Heterochronic genes control the timing of developmental programs. In C. elegans, two key genes in the heterochronic pathway, lin-4 and let-7, encode small temporally expressed RNAs (stRNAs) that are not translated into protein. These stRNAs exert negative post-transcriptional regulation by binding to complementary sequences in the 3′ untranslated regions of their target genes. stRNAs are transcribed as longer precursor RNAs that are processed by the RNase Dicer/DCR-1 and members of the RDE-1/AGO1 family of proteins, which are better known for their (...) roles in RNA interference (RNAi). However, stRNA function appears unrelated to RNAi. Both sequence and temporal regulation of let-7 stRNA is conserved in other animal species suggesting that this is an evolutionarily ancient gene. Indeed, C. elegans, Drosophila and humans encode at least 86 other RNAs with similar structural features to lin-4 and let-7. We postulate that other small non-coding RNAs may function as stRNAs to control temporal identity during development in C. elegans and other organisms. BioEssays 24:119–129, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Die Idee zu der in diesem Band dokumentierten Tagung ist im Rahmen des disziplinübergreifenden Nachwuchswissenschaftsnetzwerkes THESIS entstanden. Der Dialog über die fachlichen und disziplinären Grenzen hinweg hat bei THESIS seit dessen Gründung im Jahre 1990 stets einen großen Raum eingenommen. Anderen Fächern Respekt und Interesse entgegenzubringen und sich nicht von stereotypen Vorurteilen leiten zu lassen, ist konstitutiver Bestandteil im Selbstverständnis des Netzwerkes. Selbstverständlich gibt es in einem solchen Verbund eine Reihe von Gelegenheiten (darunter auch den einen oder anderen entwicklungsfördernden Konflikt), (...) das eigene Bild vom Anderen und das andere Bild vom Eigenen zur Sprache zu bringen und zu hinterfragen. Auf der Basis dieser bestehenden Kommunikationsstrukturen trafen sich am 11. Oktober 2003 in Göttingen 12 junge Wissenschaftlerinnen und Wissenschaftler zwischen, über und auch auf den Grenzen ihrer eigenen Herkunftsdisziplinen, um den Trendbegriff [alpha]Transdisziplinarität" auf seine Substanz zu prüfen. (shrink)

Background South Africa is likely to be the first country in the world to host an adolescent HIV vaccine trial. Adolescents may be enrolled in late 2007. In the development and review of adolescent HIV vaccine trial protocols there are many complexities to consider, and much work to be done if these important trials are to become a reality. Discussion This article sets out essential requirements for the lawful conduct of adolescent research in South Africa including compliance with consent requirements, (...) child protection laws, and processes for the ethical and regulatory approval of research. Summary This article outlines likely complexities for researchers and research ethics committees, including determining that trial interventions meet current risk standards for child research. Explicit recommendations are made for role-players in other jurisdictions who may also be planning such trials. This article concludes with concrete steps for implementing these important trials in South Africa and other jurisdictions, including planning for consent processes; delineating privacy rights; compiling information necessary for ethics committees to assess risks to child participants; training trial site staff to recognize when disclosures trig mandatory reporting response; networking among relevant ethics commitees; and lobbying the National Regulatory Authority for guidance. (shrink)

It has been claimed that ‘virtuous structures’ can foster moral agency in organisations. We investigate this in the context of employee involvement in corporate philanthropy, an activity whose moral status has been disputed. Employing Alasdair MacIntyre’s account of moral agency, we analyse the results of eight focus groups with employees engaged in corporate philanthropy in an employee-owned retailer, the John Lewis Partnership. Within this organisational context, Employee–Partners’ moral agency was evidenced in narrative accounts of their engagement in philanthropic activities and (...) in their disputes about the moral status of corporate philanthropy. (shrink)

First published in 2000. Routledge is an imprint of Taylor & Francis, an informa company.

