Selection of neutralizing antibody escape mutants with type A influenza virus HA-specific polyclonal antisera: possible significance for antigenic drift

Ten antisera were produced in rabbits by two or three intravenous injections of inactivated whole influenza type A virions. All contained haemagglutination-inhibition (HI) antibody directed predominantly to an epitope in antigenic site B and, in addition, various amounts of antibodies to an epitope in site A and in site D. The ability of untreated antisera to select neutralization escape mutants was investigated by incubating virus possessing the homologous haemagglutinin with antiserum adjusted to contain anti-B epitope HI titres of 100, 1000 and 10000 HIU/ml. Virus-antiserum mixtures were inoculated into embryonated hen's eggs, and progeny virus examined without further selection. Forty percent of the antisera at a titre of 1000 HIU/ml selected neutralizing antibody escape mutants as defined by their lack of reactivity to Mab HC10 (site B), and unchanged reactivity to other Mabs to site A and site D epitopes. All escape mutant-selecting antisera had a ratio of anti-site B (HC10)-epitope antibody[ratio]other antibodies of [gt-or-equal, slanted]2·0[ratio]1. The antiserum with the highest ratio (7·4[ratio]1) selected escape mutants in all eggs tested in four different experiments. No antiserum used at a titre of 10000 HIU/ml allowed multiplication of any virus. All antisera used at a titre of 100 HIU/ml permitted virus growth, but this was wild-type (wt) virus. We conclude that a predominant epitope-specific antibody response, a titre of [gt-or-equal, slanted]1000 HIU/ml, and a low absolute titre of other antibodies ([less-than-or-eq, slant]500 HIU/ml) are three requirements for the selection of escape mutants. None of the antisera in this study could have selected escape mutants without an appropriate dilution factor, so the occurrence of an escape mutant-selecting antiserum in nature is likely to be a rare event

A Bayesian spatio-temporal model of panel design data: airborne particle number concentration in Brisbane, Australia

This paper outlines a methodology for semi-parametric spatio-temporal modelling of data which is dense in time but sparse in space, obtained from a split panel design, the most feasible approach to covering space and time with limited equipment. The data are hourly averaged particle number concentration (PNC) and were collected, as part of the Ultrafine Particles from Transport Emissions and Child Health (UPTECH) project. Two weeks of continuous measurements were taken at each of a number of government primary schools in the Brisbane Metropolitan Area. The monitoring equipment was taken to each school sequentially. The school data are augmented by data from long term monitoring stations at three locations in Brisbane, Australia. Fitting the model helps describe the spatial and temporal variability at a subset of the UPTECH schools and the long-term monitoring sites. The temporal variation is modelled hierarchically with penalised random walk terms, one common to all sites and a term accounting for the remaining temporal trend at each site. Parameter estimates and their uncertainty are computed in a computationally efficient approximate Bayesian inference environment, R-INLA. The temporal part of the model explains daily and weekly cycles in PNC at the schools, which can be used to estimate the exposure of school children to ultrafine particles (UFPs) emitted by vehicles. At each school and long-term monitoring site, peaks in PNC can be attributed to the morning and afternoon rush hour traffic and new particle formation events. The spatial component of the model describes the school to school variation in mean PNC at each school and within each school ground. It is shown how the spatial model can be expanded to identify spatial patterns at the city scale with the inclusion of more spatial locations.Comment: Draft of this paper presented at ISBA 2012 as poster, part of UPTECH projec

