Dissertations / Theses on the topic 'Anthryl'
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Kendall, J. Kirby. "Pyrolytic behavior of anthryl mono- and dicarbenes /." The Ohio State University, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=osu148786179682149.
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Saleh, Nail Asad. "Dynamical solvent effect in 1-(9-anthryl)-3-(4-dimethylaniline) propane charge transfer reactions /." free to MU campus, to others for purchase, 2002. http://wwwlib.umi.com/cr/mo/fullcit?p3060138.
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Bradbury, Adam John, and babradbury@optusnet com au. "METAL ION ACTIVATED ANION SENSORS." Flinders University. School of Chemistry Physics and Earth Sciences, 2007. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20080319.125059.
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A series of new, octadentate, fluorescent, macrocyclic ligands have been prepared with a view to using them to study aromatic anion sequestration. The eight-coordinate Cd(II) complexes of the ligands have been shown capable of acting as receptors for a range of aromatic oxoanions. This has been demonstrated by perturbation of both 1H NMR chemical shift values and the anthracene derived fluorescence emission intensity as the potential guest anion and the host are combined. Non-linear least squares regression analysis of the resulting titration curves leads to the determination of binding constants in 20% aqueous 1,4-dioxane which lie in the range 10^2.3 M-1 (benzoate) to 10^7.5 M-1 (2,6-dihydroxybenzoate). By reference to the X-ray determined structures of related, but non-fluorescent inclusion complexes, the primary anion retention force is known to arise from hydrogen bonding between the anion and four convergent hydroxy groups that exist at the base of a cavity that develops in the complexes as their aromatic groups juxtapose upon coordination. This work reveals significant stability enhancement when hydroxy groups are positioned on the anion at points where O-H...pi hydrogen bonding to the aromatic rings that constitute the walls of the cavity becomes geometrically possible.
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Ri, Songyon. "Spectroscopic Studies on the Excited States of 4-(9-anthryl) aniline and its Dynamics of the Charge Transfer State Formation." 京都大学 (Kyoto University), 1997. http://hdl.handle.net/2433/202453.
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Carter, John Timothy. "Anthrax in Kidderminster 1900-1914." Thesis, University of Birmingham, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.422729.
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Taft, Sarah C. "Anthrax toxin immunity and receptor activity /." Cincinnati, Ohio : University of Cincinnati, 2007. http://www.ohiolink.edu/etd/view.cgi?ucin1195584188.
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Thesis (Ph.D.)--University of Cincinnati, 2007.Advisor: Alison A. Weiss. Title from electronic thesis title page (viewed Feb. 5, 2008). Keywords: Bacillus anthracis, anthrax toxin, AVA. Includes abstract. Includes bibliographical references.
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Tan, Yian Kim. "Novel functions of anthrax lethal toxin." Fairfax, VA : George Mason University, 2009. http://hdl.handle.net/1920/3451.
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Thesis (Ph.D.)--George Mason University, 2009.Vita: p. 141. Thesis director: Charles Bailey. Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biodefense. Title from PDF t.p. (viewed June 10, 2009). Includes bibliographical references (p. 110-140). Also issued in print.
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TAFT, SARAH C. "ANTHRAX TOXIN: IMMUNITY AND RECEPTOR ACTIVITY." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1195584188.
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Dupou, Laurence. "Contribution a l'etude de la dynamique et de la distribution laterale des lipides dans les membranes plasmiques de cellules eucaryotes." Toulouse 3, 1987. http://www.theses.fr/1987TOU30043.
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Fenderson, Mark. "An interpretive analysis of George Antheil's Sonata for trumpet and piano." Thesis, connect to online resource, 2008. http://digital.library.unt.edu/permalink/meta-dc-9105.
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Thesis (D.M.A.)--University of North Texas, 2008.System requirements: Adobe Acrobat Reader. Accompanied by 4 recitals, recorded Oct. 17, 2005, Mar. 27, 2006, June 4, 2007, and Apr. 14, 2008. Includes bibliographical references (p. 43-44).
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Li, Feng. "Studies on inhibition against anthrax lethal toxin." Oklahoma City : [s.n.], 2010.
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Ryan, Patricia Lynn. "Requirements for anthrax toxin entry into cells." Diss., [La Jolla] : University of California, San Diego, 2010. http://wwwlib.umi.com/cr/ucsd/fullcit?p3390726.
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Thesis (Ph. D.)--University of California, San Diego, 2010.Title from first page of PDF file (viewed Feb. 19, 2010). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 104-119).
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Miller, Michele E. "Anthrax Event Detection: Analysis of Public Opinion Using Twitter During Anthrax Scares, The Mueller Investigation, and North Korean Threats." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1609846103002063.
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Stone, Bahr Elizabeth L. "Biological weapons attribution a primer." Thesis, Monterey, Calif. : Naval Postgraduate School, 2007. http://bosun.nps.edu/uhtbin/hyperion-image.exe/07Jun%5FBahr.pdf.
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Thesis (M.A. in National Security Affairs (Defense Decision Making & Planning))--Naval Postgraduate School, June 2007.Thesis Advisor(s): Peter R. Lavoy, Anne Clunan. "June 2007." Includes bibliographical references (p. 111-117). Also available in print.
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George, Gerald D. "Earning a Living as an Author in Early Modern England: The Case of Anthony Munday." Bowling Green State University / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1143500898.
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Averette, Kathleen Marie. "Investigation of anthrax lethal toxin induced cell death." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1906407011&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Reichert, Jennifer Deanne. "Computational and combinatorial design of an anthrax antitoxin /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2005. http://wwwlib.umi.com/cr/ucsd/fullcit?p3170271.
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Kuk, Chiu Ying. "Anthrax Lethal Toxin Is a Tumor Hemorragic Toxin." Thesis, Van Andel Research Institute, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10973827.
