Vertebrate haemoglobin (Hb), the oxygen‐carrying protein of the blood, consists of two α‐ and two β‐subunits, each containing one haem, and shows cooperative oxygen binding known as the haem–haem interaction. The amino‐acid sequences of Hbs found in different species have diverged considerably and the homology in the most distantly related ones is only 40%. How can such varied amino‐acid sequences give rise to similar three‐dimensional structures and functional properties? To what extent do amino‐acid replacements affect the structure of haemoglobin? Which (...) mutations are responsible for the functional differences between haemoglobins from different species? Expression of α‐ and β‐globins in Escherichia coli has enabled us to introduce any mutations in the haemoglobin molecule at will. By X‐ray crystallographic and functional studies of the engineered mutants, we are trying to answer these questions. (shrink)

In all domains of life, transmembrane proteins from the ATP‐binding cassette (ABC) transporter family drive the translocation of diverse substances across lipid bilayers. In pathogenic fungi, the ABC transporters of the pleiotropic drug resistance (PDR) subfamily confer antibiotic resistance and so are of interest as therapeutic targets. They also drive the quest for understanding how ABC transporters can generally accommodate such a wide range of substrates. The Pdr5 transporter from baker's yeast is representative of the PDR group and, ever since (...) its discovery more than 30 years ago, has been the subject of extensive functional analyses. A new perspective of these studies has been recently provided in the framework of the first electron cryo‐microscopy structures of Pdr5, as well as emergent applications of machine learning in the field. Taken together, the old and the new developments have been used to propose a mechanism for the transport process in PDR proteins. This mechanism involves a “flippase” step that moves the substrates from one leaflet of the bilayer to the other, as a central element of cellular efflux. (shrink)

Stel dat een inbreker bij jou thuis alleen de lijsten van de kunstwerken zou wegnemen, en niet de werken zelf. Wat zou er veranderen in je omgang met de kunst? Met dat gedachte-experiment opent de Franse filosoof Jacques Derrida het essay Parergon. Parergon betekent bijzaak in het Grieks. Zoals bijvoorbeeld de lijst van het schilderij, of het kader van een opgehangen foto. Ze behoren niet tot het kunstwerk. En toch zijn ze van groot belang voor hoe het werk bekeken wordt. (...) De belangwekkende tekst van Derrida uit 1974 geeft een centrale rol aan de bijzaak van het kader. Met filosofische acrobatie maneuvreert de denker tussen de grote klassiekers van de kunstfilosofie: Plato, Kant, Hegel en Heidegger. Hij gaat op een speelse manier met hun erfenis om. Woorden worden omgedraaid. Passages die op het eerste gezicht bijzaak lijken, maakt hij tot hoofdrolspelers van zijn betoog. Dit boek presenteert Derridas belangrijkste tekst over beeldende kunst voor de eerste keer in Nederlandse vertaling. Het boek is vormgegeven door de spraakmakende ontwerpster Ines Cox. Vertaler Ben Overlaet schreef een nawoord dat de tekst van de nodige filosofische en historische context voorziet. (shrink)

Efforts to promote equitable public policy with algorithms appear to be fundamentally constrained by the “impossibility of fairness” (an incompatibility between mathematical definitions of fairness). This technical limitation raises a central question about algorithmic fairness: How can computer scientists and policymakers support equitable policy reforms with algorithms? In this article, I argue that promoting justice with algorithms requires reforming the methodology of algorithmic fairness. First, I diagnose the problems of the current methodology for algorithmic fairness, which I call “formal algorithmic (...) fairness.” Because formal algorithmic fairness restricts analysis to isolated decision-making procedures, it leads to the impossibility of fairness and to models that exacerbate oppression despite appearing “fair.” Second, I draw on theories of substantive equality from law and philosophy to propose an alternative methodology, which I call “substantive algorithmic fairness.” Because substantive algorithmic fairness takes a more expansive scope of analysis, it enables an escape from the impossibility of fairness and provides a rigorous guide for alleviating injustice with algorithms. In sum, substantive algorithmic fairness presents a new direction for algorithmic fairness: away from formal mathematical models of “fair” decision-making and toward substantive evaluations of whether and how algorithms can promote justice in practice. (shrink)

