In this review, we will focus on the role played by transcription factors of the E2F/DP family in controlling the expression of genes that carry out important cell‐cycle control functions, thereby ensuring ordered progression through the mammalian cell division cycle. The emerging picture is that cell‐cycle progression depends on the execution of a regulatory cascade of gene expression, driven by E2F/DP transcription factors, which are in turn regulated by the products of some of these genes. That E2F factors are potent (...) regulators of cell‐cycle checkpoints in mammalian cells is supported by experiments demonstrating that ectopic expression of individual E2F family members is sufficient to modulate cell proliferation and apoptosis. It is also clear that deregulation of E2F activity will result in the loss of particular checkpoint controls, thereby predisposing cells to malignant conversion. BioEssays 21:221–230. 1999. © 1999 John Wiley & Sons, Inc. -/- . (shrink)

The human body can be regarded in at least two ways: objectively, as a physical and organic body; and subjectively, as the center of orientation and lived affective unity. However, this distinction can lose sight of the fact that the ‘lived body’ is not reducible to subjective idiosyncrasies. Trans-individual norms are embodied too, as Michel Foucault and Judith Butler have shown. Phenomenological investigations of normalization and habitualization help bring these two important dimensions of embodiment together and overcome simplistic oppositions between (...) phenomenological and poststructuralist approaches. These investigations lead into issues of female body optimization and control that we take to be characteristic of contemporary neoliberalist embodiment. (shrink)

Margaret Gilbert has defended the claim that her plural subject theory can give a reasonable account of retrospective (or backward-looking) collective responsibility. On one occasion, publishing in this periodical, she writes that she deliberately left out the discussion of prospective (or forward-looking) collective responsibility, or the “responsibilities” of a collective. In the present paper, I want to show that plural subject theory, in fact, also allows accounting for prospective responsibilities of groups and institutions. In order to do so, I will (...) first sketch the social ontological background of my discussion which is, in fact, an amended version of Gilbert’s theory of plural subjects (§ 2). Based on the assumption that a prospective responsibility accrues from some kind of commissioning, I will then discuss a variety of possible sources of prospective collective responsibilities: self-commissioning, third-party commissioning and what I will call commissioning by unique capability (§ 3). Having done so, I will discuss some consequences of this account and defend it against objections (§ 4). (shrink)

The paper takes up Bell's “Everett theory” and develops it further. The resulting theory is about the system of all particles in the universe, each located in ordinary, 3-dimensional space. This many-particle system as a whole performs random jumps through 3N-dimensional configuration space – hence “Tychistic Bohmian Mechanics”. The distribution of its spontaneous localisations in configuration space is given by the Born Rule probability measure for the universal wavefunction. Contra Bell, the theory is argued to satisfy the minimal desiderata for (...) a Bohmian theory within the Primitive Ontology framework. TBM's formalism is that of ordinary Bohmian Mechanics, without the postulate of continuous particle trajectories and their deterministic dynamics. This “rump formalism” receives, however, a different interpretation. We defend TBM as an empirically adequate and coherent quantum theory. Objections voiced by Bell and Maudlin are rebutted. The “for all practical purposes”-classical, Everettian worlds exist sequentially in TBM. In a temporally coarse-grained sense, they quasi-persist. By contrast, the individual particles themselves cease to persist. (shrink)

Some commentators have recently proposed that “clinical equipoise,” although widely accepted, is not necessary for morally acceptable research on human subjects. If this concept is rejected, however, we may find that trials not in the best medical interests of their subjects—”bad deal trials”—could be justified. To avoid exploiting participants, we must find a way to distribute the risks fairly, even if it means embracing radical changes in the way clinical research is conducted.

After a short sketch of Lowe’s account of his four basic categories, I discuss his theory of formal ontological relations and how Lowe wants to account for dispositional predications. I argue that on the ontic level Lowe is a pan-categoricalist, while he is a language dualist and an exemplification dualist with regard to the dispositional/categorical distinction. I argue that Lowe does not present an adequate account of disposition. From an Aristotelian point of view, Lowe conflates dispositional predication with hôs epi (...) to poly statements about what is normally or mostly the case. (shrink)

""Catching Ourselves in the Act" is no less than an attempt to explain intelligence. Delightful how the author dismantles traditional views in.

We are currently in the midst of a revival of interest in thevirtues. A number of contemporary moral philosophers havedefended a virtue-based approach to ethics. But does thisrenewal of interest in the virtues have much to contributeto medical ethics and medical practice? This paper criticallydiscusses this question. It considers and rejects a number ofimportant arguments that purport to establish the significanceof the virtues for medical practice. Against these arguments,the paper seeks to show that while the virtues have a genuinerole to (...) play in medical ethics, it is a limited role, one thatis subordinate to the role that other moral concepts such asrules and principles play. (shrink)

What constitutes a scientific discovery? What role do discoveries play in science, its dynamics and social practices? Must every discovery be attributed to an individual discoverer (or a small number of discoverers)? The paper explores these questions by first critically examining extant philosophical explications of scientific discovery—the models of scientific discovery, propounded by Kuhn, McArthur, Hudson, and Schindler. As a simple, natural and powerful alternative, we proffer the “change-driver model”: in a nutshell, it takes discoveries to be cognitive scientific results (...) that have epistemically advanced science. The model overcomes the shortcomings of its precursors, whilst preserving their insights. We demonstrate its intensional and extensional superiority, especially with respect to the link between scientific discoveries and the dynamics of science, as well as the award system of science. Both as an illustration, and as an application to a recent scientific and political controversy, we apply the considered models of discovery to one of the most momentous discoveries of science: the expansion of the universe. We oppose the 2018 proposal of the International Astronomers’ Union as too simplistic vis-`a-vis the historical complexity of the episode. The change- driver model yields a more nuanced and circumspect verdict: (i) The redshift-distance relation shouldn’t be named the “Hubble-Lemaître Law”, but “Slipher-Lundmark-Hubble-Humason Law”; (ii) Its interpretation in terms of an expanding universe, however, Lemaître ought to be given credit for; but (iii) The establishment of the expansion of the universe, as an evidentially sufficiently warranted result, is a communal achievement, emerging in the 1950s or 1960s. (shrink)

