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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Immunoneutralization Of Cytotoxic Abrin : Insights Into Mechanisms And Therapy

Bagaria, Shradha 07 1900 (has links) (PDF)
Type II Ribosome Inactivating Proteins (RIPs), commonly known as A/B toxins are heterodimers comprising of a catalytically active A chain, an RNA N-glycosidase which inhibits protein synthesis and a lectin-like B chain required for the binding of the toxin to the cell surface and internalization of the same. Abrin is a type II RIP obtained from the mature seeds of Abrus precatorius plant that is extremely toxic and has been shown to be 75 times more potent than its well studied sister toxin, ricin. The LD50 dose for abrin is only 2.8 µg/kg body weight of mice and its potential use in bio-warfare is a cause of major concern. Abrin has been classified as a select agent by the Centre for Disease Control and Prevention, U.S.A., because it is stable, effective at very low concentrations and easy to purify and disseminate in large amounts. In spite of abrin being a potential bio-warfare agent, there is no antidote or vaccine available against this toxin till date. The first and only neutralizing monoclonal antibody (mAb) against abrin, namely D6F10, was reported from our laboratory and has been shown to rescue toxicity of abrin in cells as well as in mice. The study reported in the thesis focuses on understanding the mechanism of neutralization of abrin by the mAb D6F10 and development of a potential vaccine candidate against the toxin. In order to map the epitope corresponding to the antibody, first, overlapping gene deletion constructs spanning the entire length, 251 amino acids, of ABA were generated and checked for binding to the mAb. Fragments shorter than 1-175 did not show immuoreactivity. Analysis of the crystal structure of abrin A chain revealed that a helix spanning the amino acids 148-167 was present at the core of the protein structure and truncation in this region of the protein possibly results in loss of conformation leading to abrogation of antibody binding. Therefore, a novel strategy of epitope mapping was adopted. Abrus precatorius agglutinin (APA) is a homologue of abrin obtained from the same plant source. The A chains of abrin and APA share 67% sequence identity and their crystal structures superimpose very well but unlike abrin the APA A chain does not bind the mAb D6F10. Chimeric constructs were generated within the region 1-175 of A chains of both ABA and APA and deletions and mutations of the ABA was then made on the APA as scaffold. It could be concluded that the amino acids of the region 75¬123 are involved in the formation of the epitope. Further, based on sequence alignment of ABA and APA A chain 13 residues in the chimera ABA1-123APA124-175 were mutated and it was found that the mutation of the residues Thr 112, Gly 114 and Arg 118 resulted in loss of binding to the antibody. Furthermore, the mAb D6F10 rescues inhibition of protein synthesis by abrin in HeLa cells by internalizing in cells along with abrin and possibly occluding the active site cleft of ABA. The antibody prevents cell attachment of abrin at higher concentrations. The observations provide novel insights into mechanisms of many known neutralizing antibodies against A/B toxins. The study also highlights that chimeric protein constructs could possibly be developed as potential vaccine candidates for neutralization of abrin intoxication.
42

Losing Control: Global Security in the Twenty-first Century

Rogers, Paul F. January 2010 (has links)
'Losing Control combines a glimpse behind the security screens with sharp analysis of the real global insecurities - growing inequality and unsustainability.' The New Internationalist The attacks in New York and Washington on 11th September 2001 took most of the world by surprise. It showed that, for those living in the West, the threat of terrorist attack is now very real. Maintaining control of global security has become a matter of paramount importance to all Western governments. As the war against 'terrorism' widens into a war against particular states who may have played little part in the disaster, the idea that we can maintain global security by desperately clinging to our current security paradigm becomes increasingly improbable. In Losing Control, Paul Rogers calls for a radical re-thinking of western perceptions of security that embraces a willingness to address the core issues of global insecurity. This acclaimed book has already become an essential guide for anyone who wishes to understand the current crisis, and this updated edition contains a new preface and a new chapter which address the specific problems that have arisen since the attack on the World Trade Center and the Pentagon. Drawing on examples from around the world, Rogers analyses the legacy of the Cold War's proliferation of weapons of mass destruction; the impact of human activity on the global ecosystem; the growth of hypercapitalism and resulting poverty and insecurity; the competition for energy resources and strategic minerals; biological warfare programmes; and paramilitary actions against centres of power. The new edition brings the whole analysis right up to date, arguing persuasively that the world's elite cannot maintain control and that a far more emancipatory and sustainable approach to global security has to be developed. / Also published in Japanese
43

