Protein translocation across biological membranes is of fundamental importance for the biogenesis of organelles and in protein secretion. We will give an overview of the recent achievements in the understanding of protein translocation across mitochondrial membranes(1‐5). In particular we will focus on recently identified components of the mitochondrial import apparatus.

Walter applies the methodology of neurophilosophy to one of philosophy's centralchallenges, the notion of free will. Neurophilosophical conclusions are based on, and consistentwith, scientific knowledge about the brain and its functioning.

his paper presents a unified treatment of the propositional and first-order many-valued logics through the method of tableaux. It is shown that several important results on the proof theory and model theory of those logics can be obtained in a general way. We obtain, in this direction, abstract versions of the completeness theorem, model existence theorem (using a generalization of the classical analytic consistency properties), compactness theorem and Lowenheim-Skolem theorem. The paper is completely self-contained and includes examples of application to (...) particular many-valued formal systems. (shrink)

Many drugs have therapeutic off-label uses for which they were not originally designed. Some drugs designed to treat neuropsychiatric and other disorders may enhance certain normal cognitive and affective functions. Because the long-term effects of cognitive and affective enhancement are not known and may be harmful, a precautionary principle limiting its use seems warranted. As an expression of autonomy, though, competent individuals should be permitted to take cognition- and mood-enhancing agents. But they need to be aware of the risks in (...) chronic use of these agents and to take responsibility for their effects. A reasonable middle ground between these positions is to warn those who choose to enhance that doing so entails risks. (shrink)

This is the fullest existing collection of the texts, for the moment only in Italian translation, with an introduction, notes, general presentation of the texts, various indexes (part of this material is to be found in an attached CD).

Recent advances in human genetics suggest that it may become possible to genetically manipulate telomerase and embryonic stem cells to alter the mechanisms of aging and extend the human life span. But a life span significantly longer than the present norm would be undesirable because it would severely weaken the connections between past‐ and future‐oriented mental states and in turn the psychological grounds for personal identity and prudential concern for our future selves. In addition, the collective effects of longer lives (...) might lower the quality of life for all people. These two problems provide reasons against genetic manipulation of cells to alter the length of the human life span. (shrink)

Meta-learning offers a promising framework to make sense of some parts of decision-making that have eluded satisfactory explanation. Here, we connect this research to work in animal behaviour and cognition in order to shed light on how and whether meta-learning could help us to understand the evolution of cognition.

Deep brain stimulation (DBS) of the globus pallidus interna and subthalamic nucleus has restored some degree of motor control in many patients in advanced stages of Parkinson’s disease. DBS has also been used to treat dystonia, essential tremor (progressive neurological condition causing trembling), chronic pain, obsessive-compulsive disorder, Tourette’s syndrome, major depressive disorder, obesity, cerebral palsy, and the minimally conscious state. Although the underlying mechanisms of the technique are still not clear, DBS can modulate underactive or overactive neural circuits and restore (...) disrupted communication between and among groups of neurons in interacting regions of the brain. This can control and relieve many symptoms associated with a range of neurological and psychiatric disorders.But the procedures of implanting and stimulating the electrodes are brain-invasive and entail significant risks. Some patients receiving DBS have experienced intracerebral hemorrhage, infection, cognitive disturbances such as impulsive behavior, and affective disturbances such as mania. It is not known whether continuous electrical stimulation of the brain would reshape synaptic connectivity and permanently alter neural circuits in ways that may not be salutary. The risk of these effects indicates that DBS should be used only when a patient’s condition is refractory to all other interventions and when there is a high probability that the technique will benefit the patient and improve his or her quality of life. If a patient’s quality of life is poor and all other treatment options have been exhausted, then the likelihood of benefit can justify physicians’ exposing patients to some risk. The clinical and ethical significance of the risk in DBS underscores the obligation of physicians to obtain fully informed consent from patients undergoing the procedure. (shrink)

