975 resultados para War against drugs


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A collection of miscellaneous pamphlets on World War I.

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Thesis (Ph.D.)--University of Washington, 2016-06

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A full-length cDNA sequence coding for Echinococcus granulosus thioredoxin peroxidase (EgTPx) was isolated from a sheep strain protoscolex cDNA library by immunoscreening using a pool of sera from mice infected with oncospheres. EgTPx expressed as a fusion protein with glutathione S-transferase (GST) exhibited significant thiol-dependent peroxidase activity that protected plasmid DNA from damage by metal-catalyzed oxidation (MCO) in vitro. Furthermore, the suggested antioxidant role for EgTPx was reinforced in an in vivo assay, whereby its expression in BL21 bacterial cells markedly increased the tolerance and survival of the cells to high concentrations of H2O2 compared with controls. Immunolocalization studies revealed that EgTPx was specifically expressed in all tissues of the protoscolex and brood capsules. Higher intensity of labelling was detected in many, but not all, calcareous corpuscle cells in protoscoleces. The purified recombinant EgTPx protein was used to screen sera from heavily infected mice and patients with confirmed hydatid infection. Only a portion of the sera reacted positively with the EgTPx-GST fusion protein in Western blots, suggesting that EgTPx may form antibody-antigen complexes or that responses to the EgTPx antigen may be immunologically regulated. Recombinant EgTPx may prove useful for the screening of specific inhibitors that could serve as new drugs for treatment of hydatid disease. Moreover, given that TPx from different parasitic phyla were phylogenetically distant from host TPx molecules, the development of antiparasite TPx inhibitors that do not react with host TPx might be feasible. (C) 2003 Elsevier B.V. All rights reserved.

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Pharmacologists have generally been prejudiced against prostanoids, uncritically accepting their suppression as desirable therapy, especially for ‘quick-fix’ analgesia. This myopic perception for a long time ignored (a) the essentiality of prostanoid precursors in nutrition, (b) the physiological protective functions of natural prostaglandins (PGs) (vasculature, stomach, kidney), (c) resolution of inflammation after the expression of COX-2 and (d) increasing therapeutic use of either synthetic PGs (for erectile dysfunction, opthalmic disorders, inducing parturition, etc) or their natural precursors, e.g., ω3-rich polyunsaturated oils, to treat arthritis. Experimental studies in rats have indicated that prostaglandins (E series) are (i) useful, perhaps auto-regulators of established immunoreactivity and (ii) able to amplify (or even induce) anti-inflammatory activity with other agents. Furthermore, anti-prostanoid therapy (APT) can be arthritigenic!!, interfering with the acquisition of tolerance to some arthritigens. For patients with rheumatoid arthritis this additional side-effect of APT, barely recognised to date, may actually perpetuate their arthritis by impairing prostanoid-mediated remission processes. Hopefully, recent adverse publicity about COX-2 inhibitory drugs might stimulate serious re-assessment of some traditional anti-inflammatory therapies with low APT activity for the management of both acute pain (non-addictive cannabinoids, celery seed, etc.) and chronic inflammation, e.g., Lyprinol® (a mussel lipid extract).

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Parasite resistance to antimalarial drugs is a serious threat to human health, and novel agents that act on enzymes essential for parasite metabolism, such as proteases, are attractive targets for drug development. Recent studies have shown that clinically utilized human immunodeficiency virus (HIV) protease inhibitors can inhibit the in vitro growth of Plasmodium falciparum at or below concentrations found in human plasma after oral drug administration. The most potent in vitro antimalarial effects have been obtained for parasites treated with saquinavir, ritonavir, or lopinavir, findings confirmed in this study for a genetically distinct P. falciparum line (3D7). To investigate the potential in vivo activity of antiretroviral protease inhibitors (ARPIs) against malaria, we examined the effect of ARPI combinations in a murine model of malaria. In mice infected with Plasmodium chabaudi AS and treated orally with ritonavir-saquinavir or ritonavir-lopinavir, a delay in patency and a significant attenuation of parasitemia were observed. Using modeling and ligand docking studies we examined putative ligand binding sites of ARPIs in aspartyl proteases of P. falciparum (plasmepsins II and IV) and P. chabaudi (plasmepsin) and found that these in silico analyses support the antimalarial activity hypothesized to be mediated through inhibition of these enzymes. In addition, in vitro enzyme assays demonstrated that P. falciparum plasmepsins II and IV are both inhibited by the ARPIs saquinavir, ritonavir, and lopinavir. The combined results suggest that ARPIs have useful antimalarial activity that may be especially relevant in geographical regions where HIV and P. falciparum infections are both endemic.