The Metaphysical Club, a gathering of intellectuals in the 1870s associated with Harvard, is widely recognized as the crucible where pragmatism, America's distinctively original philosophy, was refined and proclaimed. Louis Menand's bestseller about the group was a dramatic publishing success. However, only three actual members - Oliver Wendell Holmes Jr., Charles S. Peirce, and William James - appear in this book, alongside other thinkers such as John Dewey who were never in the Club. The Real Metaphysical Club tells the full (...) story of how this influential group shifted the course of philosophy in America. In addition to pioneering pragmatism, the group explored radical empiricism and idealism, and formulated personalism and process philosophy, equally important developments. This volume contains thirty-seven important writings dating from 1870 to 1885 by the real members of the Metaphysical Club. The first section centers on pragmatism and science; the second part collects writings of the lawyers; and the third part covers idealist and personalist philosophers. Many of these writings have never been reprinted before, and nothing like this impressive collection has ever been attempted. A general introduction provides a narrative history, and the editors' three introductions to the volume's sections vividly bring to life the intense meetings, sustained debates, and pioneering thought from the Metaphysical Club. (shrink)

Frank Ramsey was the greatest of the remarkable generation of Cambridge philosophers and logicians which included G. E. Moore, Bertrand Russell, Ludwig Wittgenstein and Maynard Keynes. Before his tragically early death in 1930 at the age of twenty-six, he had done seminal work in mathematics and economics as well as in logic and philosophy. This volume, with a new and extensive introduction by D. H. Mellor, contains all Ramsey's previously published writings on philosophy and the foundations of mathematics. The (...) latter gives the definitive form and defence of the reduction of mathematics to logic undertaken in Russell and Whitehead's Principia Mathematica; the former includes the most profound and original studies of universals, truth, meaning, probability, knowledge, law and causation, all of which are still constantly referred to, and still essential reading for all serious students of these subjects. (shrink)

Corporate social responsibility is a recognised and common part of business activity. Some of the regularly cited motives behind CSR are employee morale, recruitment and retention, with employees acknowledged as a key organisational stakeholder. Despite the significance of employees in relation to CSR, relatively few studies have examined their engagement with CSR and the impediments relevant to this engagement. This exploratory case study-based research addresses this paucity of attention, drawing on one to one interviews and observation in a large UK (...) energy company. A diversity of engagement was found, ranging from employees who exhibited detachment from the CSR activities within the company, to those who were fully engaged with the CSR activities, and to others who were content with their own personal, but not organisational, engagement with CSR. A number of organisational context impediments, including poor communication, a perceived weak and low visibility of CSR culture, and lack of strategic alignment of CSR to business and personal objectives, served to explain this diversity of employee engagement. Social exchange theory is applied to help explore the volition that individual employees have towards their engagement with CSR activities, and to consider the implications of an implicit social, rather than explicit economic, contract between an organisation and its employees in their engagement with CSR. (shrink)

We attempt to extend the nominalistic project initiated in Hartry Field's Science Without Numbers to modern physical theories based in differential geometry.

This article rebuts Ramsey's earlier theory, in 'Universals of Law and of Fact', of how laws of nature differ from other true generalisations. It argues that our laws are rules we use in judging 'if I meet an F I shall regard it as a G'. This temporal asymmetry is derived from that of cause and effect and used to distinguish what's past as what we can know about without knowing our present intentions.

Digital phenotyping will potentially enable earlier detection and prediction of mental illness by monitoring human interaction with and through digital devices. Notwithstanding its promises, it is certain that a person’s digital phenotype will at times be at odds with their first-person testimony of their psychological states. In this paper, we argue that there are features of digital phenotyping in the context of psychiatry which have the potential to exacerbate the tendency to dismiss patients’ testimony and treatment preferences, which can be (...) instances of epistemic injustice. We first explain what epistemic injustice is, and why it is argued to be an extensive problem in health and disability settings. We then explain why epistemic injustice is more likely to apply with even greater force in psychiatric contexts, and especially where digital phenotyping may be involved. Finally, we offer some tentative suggestions of how epistemic injustice can be minimised in digital psychiatry. (shrink)

This paper examines the strategic use of corporate philanthropy in the 1990s by UK building societies faced with an intensification of societal pressure to change legal form from mutual to corporate status. While the economic case for mutuality has been made elsewhere, this paper examines the observation that community relationships were thought by management to be capable of assisting in the strategic positioning of mutual societies with regard to their legal form. By increasing charitable giving to respond to the level (...) of societal scrutiny and discussion on the issue of mutuality, this paper argues that charitable giving, as one proxy for community involvement, was used as a strategic tool to deflect calls for demutualisation, thereby preserving the existing mutual status of building societies. (shrink)

