1,720,955 research outputs found
Development of colloids for cell and tissue targeting: bisphosphonate-functionalized gold nanoparticles for the investigation of bone targeting
Gold nanoparticles (GNPs) possess a great potential as model systems for the investigation of nanoparticulate drug delivery due to their ease of production, low toxicity and also the high stability of the noble metal in biological fluids. Due to their unique surface chemistry, they can be used as building platform for stable self assembled monolayers of thioalkylated poly(ethylene glycol)s with different surface functionalities, allowing the investigation of different drug targeting principles.
In this thesis gold nanoparticles, also for suitable for intravenous in vivo applications, were prepared in aqueous media by citrate reduction of gold chloride, yielding particles in the size range of 40 to 150 nm with appropriate size distributions. Adjustment of the particle size was achieved by varying the ratio of citrate to gold salt and subsequently the obtained particles were investigated via photon correlation spectroscopy and transmission electron microscopy for sufficient size determination.
For a subsequent stabilization and functionalization, heterobifunctional poly(ethylene glycol) derivatives [PEG] were synthesized, carrying a thioalkyl chain for stable binding to gold and a hydrophilic PEG chain as hydrophilic coating. The synthesis of the different thioalkylated poly(ethylene glycol)s was further improved applying a new synthetic strategy, in order to avoid non binding polymer components interfering with the subsequent particle coating. For the additional functionalization with targeting ligands, the polymers were furthermore modified to provide a functional amine group, which can be used to attach hydrophilic molecules necessary for specific binding of the colloids to their target sites. In this thesis two different polymers [methoxy poly(ethylene glycol)-undecyl mercaptane and amino poly(ethylene glycol)-undecyl mercaptane] were synthesized and conjugated to a bone targeting ligand, namely a bisphosphonate, using standard DCC/NHS chemistry. The obtained polymers were characterized by 1H-NMR, HPLC and mass spectroscopy and demonstrated a high degree of purity, suitable for further immobilization on gold surfaces.
In order to functionalize the prepared gold particles, bisphosphonate and methoxy terminated poly(ethylene glycol)-undecyl mercaptane (BP-PEG-AlkSH and mPEG-AlkSH) were mixed in different ratios and used to coat the nanoparticles. The investigations demonstrated that the polymer coated nanoparticles slightly increased in size as determined by PCS, but no significant changes were observed with TEM due to the low contrast of the polymer layer. The surface charge and UV-Vis absorption spectra of the particles were also only slightly changed, indicating well separated particles and a successful replacement of the citrate coating by the different polymers. The polymer-coated nanoparticles proved to be stable in different media (5M NaCl, 200 µg/ml BSA and 10% (V/V) serum), indicating a strong binding and a well established steric stabilization of the uncharged polymers. Bisphosphonate coated particles were furthermore incubated with porous hydroxyapatite ceramics (Endobon®, Biomet) and it was observed that their adsorption to apatite was strongly dependent on the content of bisphosphonate in the particle surface and the adsorption was not affected by calcium ions or proteins added to the media.
The conducted in vivo investigations using radioactively labeled particles furthermore indicated that the functionalized and non-functionalized gold nanoparticles showed only a minimum uptake by the reticuloendothelial system (liver and spleen) and therefore circulated for very long time in the bloodstream as compared to other nanoparticulate systems. On the other hand the particles also showed a strong tendency to extravasate and distribute into other organs after intravenous injection into mice, but the largest accumulation was observed in the kidneys. Besides that a steady accumulation of the bisphosphonate functionalized nanoparticles in bone was observed in comparison to control nanoparticles, but further studies have to be conducted in order to investigate especially the long term fate in bone and the accurate location of the particles in the kidney.
Due to the beneficial in vivo behavior of the developed particles, the here presented drug delivery system may be furthermore a suitable model system for the investigation also of other active targeting strategies in many different fields
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
We 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
We 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.
Author-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
In 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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