1,720,955 research outputs found
Targeting Nanoparticles to Tumor Vasculature
Get PDFTargeting tumor vessels represents an indirect therapeutic approach in oncology by shifting the treatment away from the tumor cells themselves. Endothelial cells are generally considered genetically stable and do not use escape mechanisms against chemotherapeutic agents as frequently as tumor cells do. Also, a very large number of tumor cells can be killed by ischemia if a single vessel is occluded.
Tumor vascular markers have been identified and monoclonal antibodies targeting them have been constructed in my laboratory. There are numerous approaches to make antibodies more effective in cancer treatment. One option we have investigated is to use them for liposomal targeting to tumor vessels. Nanoparticles, and liposomes in particular, are extremely versatile because they can be adapted to carry drugs, imaging agents, or energy capture agents.
In my project, I have constructed liposomes targeted to three molecules identified as tumor vascular markers: VEGFR-2, phosphatidylserine (PS), and phosphatidylethanolamine (PE). To target VEGFR-2, I have used Fab' fragments derived from a series of rat monoclonal antibodies (RAFL) that bind to the extracellular domain of the receptor. For PS targeting, I used Fab' fragments derived from an anionic phospholipid binding antibody (bavituximab) and also a serum protein, beta-2-glycoprotein 1 (beta 2GP1). PE was targeted using a small antibiotic peptide, duramycin. All the liposome constructs bound to the purified target, as tested by solid phase assays. VEGFR-2 targeted liposomes bound to and were internalized by mouse endothelial cells expressing VEGFR-2. PS and PE targeted liposomes bound to endothelial cells that were subjected to stress factors that mimic the conditions encountered in the tumor environment. All the liposomes were also detected on the surface of endothelial cells inside tumors.
The tumor treatment potential was assessed by loading the liposomes with doxorubicin and treating mice in an orthotopic breast cancer model. The therapeutic benefit was also assessed for its ability to prolong survival in a lung pseudometastatic model. The tumor growth in the orthotopic model was not inhibited by any of the constructs compared with control liposomes, but VEGFR-2 targeted liposomes extended the survival in the pseudometastatic model. These data suggest that VEGFR-2 targeted liposomes could potentially be used as an antimetastatic agent in combination with treatments that would target the tumor of origin.
PS and PE binding liposomes were also used as probes for describing the membrane localization and exposure dynamics of PS and PE on the surface of irradiated cells. I have shown that PS and PE follow a similar exposure time course and they colocalize on the cell surface. PS and PE positive membrane patches appear to detach from the cytoskeleton and bud out from the cell surface. These findings suggest that PE and PS share common regulatory mechanisms of membrane translocation.
PS and PE binding liposomes were also used as probes for describing the membrane localization and exposure dynamics of PS and PE on the surface of irradiated cells. I have shown that PS and PE follow a similar exposure time course and they colocalize on the cell surface. PS and PE positive membrane patches appear to detach from the cytoskeleton and bud out from the cell surface. These findings suggest that PE and PS share common regulatory mechanisms of membrane translocation.
Long circulating liposomes provide benefit through passive targeting to the tumor environment. My findings imply that active targeting by adding a ligand should be done with care, so as not to impede the passive targeting effect. Compared to other vascular targeting agents, liposomes requir
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
- …
