We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate (...) assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work. This work is in the public domain (...) in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

In this article, I describe how gender bias can affect the design, testing, clinical trials, regulatory approval, and clinical use of implantable devices. I argue that bad outcomes experienced by women patients are a cumulative consequence of small biases and inattention at various points of the design, testing, and regulatory process. However, specific instances of inattention and bias can be difficult to identify, and risks are difficult to predict. This means that even if systematic gender bias in implant design is (...) an ethical issue, it is one with no clearly blameworthy player. From a practical perspective, there is no single obvious point at which to intervene. Philosophers working in other areas have explored structurally similar moral problems—sometimes referred to as “moral aggregation problems”—such as the type of environmental harm caused by small actions of many players. I describe key features of these type of problems and strategies to address them. I then draw on these to suggest an approach to gender bias in medical implant design and use. (shrink)

Many realists have maintained that the success of scientific theories can be explained only if they may be regarded as approximately true. Laurens Laudan has in turn contended that a necessary condition for a theory's being approximately true is that its central terms refer, and since many successful theories of the past have employed central terms which we now understand to be non-referential, realism cannot explain their success. The present paper argues that a realist can adopt a view of reference (...) according to which a theory might plausibly be said to be approximately true even though its central terms do not refer, or alternatively, he may construe reference in such a way as to assign reference to a range of successful older theories which includes Laudan's purported counterexamples. (shrink)

This paper rejects a traditional epistemic interpretation of conditional probability. Suppose some chance process produces outcomes X, Y,..., with probabilities P(X), P(Y),... If later observation reveals that outcome Y has in fact been achieved, then the probability of outcome X cannot normally be revised to P(X|Y) ['P&Y)/P(Y)]. This can only be done in exceptional circumstances - when more than just knowledge of Y-ness has been attained. The primary reason for this is that the weight of a piece of evidence varies (...) with the means by which it is provided, so knowledge of Y-ness does not have uniform impact on the probability of X. A better updating of the probability of X is provided by P(X|Y*), where Y* is not an outcome of the chance process being observed, but the sentence 'the outcome Y has been observed', an 'outcome' of the subsequent observation process. This alternative formula is widely endorsed in practice, but not well recognized in theory, where the oversight has generated some unsatisfactory consequences. (shrink)

Through close examination of the texts, the author shows how 15th-century philosopher Nicholas of Cusa developed an understanding of uncertainty that opened the way for human intelligence, despite its inherent weaknesses, to find out more about ourselves, the world, and what lies beyond.

Modeling metastasis in animal systems has been an important focus for developing cancer therapeutics. Xenopus laevis is a well‐established model, known for its use in identifying genetic mechanisms underlying diseases and disorders in humans. Prior literature has suggested that the drug, ivermectin, can be used in Xenopus to induce melanocytes to convert into a metastatic melanoma‐like state, and thus could be ideal for testing possible melanoma therapies in vivo. However, there are notable inconsistencies between ivermectin studies in Xenopus and the (...) application of ivermectin in mammalian systems, that are relevant to cancer and melanoma research. In this review, we examine the ivermectin‐induced phenotypes in Xenopus, and we explore the current uses of ivermectin in human research. We conclude that while ivermectin may be a useful drug for many biomedical purposes, it is not ideal to induce a metastatic melanocyte phenotype in Xenopus for testing the effects of potential melanoma therapeutics. (shrink)

À l’origine de ce dossier, on trouve un mot (et une notion) de l’épistémologie féministe, celui de « care » – terme que nous avons choisi de conserver en anglais tant il est impossible de restituer sa polysémie par un seul terme ou même une expression en français. Popularisé par l’ouvrage In a different voice de la psychologue féministe Carol Gilligan en 1982, le care est à la fois une grille de lecture du monde social et un terrain de recherche (...) inscrit dans les expériences ordinaires des ind... (shrink)

John C. Calhoun was a major actor in the political history of nineteenth-century America. His dramatic career will always be of interest. However, Calhoun is equally important as a political thinker who continues to elicit widespread interest from the most diverse points of the ideological spectrum. The Essential Calhoun is designed to present a full-fledged selection of speeches and writings taken from the entire forty-year span of his public career and from many varieties of occasions, public and private. For the (...) first time, it is possible to appreciate Calhoun fully and to seriously examine his thought within the compass of a single volume. Calhoun is known to posterity as the premier defender of the Old South and slavery and as the theorist of the concurrent majority. His contemporaries knew him as much else, including a political economist and foreign policy authority. As the range of writings shows, he was a valuable and often prophetic commentator who remains as timely as the Budget Crisis of 1990 and the Gulf War. Calhoun's thought testifies to a deep and abiding concern with moral and ethical issues that confront a government resting on the consent of the people. The fundamental question with which he wrestles in all his works is how to achieve and maintain a proper balance between power and liberty in a democratic society. By providing the most representative compendium of his thought, The Essential Calhoun invites the reader to engage in this exercise of applying the moral imagination realistically to the public business in America. Historians, American studies specialists, economists, and political scientists will find this volume indispensable. (shrink)

