Acetylation of histones is an essential element regulating chromatin structure and transcription. MYST (Moz, Ybf2/Sas3, Sas2, Tip60) proteins form the largest family of histone acetyltransferases and are present in all eukaryotes. Surprisingly, until recently this protein family was poorly studied. However, in the last few years there has been a substantial increase in interest in the MYST proteins and a number of key studies have shown that these chromatin modifiers are required for a diverse range of cellular processes, both in (...) health and disease. Translocations affecting MYST histone acetyltransferases can lead to leukemia and solid tumors. Some members of the MYST family are required for the development and self‐renewal of stem cell populations; other members are essential for the prevention of inappropriate heterochromatin spreading and for the maintenance of adequate levels of gene expression. In this review we discuss the function of MYST proteins in vivo. (shrink)

Histone acetylation has been recognized as an important post‐translational modification of core nucleosomal histones that changes access to the chromatin to allow gene transcription, DNA replication, and repair. Histone acetyltransferases were initially identified as co‐activators that link DNA‐binding transcription factors to the general transcriptional machinery. Over the years, more chromatin‐binding modes have been discovered suggesting direct interaction of histone acetyltransferases and their protein complex partners with histone proteins. While much progress has been made in characterizing histone acetyltransferase complexes biochemically, cell‐free (...) activity assay results are often at odds with in‐cell histone acetyltransferase activities. In‐cell studies suggest specific histone lysine targets, but broad recruitment modes, apparently not relying on specific DNA sequences, but on chromatin of a specific functional state. Here we review the evidence for general versus specific roles of individual nuclear lysine acetyltransferases in light of in vivo and in vitro data in the mammalian system. (shrink)

Do individuals accept a moral point of view - if they are completely oriented towards their natural preferences and interests? The present article outlines the context of discussion concerning this question within moral philosophy and the social science. In addition it suggests a game-theoretical model with the help of which the question can be answered positively.

Wie ist Kooperation möglich in einer Welt von Egoisten, in der es keine zentrale Autorität gibt? Axelrod entwickelt aus der Spieltheorie - auf der Basis des "Gefangenendilemmas" - eine verblüffende Lösung. Nicht die raffinierteste, auch nicht die aggressivste, nicht die sanfteste Strategie sichert langfristig Erfolg, sondern die grundsätzlich wohlwollende, aber stets vergeltungsbereite: TIT FOR TAT, "wie Du mir, so ich Dir". Axelrod schließt daraus, dass in der globalen arbeitsteiligen Wirtschaftsweise geradezu ein innerer Zwang zur Kooperation besteht. Gewinnbringende Kooperationen sind für (...) Unternehmen nützlicher als blinder Wettbewerb. (shrink)

Despite its complex experiential structure, the phenomenon of grief following bereavement has not been a major topic of phenomenological research. The paper investigates its basic structures, elaborating as its core characteristic a conflict between a presentifying and a ‘de-presentifying’ intention: In grief, the subject experiences a fundamental ambiguity between presence and absence of the deceased, between the present and the past, indeed between two worlds he lives in. This phenomenological structure will be analyzed under several aspects: regarding bodily experience, as (...) disruption of a shared intercorporeality; as a loss of the shared world and shared habitualities, leaving the bereaved person with ubiquitous indications of absence and with a contraction of their own self; regarding temporality, as a separation of two strands of time, namely a still ongoing past and an alienated present which become more and more desynchronized; finally, as an “as-if presence” of the deceased which the bereaved continue to feel and sometimes to perceive, leading to a cognitive-affective conflict between two experienced realities. The transforming process of grief is then analyzed as a gradual adjustment to the loss, finally enabling a re-integration of the conflicting realities. This is achieved through an incorporation and identification with the deceased on the one hand, and through various forms of representation on the other hand, in particular by recollection and symbolization. (shrink)