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Blood supply is crucial for tumor growth and metastasis. However, current anti-angiogenic therapy is not as effective as predicted, thus a better understanding of the tumor angiogenic process and new anti-angiogenic agent are urgently required. Anthrax lethal toxin (LeTx) has an anti-angiogenic effect on tumors. Tumors treated with LeTx are smaller, paler, and have lower mean vessel density compared to control treated tumors. Most interestingly, compared to current anti-angiogenic treatment, LeTx does not cause normalization of tumor vessels. Instead, tumors treated with LeTx have massive hemorrhages, pointing to a potential alternative mechanism to inhibit tumor angiogenesis. I hypothesize that instead of causing “normalization” of tumor vasculature, LeTx’s anti-angiogenic effects works in a manner similar to a hemorrhagic toxins. To test this hypothesis, I compared the effect of LeTx to snake venom metalloproteinase, a known hemorrhagic toxin, in tumor vasculature. Quantified by Nuance multispectral imaging system, both LeTx and SVMP caused an increase in tumor hemorrhage. Futher analysis of vasculature integrity using continued vessel length showed disruption of vessels by LeTx and SVMP. With these results, I conclude that the anti-angiogenic effects of LeTx are due to its hemorrhagic nature, and not due to normalization of tumor vasculature. Further understanding of LeTx mechanism can help design novel anti-angiogenic agent that compliments current therapy.
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Martel, Christine. "Civil-military relations and the anthrax vaccine debate." Thesis, Boston University, 2002. https://hdl.handle.net/2144/27711.
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Boston University. University Professors Program Senior theses.PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
2031-01-02
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Rees, Mark Lee. "The development of Bacillus sp for the efficient export of Bacillus anthracis protective antigen." Thesis, University of Newcastle Upon Tyne, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389575.
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Mukherjee, Dhritiman V. "Studies in blood-brain barrier disruption in anthrax meningitis." Fairfax, VA : George Mason University, 2009. http://hdl.handle.net/1920/4522.
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Thesis (Ph.D.)--George Mason University, 2009.Vita: p. 102. Thesis director: Serguei G. Popov. Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biosciences. Title from PDF t.p. (viewed June 10, 2009). Includes bibliographical references (p. 84-101). Also issued in print.
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Chou, Ping-Jen. "The Modulation by Anthrax Toxins of Dendritic Cell Activation." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002791.
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Rabideau, Amy Ellen. "Delivery of biomolecules into mammalian cells using anthrax toxin." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/101555.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2015.Cataloged from PDF version of thesis.
Includes bibliographical references.
The intracellular delivery of biomolecules into mammalian cells is a major challenge due to the plasma membrane, which acts as a barrier between the extracellular environment and intracellular components. Recently, a non-toxic delivery platform derived from anthrax lethal toxin has been developed to overcome this challenge for the delivery of biomolecules into the cytosol of mammalian cells. The PA/LFN delivery platform has been used to deliver over 30 known biomolecules of diverse sequences, structures, and functionalities. Collectively, these translocation studies have helped to elucidate the translocation mechanism and to probe intracellular biological processes. In this thesis, the PA/LFN delivery platform was used to analyze the delivery of assorted biomolecules through the PA pore. A facile, modular ligation strategy using sortase A was developed for the conjugation of biomolecules to LFN. The biomolecules for this analysis included antibody mimic proteins with defined sizes and secondary structures, mirror image peptides and proteins, polypeptides containing non-canonical amino acids or small molecule drugs, and cyclic peptides. Our translocation analyses have led to guidelines for translocation as well as insight into design parameters for the efficient delivery of new cargos. The PA/LFN delivery platform has also been used to translocate bioactive cargos for the disruption of intracellular protein-protein interactions (PPI). The translocation efficiency and bioactivity of a tandem monobody to Bcr-Abl, an affibody to hRaf- 1, and a mirror image peptide to MDM2 were analyzed. Efficient translocation and disruption of the intended PPI in each case indicated that the delivery platform could be used to deliver bioactive cargos into cells for therapeutic utility. As an application of this technology, the PA/LFN delivery platform was employed to analyze the intracellular stability of mixed chirality proteins. One major factor that governs a protein's stability is the N-end rule, which states that the N-terminal residue of a protein impacts its intracellular stability through the ubiquitin (Ub)/proteasome system. Utilizing the PA/LFN delivery platform, the stability of proteins containing one N-terminal D-amino acid was analyzed. In contrast to N-terminal L-amino acids, each N-terminal D-amino acid abrogates protein degradation by the N-end rule pathway.
by Amy Ellen Rabideau.
Ph. D.
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Collier, Sarah Elizabeth. "The Conquest of Woolsorters? Disease (Industrial Anthrax) That Never Happened." NCSU, 2007. http://www.lib.ncsu.edu/theses/available/etd-05042007-194510/.
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This thesis will examine the triumph over anthrax that never really happened. In the history of diseases and medicine, Triumphalism or the triumphal story is a common genre of historical writing. At first glance, it may seem as if the standard triumphal story applies to the history of anthrax. Robert Koch and Louis Pasteur, the heroes of bacteriology, made their major discoveries in anthrax in the 1870s and 1880s. Then, John Henry Bell?s work in the Bradford wool mills in England created a practical application of Koch and Pasteur?s findings. Bell makes his recommendations to the British government, and the story is over. The disease is understood, and thus there is a medical standard to follow. But it is doubtful that there will be very many more cases because science and medicine have solved the problem. Unfortunately, this narrative is just too simple, and in this thesis, I will show how anthrax does not fit into the mold of a triumphal story and is, instead, a story about an industrial disease from the beginning using outbreaks and legislation that manifested after Koch, Pasteur, and Bell made their breakthroughs in the 1880s.
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Grenha, Rosa. "Towards understanding anthrax : structural studies of proteins from distinct pathways." Thesis, University of York, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437575.
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Santos, Juliano de Castro. "Particionamento semi-automático de reduções cíclicas para execução em anthill." Universidade Federal de Minas Gerais, 2006. http://hdl.handle.net/1843/RVMR-78VMDR.