This paper examines the strategic use of corporate philanthropy in the 1990s by UK building societies faced with an intensification of societal pressure to change legal form from mutual to corporate status. While the economic case for mutuality has been made elsewhere, this paper examines the observation that community relationships were thought by management to be capable of assisting in the strategic positioning of mutual societies with regard to their legal form. By increasing charitable giving to respond to the level (...) of societal scrutiny and discussion on the issue of mutuality, this paper argues that charitable giving, as one proxy for community involvement, was used as a strategic tool to deflect calls for demutualisation, thereby preserving the existing mutual status of building societies. (shrink)

Space, Time, and Stuff is an attempt to show that physics is geometry: that the fundamental structure of the physical world is purely geometrical structure. Along the way, he examines some non-standard views about the structure of spacetime and its inhabitants, including the idea that space and time are pointless, the idea that quantum mechanics is a completely local theory, the idea that antiparticles are just particles travelling back in time, and the idea that time has no structure whatsoever. The (...) main thrust of the book, however, is that there are good reasons to believe that spaces other than spacetime exist, and that it is the existence of these additional spaces that allows one to reduce all of physics to geometry. Philosophy, and metaphysics in particular, plays an important role here: the assumption that the fundamental laws of physics are simple in terms of the fundamental physical properties and relations is pivotal."--P. [4] of cover. (shrink)

We pose and resolve several vexing decision theoretic puzzles. Some are variants of existing puzzles, such as 'Trumped' (Arntzenius and McCarthy 1997), 'Rouble trouble' (Arntzenius and Barrett 1999), 'The airtight Dutch book' (McGee 1999), and 'The two envelopes puzzle' (Broome 1995). Others are new. A unified resolution of the puzzles shows that Dutch book arguments have no force in infinite cases. It thereby provides evidence that reasonable utility functions may be unbounded and that reasonable credence functions need not be countably (...) additive. The resolution also shows that when infinitely many decisions are involved, the difference between making the decisions simultaneously and making them sequentially can be the difference between riches and ruin. Finally, the resolution reveals a new way in which the ability to make binding commitments can save perfectly rational agents from sure losses. (shrink)

An introduction to informal logic, critical thinking and rhetoric utilizing actual public discourse .

I argue that it may well be the case that space and time do not consist of points, indeed that they have no smallest parts. I examine two different approaches to such pointless spaces : a topological approach and a measure theoretic approach. I argue in favor of the measure theoretic approach.

Suppose that two geysers, about one mile apart, erupt at irregular intervals, but usually erupt almost exactly at the same time. One would suspect that they come from a common source, or at least that there is a common cause of their eruptions. And this common cause surely acts before both eruptions take place. This idea, that simultaneous correlated events must have prior common causes, was first made precise by Hans Reichenbach (Reichenbach 1956). It can be used to infer the (...) existence of unobserved and unobservable events, and to infer causal relations from statistical relations. Unfortunately it does not appear to be universally valid, nor is there agreement as to the circumstances in which it is valid. (shrink)

The common cause principle states that correlations have prior common causes which screen off those correlations. I argue that the common cause principle is false in many circumstances, some of which are very general. I then suggest that more restricted versions of the common cause principle might hold, and I prove such a restricted version.

De Marco _et al_ 1 argue that the standard account of medical ‘invasiveness’ (as ‘incision’ or ‘insertion’) fails to capture three aspects of its existing use, namely that invasiveness can come in degrees, often depends on features of alternative medical interventions and can be non-physical. They propose a new schematic account that suggests that medical interventions can possess ‘basic invasiveness’ (which can come in degrees and of which they suggest at least two types: physical and mental), and ‘threshold invasiveness’ which (...) can depend on the alternatives a specific intervention is being compared with. While we agree that the standard account of invasiveness fails to capture existing use and are supportive of their aim, here we express scepticism about the practical utility of De Marco _et al_’s revised account. Our scepticism concerns the application of De Marco _et al’s_ revised account in the narrow context of clinician–patient communication and... (shrink)