The hypothesis proposed by Macphail is that differences in intelligent behavior thought to distinguish different species were likely attributed to differences in the context of the tasks being used. Once one corrects for differences in sensory input, motor output, and incentive, it is likely that all vertebrate animals have comparable intellectual abilities. In the present article I suggest a number of tests of this hypothesis with pigeons. In each case, the evidence suggests that either there is evidence for the cognitive (...) behavior, or the pigeons suffer from biases similar to those of humans. Thus, Macphail’s hypothesis offers a challenge to researchers to find the appropriate conditions to bring out in the animal the cognitive ability being tested. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Journal of the History of Philosophy 39.1 (2001) 142-143 [Access article in PDF] Wright, John P. and Paul Potter, editors. Psyche and Soma: Physicians and Metaphysicians on the Mind-Body Problem from Antiquity to Enlightenment. New York: Oxford University Press, 2000. Pp. xii + 298. Cloth, $72.00. The mind-body problem has a long history that begins well before Descartes made it extreme by presenting mind as unextended active thinking and (...) matter as unthinking passive extension. This absolute division was motivated in some part by the desire to present the soul as an entity that can survive the death of the body. This is difficult to maintain if the soul is merely the form or the vital force motivating a human body. But the advance of physiology has led more and more to the conclusion that the functions often attributed to the soul are actually carried out by the brain. Thinking may be as natural (and perhaps as determined) a function of the body as is digestion. And if digestion does not survive the death of the body, maybe thinking does not either.This collection of studies provides a detailed introduction to both medical and metaphysical views and theories concerning the relation of mind to body. In particular, the first article by Beate Gundert on Hippocratic Medicine sets the stage by showing that "mind and body in the Hippocratic writings, while distinguished empirically by being related to different types of phenomena, are both ultimately accounted for by the same explanatory model: Human nature (physis), which embraces the totality of bodily structures, physiological processes, and psychic events" (35). T. M. Robinson shows that Plato admits of no solution as to how mind and body interact, and Philip J. van der Eijk argues that "to detach the essence of man completely from his physical make-up would run counter to Aristotle's biological approach to man as a natural living being, the ultimate implication of his view on the divinity of nous is that the fullest realization of what it is to be a human being is to go beyond the limits of corporeality and mortality, and to become, if only temporarily, a god" (77). Heinrich von Staden covers Epicurus, Herophilus, Erasistratus, the Stoics, and Galen, concluding that "The discovery of the nerves entailed the first significant erosion of the vast territory ruled by the soul in Platonic and Aristotelian philosophy, an erosion accompanied by an expansion of the rule of 'nature,' visible not only in medicine, but also in philosophy" (116). Theo K. Heckel discusses Saint Paul's insistence upon the whole person, and Gareth Matthews shows that, prior to Descartes, Augustine presents "a radically new argument for mind-body dualism... an internalist argument... that proceeds from what, allegedly, the mind can know concerning itself to the conclusion that the mind is incorporeal" (145). Emily Michael discusses Pomponazzi's view that we know the immortality of the soul only by faith and the scholastic attempts to show that the soul is a substantial form. Guillaume Lamy, for example, criticized Descartes for having a soul only of thinking, whereas the soul must be of life. Steven Voss shows how at the end of his life, Descartes did discuss in detail how thinking affects the body, particularly in the management of health and the curing of disease. But Descartes does not solve the problem of how this interaction takes place. Thomas Lennon discusses the views of Bayle on Leibniz's monadic forces and Locke's fideism. And Francois Duchesneu continues the discussion of Stahl and Leibniz, to [End Page 142] conclude that "Leibniz attempts to discover the formal foundation of the organism, which he locates in the capacity of perception-appetition proper to the dominant monad" (235).John P. Wright gives an exposition of a very important distinction between Cartesian dualism and the functional dualism that came to dominate medical thought, that is, the question of how the brain and vital organs interact. Roselyn Rey carries this discussion on to the development of theories... (shrink)

»Latenz« bezeichnet als spezifischer Modus des Verborgenseins und der Wirksamkeit aus dem Verborgenen eine ebenso alte wie virulente Figur. Das Wirken des Begriffs selbst jedoch geschieht bezeichnenderweise oft fast unbemerkt und wie aus dem Verborgenen: Nicht nur sucht man vergebens nach einer umfassenden Theorie der Latenz, auch im Einzelnen sind detaillierte Klärungen zur Struktur oder Verwendungsweise der mit Latenz verbundenen Begrifflichkeit die Ausnahme. »Latenz« taucht vielmehr fast ausschließlich als operativer Begriff auf, der einen Teil seiner spezifischen Wirksamkeit womöglich gerade seinem (...) unthematisierten, ›latenten‹ Charakter verdankt – der Ovid’schen Devise entsprechend, dass die Kunstfertigkeit darin bestehe, die ihr eigene Technik zu verbergen: ars adeo latet arte sua. (shrink)