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Single crystal X-ray structure determinations are reported for eleven compounds all of which are either biologically active or potentially biologically important. The compounds fall into two distinct classes:- 1. Substituted diaminopyrimidines 2. Substituted aminopyrimidinones The first class of compounds were all selected on the basis of their common diaminopyrimidine nucleus which has been demonstrated to be a vital requirement for antifolate activity. They may all be described as non-classical or small molecule lipophilic dihydrofolate reductase (DHFR) inhibitors, as opposed to the classical folate analogues, having the ability to cross the blood-brain barrier, enter cells via a rapid passive diffusion process, and achieve high intracellular concentrations. Thus they are an excellent choice in the search for crystallography in the solid state, providing geometrical and distance data not available from any other analytical techniques to date; supporting and enhancing data obtained in the lower resolution studies of protein crystallography. The biological importance of these compounds is discussed and an attempt is made to relate/predict their pharmacological activity to observed structural features in the crystalline environment. Special attention is focussed on hydrogen bonding, confirmational flexibility and hydrophobicity of substituents; each of which appear to make contributions to tight binding in the enzyme active site. Chapter 9 describes the use of data from the literature and the solid state modelling of an observed enzyme-substrate interaction in an attempt to define it more accurately in terms of its geometric flexibility. Of the second class, one compound (ABPP) is reported; studies in two different crystal forms. In demonstrating both antiviral and high interferon inducing activity it is possible that this compound could be useful against cancer and also viral infections.

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Human arythrocytes were used as a model system for an investigation of the mechanism of action of the antiproliferative drug Adriamycin. Erythrocytes were induced to undergo a change in morphology by elevation of intracellular calcium. It was revealed that the widely used media employed for the study of morphological change were unsuitable; a new incubation medium was developed so that cells were metabolically replete. In this medium echinocytosis took place both in a calcium concentration- and time-dependent manner. Pretreatment of erythrocytes with Adriamycin (10 M for 10 mins) protected the erythrocytes against calcium-induced echinocytosis at calcium concentrations < 150M. SDS-PAGE analysis of the cytoskeletal proteins prepared from erythrocytes revealed the calcium-induced proteolysis of two main cytoskeletal proteins: band 2:1 and band 4:1. Only the rate of the proteolysis of band 2.1 correlated with the onset of echinocytosis. Adriamycin inhibited the breakdown of band 2.1 even when the cells formed echinocytes; this raises doubts concerning the importance of band 2.1 in the maintenance of discocyte morphology. Adriamycin only marginally inhibited the purified calcium-activated thio protease (calpain). Calcium-loading of human erythrocytes increased the phosphorylation of several major cytoskeletal proteins including pp120, band 3, band 4.1 and band 4.9. The pattern of increase resembled that induced by 12-0-tetradecanoyl-phorbol-13-acetate. Pre-treatment with Adriamycin prior to calcium loading caused a general lowering of basal phosphorylation. Adriamycin had no effect on the activity of the calcium-activated phospholipid-dependent protein kinase (protein kinase C). A hypothesis is put forward that the morphological transition of erythrocytes might be dependent upon the activity of a contractile system.

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The 1641 Depositions are testimonies collected from (mainly Protestant) witnesses documenting their experiences of the Irish uprising that began in October 1641. As news spread across Europe of the events unfolding in Ireland, reports of violence against women became central to the ideological construction of the barbarism of the Catholic rebels. Against a backdrop of women's subordination and firmly defined gender roles, this article investigates the representation of women in the Depositions, creating what we have termed "lexico-grammatical portraits" of particular categories of woman. In line with other research dealing with discursive constructions in seventeenth-century texts, a corpus-assisted discourse analytical approach is taken. Adopting the assumptions of Critical Discourse Analysis, the discussion is extended to what the findings reveal about representations of the roles of women, both in the reported events and in relation to the dehumanisation of the enemy in atrocity propaganda more generally. © John Benjamins Publishing Company.