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Extracting information from large datasets is one of the challenging new demands in Computer Science. To accomplish that, several Data Mining techniques are being proposed continually in the literature. Such algorithms are computationally intensive, in addition to the fact of having to process very large input data. Besides, the new trend towards high performance computing is gearing towards clusters of computers, a cost effective alternative to the supercomputers of the past. This trend leads to a scenario in which achieving high performance must be accomplished by efficient parallel and distributed implementations of the applications. Anthill is a solution for distributed processing on clusters of workstations for which high performance have been achieved by efficient and scalable implementation of several Data Mining algorithms. In essence, it provides a framework for the development and execution of applications in distributed environments, where the applications must be decomposed into a set of filters that exchange information though streams in a pipeline fashion. The process of developing the applications, however, damands the programmers to perform such application decomposition which may not be the natural way in which they program. This work presents a tool of semiautomatic generation of such fiters from a basic sequential implementation of the algorithms. This process is divided in two stages: the first being the partition into filters of the sequential code, followed by the code generation for each of the identified filters. This work focuses mostly on the latter, the code generation itself. For the first stage, we rely on some semi-automatic steps that could be implemented to be fully automatic in future work. These steps are based on determining data dependencies within the code, and finding good partition places. Using such steps we generate an annotated version of the sequential code, that contains the partitioning information. The actual code generation is accomplished from the annotated code. Basically the annotations encompass a directed graph with vertices representing the filters and edges annotated with the data that should be communicated. We implemented a source-to-source compiler, where the initial sequential code is standard C, and the output is also C, with Anthill extensions. Most of the necessary adaptations for Anthill are generated automatically by our compiler. The compiler was validated using three different Data Mining applications that had previously been developed for Anthill. This time, we generated the Anthill code from sequential versions of the same algorithms. We evaluate the performance of the generated code and we observe that it is very similar to the hand-made implementations in most cases. This is a good result when noted that the effort to design the sequential code is much less than a fully parallel Anthill implementation. We also notice that there are some ad-hoc optimizations on the hand-made codes that could also be accomplished by a compiler in a further optimizing step. We plan to pursue such automatic optimizations as future workExtrair informação de grandes bases de dados é um desafio das novas demandas da Ciência da Computação. Além disso, diversas técnicas de Mineração de Dados são propostas continuamente na literatura. Tais algoritmos são computacionalmente intensivos, além do fato de processarem entradas de dados muito grandes. Assim, há uma nova tendência em direção ao alto desempenho de processamento e montagem de clusters de computadores, a um custo mais razoável que os supercomputadores do passado. Essa tendência nos leva a um cenário em que o alto desempenho é alcançado por eficientes implementações de aplicações paralelas e distribuídas. O Anthill é uma solução para processamento distribuído em clusters de computadores onde um alto desempenho é obtido em execuções eficientes e escaláveis de diversos algoritmos de Mineração de Dados. Ele fornece um framework para o desenvolvimento e a execução de aplicações em ambiente distribuído, onde as aplicações devem ser decompostas em filtros que se comunicam através de streams de dados, como em um pipeline. O processo de desenvolvimento das aplicações entretanto demanda do programador decompor as aplicações, que não é o caminho natural de desenvolvimento dos programas. Este trabalho apresenta uma ferramenta de geração semi-automática de filtros a partir de uma implementação seqüencial do algoritmo. Esse processo é divido em duas etapas: a primeira é o particionamento em filtros do código seqüencial, seguido pela geração do código para cada um dos filtros identificados. Este trabalho tem como foco a segunda etapa, a geração do código. Para a primeira etapa, nós realizamos de forma semi-automática alguns passos a serem automatizados em trabalhos futuros. Esse processo determina as dependências de dados no código, e identifica os pontos de corte do mesmo. A partir deste passo, é gerado uma versão anotada do código seqüencial, contendo as informações para sua divisão em filtros. A geração dos filtros é feita a partir do código anotado. Basicamente, as anotações contêm um grafo direcionado onde os vértices representam os filtros e as arestas representam os dados que são trafegados entre os filtros. Nós implementamos um gerador de código fonte onde a entrada é um algoritmos seqüencial escrito em C e a saída são os filtros, também em C, com as extensões do Anthill. A maioria das adaptações necessárias para Anthill são geradas automaticamente por essa ferramenta. O gerador de código automático foi validado usando três aplicações de Mineração de Dados que já haviam sido implementadas no Anthill. Foram gerados de forma automática o código dos filtros Anthill a partir das versões seqüenciais. Nós avaliamos o desempenho do código gerado e observamos que o resultado é similar ao código gerado manualmente na maioria dos casos. Este é um bom resultado, dado que o custo de implementação do código seqüencial é bem menor do que a implementação paralela dos filtros para o Anthill. Também foram observadas algumas otimizações presentes na implementação manual que podem ser realizadas automaticamente pela ferramenta para obtenção de um resultado mais otimizado. Como trabalhos futuros devemos prosseguir com a automatização de mais otimizações na geração do código.
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Juzak, Damian. "Effect of population characteristics and seasonal variation on anthrax epidemiology." Thesis, Södertörns högskola, Internationell hälsa, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-41631.
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Introduction Anthrax is a disease caused by the spores of Bacillus anthracis and can have a high fatality rate. It is a zoonosis and mostly affecting animals. In this study I want to find out risk factors on population scale for anthrax cases and deaths in humans and animals, and look at the relation of anthrax with weather patterns. Methods I searched for anthrax outbreaks in different countries, mainly yearly reports. I looked at human cases, human deaths, livestock deaths and wildlife deaths. Different risk factors were considered: country size, population characteristics, Human Development Index (HDI), total cattle number, cattle per human ratio, mean annual temperature, mean temperature of the warmest 1 and 3 months, annual precipitation and minimum and maximum precipitation in 1 month and 3 months. Linear regression was used. Statistics were repeated without China because it was often the single outlier in the figures. Statistics were also repeated with the countries aggregated in continents because of the modifiable area unit problem. Results Data was found for 28 countries resulting in 36 data points. There was a significant relation between human cases and cattle number, human deaths, country size and population size. There were also significant relations between wildlife deaths and population size, country size and mean temperature of the warmest month. Without China relations between human cases and maximum precipitation in 1 and 3 months, and between livestock deaths and country size were significant. For continents a significant relation between human cases and cattle ratio, cattle deaths and HDI. Conclusion This study mainly shows that high cattle numbers and cattle deaths due to anthrax are risk factors for human cases. Also seasonal precipitation is a risk factor. Bigger country size and population size may be indirect risk factors as these usually accompany higher cattle numbers.
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Meaney-Delman, Dana. "A Systematic Review of Bacillus anthracis in Pregnant and Postpartum Women." Digital Archive @ GSU, 2012. http://digitalarchive.gsu.edu/iph_theses/216.
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Objective: To describe the worldwide experience of Bacillus anthracis infection reported in pregnant and postpartum women.
