Phosphorothioate Anti-sense Oligonucleotides: The Kinetics and Mechanism of the Generation of the Sulfurising Agent from Phenylacetyl Disulfide (PADS)

The synthesis of phosphorothioate oligonucleotides is often accomplished in the pharmaceutical industry by the sulfurisation of the nucleotide-phosphite using phenylacetyl disulfide (PADS) which has an optimal combination of properties. This is best achieved by an initial ‘ageing’ of PADS for 48 hrs in acetonitrile with 3-picoline to generate polysulfides. The initial base-catalysed degradation of PADS occurs by an E1cB-type elimination to generate a ketene and acyldisulfide anion. Proton abstraction to reversibly generate a carbanion is demonstrated by H/D exchange, the rate of which is greatly increased by electron-withdrawing substituents in the aromatic ring of PADS. The ketene can be trapped intramolecularly by an o-allyl group. The disulfide anion generated subsequently attacks unreacted PADS on sulfur to give polysulfides, the active sulfurising agent. The rate of degradation of PADS is decreased by less basic substituted pyridines and is only first order in PADS indicating that the rate-limiting step is formation of the disulfide anion from the carbanion

American Association for Public Opinion Research Constituency, Party, and Representation in Congress

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Self-interest And Public Interest: The Motivations Of Political Actors

Self-Interest and Public Interest in Western Politics showed that the public, politicians, and bureaucrats are often public spirited. But this does not invalidate public-choice theory. Public-choice theory is an ideal type, not a claim that self-interest explains all political behavior. Instead, public-choice theory is useful in creating rules and institutions that guard against the worst case, which would be universal self-interestedness in politics. In contrast, the public-interest hypothesis is neither a comprehensive explanation of political behavior nor a sound basis for institutional design

Gender Difference or Parallel Publics? The Dynamics of Defense Spending Opinions in the United States, 1965-2007

Gender is now recognized as an important dividing line in American political life, and scholars have accumulated evidence that national security issues are an important reason for gender differences in policy preferences. We therefore expect that the dynamics of support for defense spending among men and women will differ. In contrast, several scholars have shown that population subgroups exhibit a ‘‘parallel’’ dynamic in which the evolution of their preferences over time is very similar, despite differences in the average level of support. Unfortunately, there is little time series evidence on gendered reactions to policy, including defense spending, that would allow one to arbitrate between these competing perspectives. In this research note, we assemble a time series of support for defense spending among men and women and model the determinants of that support for the period 1967–2007. We find that women are on average less supportive of defense spending than are men. However, we also find that the over time variation of support for defense spending among men and women is very similar—each is conditioned principally by the past year’s change in defense spending and occasionally by war casualties and a trade-off between defense and civilian spending

An agenda for ethics and justice in adaptation to climate change

As experts predict that at least some irreversible climate change will occur with potentially disastrous effects on the lives and well-being of vulnerable communities around the world, it is paramount to ensure that these communities are resilient and have adaptive capacity to withstand the consequences. Adaptation and resilience planning present several ethical issues that need to be resolved if we are to achieve successful adaptation and resilience to climate change, taking into consideration vulnerabilities and inequalities in terms of power, income, gender, age, sexuality, race, culture, religion, and spatiality. Sustainable adaptation and resilience planning that addresses these ethical issues requires interdisciplinary dialogues between the natural sciences, social sciences, and philosophy, in order to integrate empirical insights on socioeconomic inequality and climate vulnerability with ethical analysis of the underlying causes and consequences of injustice in adaptation and resilience. In this paper, we set out an interdisciplinary research agenda for the inclusion of ethics and justice theories in adaptation and resilience planning, particularly into the Sixth Assessment Report of the International Panel on Climate Change (IPCC AR6). We present six core discussions that we believe should be an integral part of these interdisciplinary dialogues on adaptation and resilience as part of IPCC AR6, especially Chapters 2 (“Terrestial and freshwater ecosystems and their services”), 6 (“Cities, settlements and key infrastructure”), 7 (“Health, wellbeing and the changing structure of communities”), 8 (“Poverty, livelihoods and sustainable development”), 16 “Key risks across sectors and regions”), 17 (“Decision-making options for managing risk”), and 18 (“Climate resilient development pathways”).: (i) Where does ‘justice’ feature in resilience and adaptation planning and what does it require in that regard?; (ii) How can it be ensured that adaptation and resilience strategies protect and take into consideration and represent the interest of the most vulnerable women and men, and communities?; (iii) How can different forms of knowledge be integrated within adaptation and resilience planning?; (iv) What trade-offs need to be made when focusing on resilience and adaptation and how can they be resolved?; (v) What roles and responsibilities do different actors have to build resilience and achieve adaptation?; (vi) Finally, what does the focus on ethics imply for the practice of adaptation and resilience planning

An Analysis of Public Attitudes Toward the Insanity Defense

Results from a public opinion survey of knowledge, attitudes, and support for the insanity defense indicate that people dislike the insanity defense for both retributive and utilitarian reasons: they want insane law-breakers punished, and they believe that insanity defense procedures fail to protect the public. However, people vastly overestimate the use and success of the insanity plea. Several attitudinal and demographic variables that other researchers have found to be associated with people\u27s support for the death penalty and perceptions of criminal sentencing are also related to support for the insanity defense. Implications for public policy are discussed

Black Hole Evaporation and Compact Extra Dimensions

We study the evaporation of black holes in space-times with extra dimensions of size L. We first obtain a description which interpolates between the expected behaviors of very large and very small black holes and then show that the luminosity is greatly damped when the horizon shrinks towards L from a larger value. Analogously, black holes born with an initial size smaller than L are almost stable. This effect is due to the dependence of both the Hawking temperature and the grey-body factor of a black hole on the dimensionality of space. Although the picture of what happens when the horizon becomes of size L is still incomplete, we argue that there occurs a (first order) phase transition, possibly signaled by an outburst of energy which leaves a quasi-stable remnant.Comment: RevTeX, 13 pages, 6 figures include