Most people are familiar with Justice Stewart's now classic statement that while he cannot describe pornography, he certainly knows it when he sees it. We instantly identify with Justice Stewart. Pornography is not difficult to recognize, but it does elude description. This is because traditional attempts at description are attempts that seek to explain at either an abstract or empirical level rather than at the level that accounts for experience in its totality. Justice Stewart's lament represents the need to understand (...) the subjective experience of pornography and cease trying to explain it in purely objective terms. Much feminist literature in general and Catharine MacKinnon's work in particular seeks to do just this. MacKinnon argues that pornography should not be explained in familiar First Amendment freedom-of-expression terms, but rather in terms of the actual sexual abuse it constitutes in experience. Then, and only then, are we able to select the appropriate legal remedy. This essay suggests that MacKinnon's position not only needs the support of a non-traditional philosophical approach, but has one readily available in the phenomenology of philosopher Edmund Husserl. (shrink)

In-depth study of the enduring impact of the 1970s debate between state theorists Ralph Miliband and Nicos Poulantzas. We have recently lived through the turmoil of a global financial crisis that originated in the United States and, despite the platitudes of neo-liberal ideology, nation-states were deeply involved in managing this crisis. If “the state” is again a preeminent actor in the global economy, then state theory and the problem of the state should also return to the forefront of political theory. (...) Toward a Critical Theory of States is an intensive analysis of the 1970s debate between state theorists Ralph Miliband and Nicos Poulantzas, including its wider impact on Marxist theories of the state in subsequent decades. Clyde W. Barrow makes unique arguments and contributions to this continuing discussion in state theory and lays the foundation for more theoretically informed empirical and historical research on the state in the age of globalization. He argues that by merely moving past the Poulantzas-Miliband debate, as some have recommended, scholars have abandoned much that is valuable in understanding the state, particularly the need to comprehend the contemporary transformation of the state form and the state apparatuses as part of the new conditions of globalization and transnational capital accumulation. Building upon themes of state restructuring found in Poulantzas and Miliband, Barrow establishes the outlines of an approach that integrates the thought of both to propose a synthetic understanding of the new imperialism. (shrink)

Women are under-represented in surgery, especially in leadership and academic roles, and face a gender pay gap. There has been little work on the role of implicit biases in women’s under-representation in surgery. Nor has the impact of epistemic injustice, whereby stereotyping influences knowledge or credibility judgements, been explored. This article reports findings of a qualitative in-depth interview study with women surgeons that investigates gender biases in surgery, including subtle types of bias. The study was conducted with 46 women surgeons (...) and trainees of the Royal Australasian College of Surgeons. Maximum variance sampling strategies ensured a comprehensive set of perspectives. Data were analysed using iterative thematic analysis to document and classify forms of gender bias experienced by the participants, including implicit bias and epistemic injustice. It found four types of bias affecting women surgeons: (1) workplace factors such as access to parental leave and role models; (2) epistemic injustices—unfair assessments of women surgeons’ credibility by patients and colleagues; (3) stereotyped expectations that they will carry out more of surgery’s carework, such as meeting the emotional needs of patients and (4) objectification. Implicit biases arose in each category. Given that many of the biases identified in this study are small, are harmless on their own and are not necessarily under anyone’s conscious control, important questions arise regarding how they cause harm and how to address them. I draw on theoretical work on cumulative harm to answer these questions. (shrink)

This paper raises questions about the epistemological foundations of evidence-based medicine . We argue that EBM is based upon reliabilist epistemological assumptions, and that this is appropriate - we should focus on identifying the most reliable processes for generating and collecting medical knowledge. However, we note that this should not be reduced to narrow questions about which research methodologies are the best for gathering evidence. Reliable processes for generating medical evidence might lie outside of formal research methods. We also question (...) the notion of the knower that is assumed by EBM. We argue that EBM assumes an enlightenment conception of knowers as autonomous, substitutable individuals. This conception is troubled by the way that clinicians learn the role of anecdote in health care and the role of patient choice, all of which bring into play features of clinicians and patients as situated individuals with particular backgrounds and experiences. EBM's enlightenment conception of the knower is also troubled by aspects of the way evidence is produced. Given these limitations, we argue that EBM should retain its reliabilist bent, but should look beyond formal research methodologies in identifying processes that yield reliable evidence for clinical practice. We suggest looking to feminist epistemology, with its focus on the standpoints of individual situated knowers, and the role of social context in determining what counts as knowledge. (shrink)

A revision of the author's thesis, Yale University. Bibliography: p. 223-227.

A beautifully illustrated reminder that God paints his love on every face he creates.

The effects of the theological revolution have been felt most acutely in European Protestantism, but it has by no means been limited either to Europe or to Protestantism. Its influence has been felt in Judaism, Catholicism, and to a lesser degree in Eastern Orthodoxy. Even Humanism has felt its force. From Europe it has spread to America, and also to Asia and Africa.