1,720,958 research outputs found
Identification of screening biomarkers for chromosomal anomalies and pregnancy-related disorder using quantitative plasma proteomics
Get PDFDue to the risk associated with invasive procedures, a large research effort has been expended to the development of risk free alternatives. Current results indicate that we may be approaching the long sought goal of Non-Invasive Prenatal Diagnosis (NIPD), whereby it will be possible to identify hereditary single gene disorders or a chromosomal abnormality in the growing fetus.
One of the routes explored for NIPD was via the enrichment of fetal cells, specifically erythroblasts, from maternal blood. After the enrichment, the putative fetal cells were examined by FISH analysis for the presence of a chromosomal anomaly. In the large a multi-centre NIFTY study it was concluded that although promising, the sensitivity and specificity was below the required clinical application.
Proteomics is defined as the analysis of whole protein component of a tissue (e.g. brain), cell (e.g. yeast) or a body fluid (blood or urine). More precisely it involves the determination of identity of the protein present in the mixture and its relative and absolute quantity. Recently it is also used to identify protein modifications (e.g. phosphorylation, glycosylation). Applications of proteomics are very wide, with the major application in clinical research being applied for the better understanding of biological processes and disease state. Examples are, to find and validate new biomarkers (diagnostic and prognostic) or to understand the pharmacodynamics and pharmacokinetics of a drug compound.
A specific proteome is very dynamic and can provide lot of information on the expression pattern on normal vs. disease or control vs. treated. To study the proteome in its complexity, advanced tool are required, and in this context mass spectroscopy has emerged as a powerful technique for proteomic analysis.
A typical mass spectroscopy based proteomics workflow involves the digestion of protein in-gel or in liquid. Online or off-line fractionation of the peptides is performed by liquid chromatography (LC) and followed by ionization. The peptides are converted into ions and mass analysis is done on these ions, following which the mass to charge ratio is recorded. The resulting fragment masses are used to search of large protein databases search, resulting in the identification of the peptide and protein.
Plasma is an attractive entity for the proteomics studies. It contains different proteins from the various organs in high or low abundance. Many pathology or disease associated proteins are often present in plasma. Due to there low abundance, a number of different strategies have been developed to detect these in the plasma proteome, of which a few are discussed below.
In traditional 2D gel electrophoresis the most preferred staining method is by Coomassie Brilliant Blue (CBB) or sliver stains. After staining intensity of the protein spot is used for relative quantitation when compare with the gel which is run in parallel. But CBB has poor detection sensitivity, where as sliver stain is not compatible with the down stream mass spectroscopy analysis. To over come this problem the proteins were label with fluorescent cyanine dye (cy2, cy3 and cy5) before the 2D separation. This method in know as 2-D differential gel electrophoresis (2D DIGE) to avoid the gel to gel variation. In same gel one can run control and experimental sample as well the internal standard. Internal standard is made by mixing equal amount of control and experimental sample and is used for the relative quantitation. After the run the gel is scanned with the special Typhoon variable mode imager and DeCyder software is used for the differential analysis.
Over a decade MS has evolved as a powerful technique. This has lead to the development of shotgun proteomics, which is a useful tool as it bank ready quantification using special reagent and technique. Lately there are different techniques available for the labeling which enables the quantification of the protein like stable isotope labeling of amino acid in cell cultures (SILAC), isotopic-coded affinity tags (ICAT) and isobaric tags for relative and absolute quantitation (iTRAQ).
iTRAQ is an isobaric chemical labeling approach currently the only technique capable of multiplexing up to eight different samples for relative quantification. 8-plex chemically identical iTRAQ reagents are available, named 114, 115, 116, 117, 118, 119, and 121 which have the same overall mass. Each label is composed of a peptide reactive group (NHS ester) and an isobaric tag of 145 Da that consists of a balancer group (carbonyl) and a reporter group (based on N-methyl piperazine), between the balancer and the reporter group is a fragmentation site. The peptide reactive group attaches specifically to free primary amino groups – N-termini and ε-amino groups of lysine residues.
Each sample to be analyzed is tryptic digested and labeled with the single iTRAQ label after which sample are pooled for tandem mass analysis. The peptide product ion spectra is then used for the identification of the proteins and relative quantitation is derived from the peak intensities of the 8-plex iTRAQ reporter ions detected in the 114-121 m/z region of the fragmented ion spectra. Data acquired is always compared to a reference sample, and the quantity of each peptide is expressed as a ratio relative to the reference sample. As the field of shotgun proteomics is evolving rapidly, it is likely to play a role in the detection of biomarkers. iTRAQ has been shown to permit very reliable quantitation of proteins in complex mixture such as plasma, serum or urine. As such it has been suggested to be a useful tool for the detection of biomarkers. Hence, it is likely to play a key role in this field.
Selected Reaction Monitoring (SRM) is very rapidly developing tool for the MS based quantitation. It exploits the unique future of the triple quadrupole. The first and third quadrupole act as a filter to select the ion of defined m/z and the second quadrupole is a collision cell. The research carried out in this thesis does however demonstrate that it is possible to mine the maternal plasma proteome for new biomarkers. Their verification will however need to be carried out in much larger studies, and using more convenient techniques
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Variations on the Author
Get PDF“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
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe 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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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