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Tavaly ünnepelte a közgazdász-társadalom Milton Friedman Nobel-díjas közgazdász születésének századik évfordulóját. A jubileumi megemlékezésnek különös aktualitást ad, hogy a 2008 óta tartó pénzügyi világválság hátterében ismét fellobbant a 20. századi közgazdaságtan két meghatározó irányzata - a Friedman nevével fémjelzett monetarizmus és a Keynes és követői által követett keynesizmus - közötti vita. E szerteágazó vitasorozat egyik "gyöngyszeme" két nemzetközileg ismert és elismert közgazdász, Tim Congdon és Robert (Lord) Skidelsky, összecsapása a Standpoint hasábjain 2009-ben. A szerző megmutatja, hogy a vita valójában nem a pénz fontosságáról vagy a mennyiségi pénzelmélet igazságáról folyt, hanem egyrészt egy sokkal elvontabb fogalomról: a bizonytalanság közgazdasági szerepéről, másrészt gyakorlati, gazdaságpolitikai kérdésekről: a monetáris és a fiskális politika lehetséges hatékonyságáról. A máig is tartó vitában "az inga többször kilengett", hol a keynesiánusok, hol a monetaristák javára, de még semmi nem dőlt el. ____ Last year economists marked the centenary of the birth of genius among them, Milton Friedman. The commemoration was especially topical because the world financial crisis that erupted in 2008 has brought sharply into focus again the old division in 20th-century economics between monetarism and Keynesianism. One highlight in this series of disputes was the 2009 clash between two internationally known and appreciated economists Tim Congdon and Robert (Lord) Skidelsky in the columns of Standpoint. The central element in the discussion is the role of money: what kind of economic policy to pursue, monetary or fiscal, to pull troubled economies out of crisis. The question closely resembles a decisive dilemma for Keynes in the 1930s. Though Keynes turned against some basic propositions of neoclassical economics, he never challenged the importance of money to the functioning of the economy, or the validity of the quantity theory of money. The author argues here that the issue is not about the formal category of money or demand for it, but about the far deeper economic concept of the role of uncertainty in economics. Another aspect concerns the relative efficiency of various kinds of economic policy, i. e. the strengths and weaknesses of monetary and fiscal policies.

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In our study the application of mint species (spearmint, peppermint ‘Mitcham’ and peppermint ‘Mexian’) and cinnamon was investigated against Fusarium head blight of winter wheat in vitro and in vivo. The effect of crude drugs and the aqueous extract of mint, and the effect of essential oils of mint and cinnamon on mycelial growth were evaluated in lab. On artificial media the crude drug showed higher inhibition than aqueous plant extracts. Cinnamon and spearmint oils e.ectively inhibited mycelia growth. In field trial artificially inoculated winter wheat was treated with the in vitro effective oils under small-plot conditions. The disease incidence was most inhibited by cinnamon oil, applied curative. According to our results the essential oil of cinnamon can be an appropriate candidate for the research of alternative disease control.

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The purpose of the research is to study the relationship between international drug interdiction policies and domestic politics in fragile democracies, and to demonstrate how international drug control policies and the use of force fit the rhetoric of war, are legitimized by the principles of a just war, but may also cause collateral damage and negative unintended consequences. The method used is a case study of the Dominican Republic. The research has found that international drug control regimes, primarily led by the U.S. and narrowly focused on interdiction, have influenced an increasingly militarized approach to domestic law enforcement in the Dominican Republic. The collateral damage caused by militarized enforcement comes in the form of negative perceptions of citizen security, loss of respect for the rule of law and due process, and low levels of civil society development. The drug war has exposed the need for significant reform of the institutions charged with carrying out enforcement, the police force and the judicial system in particular. The dissertation concludes that the extent of drug trafficking in the Dominican Republic is beyond the scope of domestic reform efforts alone, but that the programs implemented do show some potential for future success. The dissertation also concludes that the framework of warfare is not the most appropriate for the international problems of drug traffic and abuse. A broader, multipronged approach should be considered by world policy makers in order to address all conditions that allow drugs to flourish without infringing upon democratic and civil rights in the process.