This paper argues against the moral Turing test as a framework for evaluating the moral performance of autonomous systems. Though the term has been carefully introduced, considered, and cautioned about in previous discussions :251–261, 2000; Allen and Wallach 2009), it has lingered on as a touchstone for developing computational approaches to moral reasoning :98–109, 2015). While these efforts have not led to the detailed development of an MTT, they nonetheless retain the idea to discuss what kinds of action and reasoning (...) should be demanded of autonomous systems. We explore the flawed basis of an MTT in imitation, even one based on scenarios of morally accountable actions. MTT-based evaluations are vulnerable to deception, inadequate reasoning, and inferior moral performance vis a vis a system’s capabilities. We propose verification—which demands the design of transparent, accountable processes of reasoning that reliably prefigure the performance of autonomous systems—serves as a superior framework for both designer and system alike. As autonomous social robots in particular take on an increasing range of critical roles within society, we conclude that verification offers an essential, albeit challenging, moral measure of their design and performance. (shrink)

In “Tense and Reality”, Kit Fine () proposed a novel way to think about realism about tense in the metaphysics of time. In particular, he explored two non-standard forms of realism about tense, arguing that they are to be preferred over standard forms of realism. In the process of defending his own preferred view, fragmentalism, he proposed a fragmentalist interpretation of the special theory of relativity, which will be our focus in this paper. After presenting Fine's position, we will raise (...) a problem for his fragmentalist interpretation of STR. We will argue that Fine's view is in tension with the proper explanation of why various facts obtain. We will then consider whether similar considerations also speak against fragmentalism in domains other than STR, notably fragmentalism about tense. (shrink)

This series offers central philosophical treatises of Aquinas in new, state-of-the-art translations distinguished by their accuracy and use of clear and nontechnical modern vocabulary. Annotation and commentary accessible to undergraduates make the series an ideal vehicle for the study of Aquinas by readers approaching him from a variety of backgrounds and interests.

Cognitivism about trust says that it requires belief that the trusted is trustworthy; non-cognitivism denies this. At stake is how to make sense of the strong but competing intuitions that trust is an attitude that is evaluable both morally and rationally. In proposing that one's respect for another's agency may ground one's trusting beliefs, second-personal accounts provide a way to endorse both intuitions. They focus attention on the way that, in normal situations, it is the person whom I trust. My (...) task is to develop an account of the latter insight without the controversial theoretical commitments of the former. I propose a functional account for why the second and third-personal ‘systems’ operate not just in parallel, but in tandem, in support of a cognitivist account of trust. (shrink)

In the years since Enron corporate social responsibility, or “CSR,” has become a ubiquitous phenomenon in both research and business practice. CSR is used as an umbrella term to describe much of what is done in terms of ethics-related activities in firms around the globe to such an extent that some consider it a “tortured concept” (Godfrey and Hatch 2007, Journal of Business Ethics 70, 87–98). Addressing this skepticism, I argue in this article that the focus on CSR is indeed (...) problematic for three main reasons: (1) the term carries a lot of historical baggage – baggage that is not necessarily conducive to the clarity of the concept; (2) it is the object of increasing ethical instrumentalism; and (3) given the multiple ethical challenges that corporations face, and given the fact that the “social” responsibilities of business are but one set of corporate responsibilities, a suitable term would have to be more inclusive and integrative. I therefore suggests moving instead toward a sound definition of corporate integrity and aim in this article to develop a working definition by fleshing out “7 Cs” of integrity: commitment, conduct, content, context, consistency, coherence, and continuity. I then discuss how these 7 Cs impact our understanding of CSR or, more broadly, corporate responsibility in general. (shrink)

A new public philosophy began to emerge in the United States during the Progressive Era. Promoted by such intellectuals as John Dewey, William James, and the coUectivists of the New Republic magazine, it called for a citizenry trained in an experimental milieu, free of dogma and emancipated from sources of allegiance other than the new centralized democratic state then being forged. Catholics, however, neither capitulated to the new creed nor retreated into a self-righteous isolation. In a culture whose chief value (...) was pluralism they insisted on the uniqueness of the Church and the need for making value judgments based on a sound philosophy of man. (shrink)