In recent years Mullins and Craig have argued that there is a problem for a timeless God creating, with Mullins formulating the argument as follows: (1) If God begins to be related to creation, then God changes. (2) God begins to be related to creation. (3) Therefore, God changes. (4) If God changes, then God is neither immutable nor timeless. (5) Therefore, God is neither immutable nor timeless. In this paper I argue that all the premises, (1), (2), and (4) (...) are false, and then provide a revised formulation of the argument which more clearly represents what Mullins and Craig wish to argue, given the explication and commentary they give when discussing this objection to timelessness. I then call into question this argument, and conclude by stating what I think Mullins and Craig should really be arguing given the specific views they have about creation ex nihilo and in virtue of what timelessness requires. (shrink)

In this paper, I discuss Hud Hudson's compatibilistic interpretation of Kant's theory of free will, which is based on Davidson's anomalous monism. I sketch an alternative interpretation of my own, an incompatibilistic interpretation according to which agents qua noumena are responsible for the particular causal laws which determine the actions of agents qua phenomena. Hudson's interpretation should be attractive to philosophers who value Kant's epistemology and ethics, but insist on a deflationary reading of things in themselves. It is in an (...) incompatibilist interpretation of Kant's theory of free will that a "positive" conception of noumena is at its most important. If a compatibilistic interpretation is acceptable, one might suppose that we can do without a "positive" conception of noumena throughout Kant's philosophy. I demonstrate, however, that there are central elements of Kant's theory of free will that cannot be accommodated within Hudson's interpretation. (shrink)

My students sometimes worry that if eternalism is true then they can’t have libertarian freedom. They aren’t alone, as this sentiment is also expressed, albeit typically briefly, by various philosophers. However, somewhat surprisingly, those working within the free will literature have largely had nothing to say about libertarianism’s relationship to time, with this also being similar in the case of those working in the philosophy of time, apart from some work which has mainly focused on nonlibertarian views of freedom. In (...) this short paper I note why I’m currently unconvinced that there’s an incompatibility between eternalism and libertarianism, and in doing so one will see why I think they are compatible. (shrink)

The stakeholder model of the firm (SMF) was originally conceived as a theory of strategic management, intended to remedy the biases of the stockholder model. As the model became more normative, it effectively turned into a theory of business ethics. This paper reproduces material focusing on the contribution of Professor Ed Freeman to stakeholder theorizing. These portions were extracted from a longer manuscript which argues that: 1. SMF generated a series of new questions which constitute some of the defining problems (...) of business ethics at present; yet 2. its inherent company-centered perspective prevents it from resolving these defining problems. (shrink)

According to G. E. Moore, moral expertise requires abilities of several kinds: the ability to factor judgments of right and wrong into (a) judgments of good and bad and (b) judgments of cause and effect, (2) the ability to use intuition to make the requisite judgments of good and bad, and (3) the ability to use empirical investigation to make the requisite judgments of cause and effect. Moore’s conception of moral expertise is thus extremely demanding, but he supplements it with (...) some very simple practical guidance. (shrink)

The map is not the territory - from ontology to epistemology in knowledge construction -- Dialectics: a mechanism of knowledge construction -- Reflectivity reconsidered -- Reflectivity and the researchers' perspective -- Reflectivity and the participants' perspective -- Ethical differences and similarities as sources of reflection and knowledge construction -- Research relations and power differentials: from resistance to collaboration and in-between -- Frames of reference and the control of knowledge -- Reciprocity: the nature and attributes of research relations and power -- (...) Epilogue: from dialectics to dialog across liminal spaces. (shrink)

Within educational philosophies that utilise the Heideggerian idea of ‘authenticity’ there can be distinguished at least two readings that correspond with the categories of ‘weak’ and ‘strong’ utopianism. ‘Strong-utopianism’ is the nostalgia for some lost Edenic paradise to be restored at some future time. Here it is the ‘world’ that needs to be transcended for it is the source of our inauthenticity, where we are the puppets of modernist-capitalist ideologies. ‘Authenticity’ here is a value-judgment, understood as something that makes you (...) a better person. The ‘inauthentic’ person is simply deceived. ‘Weak-utopianism’ is recognising the forces for change in the ‘everyday-immanent’ where we do not look to overcome the world but own it as ‘heritage’. ‘Authenticity’ here is an ontological choice, a modification of inauthenticity, not its opposite. The ‘cult of the authentic’ relates to the ‘strong utopianism’ where ‘authenticity’ has become fetishized, harking back to a purer, pre-modern state, untainted by the ideals of the Enlightenment and ethos of capitalism. ‘Authentic education’ is the overcoming of our environments and socio-historical contexts, opening up new horizons of meaning. The radical notion of freedom that this implies, where one is free from rather than free in the realisation of constraint, may also be another dividing line between the ‘strong’ and ‘weak’ readings, which lend themselves to a Messianic narrative. It will be argued that if ‘authentic education’ is understood through a ‘strong utopianism’ it actually re-enforces those very same dystopian ideals they look to overcome as characterised by ‘enframing’. (shrink)