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The philosopher and novelist Ayn Rand (1905–1982) is an icon of American culture. That culture misunderstands her, however. It perceives her solely as a pure market conservative. In the first forty years of her life, Rand's individualism was intellectual and served as a defense for the free trade of ideas. It originated in the Russian Revolution. In 1926, when Rand left the Soviet Union, she developed her individualism into an American philosophy. Her ideas of the individual in society belonged to a debate where intellectuals intended to abolish the State and free man and woman from its intellectual snares. To present Rand as a freethinker allows me to examine her anticommunism as a reaction against Leninism and to consider the relation of her ideas to Marxism. This approach stresses that Rand, as Marx, opposed the State and argued for the historical importance of a capitalist revolution. For Rand the latter, however, depended on an entrepreneurial class that rejected Protestantism as ideology – which she contended threatened its interests because Christianity had lost its historical significance. This exposes the nature of Rand's intellectual individualism in American society, where the majority on the entire political spectrum still identified with the teachings of Christ. It also reveals the dynamics of her anticommunism. From 1926 to 1943, Rand remodeled American individualism and as she did so, she determined her opposition first to the New Deal liberals and second business conservatives. To these ends, Marxism and Protestantism served Rand's individualism and made her an American icon of the twentieth century.

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For the first time in more than fifty years, the domestic and external conflicts in Latin America and the Caribbean (LAC) are not primarily ideological in nature. Democracy continues to thrive and its promise still inspires hope. In contrast, the illegal production, consumption, and trading of drugs – and its links to criminal gangs and organizations – represent major challenges to the region, undermining several States’ already weak capacity to govern. While LAC macroeconomic stability has remained resilient, illegal economies fill the region, often offering what some States have not historically been able to provide – elements of human security, opportunities for social mobility, and basic survival. Areas controlled by drug trafficking organizations (DTOs) are now found in Central America, Mexico, and the favelas of Rio de Janeiro and São Paulo, reflecting their competition for land routes and production areas. Cartels such as La Familia, Los Zetas, and Primeiro Comando da Capital (PCC-Brazil), among others, operate like trade and financial enterprises that manage millions of dollars and resources, demonstrating significant business skills in adapting to changing circumstances. They are also merciless in their application of violence to preserve their lucrative enterprises. The El Salvador-Guatemala-Honduras triangle in Central America is now the most violent region in the world, surpassing regions in Africa that have been torn by civil strife for years. In Brazil’s favelas and Guatemala’s Petén region, the military is leaving the barracks again; not to rule, however, but to supplement and even replace the law enforcement capacity of weak and discredited police forces. This will challenge the military to apply lessons learned during the course of their experience in government, or from the civil wars that plagued the region for nearly 50 years during the Cold War. Will they be able to conduct themselves according to the professional ethics that have been inculcated over the past 20 years without incurring violations of human rights? Belief in their potential to do good is high according to many polls as the Armed Forces still enjoy a favorable perception in most societies, despite frequent involvement in corruption. Calling them to fight DTOs, however, may bring them too close to the illegal activities they are being asked to resist, or even rekindle the view that only a “strong hand” can resolve national troubles. The challenge of governance is occurring as contrasts within the region are becoming sharper. There is an increasing gap between nations positioned to surpass their “developing nation” status and those that are practically imploding as the judicial, political and enforcement institutions fall further into the quagmire of illicit activities. Several South American nations are advancing their political and economic development. Brazil in particular has realized macro-economic stability, made impressive gains in poverty reduction, and is on track to potentially become a significant oil producer. It is also an increasingly influential power, much closer to the heralded “emerging power” category that it aspired to for most of the 20th century. In contrast, several Central American States have become so structurally deficient, and have garnered such limited legitimacy, that their countries have devolved into patches of State controlled and non-State-controlled territory, becoming increasingly vulnerable to DTO entrenchment. In the Caribbean, the drug and human trafficking business also thrives. Small and larger countries are experiencing the growing impact of illicit economies and accompanying crime and violence. Among these, Guyana and Suriname face greater uncertainty, as they juggle both their