This issue includes a number of papers on reproductive ethics, broadly construed. In a recent book, Anja Karnein proposed that embryos created in vitro should be offered up for adoption before being discarded or used in research;1 here Timothy Murphy offers a critical response . Elsewhere, Tak Chan and Stark & Delatycki debate the role of medical professionals in providing parentage determination. Chan argues that doctors are obliged to provide parentage tests when this is requested by parents, provided there is (...) a low risk that the child will be abandoned . Stark & Delatycki discuss some difficulties raised by the ‘risk of abandonment’ condition . Finally, papers by Kate Greasley and David Lang discuss the controversy surrounding the criminal prosecution of abortion doctor Kermit Gosnell. Greasley criticises the way in which some commentators capitalised on horror at Gosnell's extreme practices to advance more general anti-abortion objectives . Lang argues, against Greasley, that the dominant pro-life response to the case was neither self-contradictory nor intellectually dishonest .The issue is dominated, however, by discussions of ‘bioenhancement’ – the use of biomedical technologies to augment human capacities. A common criticism of bioenhancements is that they are anti-social: though they may benefit the user, they will have a negative effect on society-at-large. Such concerns are perhaps well placed in relation to the most obvious contemporary examples of bioenhancement: doping in sport, aesthetic medicine, and the use of stimulants to enhance examination performance. However, two varieties of bioenhancement discussed in this issue might be thought to have more positive social effects.David Shaw discusses the possible use of cognitive enhancing drugs to improve health outcomes in disadvantaged segments of society . Such enhancements might be thought to have desirable social …. (shrink)

The mathematician G.F.C. Griss is known for his program of negationless intuitionistic mathematics. Although Griss’s rejection of negation is regarded as characteristic of his philosophy, this is a consequence of an executability requirement that mental constructions presuppose agents’ executing corresponding mental activity. Restoring Griss’s executability requirement to a central role permits a more subtle characterization of the rejection of negation, according to which D. Nelson’s strong constructible negation is compatible with Griss’s principles. This exposes a ‘holographic’ theory of negation in (...) negationless mathematics, in which a full theory of negation is ‘flattened’ in a putatively negationless setting. (shrink)

Codes of ethics are directly aimed at behavioral control, but they also affect a company’s ethical culture, which in turn concerns compliance and ethical behavior. To positively influence a company’s ethical culture, employees must be familiar with its code of ethics, perceive that top management is committed to the code, and believe that their peers also comply with the code. The evidence on whether a code’s design affects a company’s ethical culture is limited. This study’s factorial survey experiment contributes to (...) this gap in two ways: first, it investigates whether a code’s design affects how easily the code can be learned and, therefore, contributes to code familiarity. Second, it examines how a code can convey expectations regarding top management’s commitment and peers’ behavior, both of which are part of ethical culture. The results indicate that a positive tone increases code familiarity, and a code signed by top managers sends a strong signal of their commitment to the code. Finally, various implications of the results for research and practice are discussed. (shrink)

Horwich proposes a solution to the liar paradox that relies on a particular notion of grounding—one that, unlike Kripke’s notion of grounding, does not invoke any “Tarski-style compositional principles”. In this short note, we will formalize Horwich’s construction and argue that his solution to the liar paradox does not justify certain generalizations about truth that he endorses. We argue that this situation is not resolved even if one appeals to the \-rule. In the final section, we briefly discuss how Horwich (...) might respond to the situation. (shrink)

Quantum mechanics has provided philosophers of science with many counterintuitive insights and interpretive puzzles, but little has been written about the role that time plays in the theory. One reason for this is the celebrated argument of Wolfgang Pauli against the inclusion of time as an observable of the theory, which has been seen as a demonstration that time may only enter the theory as a classical parameter. Against this orthodoxy I argue that there are good reasons to expect certain (...) kinds of 'time observables' to find a representation within quantum theory, including clock operators and event time operators, which provide predictions for the time at which a particular event occurs, such as the appearance of a dot on a luminescent screen. I contend that these time operators deserve full status as observables of the theory, and on reflection provide a uniquely compelling reason to expand the set of observables allowed by the standard formalism of quantum mechanics. In addition, I provide a novel association of event time operators with conditional probabilities, and propose a temporally extended form of quantum theory to better accommodate the time of an event as an observable quantity. This leads to a proposal to interpret quantum theory within an event ontology, inspired by Bertrand Russell's Analysis of Matter. On this basis I mount a defense of Russell's relational theory of time against a recent attack. (shrink)