Data Sources: Studies were identified through MEDLINE, WEB OF SCIENCE, EMBASE, and GLOBAL HEALTH databases from inception until April 2012. The keywords [(“anthrax” or “anthracis”) and (“pregna*” or “matern*” or “post partum” or “postpartum” or “puerperal” or “lact*” or “breastfed*” or “fetal” or “fetus” or “neonate” or “newborn” or “abort*” or “uterus”)] were used. In addition, all references from selected articles were reviewed, hand searches were conducted and relevant authors were contacted.
Methods of Study Selection: The inclusion criteria were: 1) published articles referring to women diagnosed with an anthrax infection during pregnancy or within six months postpartum, 2) any article type reporting patient-specific data, 3) articles in any language, and 4) non-duplicate cases. Non-English articles were professionally translated. Duplicate reports, unpublished reports and review articles depicting previously identified cases were excluded.
Tabulation, Integration and Results: Two authors independently reviewed articles for inclusion. The primary search of the 4 databases yielded 800 articles and the secondary cross-reference search revealed 146 articles. Seven articles from these searches met inclusion criteria. By contacting the lead author of the largest systematic review of inhalation anthrax to date, 6 additional articles, published before the databases’ inception, were identified that met inclusion criteria. In total, 19 cases of anthrax infection were found, 16 in pregnant women and 3 in postpartum women.
Conclusions: Based on these case reports, anthrax infection in pregnant and postpartum women is associated with high rates of maternal and fetal death. Evidence of possible maternal-fetal transmission of B. anthracis was identified in early case reports. Transmission of B. anthracis through breast milk has not been reported. This review provides important insight to guide anthrax treatment and prophylaxis recommendations for pregnant and postpartum women.
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Thwaite, Joanne E. "Factors influencing the production of Bacillus anthracis protective antigen in Bacillus subtilis." Thesis, University of Newcastle Upon Tyne, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369784.
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Smith, Phillip R. "Generation of Biomarkers from Anthrax Spores by Catalysis and Analytical Pyrolysis." Diss., CLICK HERE for online access, 2005. http://contentdm.lib.byu.edu/ETD/image/etd1005.pdf.
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Ribeiro, Suzie Jesus. "A study of DNA/Dendron nanoparticles for genetic immunisation against anthrax." Thesis, University College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439784.
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Poff, Sherry Ann. "Expression of Bacillus Anthracis Protective Antigen in Vaccine Strain Brucella Abortus Rb51." Thesis, Virginia Tech, 1997. http://hdl.handle.net/10919/10039.
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Bacillus anthracis is a facultative intracellular bacterial pathogen that can cause cutaneous, gastrointestinal or respiratory disease in many vertebrates, including humans. Commercially available anthrax vaccines for immunization of humans are of limited duration and do not protect against the respiratory form of the disease. Brucella abortus is a facultative intracellular bacterium that causes chronic infection in animals and humans. As with other intracellular pathogens, cell mediated immune responses (CMI) are crucial in affording protection against brucellosis. B. abortus strain RB51 has been shown to be useful in eliciting protective cell mediated immunity and humoral responses against Brucella in cattle and other animal species. Since the protective antigen (PA) of B. anthracis is known to induce protective antibodies, it was decided that the objective of this research was to test whether the gene encoding PA could be expressed in Brucella producing a bivalent vaccine to protect against both brucellosis and anthrax. The pag gene was transcriptionally fused to promoters of genes encoding superoxide dismutase or heat shock protein groE, subcloned into a broad host range plasmid (pBBR1MCS) and shown to express in E. coli by immunoblotting using antiserum specific for PA. The immunoblot results revealed that E. coli produced a PA protein of the expected size. In addition, the culture medium was shown to contain the same PA protein using immunoblotting. These results show that E. coli is capable of expressing B. anthracis PA in both the cellular and extracellular forms. The pBB/PA plasmid was used to transform B. abortus RB51 and CmR clones screened for the expression of PA by immunoblotting. Twenty clones of strain RB51/pBBSOD were show to express a 30kDa PA protein. Three clones of strain RB51/pBBGroE-PA were shown to express a 63-83kDa protein as detected by antiserum specific for PA. Using the A/J mouse, an immunocompromised vertebrate model, immunization and challenge studies were performed. Preliminary results demonstrate that the bivalent vaccine is capable of producing protection against a live challenge with B. abortus and some protection against live non-disease producing spores of B. anthracis.Master of Science
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Brenneman, Karen Elaine. "Investigation and characterization of the enhanced humoral response following immunization with the lethal and edema toxins of bacillus anthracis." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1174317572.
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Lewis, Jana Ann-Sook. "Heterocyclic metal-binding Groups for matrix metalloproteinase and anthrax lethal factor inhibition." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3249668.
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Thesis (Ph. D.)--University of California, San Diego, 2007.Title from first page of PDF file (viewed Apr. 3, 2007). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Lindeque, Pauline Mary. "Factors affecting the incidence of anthrax in the Etosha National Park, Namibia." Thesis, Open University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315333.
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Fireman, Daniel Lacet de Faria. "Suporte para a adição de instâncias em tempo de execução no anthill." Universidade Federal de Minas Gerais, 2009. http://hdl.handle.net/1843/SLSS-7WJNE6.
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On one hand, the continuous evolution of technology in various areas of knowledge is leading to an increase of size of available data sets, reaching the order of petabytes. In this scenario, it is essential to use distributed resources to process data in a timely fashion. On the other hand, with the popularization of platforms composed by workstations, distributed computing systems have become inherently dynamic: resources may be added or are subjected to faults. However, the use of these resources as a platform for high performance computing is still restricted, since the development of efficient and scalable parallel systems remains a difficult task, even for experienced programmers. Anthill is a parallel programming environment based on the filter-stream paradigm. This paradigm allows to efficiently process large volumes of data, since it can exploit the parallelism in a simple and intuitive manner. However, Anthill has been built as a static environment and as such, it does not allow to modify the application's component distribution at runtime. This work presents a set of extensions that add support for augmenting the runtime platform of an Anthill application. Our solution exploits the locality of reference and the asynchrony which many Anthill application could make use. The results of our experimental evaluation show that this implementation allows the use of more computational power at runtime, keeping with low cost, the execution consistency and the asynchronous exploitation of different levels of parallelism.De um lado, a contínua evolução tecnológica nas diversas áreas do conhecimento vem fazendo com que conjuntos cada vez maiores de dados se tornem disponíveis, atingindo a ordem de petabytes. Nesse cenário, faz-se imprescindível a utilização de recursos distribuídos para realizar o processamento de dados em tempo hábil. Do outro lado, com a popularização das plataformas de execução compostas por estações de trabalho, os sistemas de computação vêm se tornando inerentemente dinâmicos: recursos podem ser adicionados ou estão sujeitos à falhas. Entretanto, a utilização desses recursos como plataforma de computação de alto desempenho ainda é restrita, uma vez que o desenvolvimento de sistemas paralelos eficientes e escaláveis se mantém uma tarefa difícil, até mesmo para programadores experientes.O Anthill é um ambiente de programação paralela baseado no paradigma filtro fluxo. Esse paradigma permite o processamento eficiente de grandes volumes de dados, uma vez que o paralelismo pode ser explorado de maneira simples e intuitiva. Entretanto, o Anthill foi construído como um ambiente de execução estático e, como tal, não permite que a distribuição dos componentes da aplicação seja modificada em tempo de execução. Neste trabalho apresentamos um conjunto de extensões que adicionam suporte eficiente ao aumento dinâmico da plataforma execução de uma aplicação Anthill. Nossa solução explora a localidade de referência e a assincronia que muitas aplicações Antill podem fazer uso. Os resultados de nossa avaliação experimental mostram que esta implementação viabiliza a utilização de mais poder computacional em tempo de execução, mantendo, com baixo custo, a consistência e a continuidade da exploração assíncrona do paralelismo em diversos níveis.