Civil society organizations (CSOs) have significantly impacted on the politics of health research and the field of bioethics. In the global HIV epidemic, CSOs have served a pivotal stakeholder role. The dire need for development of new prevention technologies has raised critical challenges for the ethical engagement of community stakeholders in HIV research. This study explored the perspectives of CSO representatives involved in HIV prevention trials (HPTs) on the impact of premature trial closures on stakeholder engagement. Fourteen respondents from South (...) African and international CSOs representing activist and advocacy groups, community mobilisation initiatives, and human and legal rights groups were purposively sampled based on involvement in HPTs. Interviews were conducted from February-May 2010. Descriptive analysis was undertaken across interviews and key themes were developed inductively. CSO representatives largely described positive outcomes of recent microbicide and HIV vaccine trial terminations, particularly in South Africa, which they attributed to improvements in stakeholder engagement. Ongoing challenges to community engagement included the need for principled justifications for selective stakeholder engagement at strategic time-points, as well as the need for legitimate alternatives to CABs as mechanisms for engagement. Key issues for CSOs in relation to research were also raised. (shrink)

I argue that standard decision theories, namely causal decision theory and evidential decision theory, both are unsatisfactory. I devise a new decision theory, from which, under certain conditions, standard game theory can be derived.

The ‘Principal Principle’ states, roughly, that one's subjective probability for a proposition should conform to one's beliefs about that proposition's objective chance of coming true. David Lewis has argued (i) that this principle provides the defining role for chance; (ii) that it conflicts with his reductionist thesis of Humean supervenience, and so must be replaced by an amended version that avoids the conflict; hence (iii) that nothing perfectly deserves the name ‘chance’, although something can come close enough by playing the (...) role picked out by the amended principle. We show that in fact there must be ‘chances’ that perfectly play what Lewis takes to be the defining role. But this is not the happy conclusion it might seem, since these ‘chances’ behave too strangely to deserve the name. The lesson is simple: much more than the Principal Principle—more to the point, much more than the connection between chance and credence—informs our understanding of objective chance. 1 Introduction 2 Preliminaries 3 Undermining futures and the New Principle 4 The Old Principle rescued? 5 The New Bug 6 Conclusion. (shrink)

Over the past 40 years a tradition of Marx interpretation has built up around a single passage concerning black slavery in an 1853 letter from Marx to Engels, in order to demonstrate that Marx’s support for emancipation was conditional on the level of ‘civilization’ attained by black slaves. I will argue that this interpretation, which attempts to prove Marx’s racist defense of slavery, is overdetermined by an inattention to historical context and a hypersensitivity to Marx’s nineteenth-century epithets. This is important (...) because the alleged anti-black racism of Marx and the place black workers occupy in his historical materialist vision of class struggle are of the utmost significance for properly conceptualizing the relationship between Marxism and black liberation. (shrink)

Civil society organizations (CSOs) have significantly impacted on the politics of health research and the field of bioethics. In the globalHIVepidemic,CSOs have served a pivotal stakeholder role. The dire need for development of new prevention technologies has raised critical challenges for the ethical engagement of community stakeholders inHIVresearch. This study explored the perspectives ofCSOrepresentatives involved inHIVprevention trials (HPTs) on the impact of premature trial closures on stakeholder engagement. Fourteen respondents fromSouthAfrican and internationalCSOs representing activist and advocacy groups, community mobilisation initiatives, (...) and human and legal rights groups were purposively sampled based on involvement inHPTs. Interviews were conducted fromFebruary‐May 2010. Descriptive analysis was undertaken across interviews and key themes were developed inductively.CSOrepresentatives largely described positive outcomes of recent microbicide andHIVvaccine trial terminations, particularly inSouthAfrica, which they attributed to improvements in stakeholder engagement. Ongoing challenges to community engagement included the need for principled justifications for selective stakeholder engagement at strategic time‐points, as well as the need for legitimate alternatives toCABs as mechanisms for engagement. Key issues forCSOs in relation to research were also raised. (shrink)