This is the first complete English translation of _On the Purity of the Art of Logic, _a handbook of logic written in Latin by English philosopher Walter Burley. The work circulated in the Middle Ages in two versions, a shorter and a longer one, both translated here by Paul Vincent Spade. The translations are based on the only complete edition of Burley’s treatises, corrected by Spade on the basis of one of the surviving manuscripts. The book also includes an (...) extensive introduction, explanatory notes, a table of corresponding passages between the two versions, a select annotated bibliography, and three indexes. A contemporary of John Duns Scotus and William of Ockham, Burley was active at the universities of both Paris and Oxford. He became one of the most important figures in the transformation of medieval logic and semantics that took place in the early fourteenth century. Burley used new tools and techniques of logical and semantical analysis, yet in many cases he used them in defense of traditional views, such as a realist metaphysical theory of “universals_._”_ On the Purity of the Art of Logic_ shows_ _both these sides of Burley—the innovator and the conservative—as well as some of the ways in which his views corresponded or clashed with those of William of Ockham. (shrink)

Mental causation, our mind's ability to causally affect the course of the world, is part and parcel of our ‘manifest image’ of the world. That there is mental causation is denied by virtually no one. How there can be such a thing as mental causation, however, is far from obvious. In recent years, discussions about the problem of mental causation have focused on Jaegwon Kim's so-called Causal Exclusion Argument, according to which mental events are ‘screened off’ or ‘preempted’ by physical (...) events unless mental causation is a genuine case of overdetermination or mental properties are straightforwardly reducible to physical properties. (shrink)

Many believe that it is morally wrong to give lower priority for a liver transplant to alcoholics with end-stage liver disease than to patients whose disease is not alcohol-related. Presumably, alcoholism is a disease that results from factors beyond one's control and therefore one cannot be causally or morally responsible for alcoholism or the liver failure that results from it. Moreover, giving lower priority to alcoholics unfairly singles them out for the moral vice of heavy drinking. I argue that the (...) etiology of alcoholism may involve enough control for the alcoholic to be responsible for his condition and accordingly have a weaker claim to receive a new liver than someone who acquires the disease through no fault of his own. In addition, I show why it is more plausible to reframe the question of priority in terms of control and responsibility rather than virtue and vice. Given that medical resources like livers are scarce, some people may justifiably be given lower priority than others in receiving these resources. (shrink)

In this article, we revisit the longstanding debate of whether there is a pattern in the evolution of organisms towards greater complexity, and how this hypothesis could be tested using an interdisciplinary lens. We argue that this debate remains alive today due to the lack of a quantitative measure of complexity that is related to the teleonomic (i.e., goal-directed) nature of living systems. Further, we argue that such a biological measure of complexity can indeed be found in the vast literature (...) produced within life history theory. We propose that an ideal method to quantify this complexity lies within life history strategies (i.e., schedules of survival and reproduction across an organism’s life cycle), as it is precisely these strategies that are under selection to optimize the organism’s fitness. In this context, we set an agenda for future steps: (1) how this complexity can be measured mathematically, and (2) how we can engage in a comparative analysis of this complexity across species to investigate the evolutionary forces driving increases or, for that matter, decreases in teleonomic complexity. (shrink)

Neuroimaging, psychosurgery, deep-brain stimulation, and psychopharmacology hold considerable promise for more accurate prediction and diagnosis and more effective treatment of neurological and psychiatric disorders. Some forms of psychopharmacology may even be able to enhance normal cognitive and affective capacities. But the brain remains the most complex and least understood of all the organs in the human body. Mapping the neural correlates of the mind through brain scans, and altering these correlates through surgery, stimulation, or pharmacological interventions can affect us in (...) both positive and negative ways. We need to carefully weigh the potential benefit against the potential harm of such techniques. This paper examines some of these techniques and explores the emerging ethical issues in clinical neuroscience. (shrink)