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Steenkamp, Pieter Johannes. "Ecological suitability modelling for anthrax in the Kruger National Park, South Africa." Diss., University of Pretoria, 2013. http://hdl.handle.net/2263/23358.
Full textAbstract:
Bacillus anthracis is the causal agent of anthrax which primarily affects ungulates, occasionally carnivores and less frequently humans. The endospores of this soil-borne bacterium are highly resistant to extreme conditions, and under ideal conditions, anthrax spores can survive for many years in the soil. The bacterium is generally found in soil at sites where infected animals have died. When these spores are exposed, they have the potential to be ingested by a mammalian species which could lead to an anthrax outbreak. Anthrax is almost never transmitted directly from host to host, but is rather ingested by herbivores while drinking, grazing or browsing in a contaminated environment, with the exception of scavengers and carnivores consuming infected prey. Anthrax is known to be endemic in the northern part of Kruger National Park (KNP) in South Africa (SA), with occasional epidemics spreading southward into the non-endemic areas. The aim of this study is to identify and map areas that are ecologically suitable for the harbouring of B. anthracis spores within the KNP. Anthrax surveillance data and selected environmental variables were used as inputs to the maximum entropy (Maxent) species distribution modelling method. Five-hundred and ninety-seven anthrax occurrence records, dating from the year 1988 to 2011, were extracted from the Skukuza State Veterinary Office’s database. A total of 40 environmental variables were used and their relative contribution to predicting suitability for anthrax occurrence was evaluated using Maxent software (version 3.3.3k). Variables showing the highest gain were then used for subsequent, refined model iterations until the final model parameters were established. The environmental variables that contributed the most to the occurrence of anthrax were soil type, normalized difference vegetation index (NDVI), land type and precipitation. A map was created using a geographic information system (GIS) that illustrates the sites where anthrax spores are most likely to occur throughout the Park. This included the known endemic Pafuri region as well as the low lying soils along the Shingwedzi-Phugwane-Bubube rivers and the Letaba-Olifants river drainage area. The outputs of this study could guide future targeted surveillance efforts to focus on areas predicted to be highly suitable for anthrax, especially since the KNP uses passive surveillance to detect anthrax outbreaks. Knowing where to look can improve sampling efficiency and lead to increased understanding of the ecology of anthrax within the KNP.Dissertation (MMedVet)--University of Pretoria, 2013.
Production Animal Studies
unrestricted
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Ascough, Stephanie. "Analysis of the CD4+ T cell immune response to Anthrax Lethal Factor." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/9465.
Full textAbstract:
The Gram-positive bacterium Bacillus anthracis is the causative agent of the potentially fatal illness, anthrax. A major determinant of B. anthracis pathogenicity is a binary toxin composed of Protective Antigen (PA) and one of two subunits; Lethal Factor (LF) or Edema Factor (EF). Translocation by PA into the host cell cytosol allows LF, which is a zinc metalloprotease, to inactivate the mitogen-activated protein kinase (MAPK) pathway. The expected consequences for the immune response include subversion of antigen presentation and T cell priming. In contrast to this, long term CD4+ T cell responses to LF were identified following natural human anthrax infection and vaccination, indicating that this toxin component is a principle B. anthracis antigen which may confer protective immunity. It has been observed that polymorphism in the HLA class II alleles at the DR and DQ loci affects susceptibilty to infectious disease outcome. In order to map the human response within a defined genetic background, transgenic mice expressing individual HLA heterodimers in the absence of endogenous MHC class II were utilised. HLA-DR1, HLA-DR15, HLA-DR4, HLA-DQ8 and HLA-DQ6 (the latter generated as part of this project) transgenic mice were compared in terms of response magnitude to LF and HLA expression levels. This was correlated with survival following live anthrax challenge. Immunodominant epitopes within LF were elucidated for all HLA-transgenic lines. Immunogenicity in the transgenic model was shown to be primarily restricted to epitopes from domains II and IV. Dominant epitopes, which were common to all HLA types, were identified in domain II. HLA-DR specific epitopes were also identified. T cell responses to cryptic epitopes, revealed following immunisation with the individual peptides, were compared to the immunodominant epitope hierarchy. A peptide epitope of LF was identified with a strong relative binding affinity for HLA-DR15, making it a candidate therapeutic for ‘MHC blockade’ strategies. This epitope was tested for therapeutic blockade in a humanised transgenic mouse model which develops spontaneous paralysis with central nervous system (CNS) pathology similar to human multiple sclerosis (MS). Disease is characterised by an autoimmune response to a DR15 restricted epitope of myelin basic protein (MBP). The LF peptide was found to prevent induction of antigen-specific T cell responses, presumably by HLA class II, reducing the inflammatory response to self-peptide both in vitro and in vivo.
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Sutherland, Marjorie D. "Tissue and intracellular trafficking of Poly-y-D-Glutamic acid, the capsular antigen from Bacillus anthracis /." abstract and full text PDF (UNR users only), 2008. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3329572.
