Editors Wanda Teays, John-Stewart Gordon, and Alison Dundes Renteln have assembled the works of an interdisciplinary, international team of experts in bioethics into a comprehensive, innovative and accessible book. Topics covered range from torture and lethal injection to euthanasia, sex selection, vulnerable human subjects, to health equity, safety and public health, and environmental disasters like Bhopal, Fukushima, and more.

© Copyright 2015, Mary Ann Liebert, Inc..Signal transducer and activator of transcription factor 3 is hyperactivated in head and neck squamous cell carcinomas. Cumulative evidence indicates that IL-6 production by HNSCC cells and/or stromal cells in the tumor microenvironment activates STAT3 and contributes to tumor progression and drug resistance. A library of 94,491 compounds from the Molecular Library Screening Center Network was screened for the ability to inhibit interleukin-6 -induced pSTAT3 activation. For contractual reasons, the primary high-content screening campaign was (...) conducted over several months in 3 distinct phases; 1,068 primary HCS actives remained after cytotoxic or fluorescent outliers were eliminated. One thousand one hundred eighty-seven compounds were cherry-picked for confirmation; actives identified in the primary HCS and compounds selected by a structural similarity search of the remaining MLSCN library using hits identified in phases I and II of the screen. Actives were confirmed in pSTAT3 IC50 assays, and an IFNγ-induced pSTAT1 activation assay was used to prioritize selective inhibitors of STAT3 activation that would not inhibit STAT1 tumor suppressor functions. Two hundred three concentration-dependent inhibitors of IL-6-induced pSTAT3 activation were identified and 89 of these also produced IC50s against IFN-γ-induced pSTAT1 activation. Forty-nine compounds met our hit criteria: they reproducibly inhibited IL-6-induced pSTAT3 activation by ≥70% at 20 μM; their pSTAT3 activation IC50s were ≤25 μM; they were ≥2-fold selective for pSTAT3 inhibition over pSTAT1 inhibition; a cross target query of PubChem indicated that they were not biologically promiscuous; and they were ≥90% pure. Twenty-six chemically tractable hits that passed filters for nuisance compounds and had acceptable drug-like and ADME-Tox properties by computational evaluation were purchased for characterization. The hit structures were distributed among 5 clusters and 8 singletons. Twenty-four compounds inhibited IL-6-induced pSTAT3 activation with IC50s ≤20 μM and 13 were ≥3-fold selective versus inhibition of pSTAT1 activation. Eighteen hits inhibited the growth of HNSCC cell lines with average IC50s ≤ 20 μM. Four chemical series were progressed into lead optimization: the guanidinoquinazolines, the triazolothiadiazines, the amino alcohols, and an oxazole-piperazine singleton. (shrink)

The purpose of this article is to develop a conception of death with dignity and to examine whether it is vulnerable to the sort of criticisms that have been made of other conceptions. In this conception “death” is taken to apply to the process of dying; “dignity” is taken to be something that attaches to people because of their personal qualities. In particular, someone lives with dignity if they live well (in accordance with reason, as Aristotle would see it). It (...) follows that health care professionals cannot confer on patients either dignity or death with dignity. They can, however, attempt to ensure that the patient dies without indignity. Indignities are affronts to human dignity, and include such things as serious pain and the exclusion of patients from involvement in decisions about their lives and deaths. This fairly modest conception of death with dignity avoids the traps of being overly subjective or of viewing the sick and helpless as “undignified”. (shrink)

[1] The rise of modern paganism.--v. 2. The science of freedom.

The historian Ibn Khaldūn (d. 1406) is most often treated by historians of philosophy as part of the story of political philosophy in the Islamic world. While this is perfectly legitimate, it may be misleading when it comes to the question of the method he proposes for the historian. This paper argues that that method is in fact based on a different branch of (Aristotelian) science: natural philosophy. After rendering this proposition initially plausible by noting frequent references to "nature" in (...) the _Muqaddima_, the paper discusses a number of parallels between natural philosophy and history as Ibn Khaldūn conceives it. Ultimately it is suggested that this method is legitimated insofar as history is for Ibn Khaldūn a study of human nature. (shrink)

Feminist philosophy has had a powerful impact not just on philosophy but on other disciplines as well. This imaginatively edited anthology enables readers to sample this literature widely and to trace the breadth and the depth of its influence.

This study presents a substantial and often radical reinterpretation of some of the central themes of Locke's thought. Professor Alexander concentrates on the Essay Concerning Human Understanding and aims to restore that to its proper historical context. In Part I he gives a clear exposition of some of the scientific theories of Robert Boyle, which, he argues, heavily influenced Locke in employing similar concepts and terminology. Against this background, he goes on in Part II to provide an account of Locke's (...) views on the external world and our knowledge of it. He shows those views to be more consistent and plausible than is generally allowed, demonstrating how they make sense and enable scientific explanations of nature. In examining the views of Locke and Boyle together, the book throws light both on the development of philosophy and the beginnings of modern science, and in particular it makes a considerable and original contribution to our understanding of Locke's philosophy. (shrink)

Journal Name: Philologus Issue: Ahead of print.

sirThe recent article by Evans in the journal on the single blind placebo in drug research is timely and its conclusions were persuasive. The basic premiss that single blind placebo “washout” periods are ethically specious was well argued and I agree that from a scientific point of view they have no valid justification. The real reasons ….