internal affairs and their relations with Brazil and Venezuela. Cuba also faces new challenges as it continues focusing on internal rather than external affairs and attempts to ensure a stable leadership succession while simultaneously trying to reform its economy. Loosening the regime’s tight grip on the economy while continuing to curtail citizen’s civil rights will test the leadership’s ability to manage change and prevent a potential socio-economic crisis from turning into an existential threat. Cuba’s past ideological zest is now in the hands of Venezuela’s President Hugo Chavez, who continues his attempts to bring the region together under Venezuelan leadership ideologically based on a “Bolivarian” anti-U.S. banner, without much success. The environment and natural disasters will merit more attention in the coming years. Natural events will produce increasing scales of destruction as the States in the region fail to maintain and expand existing infrastructure to withstand such calamities and respond to their effects. Prospects for earthquakes, tsunamis, and hurricanes are high, particularly in the Caribbean. In addition, there are growing rates of deforestation in nearly every country, along with a potential increase in cross-sector competition for resources. The losers might be small farmers, due to their inability to produce quantities commensurate to larger conglomerates. Regulations that could mitigate these types of situations are lacking or openly violated with near impunity. Indigenous and other vulnerable populations, including African descendants, in several Andean countries, are particularly affected by the increasing extraction of natural resources taking place amongst their terrain. This has led to protests against extraction activities that negatively affect their livelihoods, and in the process, these historically underprivileged groups have transitioned from agenda-based organization to one that is bringing its claims and grievances to the national political agenda, becoming more politically engaged. Symptomatic of these social issues is the region’s chronically poor quality of education that has consistently failed to reduce inequality and prepare new generations for jobs in the competitive global economy, particularly the more vulnerable populations. Simultaneously, the educational deficit is also exacerbated by the erosion of access to information and freedom of the press. The international panorama is also in flux. New security entities are challenging the old establishment. The Union of South American Nations, The South American Defense Council, the socialist Bolivarian Alliance, and other entities seem to be defying the Organization of American States and its own defense mechanisms, and excluding the U.S. And the U.S.’s attention to areas in conflict, namely Iraq, Afghanistan, and Pakistan – rather than to the more stable Latin America and Caribbean – has left ample room for other actors to elbow in. China is now the top trading partner for Brazil. Russian and Iran are also finding new partnerships in the region, yet their links appear more politically inclined than those of China. Finally, the aforementioned increasing commercial ties by LAC States with China have accelerated a return to the preponderance of commodities as sources of income for their economies. The increased extraction of raw material for export will produce greater concern over the environmental impact that is created by the exploitation of natural resources. These expanded trade opportunities may prove counterproductive economically for countries in the region, particularly for Brazil and Chile, two countries whose economic policies have long sought diversification from dependence on commodities to the development of service and technology based industries.

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The purpose of the research is to study the relationship between international drug interdiction policies and domestic politics in fragile democracies, and to demonstrate how international drug control policies and the use of force fit the rhetoric of war, are legitimized by the principles of a just war, but may also cause collateral damage and negative unintended consequences. The method used is a case study of the Dominican Republic. The research has found that international drug control regimes, primarily led by the U.S. and narrowly focused on interdiction, have influenced an increasingly militarized approach to domestic law enforcement in the Dominican Republic. The collateral damage caused by militarized enforcement comes in the form of negative perceptions of citizen security, loss of respect for the rule of law and due process, and low levels of civil society development. The drug war has exposed the need for significant reform of the institutions charged with carrying out enforcement, the police force and the judicial system in particular. The dissertation concludes that the extent of drug trafficking in the Dominican Republic is beyond the scope of domestic reform efforts alone, but that the programs implemented do show some potential for future success. The dissertation also concludes that the framework of warfare is not the most appropriate for the international problems of drug traffic and abuse. A broader, multipronged approach should be considered by world policy makers in order to address all conditions that allow drugs to flourish without infringing upon democratic and civil rights in the process.