The Alien Tort Statute, Civil Society, and Corporate Responsibility

The topic of this panel is civil participation in the global trading system, with a particular focus on Doe v. Unocal Corp. and use of the Alien Tort Statute (ATS) to enforce fundamental human rights norms against multinational corporations. These comments will therefore attempt to locate Doe v. Unocal and other ATS litigation in the broader efforts of civil society to establish and maintain normative principles for corporate responsibility in the global trading regime. This comment first explains the role of ATS litigation in the broader civil society context and the contribution of ATS cases to the development and enforcement of international human rights law. It then briefly responds to two recent criticisms of ATS litigation: that ATS litigation is spiraling out of control and that suits under the ATS improperly infringe on U.S. foreign relations. I argue that ATS litigation has played an important role in the recent overall global development of enforceable human rights norms, that traditional procedural and prudential mechanisms are working effectively to identify appropriate ATS claims, and that extraordinary measures such as the current administration\u27s attempts to obtain dismissal of corporate ATS suits are contrary to longstanding U.S. human rights policy and simply damage the United States\u27 standing as an international leader in the promotion and protection of human rights

Foreign Authority, American Exceptionalism, and the \u3ci\u3eDred Scott\u3c/i\u3e Case

At least since Alexis de Tocqueville wrote in 1831, the idea that America is distinctive from other nations has permeated much political and social commentary. The United States has been variously perceived as unique in its history, its culture, its national values, its social movements, and its social and political institutions. While the term technically refers only to distinctiveness or difference, exceptionalism may have positive or negative aspects – what Harold Koh has called America\u27s Jekyll-and-Hyde exceptionalism. In the legal realm, claims of exceptionalism have been offered to support what Michael Ingnatieff identifies as legal isolationism – or refusal by domestic courts to consider foreign practices and international legal rules in the construction of U.S. law

Legal Status and Rights of Undocumented Workers: Advisory Opinion OC-18

In Advisory Opinion OC-18 of September 17, 2003, the Inter-American Court of Human Rights ruled that international principles of nondiscrimination prohibit discriminating against undocumented migrant workers in the terms and conditions of work. The Court acknowledged that governments have the sovereign right to deny employment to undocumented immigrants, but held that such workers are equally protected by human rights in the workplace once an employment relationship is initiated. In other words, states may not further their immigration policies by denying basic workplace protections to undocumented employees

Norm Internalization and U.S. Economic Sanctions

The fifty years since the adoption of the Universal Declaration of Human Rights have seen a revolution in the promulgation and universalization of human and labor rights. Human rights conventions have proliferated in the areas of civil and political rights, social and economic rights, and the rights of women, children, minorities, and refugees. Many of these conventions have been ratified by a majority of the nations of the world. International monitoring of human and labor rights compliance is conducted by international institutions such as the U.N. Human Rights Commission and the International Labour Organization (ILO), by regional entities such as the Inter-American Commission on Human Rights, by non-governmental organizations (NGOs) such as Human Rights Watch and Amnesty International, and by national governments. Since the end of the Cold War, significant steps toward international judicial enforcement have been made through the development of regional courts such as the European and Inter- American Courts of Human Rights, through the creation of the International Criminal Tribunals for the Former Yugoslavia (ICTY) and Rwanda (ICTR), and through the 1998 agreement to establish a Permanent International Criminal Court. Peacekeeping efforts such as that of the United Nations in East Timor and the military intervention of the North Atlantic Treaty Organization (NATO) in Kosovo also have been motivated substantially by human rights concerns. The ICTY\u27s indictment last year of Slobodan Milosevic, a sitting head of state, was a striking pronouncement of the extent to which international human rights enforcement mechanisms have developed

\u3ci\u3eHamdi\u3c/i\u3e Meets \u3ci\u3eYoungstown\u3c/i\u3e: Justice Jackson\u27s Wartime Security Jurisprudence and the Detention of Enemy Combatants

More than any Justice who has sat on the United States Supreme Court, Associate Justice Robert H. Jackson explained how our Eighteenth Century Constitution – that Eighteenth-Century sketch of a government hoped for – struggles both to preserve fundamental liberties and to protect the nation against fundamental threats. Drawing upon his collective experience as a solo practitioner with only one year of formal legal education at Albany Law School; government tax and antitrust lawyer, Solicitor General, and Attorney General in the Roosevelt Administration; Associate Justice to the Supreme Court; and Representative and Chief of Counsel for the United States at Nuremberg, Justice Jackson sought to explain how the foreign affairs powers were distributed within the national government, how they related to constitutional civil liberties, and the appropriate role of the courts in achieving that balance