Plato and the trial of Socrates -- What is philosophy? -- Euthyphro : defining philosophical terms -- The apology, Phaedo, and Crito : the trial, immortality, and death of Socrates -- Philosophy of religion -- Can we prove that God exists? -- St. Anselm : the ontological argument -- St. Thomas Aquinas : the cosmological argument -- William Paley : the teleological argument -- Blaisepascal : it is better to believe in God's existence than to deny it -- William James (...) : free choice is the basis of belief -- Does the idea of a good God exclude evil? -- Gottfried Wilhelm Leibniz : God can allow some evil -- David Hume : a good God would exclude evil -- Ethics -- Are ethics relative? -- Ruth Benedict : ethics are relative -- W.T. Stace : ethics are not relative -- Are humans always selfish? -- Humans are always selfish : Glaucon's challenge to Socrates -- James Rachels : humans are not always selfish -- Which is basic in ethics : happiness or obligation? -- Aristotle : happiness is living virtuously -- Jeremy Bentham : happiness is seeking the greatest pleasure for the greatest number of people -- Immanuel Kant : duty is prior to happiness -- Friedrich Nietzsche : happiness is having power -- Jean-Paul Sartre : existentialist ethics -- Rosemarie Tong : feminist ethics are different -- Contemporary moral problems : abortion, homosexuality, animal rights -- Jane English : are most abortions moral? -- Peter Singer : do animals have rights? -- Knowledge -- What is knowledge? -- Plato : knowledge is warranted, true belief -- What method is best for acquiring knowledge? -- Charles Sanders Peirce : four approaches to philosophy -- How do we acquire knowledge? -- René Descartes : knowledge is not ultimately sense knowledge -- John Locke : knowledge is ultimately sensed -- Immanuel Kant : knowledge is both rational and empirical -- How is truth established? -- Bertrand Russell : truth is established by correspondence -- Francis H. Bradley : truth is established by coherence -- William James : truth is established on pragmatic grounds -- Can we know the nature of causal relations? -- David Hume : cause means regular association -- David Hume : there are no possible grounds for induction -- Metaphysics -- Why is there something rather than nothing? -- Parmenides : being is uncaused -- Lao-Tzu : non-being is the source of being -- Is reality general or particular? -- Plato : universals are real -- David Hume : particulars are real -- Of what does reality consist? -- René Descartes : reality consists of mind and matter -- Paul Churchland : reality consists of matter -- George Berkeley : reality consists of ideas -- John Dewey : reality consists of mental and physical qualities -- Are humans free? -- Holbach : humans are determined -- Robert Kane : humans are free -- Social and political philosophy -- What is liberty? -- Fyodor Dostoevski : liberty and authority -- John Stuart Mill : liberty is independence from the majority's tyranny -- Martin Luther King, Jr. : liberty and racial prejudice -- Which government is best? -- Thomas Hobbes : monarchy is best -- John Locke : democracy is best -- Karl Marx : communism and nonalienated labor is best -- Alexis de Tocqueville : democracy can have serious problems -- Karl Popper : utopias lead to violence -- Aesthetics -- What constitutes the experience of beauty? -- Plotinus : beauty, sensuous, and ideal -- What is the function of art? -- Aristotle : the nature of tragedy -- Henri Bergson : the nature of comedy -- Philosophy and the good life -- Classic views of the good life -- Epicurus : Epicurus and the pleasant life -- Epictetus : Epictetus and the life of self-control -- What gives life meaning? -- Leo Tolstoy : faith provides life's meaning -- Albert Camus : each person determines his or her life's meaning -- What is the value of philosophy? -- Bertrand Russell : the value of philosophy. (shrink)

The essays in this volume address three fundamental questions in the philosophy of science: What is required for some fact to be evidence for a scientific ...

[Peter Lipton] From a reliabilist point of view, our inferential practices make us into instruments for determining the truth value of hypotheses where, like all instruments, reliability is a central virtue. I apply this perspective to second-order inductions, the inductive assessments of inductive practices. Such assessments are extremely common, for example whenever we test the reliability of our instruments or our informants. Nevertheless, the inductive assessment of induction has had a bad name ever since David Hume maintained that any (...) attempt to justify induction by means of an inductive argument must beg the question. I will consider how the inductive justification of induction fares from the reliabilist point of view. I will also consider two other well-known arguments that can be construed as inductive assessments of induction. One is the miracle argument, according to which the truth of scientific theories should be inferred as the best explanation of their predictive success; the other is the disaster argument, according to which we should infer that all present and future theories are false on the grounds that all past theories have been found to be false. \\\ [John Worrall] Science seems in some ways to have been remarkably successful. What does this success tell us about the epistemological status of current scientific claims? Peter Lipton considers various meta-inductive arguments each of which start from premises about science's 'track record'. I show that his endorsements of the 'strongest' of these are, on analysis, remarkably weak. I argue that this is a reflection of difficulties within the general epistemological framework that he adopts-that of reliabilism. Finally, I briefly outline the quite different approach that I take to this issue, in the process responding to Lipton's criticisms of the 'pessimistic meta-induction'. (shrink)

