1,720,953 research outputs found
Design of functional polymeric materials for cancer-targeted drug delivery and cellular capture and isolation
Doctor of PhilosophyDepartment of Chemical EngineeringJennifer L. AnthonyRyan R. HansenSynthetic polymeric materials offer many exciting advantages with the plethora of functionalization techniques affording materials with unique properties, multiple functionalities, and elaborate architectures for a variety of applications. In the drug delivery field, the use of synthetic polymers as nano-sized drug carriers in cancer nanomedicine has gained tremendous interest as an alternative to conventional small molecule anticancer drugs to reduce drug-related toxicity and increase targetability. Like other nanocarriers, synthetic polymeric nanocarriers rely on passive-drug targeting, also known as the Enhanced Permeability and Retention (EPR) effect in leaky tumor vasculature for delivery of therapeutics. The biological complexity and barriers that exist in the body however have proven to be a huge challenge in selectively delivering therapeutics to cancer cells. Synthetic polymers also offer significant advantages for improved isolation and characterization of microbes attached to surfaces compared to conventional techniques. However, the retrieval of microbes from synthetic polymer interfaces with high spatial precision without damaging the underlying live bacterial cells remains a critical challenge for further characterization. Therefore, the goal of this dissertation is to explore and develop synthetic, functional, stimulus-responsive polymeric interfaces (polymeric micelles, photodegradable hydrogels) for targeted drug delivery to cancer cells and improved isolation of microbes for molecular characterization.
The majority of this thesis (chapters 2, 3, and 4) focuses on utilizing the intrinsic properties present in tumor microenvironments (TME), mainly elevated levels of reactive oxygen species (ROS) and overproduction of matrix metalloproteinase-2 (MMP-2) enzyme for the design and synthesis of stimuli-sensitive synthetic block copolymer polymeric micelles (BCPMs) by reversible addition-fragmentation chain transfer (RAFT) polymerization for targeted delivery of therapeutics to cancer cells. The synthesized BCPMs were extensively studied and evaluated for their chemistry and biological functions in in vitro cancer therapy. In chapter 2, the conventional chemotherapeutic drug, Doxorubicin (DOX) was loaded physically into the hydrophobic core of BCPMs bearing a library of oxidation-sensitive thioether groups. Results showed that the micelles, especially micelles with intermediate ROS sensitivity, significantly increased toxicity of DOX in liver cancer cells (HepG2) but protected normal cells, human umbilical endothelial cells (HUVECs) from DOX cytotoxicity. Taking it a step further, in chapter 3, hydrogen sulfide (H₂S) prodrug (ADT) was chemically conjugated to the core of BCPMs bearing oxidation-sensitive thioether group and the anti-cancer effects of H₂S in colon cancer cells (HT29) were evaluated. A greater anti-proliferative effect was observed in HT29 cells with no significant toxicity in HUVEC cells. In chapter 4, a different approach was taken where BCPM bearing MMP-2 enzyme cleavable peptide motifs and chemically conjugated ADT was designed for site-specific delivery of H₂S to cancer cells. The greater release of H₂S from MMP-2 sensitive micelles exhibited stronger anti-proliferative activity in HT29 cells. The final portion of this thesis (chapter 5) focuses on the development of the polymer surface dissection (PSD) method which uses biofunctionalized, photodegradable polyethylene glycol (PEG)-based hydrogels for the isolation of microbes from polyvinylidene difluoride wastewater membrane surfaces. The flocs were extracted with high spatial precision and minimal DNA damage after exposure to spatiotemporally controlled ultraviolet (UV) light using a patterned illumination tool, allowing for follow-up characterization by 16S rRNA sequencing. The technique allows for the identification of microbes that form small flocs on membrane surfaces without requiring a culture step for enrichment, and will be used in future work to identify communities of microorganisms that initiate membrane biofilms in bio-separation processes
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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