1,720,961 research outputs found
An in vitro approach to evaluate and develop potential Sn-117m based bone-seeking radiopharmaceuticals
No full textIt has become standard practice in the development of radiopharmaceuticals to evaluate/assess the efficacy of prospective therapeutic or diagnostic agents by animal models, which generally calls for subjecting a substantial number of animals to intensive test and retest measurements for obtaining representative and conclusive results/data. This work communicates the advantage of combining various analytical modalities with mathematical and computational modeling as a multifaceted tool, for pre-vivo screening of prospective radiopharmaceuticals intended for the treatment of metastases in bone. Ultimately, the methods applied here could help curtail the number of futile tests, and in so doing reduce the number of animals used in the typical trial-and error approach of developing radiopharmaceuticals, in particular metal-chelate type drugs. The benefits being that of an ethical nature as well as cost minimization - in terms of time, facilities and professional consultation hours (vets, radiographers, etc) required. The Sn-117m radionuclide was identified as an ideal radiopharmaceutical component for the treatment of bone pain, owing to its favourable radiation properties – with a half life of 13.6 days and decay emission of conversion (Auger) electrons. The short emission range of the Auger electrons lends itself to minimizing radioxicity/radiation dose to the sensitive bone marrow. In order to best exploit the radiation characteristics of Sn-117m for therapy various methods were considered for the preparation of the isotope with high specific activity. The quintessence of the production techniques attempted employed the Szilard-Chalmers effect, whereby the product atoms or ions are separable from the original target matrix due to chemical and/or structural differences incurred during nuclear bombardment, or as a result of recoil of the atoms from the target lattice due to extreme activation/excitation energy acquired. The nuclear reactions considered were that of neutron capture, Sn-116(n,gamma)Sn-117m, and photonuclear, Sn(IV)-118(gamma,n)Sn(II)-117m. Chemical separation and isolation methods were unique for each reaction, namely recoil capture of Sn-117m in the (n,gamma) reaction followed by chemical extraction – yielding a specific activity of 2.53 MBq/mmol (0.07 % yield); and anion exchange chromatography for (gamma,n) reaction, which produced Sn-117m with a yield of 60% and specific activity of 2.94 GBq/mA/h/mg (349.01 GBq/mA/h/mmol). Two tin-bisphosphonate complexes were studied in this thesis, namely Sn(II)-APDDMP and Sn(IV)-PEI-MP, where the bisphosphonate ligands are N,N-dimethylenephosphonate-1-hydroxy-4-aminopropylidenediphosphonate and N,N’,N’-trimethylenephosphonate-polyethyleneimine, respectively. Using glass electrode potentiometry, the complexes of the former were studied for divalent tin (Sn(II)) and compared against those of the most prominent physiological metal ions, namely Ca(II), Mg(II), Zn(II), which revealed that Ca(II) formed more stable with APDDMP and was therefore prone to displacing the Sn(II). As a result of the dissociation the Sn(II) could then be taken up by amino acids in the plasma thus negating the tumour targeting. The biodistribution of [Sn-117m]Sn(II)-APDDMP was tested in a rodent model, which showed fairly rapid renal clearance of the [Sn-117m]Sn(II). With the aid of blood plasma modeling software, ECCLES, various postulates were tested to explain the observed biodistribution. This confirmed that the complexes did in fact dissociate as a result of Ca(II) competition, resulting in the formation of Sn(II)-complexes with histidine and cysteine, which were then excreted via the kidneys. In an attempt to improve the tumour selectivity and uptake, the water soluble phosphonate polymer PEI-MP was studied, exploiting a phenomenon known as the Enhanced Permeation and Retention effect (EPR), whereby macromolecules, e.g. polymers, selectively accumulate within tumours due to irregularities in the vasculature and poor lymphatic clearance. PEI-MP was complexed with Sn(IV), and in similar fashion as had been performed for Sn(II)-APDDMP, the susceptibility was tested by ECCLES blood plasma modeling. The simulation suggested that the complexes would dissociate within blood plasma, resulting the formation of Sn(IV)-glutamine complexes and Ca-PEI-MP. The stability of Sn(IV)-PEI-MP was lower than that of its Sn(II) counterpart. Therefore, biodistribution studies were averted, given the validity of previous modeling predictions – i.e. Sn(II)-APDDMP and Sn(II)-PEI-MP. When working with tin, and especially Sn(II), an argument ensues as to valence stability of the metal ion(s), that when preparing or injecting a complex of tin with a particular oxidation state, is it certain to remain in that form and not be oxidized (Sn(II)) or reduced (Sn(IV)) within the environment of blood plasma – given the inherent reducing nature of Sn(II) and the oxygen abundance of blood. A study of the tin-phosphonate complexes by P-31 NMR was successful in addressing this question. The coordination of the ligands to Sn(II) and Sn(IV) were distinguishable by the chemical shift of the phosphorous signal. In so doing any interconversion of oxidation states could be easily monitored by changes in intensity of the respective P-31 peaks. The complexes were put through their paces by observing their P-31 spectra in time, and applying oxidative pressure in the form of hydrogen peroxide, and inversely, using glutathione (GSH) to reverse the oxidation. The extreme conditions required to achieve complete conversion was considerably beyond that which can be expected in blood plasma, therefore it was concluded that the tin within the complexes would essentially remain unchanged for the duration of treatment. Concurrently with the blood plasma modeling assessment, the prospective “bone seeking” agents Sn(IV)-PEI-MP and Sn(II)-PEI-MP were tested for their adsorption characteristics with hydroxyapatite, which served as an in vitro model for bone mineral. The adsorption of the complexes as well as the free ligand was adequately described by Langmuir adsorption isotherms – deriving information about the adsorption affinity and the maximum adsorption capacity of each for hydroxyapatite. The ideal combination for optimum complex adsorption was determined, taking into account the polymer, with size fractions of 10-30kDA or 30-50kDa, and the particular valence form of tin. The Sn(II)-PEI-MP complex, with a polymer size of 10-30kDa, was best. This complemented the blood plasma modeling findings, and the adsorption speciation substantiated speciation results obtained by the potentiometry, with M2L complexes forming for Sn(II)-PEI-MP and ML species for Sn(IV)-PEI-MP. Furthermore, the presence of tin favourably enhanced the adsorption of the complex(es), which was evident by: (i) the superior adsorption data/figures of the tin complexes over that of the free ligand; and (ii) dinuclear complexes (M2L) of Sn(II)-PEI-MP. In general this thesis provides a holistic approach to investigating some of the fundamental issues in the development of radiopharmaceuticals – intended particularly for the treatment of bone metastases. The combination of the methods used in this study made it possible to better understand and predict the behaviour of novel drug concepts without the conventional and elaborate animal models – save for the rodent biodistribution study of [Sn-117m]Sn(II)-APDDMP, which, in retrospect, validated the adequacy of the thermodynamic blood plasma model. The study leaves room for adaptation and inclusion of additional techniques – depending on the expected activity of, or hypotheses surrounding the drug being considered, which could help resolve many of the underlying factors influencing efficacy. These could include: cell assays; and dissociation kinetic measurements by free-ion selective radiotracer extraction (FISRE), for example.Department of Radiation, Radionuclides & Reactors (TUDelft), and the Department of Radiochemistry (Necsa)Applied Science
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
- …