Embedded International Law and the Constitution Abroad

This Essay explores the role of embedded international law in U.S. constitutional interpretation, in the context of extraterritorial application of the Constitution. Traditional U.S. understandings of the Constitution\u27s application abroad were informed by nineteenth-century international law principles of jurisdiction, which largely limited the authority of a sovereign state to its geographic territory. Both international law and constitutional law since have developed significantly away from strictly territorial understandings of governmental authority, however. Modern international law principles of jurisdiction and state responsibility now recognize that states legitimately may exercise power in a number of extraterritorial contexts, and that legal obligations may apply to situations abroad over which states exercise effective control. International bodies, including the European Court of Human Rights, have applied the principle of effective control to constrain state conduct abroad. Prior to the Supreme Court\u27s decision in Boumediene, however, embedded international norms had produced a bifurcated approach to the extraterritorial Constitution. Rules governing the Constitution\u27s application to U.S. nationals abroad reflected an evolutionary relationship between international and constitutional norms, evolving largely in concert with modern international doctrines. The United States, however, asserted an entrenched approach to the Constitution\u27s extraterritorial application to aliens, that continued to be dictated by antiquated, territorial conceptions of international jurisdiction. In adopting a functional approach to extraterritoriality in Boumediene, the Supreme Court abandoned formalistic limits on the Constitution\u27s application based on formal sovereignty or citizenship, and returned to an evolutionary framework. Much work remains to be done in elaborating on the Boumediene test and applying it to particular constitutional provisions and contexts. But the Court\u27s evolutionary approach opened a space for aligning U.S. domestic obligations more closely to contemporary international legal approaches, the expectations and obligations of our allies, and the modern realities of the exercise of state power

Norm Internalization and U.S. Economic Sanctions

The fifty years since the adoption of the Universal Declaration of Human Rights have seen a revolution in the promulgation and universalization of human and labor rights. Human rights conventions have proliferated in the areas of civil and political rights, social and economic rights, and the rights of women, children, minorities, and refugees. Many of these conventions have been ratified by a majority of the nations of the world. International monitoring of human and labor rights compliance is conducted by international institutions such as the U.N. Human Rights Commission and the International Labour Organization (ILO), by regional entities such as the Inter-American Commission on Human Rights, by non-governmental organizations (NGOs) such as Human Rights Watch and Amnesty International, and by national governments. Since the end of the Cold War, significant steps toward international judicial enforcement have been made through the development of regional courts such as the European and Inter-American Courts of Human Rights, through the creation of the International Criminal Tribunals for the Former Yugoslavia (ICTY) and Rwanda (ICTR), and through the 1998 agreement to establish a Permanent International Criminal Court. Peacekeeping efforts such as that of the United Nations in East Timor and the military intervention of the North Atlantic Treaty human rights concerns. The ICTY\u27s indictment last year of Slobodan Milosevic, a sitting head of state, was a striking pronouncement of the extent to which international human rights enforcement mechanisms have developed. Despite significant progress in the identification, definition, and promulgation of human and labor rights norms, however, international mechanisms for their enforcement remain underdeveloped. International monitoring bodies lack enforcement authority and rely substantially on the mobilization of shame to encourage governments to comply with international norms. The International Court of Justice (ICJ) remains limited in its effectiveness, and the restricted jurisdiction of the Rwanda and Yugoslavia war crimes tribunals, and the United States\u27 refusal to join the International Criminal Court, indicate that effective international judicial enforcement for even the most fundamental human rights violations such as genocide, torture, and crimes against humanity may be years away. There is, to date, no international institution capable of holding individuals such as the late Pol Pot, General Pinochet, and Baby Doc Duvalier accountable for even the most basic human rights violations. Nor do any international enforcement mechanisms exist to reach nations and private corporations that utilize forced labor, murder labor organizers, or engage in other fundamental violations of international labor rights