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Pinzon-Arango, Paola A. "Investigation of the Biological and Physicochemical Properties of Bacillus anthracis Spores during Germination, Virulence, and Killing." Digital WPI, 2012. https://digitalcommons.wpi.edu/etd-dissertations/21.
Full textAbstract:
Bacillus anthracis has been classified as one of the most dangerous bioterrorism agents causing high mortality rates in short periods of time. Anthrax spores are extremely resistant to chemical and environmental factors, and have the ability to return into a vegetative (virulent) state during the process of germination. Previous research has suggested that spores can be eradicated with common disinfectants after germination and release of spore coats. During germination, the spore coat is degraded, making the spore susceptible to penetration of chemicals into the spore core. While previous research has focused on a qualitative understanding of germination of spores by obtaining high-resolutions images of spore coats to understand how protein coat layers change during germination, very few studies have evaluated changes in mechanical properties of spores during germination, and how germination affects virulence of macrophages. In this study, we performed a series of in vitro experiments to do an in-depth analysis of germination and virulence of B. anthracis. Atomic force microscopy (AFM) was used to investigate changes in spore surface properties during germination including morphology, roughness, elasticity, and spring constant. AFM results suggested that germination mechanisms depend on germinants used to trigger germination and roughness of Bacillus species increase during germination. In addition, the elasticity and spring cell constant of B. anthracis spores are affected during germination since the elastic moduli and cell spring constant values decreased with time as the spore was germinating, making the cells more susceptible. Spore killing was also tested both in sporulated and vegetative B. anthracis using the antimicrobial peptide chrysophsin-3 and the surfactant dodecylamine (DDA). Both killing agents were capable of eradicating B. anthracis spores, but more killing was observed for spores that were germinating or had become vegetative. The presence of germinant receptors from the Ger operon and its role on germination kinetics of B. anthracis was also investigated. The germination of mutant spores that carried one receptor or lacked all germinant receptors was compared to the germination kinetics of wild-type B. anthracis. Our results suggest that germination of spores is modified by the presence or absence of germinant receptors. Furthermore, the mutant B. anthracis strain lacking all receptors germinated suggesting that other receptor independent pathways may exist in B. anthracis. Finally the ability of B. anthracis to adhere, grow, and invade macrophages was investigated. Invasion of macrophages by B. anthracis was dependent on germinant receptors and the ability of spores to germinate and multiply. Our results suggest that macrophages were not capable of killing infecting spores, and on the contrary, germination of spores inside macrophages caused the lysis of macrophages. An uncontrolled release of cytokines by macrophages was elicited by spores and germinated B. anthracis. Our study helps understand the process of germination of B. anthracis spores at a nanomolecular level. Our investigation may be a valuable tool in the design and development of antisporal compounds.
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Scott, Harry W. III. "USING ELECTRON MICROSCOPY TO GAIN STRUCTURAL INSIGHT INTO BIOLOGICALLY RELEVANT, LABILE OR DESTABILIZED PROTEIN COMPLEXES." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1544544216569183.
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Duverger, Alexandra. "Régulation des réponses immunes des muqueuses par les dérivés de la toxine oedémateuse de l'anthrax." Phd thesis, AgroParisTech, 2007. http://pastel.archives-ouvertes.fr/pastel-00004594.
Full textAbstract:
Les vaccins des muqueuses s'administrent facilement et favorisent une immunité humorale et cellulaire au niveau des muqueuses. Ainsi, ils offrent une protection optimale contre les pathogènes envahissant par les muqueuses. Cependant, la mise sur le marché de nouveaux vaccins des muqueuses est entravée par le manque d'adjuvants des muqueuses efficaces et sans effets secondaires. La toxine cholérique (CT) est une entérotoxine à fort pouvoir adjuvant mais sa toxicité empêche son utilisation chez l'homme. En tant que modèle expérimental, elle a permis de comprendre l'importance de l'activité enzymatique et des récepteurs dans l'adjuvanticité. Notre travail se base sur l'observation que des doses sublétales de la toxine œdémateuse de Bacillus anthracis (EdTx) n'inhibent pas la réponse immune à des vaccins « nasaux » contenant CT comme adjuvant. Nous avons montré que les dérivés EdTx représentent une nouvelle classe d'adjuvants qui donnent des réponses systémiques et des muqueuses à des protéines vaccinales administrées par de multiples voies, notamment nasale. Contrairement à CT qui se fixe aux gangliosides, EdTx se fixe aux récepteurs des toxines de l'anthrax et ne cible pas les tissus du système nerveux central après administration nasale. Le facteur inné nerve growth factor intervient dans les réponses des muqueuses induites par CT mais n'affecte pas l'adjuvanticité d'EdTx in vivo. L'activité adjuvante d'EdTx implique aussi l'augmentation des fonctions de présentation de l'antigène. Enfin, nous avons montré qu'EdTx est un adjuvant efficace par les voies transcutanée et sublinguale, bien que les IgA des muqueuses ne soient induits qu'après immunisation sublinguale.
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Sariyanni, Zoe-Elizabeth. "Coherent effects in atomic and molecular media: applications to anthrax detection and quantum information." Texas A&M University, 2006. http://hdl.handle.net/1969.1/4242.
Full textAbstract:
In the present quantum optics and laser physics study, the non-linear interaction
of electromagnetic fields with atomic, molecular and biomolecular media is analyzed.
Particular emphasis is given to coherent phenomena, while propagation and dispersion
effects are also extensively investigated. The fields involved vary from ultra short
pulses to continuous waves; while their energies range from the very strong that are
addressed classically, to the very weak which are described quantum mechanically.
Applications and problems addressed span a wide range. A scheme for a real time
detector of chemical and biological hazards, like anthrax spores, is presented; in it,
a strong spectroscopic signature is obtained from complex molecules by using ultrashort,
femtosecond, laser pulses and inducing vibrational coherence on them. Furthermore,
a way of reversing the phase matching condition in coherent spectroscopy,
based on dispersion, is developed; which allows for the use of such spectroscopic methods
in remote detection. More fundamental questions addressed include a resolution
of the centennial old paradox of Maxwell's demon via quantum thermodynamics, and
the role of atomic coherence in enhancing the efficiency of a heat engine as well as
in obtaining lasing without population inversion. Additionally, a quantum storage
scheme is presented, in which the information contained in an optical pulse is stored
and restored via photon echoes.