[Peter Simons] Commonsense ontology contains both continuants and occurrents, but are continuants necessary? I argue that they are neither occurrents nor easily replaceable by them. The worst problem for continuants is the question in virtue of what a given continuant exists at a given time. For such truthmakers we must have recourse to occurrents, those vital to the continuant at that time. Continuants are, like abstract objects, invariants under equivalences over occurrents. But they are not abstract, and their being (...) invariants enables us to infer both their lack of temporal parts and that non-invariant predications about them must be relativized to times. \\\ [Joseph Melia] In this paper I try to eliminate occurrents from our ontology. I argue against Simons' position that occurrents are needed to supply truthmakers for existential claims about continuants. Nevertheless, those who would eliminate occurrents still need some account of our willingness to assert sentences that logically entail their existence. Though it turns out to be impossible to paraphrase away our reference to occurrents, I show that the truthmakers for such sentences are facts that involve only continuants. This is enough to allow us to regard our ordinary talk about occurrents as fictional. Finally, I argue that a proper conception of the underlying temporal facts about continuants can both avoid the problematic tensed theory of time and the problem of temporary intrinsics. (shrink)

Theories of explanation are characterized as being either pragmatic or non-pragmatic, without a clear sense of what this is supposed to mean. The present paper offers a definition of a "pragmatic explanation-sentence", and in terms of this, of a "pragmatic theory of explanation". It is argued that van Fraassen's theory of explanation, despite claims to the contrary, is not genuinely pragmatic. By contrast, the author's own "illocutionary" theory is pragmatic. Attention is devoted particularly to sentences of the form "E is (...) a good explanation of q", which, it is urged, are pragmatic in a strong sense. In defense of this claim, and of the advantages of a pragmatic account generally, appeal is made to Rutherford's 1911 subatomic explanation of the results of his scattering experiments. Implications of a pragmatic theory are drawn for the debate between realists and anti-realists and absolutists and relativists. (shrink)

Immanuel Kant spent many of his younger years working on what are generally considered his masterpieces: the three _Critiques_. But his work did not stop there: in later life he began to reconsider subjects such as anthropology, and topics including colonialism, race and peace. In _Late Kant_, Peter Fenves becomes one of the first to thoroughly explore Kant's later writings and give them the detailed scholarly attention they deserve. In his opening chapters, Fenves examines in detail the various essays (...) in which Kant invents, formulates and complicates the thesis of 'radical evil' - a thesis which serves as the point of departure for all his later writings. _Late Kant_ then turns towards the counter-thesis of 'radical mean-ness', which states that human beings exist on earth for the sake of another species or race of human beings. The consequences of this startling thesis are that human beings cannot claim possession of the earth, but must rather prepare the earth for its rightful owners. _Late Kant _is the first book to develop the 'geo-ethics' of Kant's thought, and the idea that human beings must be prepared to concede their space for another kind of human. It is essential reading for anyone interested in the later works of Immanuel Kant. (shrink)

Avicenna is the greatest philosopher of the Islamic world. His immense impact on Christian and Jewish medieval thought, as well as on the subsequent Islamic tradition, is charted in this volume alongside studies which provide a comprehensive introduction to and analysis of his philosophy. Contributions from leading scholars address a wide range of topics including Avicenna's life and works, conception of philosophy and achievement in logic and medicine. His ideas in the main areas of philosophy, such as epistemology, philosophy of (...) religion and physics, are also analyzed. While serving as a general introduction to Avicenna's thought, this collection of critical essays also represents the cutting edge of scholarship on this most influential philosopher of the medieval era. (shrink)

Peter Gardner; Religious Upbringing and the Liberal Ideal of Religious Autonomy, Journal of Philosophy of Education, Volume 22, Issue 1, 30 May 2006, Pages 89–1.

Peter Gardner; Religious Upbringing and the Liberal Ideal of Religious Autonomy, Journal of Philosophy of Education, Volume 22, Issue 1, 30 May 2006, Pages 89–1.

Shows that the dialogue in Plato's Phaedo is primarily devoted to presenting Socrates' final defense of the philosophical life against the theoretical and political challenge of religion.

I consider and reject William Whewell's attack on the inductivism of Isaac Newton and John Stuart Mill, as well as John Norton's attack on any universal system of inductive rules. I also explain how a system of inductive rules of the sort proposed by Newton and Mill should be understood.

Drawing on all the extant philosophical works of Miskawayh, including his well known Refinement of Character, this paper aims to determine his attitudes towards the psychological capacities and moral standing of non-human animals. Miskawayh most often mentions animals as a contrast to the rationality of humans, but also grants animals likenesses or lesser versions of typically human traits like virtues and friendship. It is argued that for Miskawayh, the teleological design of animals gives humans reasons to show them justice.