens' on the basis of the known or imputed amount or activity of a component; (iii) model testing through visualization and quantitative analysis of the movement of tokens through the pathway, using the network analysis tool Graphia Professional and (iv) optimization of model parameterization and experimentation. This is the first modeling approach that combines a sophisticated notation scheme for depicting biological events at the molecular level with a Petri net–based flow simulation algorithm and a powerful visualization engine with which to observe the dynamics of the system being modeled. Unlike many mathematical approaches to modeling pathways, it does not require the construction of a series of equations or rate constants for model parameterization. Depending on a model's complexity and the availability of information, its construction can take days to months, and, with refinement, possibly years. However, once assembled and parameterized, a simulation run, even on a large model, typically takes only seconds. Models constructed using this approach provide a means of knowledge management, information exchange and, through the computation simulation of their dynamic activity, generation and testing of hypotheses, as well as prediction of a system's behavior when perturbed
Tilting at Windmills : BLDSC and the UK Higher Education Community
No full textPurpose - To provide an overview of, the relationship between the British Library and higher education libraries in the 1990s, with particular relation to document supply. It also goes on to explore current developments in scholarly communication. Design/methodology/approach - The author played a role in several of the events described and uses the available literature to enlarge on a personal view of that decade. Findings - The paper shows that the relationship was a strained one caused in part by a mismatch of resources, but is in any case dwarfed by the larger external forces and changing opportunities and technologies for scholarly communication. Originality/value - Provides a record of the period
Improving International Comparisons of Real Output: The ICP 2005 Benchmark and its Implications for China
No full textThe latest round of the International Comparisons Program (ICP 2005) compares the purchasing power of currencies and real output of 146 countries. Using price quote data from nine countries in the Asia-Pacific region, we consider ways of improving the methods used in ICP 2005 and new applications of these methods (e.g., for calculating rural-urban price differentials). The most striking result in ICP 2005 was that China came out 40 percent smaller than previously thought. We also evaluate the extent to which this finding can be attributed to excessive sampling of prices in China from urban areas or of unrepresentative products.International Comparisons Program; Country-Product-Dummy Method; Price Index; Basic Heading; Urban-Rural Price Differences; Representative and Unrepresentative Products; Asia-Pacific Region
Evolution of the G+C content frontier in the rat cytomegalovirus genome
No full textWithin the 230138 bp of the rat cytomegalovirus (RCMV) genome, the G+C content changes abruptly at position 142644, constituting a G+C content frontier. To the left of this point, overall G+C content is 69.2%, and to the right it is only 47.6%. A region of extremely low G+C content (33.8%) is found in the 5 kb immediately to the right of the frontier, in which there are no predicted coding sequences. To the right of position 147501, the G+C content rises and predicted coding sequences reappear. However, these genes are much shorter (average 848bp, 50% G+C) than those in the left two-thirds of the genome (average 1462bp, 70% G+C). Whole genome alignment of several viruses indicates that the initial ultra-low G+C region appeared in the common ancestor of the genera Cytomegalovirus and Muromegalovirus, and that the lowering of G+C in the right third has been a subsequent process in the lineage leading to RCMV. The left two-thirds of RCMV has stop codon occurrences at 67.5% of their expected level, based on a modified Markov chain model of stop codon distribution, and the corresponding figure for the right third is 78%. Therefore, despite heavy mutation pressure, selective constraint has operated in the right third of the RCMV genome to maintain a degree of gene length unusual for such low G+C sequences
Derek Price’s Puzzles: Numerical Metaphors for the Operation of Science
No full textTwo of Derek Price’s scientometric models are examined-one showing bibliographic references snrong papers in the self-contsined speciafty dealing with N-rays, the nther showing exponential growth of the scientific literature, The author compares his own observations on the aging of the literature with those of %Ice, concluding that the rapid aging of scientific knowledge may he a relatively recent phenomenon, Also examined are the effects of the world wars on scientific growth
Severe sepsis and septic shock [author's reply]
No full textTo the Editor: We would like to address two potentially confusing issues concerning venous oxygen saturation (Svo(2)) as presented in Table 1 of the review by Angus and van der Poll (Aug. 29 issue).(1) First, Table 1 suggests that Svo(2) is raised in sepsis, severe sepsis, and septic shock. Depending on the timing of patient presentation and the type of sepsis and septic shock, Svo(2) may indeed be elevated as a result of microcirculatory shunting or mitochondrial dysfunction. However, in septic shock, Svo(2) can be depressed, reflecting an increase in the extraction of oxygen du
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