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Kharazi, Alexandra. "Generation and molecular analysis of dominant negative alleles of anthrax lethal factor in Drosophila." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p1453196.
Full textAbstract:
Thesis (M.S.)--University of California, San Diego, 2008.Title from first page of PDF file (viewed July 8, 2008). Available via ProQuest Digital Dissertations. Includes bibliographical references (p. 26).
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Poff-Reichow, Sherry Ann. "Development of Brucella abortus RB51 as a Vaccine to Protect Against Brucellosis and Anthrax." Diss., Virginia Tech, 1999. http://hdl.handle.net/10919/11144.
Full textAbstract:
Bacillus anthracis is a facultative extracellular bacterial pathogen that causes cutaneous, gastrointestinal or respiratory disease in many vertebrates, including humans. Commercially available anthrax vaccines for immunization of humans are known to provide protection of limited duration and may not protect against the respiratory form of the disease. Commercially available live vaccines for animals have been shown to cause disease in certain species. Brucella abortus is a facultative intracellular bacterium that causes chronic infection in animals and humans. As with other intracellular pathogens, cell mediated immune responses (CMI) are crucial in affording protection against brucellosis. B. abortus strain RB51 has been shown to be useful in eliciting protective CMI and antibody responses against Brucella in cattle and other animal species. Since the protective antigen (PA) of B. anthracis is known to induce antibodies, the pag gene encoding PA was expressed in B. abortus RB51, producing a dual vaccine to protect against both brucellosis and anthrax. In a previous study, the entire pag gene was expressed in strain RB51 and following immunization the vaccine induced antibodies against PA in A/J mice. However, PA stability and protective efficacy were less than desirable as only 1/6 were protected. The studies in this dissertation involved synthesizing a gene corresponding to domain 4 (PA4) of the pag gene utilizing the native codon usage of Brucella. The PA4 domain was fused to Brucella signal sequences of Brucella 18kDa protein, superoxide dismutase or no signal sequence to localize the PA4 to the outside cell envelope, periplasmic space or cytosol respectively. Comparisons of the expression level and stability of the native and synthetic PA4 in B. abortus strain RB51 were assessed by immunoblot. The protective efficacy of PA4 expressed in Brucella was assessed by immunization and protection studies in A/J mice against a live challenge with either B. abortus or B. anthracis Sterne spores. ELISA and western blot indicate the induction of PA specific antibodies by these recombinant strain RB51 vaccine constructs. Results based on subisotype antibody ELISA (IgG, IgG1, IgG2a and IgM) and CMI assays (cytokine ELISA of IL-4 and INF-g, and LPA) suggest a Th1 based immune response to strain RB51 and PA. B. abortus strain RB51 expressing PA4 fused to the signal sequence of Brucella 18kDa protein was able to induce 50% protection, while strain RB51 expressing PA4 with no signal sequence gave 17% protection against B. anthracis Stern spore challenge. Mice were boosted with an intraperitoneal injection of purified PA after an initial immunization with Brucella vaccine candidates, sterile saline or pure PA. Protection assessed by live challenge with B. anthracis Sterne spores increased following boosting with PA in 4 cases. Immunization with purified PA, and 3 strain RB51/PA vaccines and a PA boost gave protection against a spore challenge ranging from partial to full. This study suggests that additional work is needed to define the antigens of B. anthracis involved in the induction of specific CMI.Ph. D.
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Bernhards, Casey Brianne. "Regulation of the Spore Cortex Lytic Enzyme SleB in Bacillus anthracis." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/64780.
Full textAbstract:
Bacillus anthracis is the causative agent of the disease anthrax and poses a threat due to its potential to be used as a biological weapon. The spore form of this bacterium is an extremely resistant structure, making spore decontamination exceptionally challenging. During spore germination, nutrient germinants interact with Ger receptors, triggering a cascade of events. A crucial event in this process is degradation of the cortex peptidoglycan by germination-specific lytic enzymes (GSLEs), resulting in cells that are easily killed. This work investigated the regulation of the GSLE SleB by other proteins in the spore. A full understanding of how GSLEs are held inactive in the dormant spore and are activated during germination could lead to development of simplified spore decontamination strategies in which spore germination is the first step.
It was found that SleB and YpeB are co-dependent. In the absence of one protein, the other is degraded during sporulation by an unidentified protease(s), although HtrC and SpoIVB are not likely responsible. Specific regions and residues of YpeB were also identified as being important to its relationship with SleB. While some evidence suggests that SleB and YpeB physically interact, a direct interaction was not observed in vivo or in vitro. YpeB was demonstrated to be proteolytically processed by HtrC during germination, resulting in stable products containing the YpeB C-terminus. The presence of inhibitory PepSY domains at the C-terminus of YpeB, coupled with YpeB degradation during germination, may suggest that YpeB processing results in SleB activation. Modification of the predominant YpeB cleavage sites or
deletion of htrC reduced proteolysis, but cleavage at other sites still resulted in YpeB instability. Additionally, these changes did not have a significant impact on SleB activity.
SleB regulation by other spore proteins was also examined. To test if SleB activation is Ger receptor-dependent, Bacillus subtilis strains lacking Ger receptors and/or GSLEs were germinated via non-nutrient means. Results indicated SleB can be activated independent of these proteins. B. anthracis homologs of the B. subtilis lipoproteins YlaJ and YhcN were also studied, but deletion of these genes did not result in significant changes in SleB stability or activity.Ph. D.
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Sayer, Cameron Vincent. "Identification and Analysis of Germination-Active Proteins in Bacillus Spores." Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/90885.
Full textAbstract:
Many spore forming bacteria are the causative agents of severe disease, such as Bacillus anthracis and anthrax. In these cases, the spore often acts as the infectious agent. Spores boast extreme resistance to chemical and UV damage among other bactericidal conditions. This is problematic due to the difficulty and economic costs of decontaminating exposure sites. The present work focuses on identifying and characterizing proteins active within spore germination, with a focus towards understanding the triggering of the major stages of germination. Understanding how each stage is initiated could allow for development of methods that induce these processes to efficiently germinate spores, thus facilitating cheap and effective decontamination.
Sequencing of a spore transposon insertion library after exposure to germinants led to the identification of 42 genes with previously uncharacterized roles in spore germination. Fourteen of the genes, encoding proteins associated with the inner spore membrane, were further characterized. Mutants lacking these genes portrayed phenotypes consistent with failure of a GerA receptor-mediated germination response, and these genes affect the earliest stages of germination.