This paper will examine the topic of identity in Roman Catholicism from the perspective of topics contained in or absent from mission statements of 25 Catholic health care institutions. In particular, I will look at these from the perspective of social justice as well as how this and other topics such as human dignity, the sanctity of life, stewardship, pastoral care and the likelihood of mergers with other institutions will affect the healing ministry of Catholic health care providers. The article (...) will conclude that there are three key dimensions to Catholic health care: leadership in advocating reform of the current health care system, care for the marginalized and under-insured, and the provision of pastoral care in all institutions. (shrink)

Many of the problems studied in cognitive science are inductive problems, requiring people to evaluate hypotheses in the light of data. The key to solving these problems successfully is having the right inductive biases—assumptions about the world that make it possible to choose between hypotheses that are equally consistent with the observed data. This article explores a novel experimental method for identifying the biases that guide human inductive inferences. The idea behind this method is simple: This article uses the responses (...) produced by a participant on one trial to generate the stimuli that either they or another participant will see on the next. A formal analysis of this “iterated learning” procedure, based on the assumption that the learners are Bayesian agents, predicts that it should reveal the inductive biases of these learners, as expressed in a prior probability distribution over hypotheses. This article presents a series of experiments using stimuli based on a well-studied set of category structures, demonstrating that iterated learning can be used to reveal the inductive biases of human learners. (shrink)

As phenomenology rose to prominence at the beginning of the 20th century, several aestheticians tried to establish the Husserlian method of “phenomenological reduction” in the field of aesthetics. These ventures were met with resistance from psychological aesthetics, which was the predominant form of aesthetics in the German-speaking world at the time. This paper examines, first, practical attempts to apply the method of “phenomenological reduction” in aesthetics. Using Waldemar Conrad and Moritz Geiger as examples, I try to trace what aestheticians actually (...) did when they applied this method in their investigations. Secondly, I reconstruct the four central objections with which psychological aesthetics reacted to such attempts. I have identified four central counterarguments in the work of Johannes Volkelt and Oswald Külpe, who were among the most eminent critics of phenomenological aesthetics: the transcendental argument, the susceptibility-to-errors argument, the constructivism argument, and the non-normativity argument. Finally, I also discuss the refusal of psychological aesthetics to acknowledge that a genuine phenomenological method even existed and the consequences of this refusal. (shrink)

Ancient moral philosophers, especially Aristotle and his followers, typically shared the assumption that ethics is primarily concerned with how to achieve the final end for human beings, a life of “happiness” or “human flourishing.” This final end was not a subjective condition, such as contentment or the satisfaction of our preferences, but a life that could be objectively determined to be appropriate to our nature as human beings. Character traits were treated as moral virtues because they contributed well toward this (...) ideal life, either as means to it or as constitutive aspects of it. Traits that tended to prevent a “happy” life were considered vices, even if they contributed to a life that was pleasant and what a person most wanted. The idea of “happiness” was central, then, in philosophical efforts to specify what we ought to do, what sort of persons we should try to become, and what sort of life a wise person would hope for. (shrink)

Abstractabstract:There are two ways of hearing Philo's unexpected endorsement of a version of the design hypothesis in the final part of Hume's Dialogues. We might register it in accordance with Cleanthes's descriptivist approach to religious speech, taking Philo to be reasoning with Cleanthes in Cleanthes's own way. Or we might hear Philo's words in accordance with his own expressivist account of religious speech, an account that Philo appears to have borrowed from Hobbes. I argue that Hume intended this double layering (...) of meanings, presenting us with two distinct ways we might understand Philo's closing remarks. Each possible reading reveals a distinct Humean lesson about the limitations of natural theology. (shrink)

The article focuses on the ability of some animals and plants to respond to changing environmental conditions by temporarily suspending metabolic processes. In contemporary biology, this state between life and death is commonly labelled ‘cryptobiosis’, combining the Greek kryptos (hidden, concealed, secret) with biōsis (mode of life). I argue that the notion of ‘cryptobiosis’ does not account sufficiently for the processual and relational dimensions of ametabolic life. The article advances a related but different concept, which better addresses this liminal state (...) of biological organisation: s uspended life. While cryptobiosis still nurtures the imaginary of some latent life, suspended life stresses the liminality of the neither-nor life and death. The notion also grasps the dynamic and ongoing transfer between the biological and the technological. While the debate on cryptobiosis has so far remained confined to the description of natural processes, suspended life (or limbiosis) promises to account for contemporary technological practices of cryopreservation. (shrink)