We argue that word meanings are not stored in a mental lexicon but are generated in the context of working memory from long-term memory traces that record our experience with words. Current statistical models of semantics, such as latent semantic analysis and the Topic model, describe what is stored in long-term memory. The CI-2 model describes how this information is used to construct sentence meanings. This model is a dual-memory model, in that it distinguishes between a gist level and an (...) explicit level. It also incorporates syntactic information about how words are used, derived from dependency grammar. The construction of meaning is conceptualized as feature sampling from the explicit memory traces, with the constraint that the sampling must be contextually relevant both semantically and syntactically. Semantic relevance is achieved by sampling topically relevant features; local syntactic constraints as expressed by dependency relations ensure syntactic relevance. (shrink)

I claim that Berkeley's main argument against abstraction comes into focus only when we see Descartes as one of its targets. Berkeley does not deploy Winkler's impossibility argument but instead argues that what is impossible is inconceivable. Since Descartes conceives of extension as a determinable, and since determinables cannot exist as such, he falls within the scope of Berkeley's argument.

Interdisciplinary research is becoming more and more popular. Many funding bodies encourage interdisciplinarity, as a criterion that promises scientific progress. Traditionally this has been linked to the idea of integrating or unifying disciplines. Using evolutionary game theory as a case study, Till Grüne-Yanoff (2016) argued that there is no such necessary link between interdisciplinary success and integration. Contrary to this, this paper argues that evolutionary game theory is a genuine case of successful integration between economics and biology, shedding lights on (...) the many dimensions along which integration can take place. (shrink)

This title was first published in 2002: This book is an analysis of the ways in which mental states ground attributions of responsibility to persons. Particular features of the book include: attention to the agent's epistemic capacity for beliefs about the foreseeable consequences of actions and omissions; attention to the essential role of emotions in prudential and moral reasoning; a conception of personal identity that can justify holding persons responsible at later times for actions performed at earlier times; an emphasis (...) on neurobiology as the science that should inform our thinking about free will and responsibility; and the melding of literature on free will and responsibility in contemporary analytic philosophy with legal cases, abnormal psychology, neurology and psychiatry, which offers a richer texture to the general debate on the relevant issues. (shrink)

In the late eighteenth century, Adam Smith significantly shaped the modern world by claiming that when people individually pursue their own interests, they are together led towards achieving the common good. But can a population of selfish people achieve the economic common good in the absence of moral constraints on their behavior? If not, then what are the moral conditions of market interaction which lead to economically efficient outcomes of trade? Answers to these questions profoundly affect basic concepts and principles (...) of economic theory, legal theory, moral philosophy, political theory, and even judicial decisions at the appellate level. Walter Schultz illustrates the deficiencies of theories which purport to show that markets alone can provide the basis for efficiency. He demonstrates that efficient outcomes of market interaction cannot be achieved without moral normative constraints and then goes on to specify a set of normative conditions which make these positive outcomes possible. (shrink)

This book presents a range of essays on the conceptual foundations of physicalism, mental causation and human agency, written by established and leading authors ...

The popular Cartesian reading of George Berkeley's philosophy of mind mischaracterizes his views on the relations between substance and essence and between an idea and the act of thought in which it figures. I argue that Berkeley rejects Descartes's tripartite taxonomy of distinctions and makes use of a fourth kind of distinction. In addition to illuminating Berkeley's ontology of mind, this fourth distinction allows us to dissolve an important dilemma raised by Kenneth Winkler.

Frank Jackson and Philip Pettit have defended a non-reductive account of causal relevance known as the ‘program explanation account’. Allegedly, irreducible mental properties can be causally relevant in virtue of figuring in non-redundant program explanations which convey information not conveyed by explanations in terms of the physical properties that actually do the ‘causal work’. I argue that none of the possible ways to spell out the intuitively plausible idea of a program explanation serves its purpose, viz., defends non-reductive physicalism against (...) Jaegwon Kim’s Causal Exclusion Argument according to which non-reductive physicalism is committed to epiphenomenalism because irreducible mental properties are ‘screened off’ from causal relevance by their physical realizers. Jackson and Pettit’s most promising explication of a program explanation appeals to the idea of invariance of effect under variation of realization , but I show that invariance of effect under variation of realization is neither necessary nor sufficient for causal relevance. (shrink)

The American Journal of Bioethics, Volume 11, Issue 8, Page 48-49, August 2011.