Chemical cross-linking was used to characterize protein interactions important for stage II of spore germination. Site-directed in vivo crosslinking indicated that YpeB may exist as a multimer within the dormant spore. Further investigation of individual protein domains using bacterial two-hybrid analysis suggested that both N- and C-terminal domains of YpeB contribute to the formation of a multimer. In addition, the uncharacterized YpeB N-terminal domain was demonstrated to have strong self-association and may mediate self-association within the dormant spore.
Additional genes that contribute to efficient initiation of spore germination in a GerA-dependent manner were identified via TnSeq. Chemical cross-linking of dormant spores was implemented to characterize protein interactions leading to stabilization and activation of an important enzyme that contributes to cortex degradation in stage II of germination. The presented studies employed a variety of techniques to provide additional insight into both stages of spore germination with a goal of furthering understanding of specific events that contribute to a loss of spore dormancy.Doctor of Philosophy
Few bacterial species can undergo a specialized division process leading to the generation of a bacterial endospore. Endospores are dormant cells that boast resistance to a variety of environmental conditions that would otherwise cause bacterial cell death. These resistance traits make endospores immune to traditional bactericidal methods, making decontamination a nontrivial task. Further complicating the matter, spores are often the infectious particle of the associated disease, including hospital acquired diarrhea, infant botulism, anthrax, and many others. Presented work focuses on furthering understanding the process by which a dormant spore returns to a typical growing bacteria cell. Comprehension of major steps in this process may lead to novel methods for spore cleanup in which mechanisms within the spore are subverted to force a return to a typical bacterial cell state.
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Rajanayagam, Kavitha. "Chemical and biochemical redox reactions of the anthra quinone anticancer drug Mitoxantrone." Thesis, Queen Mary, University of London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417075.
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Santiesteban, Oscar. "Assessment of molecular interactions via magnetic relaxation: a quest for inhibitors of the anthrax toxin." Doctoral diss., University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5481.
Full textAbstract:
Anthrax is severe disease caused by the gram-positive Bacillus anthracis that can affect humans with deadly consequences. The disease propagates via the release of bacterial spores that can be naturally found in animals or can be weaponized and intentionally released into the atmosphere in a terrorist attack. Once inhaled, the spores become activated and the anthrax bacterium starts to reproduce and damage healthy macrophages by the release of the anthrax toxin. The anthrax toxin is composed of three virulent factors: (i) anthrax protective antigen (APA), (ii) anthrax lethal factor (ALF), and (iii) anthrax edema factor (AEF) that work in harmony to effectuate the lethality associated with the disease. Out of the two internalized factors, ALF has been identified to play a critical role in cell death. Studies in animals have shown that mice infected with an anthrax strain lacking ALF survive the infection whereas when ALF is present the survivability of the mice is eliminated. Although the current therapy for anthrax is antibiotic treatment, modern medicine faces some critical limitations when combating infections. Antibiotics have proven very efficient in eliminating the bacterial infection but they lack the ability to destroy or inhibit the toxins released by the bacteria. This is a significant problem since ALF can remain active in the body for days after the infection is eliminated with no way of inhibiting its destructive effects. The use of inhibitors of ALF is an attractive method to treat the pathogenesis of anthrax infections. Over the last decade several inhibitors of the enzymatic activity of ALF have been identified. In order to identify inhibitors of ALF a variety of screening approaches such as library screenings, Mass Spectroscopy- based screenings and scaffold-based NMR screening have been used. Results from these screening have yielded mainly small molecules that can inhibit ALF in low micromolar to nanomolar concentrations. Yet, although valuable, these results have very little significance with regards to treating ALF in a real-life scenario since pharmaceutical companies are not willing to invest in further developing these inhibitors. Furthermore, the low incidence of inhalation anthrax, the lack of a market for an ALF inhibitor, and the expenses associated with the approval process of the FDA, have hindered the motivation of pharmaceutical companies to pursuit these kind of drugs. Therefore we have screened a small-molecule library of FDA approved drugs and common molecules in order to identify currently approved FDA drugs that can also inhibit ALF (Chapter III). The screening revealed that five molecules: sulindac, fusaric acid, naproxen, ketoprofen and ibuprofen bound to either ALF or APA with sulindac binding both. Additionally, we have developed a nanoparticle-based screening method that assesses molecular interactions by magnetic relaxation changes (Chapter II). Using this assay, we were able to accurately measure the dissociation constants of different interactions between several ligands and macromolecules. Moreover, we have used computational docking studies to predict the binding site of the identified molecules on the ALF or APA (Chapter IV). These studies predicted that two molecules sulindac and fusaric acid could be potential inhibitors of ALF since they bind at the enzymatic pocket. As a result, we tested the inhibitory potential of these molecules as well as that of the metabolic derivatives of sulindac (Chapter V). Results from these studies provided conclusive evidence that fusaric acid and sulindac were both strong inhibitors of ALF. Furthermore, the metabolic derivatives of sulindac, sulindac sulfide and sulindac sulfone also inhibited ALF. Overall, taking together these results we have discovered the alternate use of a currently used drug for the treatment of ALF pathogenesis.Ph.D.
Doctorate
Chemistry
Sciences
Chemistry
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Rempfer, Thomas L. "Anthrax vaccine as a component of the strategic national stockpile: a dilemma for Homeland Security." Thesis, Monterey, California : Naval Postgraduate School, 2009. http://edocs.nps.edu/npspubs/scholarly/theses/2009/Dec/09Dec%5FRempfer.pdf.
Full textAbstract:
Thesis (Master of Arts in Security Studies(Homeland Security and Defense))--Naval Postgraduate School, December 2009.Thesis Advisor: Supinski, Stanley. Second Reader: Lynch, Dean. "December 2009." Description based on title screen as viewed on January 29, 2010. Author(s) subject terms: Anthrax Vaccine Adsorbed; AVA; BioThrax; Homeland Security; Strategic National Stockpile; biodefense; bioterrorism; biological warfare; Amerithrax; Anthrax Vaccine Immunization Program; AVIP; Gulf War Illness; Gulf War Syndrome; Investigational New Drug, IND; Experimental; Civilian Control of the Military, Presidential Study Directive; PSD; Presidential Policy Directive; PPD. Includes bibliographical references (p. 195-237). Also available in print.