The great plague in London in 1665 was the last in a series of epidemics that had begun with the Black Death in the 14th century. Plagues continued elsewhere in Europe into the 18th century, but after 1679 no cases of plague were reported in England at all. The disease seemed to have disappeared. How could that be explained? The purpose of this paper is to discover when contemporaries began to think that plague had gone for good, and why they (...) thought that had happened. The paper falls into two parts. The first concentrates on the decade of the 1720s, when plague was expected to come from Marseilles and never arrived. In the space of a few months there was fierce and concentrated public debate about a new Quarantine Act to be enforced if an epidemic developed, much of it arguing that the Act was unnecessary because plague was plainly not contagious at all. It depended wholly on local environments, and in England they had been improving ever since the Great Fire of London. The second part of the paper takes the story forward into the later 18th century, when there was no longer much dispute that plague was indeed contagious, but it was confidently supposed that England now enjoyed the double protection of further environmental improvement at home combined with effective quarantine of shipping abroad, especially in the Mediterranean. Over the century, contending explanations for plague were debated, interpretations of the past disputed and sometimes falsified, and expectations and ambitions for the future remodelled, because one epidemic threat had disappeared for good. (shrink)

Time travel has been a staple of science fiction. With the advent of general relativity it has been entertained by serious physicists. But, especially in the philosophy literature, there have been arguments that time travel is inherently paradoxical. The most famous paradox is the grandfather paradox: you travel back in time and kill your grandfather, thereby preventing your own existence. To avoid inconsistency some circumstance will have to occur which makes you fail in this attempt to kill your grandfather. Doesn't (...) this require some implausible constraint on otherwise unrelated circumstances? We examine such worries in the context of modern physics. (shrink)

Zeno argued that since at any instant an arrow does not change its location, the arrow does not move at any time, and hence motion is impossible. I discuss the following three views that one could take in view of Zeno's argument:(i) the "at-at" theory, according to which there is no such thing as instantaneous velocity, while motion in the sense of the occupation of different locations at different times is possible,(ii) the "impetus" theory, according to which instantaneous velocities do (...) exist but these are only contingently and causally related to the temporal developments of positions,(iii) the "no instants" theory, according to which instants in time do not exist, and hence instantaneous velocities do not exist, while motion, in the sense of different areas occupied during different time intervals, is possible.I argue that, despite the fact that there have been interesting and relevant developments in mathematics and physics since the time of Zeno, each of these views still has serious drawbacks. (shrink)

In this paper, I critically evaluate several related, provocative claims made by proponents of data-intensive science and “Big Data” which bear on scientific methodology, especially the claim that scientists will soon no longer have any use for familiar concepts like causation and explanation. After introducing the issue, in Section 2, I elaborate on the alleged changes to scientific method that feature prominently in discussions of Big Data. In Section 3, I argue that these methodological claims are in tension with a (...) prominent account of scientific method, often called “Inference to the Best Explanation”. Later on, in Section 3, I consider an argument against IBE that will be congenial to proponents of Big Data, namely, the argument due to Roche and Sober Analysis, 73:659–668, that “explanatoriness is evidentially irrelevant.” This argument is based on Bayesianism, one of the most prominent general accounts of theory-confirmation. In Section 4, I consider some extant responses to this argument, especially that of Climenhaga Philosophy of Science, 84:359–368,. In Section 5, I argue that Roche and Sober’s argument does not show that explanatory reasoning is dispensable. In Section 6, I argue that there is good reason to think explanatory reasoning will continue to prove indispensable in scientific practice. Drawing on Cicero’s oft-neglected De Divinatione, I formulate what I call the “Ciceronian Causal-nomological Requirement”, which states, roughly, that causal-nomological knowledge is essential for relying on correlations in predictive inference. I defend a version of the CCR by appealing to the challenge of “spurious correlations,” chance correlations which we should not rely upon for predictive inference. In Section 7, I offer some concluding remarks. (shrink)

Moral puzzles about actions which bring about very small or what are said to be imperceptible harms or benefits for each of a large number of people are well known. Less well known is an argument by Warren Quinn that standard theories of rationality can lead an agent to end up torturing himself or herself in a completely foreseeable way, and that this shows that standard theories of rationality need to be revised. We show where Quinn's argument goes wrong, and (...) apply this to the moral puzzles. (shrink)