Rawls’s theory of justice has been criticized for allowing individuals by their own voluntary choice to make themselves members of the ‘least advantaged’ class and thereby eligible, albeit undeservedly, for the benefits mandated by the Difference Principle. I argue, first, that this criticism overlooks the fact that the Difference Principle applies only to the lifetime expectations of representative persons and, second, that it is possible to implement the Difference Principle (and the social minimum) through policies that do not create work (...) disincentives or require making objectionable moral judgments about who is and who is not deserving of assistance. (shrink)

Epistemological approaches to mental causation argue that the notorious problem of mental causation as captured in the question “How can irreducible, physically realized, and potentially relational mental properties be causally efficacious in the production of physical effects?” has a very simple solution: One merely has to abandon any metaphysical considerations in favor of epistemological considerations and accept that our explanatory practice is a much better guide to causal relevance than the metaphysical reasoning carried out from the philosophical armchair. I argue (...) that epistemological approaches to mental causation do not enjoy any genuine advantage over theories which treat the problem of mental causation as a genuinely metaphysical problem. (shrink)

A non-inferiority design accepts the possibility of some efficacy loss, as part of a “successful”, statistically significant result. That loss may be excessive when the non-inferiority threshold is lenient. However, even stringent significance thresholds and safety monitoring may fail to adequately protect study participants when the primary outcome is death. The OPTIMAAL trial, a large randomized clinical trial performed in high-risk patients, is discussed as an example, using the Belmont Report principles as an ethical frame of reference. OPTIMAAL compared losartan, (...) a new drug, to captopril, a drug known to reduce the risk of death in patients with heart failure after a myocardial infarction. Serious ethical challenges occurred in that study. Firstly, subjects had to tolerate captopril to participate, meaning that participation implied the possibility of higher risk of death if randomized to the losartan arm, as compared to the standard of care. Additionally, the stopping rules had to ensure enough powe... (shrink)

Virtues are standardly understood as (1) essentially dispositions to perform certain actions and (2) having only instrumental value as motives to fulfill moral duties which can be fulfilled by persons lacking the virtue because the duties mandate only certain act-types. The argument of this article is that the duties of beneficence, gratitude and self-respect cannot be stated in terms of obligatory act-types because they cannot be fulfilled (except in deficient form) by persons lacking the appropriate virtue; they are, rather, duties (...) to cultivate specific virtues which therefore cannot themselves be defined in terms of obligatory actions. (shrink)

This article canvases the main areas of controversy: the nature of Lockean signification and his position on propositions and particles.

Introduction -- Christian and Greek -- Situating Gadamer philosophically -- Wholes -- Temporality and art -- Art, religious experience, philosophy -- Intellectualism.

There is no safe place and no single locus of enunciation from where the uni-versal could be articulated for all and forever. Hindu nationalism and Western neo-liberalism are entangled in a long history of the logic of coloniality (domination, oppression, exploitation) hidden under the rhetoric of modernity (salvation, civilization, progress, development, freedom and democracy). There are, however, needs and possibilities for Indians and Western progressive intellectuals working together to undermine and supersede the assumptions that liberal thinkers in the West are (...) better placed to understand what is the common good better than Indian thinkers in post-partition India. Science, in the last analysis, doesn't carry in itself an ethics and politics. Therefore, it is doubtful to argue that science is beyond both, and only concerned with the advancement of the frontier of knowledge and understanding. Science could be (like Christianity, Hinduism, Liberalism or Marxism) both imperial and liberating. Knowledge and understanding, rather than science; gnoseology rather than epistemology, should be thought out as which the horizon toward a dialogical and critical cosmopolitanism (e.g., pluriversallity as universal project), could be envisioned beyond East and West, Hindu nationalism and Westertn (neo) liberalism. (shrink)