生物戰對我國國家安全威脅之研究

潘建華 Unknown Date (has links)
在後911時代,世界各國體認到國家安全的領域已從過去單純國防方面轉移到全方位的整體安全。單純的軍事力量已不足已維護國家安全,在面對各式挑戰和衝突時,必須以更全面的思考來應對。生物戰劑,在過去大多是在教科書和軍事準則上提到的可能威脅之一,但真正威脅到國家安全則是在911之後的炭疽信件。世人瞭解到我們是處於多麼真實且危險的世界。生物科技的進步一方面提昇人類的生活品質和生命長度,另一方面則是直接威脅到人類的生存。生物戰劑的運用方式可以相當多樣且多變,正是製造恐怖的最佳武器。 生物戰劑的目標可以從個人的暗殺、殺傷大量人員、影響農牧業及糧食供應、破壞經濟和社會秩序、影響政治選擇到製造動亂。而各種疾病和生物戰劑的散佈很難區分,更是增加防疫和應變上的困難。 我國在防疫措施上雖然在SARS之後已經有應變機制,但面對多樣的生物戰劑攻擊,仍然顯得捉襟見肘。吾人應分析可能的生物戰劑威脅並擬定相關應變措施,建立有關國家安全生物防護網,發揮全民國防之功能,維護整體國家安全。 關鍵詞:生物戰劑、應變機制、國家安全生物防護網、全民國防 / After 911-terrorism attack, nations all over the world finally realized that the national security field have transformed from national defense to full-spectrum national security. Military force cannot defense national security alone. When face kinds of challenges and threatens, we should think and concern more complete. Biological warfare threat, in past, just only text on textbook and field manual. But after 911 anthrax envelope events, people realized that the biological warfare threat have come to the real world and what dangerous world we live with. Biological science and technology have improved people's quality of life and prolonged our length of life, in the other hand, it also threaten human being's survival. Biological warfare can be use in many different ways and can be the best weapon to make terror. The target or strategic goal can be used to assassin, cause mass casualty, bloke or disturb food supply, destroy economics and social order, influence political choose and make chaos. It is not easy to find the difference between distribution of disease and biological warfare. Moreover, that made counter insurgence more difficult. We have counter insurgence mechanism to deal with biological warfare attack and disease distribution, when face kinds of biological threat, it shows insufficient. We need to improve our anti-bioterrorism capability continuously. Analysis possible threat and get counter insurgence plan, build national bio-shied framework and all-out defense system to protect national security. Keyword: biological warfare, insurgence mechanism, national bio-shied framework, all-out defense system
44

Epidemic events : state-formation, class struggle and biopolitics in three epidemic crises of modern China

Lynteris, Christos January 2010 (has links)
Based on extended research on Chinese medical and epidemiological archival material dating back to the beginning of the 20th century, and on six months of internship in epidemiology in Beijing’s Medical School and in Haidian District’s Centre of Disease Control and Prevention, this thesis explores the conjunction of three major epidemiological crises in modern Chinese history with processes of State formation: the 1911 Manchurian pneumonic plague, the 1952 germ-warfare, and the 2003 SARS outbreak. Analysing the three crises as Events in line with Alain Badiou’s epistemology it seeks to establish how different strategies of governmental fidelity to the imagined cause of each crisis have led to distinct modes of organisation and valorisation of the social: Republican China and its decline to fascism; the clash between professional revolutionaries and technocrats in Maoist China; and the emergence of the “Harmonious Society” of mass exploitation and repression today. This conjunction between State formation and epidemiological Events is explored with the use of Foucault’s genealogical method in a quest for a historical materialist approach that posits at its epicentre processes of class composition, decomposition and recomposition, and their contested enclosure by the governmental apparati of capture. The present thesis thus examines the three major epidemiological crises of modern China as forming grounds for biopolitical strategies that give rise to modes of subjectivation and circuits of debt/guilt within the context of the class struggle. And at the same time, it aims to create a new field of investigation for anthropology: the relation of State and Event, from a viewpoint that contests the accepted relation of event and structure expounded by Marshall Sahlins, proposing as the main object of this investigation the conjunction between necessity and will that can never be reduced either to the naturalism of historical determinism, nor to the culturalism of subjective contingency.
45

State and local policy considerations for implementing the National Response Plan

Cline, John J. 03 1900 (has links)
CHDS State/Local / Approved for public release, distribution is unlimited / Threatened with the loss of federal funding for Homeland Security and emergency management preparedness programs, state and local entities must implement the National Response Plan and the National Incident Management System, which includes the Incident Command System, Unified Command, and the Multiagency Coordination System. Although mandated by Congress and implemented by Homeland Security Presidential Directive 5, underdeveloped areas of Indian country and small towns, especially farming and ranching communities and agriculturally-based counties are likely to find that they do not have the capacity to fully implement these mandated federal response programs. A theoretical terrorist-induced multistate Foot and Mouth Disease (FMD) outbreak is used to examine the impact of implementing newly established federally mandated response management programs on rural and tribal communities in agrarian states. Recovering from such an agroterrorism bioattack would require a coordinated multi-disciplinary response that is heavily dependent on local, tribal, state, and private sector personnel. However, because the United States has not experienced an outbreak of FMD since 1929, many of the skills required to quickly diagnose and respond may no longer exist. This thesis identifies potential methods for obtaining and deploying the FMD virus in a coordinated bioattack on the U.S. economy. / Director, Idaho Bureau of Disaster Services

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