Questions of ethics - about how we should act, our responsibilities to one another, the difference between right and wrong - have long been debated by philosophers the world over and form the foundations of government, culture and religion. Here, in concise, easy-to-read chapters, Ben Dupré explains the fundamentals of this discipline and how it is relevant to our lives today. Covering essential ethical concepts, including relativism, the golden rule and utilitarianism, as well as high-profile issues such as terrorism, censorship (...) and the death penalty, 50 Ethics Ideas You Really Need to Know will lead you through the moral maze - and rattle your conscience in the process. (shrink)

Oswald Spengler was one of the most important thinkers of the Weimar Republic. In Oswald Spengler and the Politics of Decline, Ben Lewis completely transforms our understanding of Spengler by showing how well-connected this philosopher was and how, at every stage of his career, he attempted to intervene politically in the very real-life events unfolding around him. The volume explains Spengler's politics as the outcome of a dynamic interplay between his meta-historical considerations on world history on the one hand, and (...) the practical demands and considerations of Realpolitik on the other hand. (shrink)

Sometimes our thought is transparently clear. It is as if we were looking through a window whose clarity was an invitation for the world to come in. The pleasure we take in thinking transparent thoughts is like that we take in the unimpeded use of any ability; but such transparency is unique in that it suggests easy communication with oneself and others, the ability to nullify problems by seeing through them, and a clean, physically effortless mastery of life.

James Rachels argued against the possibility of finding some moral capacity in humans that confers upon them a unique dignity. His argument contends that Darwinism challenges such attempts, because Darwinism predicts that any morally valuable capacity able to bestow a unique dignity is likely present to a degree within both humans and non-human animals alike. I make the case, however, that some of Darwin's own thoughts regarding the nature of conscience provide a springboard for criticising Rachels's claim here. Using Darwin's (...) thoughts regarding conscience, I begin the project of grounding a revised account of human dignity in the human tendency to enshrine products of conscience within institutions. Specifically, I argue that this new account of human dignity is partly contingent upon humans creating institutions morally respectful of the values present within non-human nature. (shrink)

This article examines Gadamer's claim that language is fundamentally metaphorical from the perspective of Ricoeur's complementary analysis of metaphor. I argue that Gadamer's claim can only be understood in relation to a broader understanding of metaphor in which metaphor is not regarded as secondary to literal meaning. From this context one is better able to understand the connection Gadamer makes between language and ontology, which is found in his statement "Being that can be understood is language.".

I argue that a reasonable understanding of Leopold’s ‘Land Ethic’ is one that identifies possession of health as being a sufficient condition for moral consideration. With this, Leopold extends morality not only to biotic wholes, but to individual organisms, as both can have their health undermined. My argument centers on explaining why Leopold thinks it reasonable to analogize ecosystems both to an organism and to a community: both have a health. My conclusions undermine J. Baird Callicott’s rhetorical dismissal of the (...) organism analogy’s importance, a dismissal crucially serving his thesis that Leopoldians should hold community membership necessary for moral standing. (shrink)

The 70th anniversary of Aldo Leopold’s A Sand County Almanac (1949) approaches. For philosophers—environmental ethicists in particular—this text has been highly influential, especially the ‘Land Ethic’ essay contained therein. Given philosophers’ acumen for identifying and critiquing arguments, one might reasonably think a firm grasp of Leopold’s ideas to have emerged from such attention. I argue that this is not the case. Specifically, Leopold’s main interpreter and systematiser, philosopher J. Baird Callicott, has shoehorned Aldo Leopold’s ideas into differing monistic moral theories (...) that ill-serve a proper understanding. Against Callicott, my paper argues that Aldo Leopold embraces a robust moral pluralism, one that goes beyond mere pragmatics, and he does so while seeking a consistency maximisation of values. A new, improved understanding of Leopold’s ideas thus emerges. (shrink)