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생기능성 나노물질에 의한 올리고핵산 약물전달, 세포 반응, RNA 감지에 관한 연구
No full text학위논문(박사) - 한국과학기술원 : 화학과, 2012.8,[xi, 122 p. :]Gene therapy may be therapeutically useful in relieving symptoms and treating any kind of diseases which hybridize with their complementary target site in mRNA, blocking translation to protein expression of patho-physiologic genes. These strategies include DNAzymes, siRNA, antisense oligonucleotides (ASO), ribozymes, and aptamers. Among these molecules, deoxyribozymes (DNAzyme, Dz) have been paid attention as therapeutics both in cell-based assays and in preclinical models of diseases including cancer and viral infectious diseases. The “10-23” RNA cleaving DNAzyme has been shown to cleave any purine-pyrimidine junction under simulated physiological conditions, therefore efficiently inhibiting expression of target proteins in vitro and in vivo studies. These molecules ideally combine the catalytic activity of ribozymes with the stability of oligodeoxynucleotides, are easy to synthesize and less sensitive to chemical and enzymatic degradation than RNA-based reagents. Factors to influence the eventual therapeutic use of DNAzymes include its efficient cellular uptake, subcellular localization, and stability. A particularly important challenge to achieve the successful down-regulation of gene expression is to deliver DNAzymes efficiently to its intended site of action.
Since various nanomaterials have unique, useful chemical, physical, and mechanical properties, they can be used for a wide variety of applications including nano-based biosensors, drug delivery devices, diagnostic tools, and means for tissue engineering and fundamental cell biology studies, etc.
In chapter 2, we describe synthesis and characterization of a multifunctional magnetic nanoparticle (MION) for both noninvasive in vivo imaging and delivery of DNAzyme to target organ for hepatitis C treatment. Hepatitis C is one of the infectious diseases in the liver caused by the hepatitis C virus (HCV), a small-sized, enveloped, positive sense single strand RNA virus. The multifunctional nanoparticles consist of magnetic nanoparticles labeled with near-infrared fluorescent dye and conjugated to a synthetic DNAzyme targeting a gene of interest. In addition, these nanoparticles are tailored with cell-penetrating peptides (CPPs) helping membrane translocation process. We demonstrated the silencing effect of a gene of interest by Dz-loaded multifunctional nanoparticles in cultured human liver cells (Huh-7). For in vivo study in mice, we performed the alkaline phosphatase activity assay using sera to measure the efficiency of DNA transfection, and found that the hydrodynamic delivery of the reporter plasmid elicited and was maintained over-expression in mice for some periods. The delivery of the nanoparticles would be monitored in dual fashions in vitro and in vivo. We believe that our Dz-conjugated nanoparticles will be one of the widely applicable therapeutic options for the efficient HCV treatment in near future.
Carbon based nanomaterials have shown much interest due to their unique structural and electrical properties such as mechanical strength, flexibility, electrical transport capability, young’s modulus, lightness and chemical inertness. Especially, graphene has the infinite possibilities to serve as novel nanoscale building blocks to create distinctive macroscopic materials. Due to their outstanding thermal and mechanical properties and high electrical conductivity, graphene sheets have been considered as a promising candidate for nanoelectronic devices, quantum computer, transparent electrode, and nanocomposite materials.
Conductive substrate show great potential in biological applications such as tissue engineering, implants, drug delivery carriers, biochips for diagnostics and nano-devices for biological study. Substrates for immobilizing cells and tissues are valuable in use of biological and medical field study. The adhesion and spreading of mammalian cells is mediated by the binding of cell-surface integrin receptors to peptide ligands from the extracellular matrix (ECM) and the clustering of these receptors into focal adhesion complexes. Integrins play a critical role in the formation of focal adhesions, which attach cells to the extracellular matrix. It has been reported that the interaction between cells and ECM depends on the multiple substrate characters such as chemical composition, geometry, and topological aspects, ligand organization, and substrate stiffness. In addition, these factors of engineered substrates based on nanomaterials can affect and even lead to various cellular responses and cell physiology. Little is to investigate their properties that make the influence of carbon based nanomaterials including graphene sheet on living system. While the advancements in technology may be considerable, there is also concern about unintended effects of exposure to nanomaterials.
In chapter 3, the chemically modified graphene oxides were immobilized on the glass substrates and used as a substrate for mammalian cells as a model of biological system to examine their influence on cell adhesion, spreading pattern and proliferation by various assays. We believe our result could serve as a fundamental standard for biological investigation of chemically prepared graphene-based nanomaterials.
As biomolecules inside cells including proteins, nucleic acids, and small molecules show a variety of expression level and pattern, localization or distribution, they are considered as the critical parameters that reflect the state of organism including cellular behaviors, function, proliferation, development, physiological and pathological states. In that point of view, the build-up of the biomolecule detection method is one of the important issues in the biomedical field for the treatment process of all sorts of diseases.
MicroRNAs (miRNAs) are a class of small-sizes (10~25nt) and non-coding RNA molecules that play an important regulatory role in the expression of diverse genes. Interestingly, miRNAs as the attractive biomolecule have been paid great attentions in a wide range of biological processes like development and metabolism and pathological progresses of disease/ disorders. Here, we fabricated the microRNA analytical platform for rapid, simple, and sensitive detection using nano-sized graphene oxide and detection probe PNA (peptide nucleic acid) for this study.
In chater 4, we evaluated that 1) the probe-nanographene complex can work as microRNA sensing platform with efficient fluorescence quenching and recovery ability, 2) nanographene oxide sheets can serve as a delivery carrier of detection probe into live cells for real-time monitoring and quantitative analysis of microRNA and 3) the nanogrpahene oxide sheets provide the stable loading platform in the complex biological solutions and samples.한국과학기술원 :화학과
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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