Hidden in Historicism considers how the nineteenth-century philosophy of historicism depicts three "forgotten time regimes": a time of rise and fall, an ambiguous time of synchronicity of the non-synchronous, and a time in which decisive moments dominate. Before the eighteenth century, time was past-oriented. This inversed in the Enlightenment, when the future became dominating. Today, this time of progress continues to be embraced as a "time of the modern". Yet, inequality, increasing violence and climate change lead to doubts over a (...) bright future. In this book, Harry Jansen moves away from the heritage of Reinhart Koselleck and his single time of the modern towards a historicist, threefold temporal approach to history writing. In the time regime of the twenty-first century past, present and future coexist. It is a heterogeneous time that takeson the three forms of historicism. Jansen's study shows how all three times exist together in current historiography and contribute to a better understanding of the world today. Based on the idea that an incarnated time rules everything that happens it reality, the book offers a fresh perspective on the ongoing discussion about time and time regimes in contemporary philosophy and theory of history for students and scholars, both time specialists and the non-specialist. (shrink)

What standard or principle should guide decisionmaking concerning the permissibility of allowing children to be organ donors? For a long time, it has been widely assumed that the best interest of the child is the appropriate standard. But recently, several critics have charged that this standard fails to give due weight to the interests of the family and the intimate relationships that the family makes possible.1,2 This article reviews and rejects both the best-interest standard and the alternative standard recommended by (...) the critics. I then propose a new standard to help parents, healthcare professionals, and judges decide when it is and is not permissible for children to serve as organ donors. This new standard modifies and broadens the best-interest standard to allow it to account adequately for the contribution that intimate relationships make to the well-being of children. (shrink)

In the following paper, I review and critically assess the four standard routes commonly taken to establish that gravitational waves possess energy-momentum: the increase in kinetic energy a GW confers on a ring of test particles, Bondi/Feynman’s Sticky Bead Argument of a GW heating up a detector, nonlinearities within perturbation theory, taken to reflect the fact that gravity contributes to its own source, and the Noether Theorems, linking symmetries and conserved quantities. Each argument is found to either to presuppose controversial (...) assumptions or to be outright spurious. I finally examine the standard interpretation of binary systems, according to which orbital decay is explained in terms of the system’s energy being via GW energy- momentum transport. I contend that a better interpretation, drawing only on the general-relativistic Equations of Motions and the Einstein Equations, is available - and in fact preferable; thereby also an inference to the best explanation for the vindication of GW energy-momentum is blocked. (shrink)

In Republic X, the “problem of the irrational part” is this: Greek tragedy interacts with non-reasoning elements of the soul, affecting audiences in ways that undermine their reasoned views about virtue and value. I suggest that the common construal of Socrates’s critique of Greek tragedy is inadequate, in that it belies key elements of Plato’s audience psychology; specifically, the crucial role of the spirited part and the audience’s cognitive contribution to spectatorship. I argue that Socrates’s emphasis on the audience’s cognitive (...) contribution to spectatorship allows him to anticipate a non-authoritarian solution to the problem of the irrational part. (shrink)

This article revisits Karl Popper’s falsificationist methodology with respect to three tasks. The first is to illuminate and systematize Popper’s methodological views in light of his core epistemological commitments. A second and related objective is to gauge which aspects of falsificationism should be identified as “conventionalist”—a label that Popper himself uses (albeit with qualifications) but that is compromised by and, thus, stands in need of elucidation because of Popper’s idiosyncratic understanding of conventionalism. Third, by elaborating Popper’s virtue-epistemological, dialogical model of (...) rationality, I show how Popper’s conventionalism, fallibilism, and critical rationalism form a coherent system. This system allows Popper to accord science the status of a privileged source of knowledge—without naïve appeal to authority. My systematization of Popper’s views yields an intrinsically and exegetically more satisfactory reading of Popper’s falsificationism than usual presentations. Thanks to its marked flexibility and methodological liberalism, it bypasses many standard objections but still offers sound and relevant methodological advice. With its “virtue-methodological” thrust, Popper sketches an original and promising approach to methodology, the fertility of which deserves further exploration for contemporary debates. (shrink)

Classical physics is about real objects, like apples falling from trees, whose motion is governed by Newtonian laws. In standard quantum mechanics only the wave function or the results of measurements exist, and to answer the question of how the classical world can be part of the quantum world is a rather formidable task. However, this is not the case for Bohmian mechanics, which, like classical mechanics, is a theory about real objects. In Bohmian terms, the problem of the classical (...) limit becomes very simple: when do the Bohmian trajectories look Newtonian? (shrink)

The present paper revisits the debate between realists about gravitational energy in GR and anti-realists/eliminativists. I re-assess the arguments underpinning Hoefer’s seminal eliminativist stance, and those of their realist detractors’ responses. A more circumspect reading of the former is proffered that discloses where the so far not fully appreciated, real challenges lie for realism about gravitational energy. I subsequently turn to Lam and Read’s recent proposals for such a realism. Their arguments are critically examined. Special attention is devoted to the (...) adequacy of Read’s appeals to functionalism, imported from the philosophy of mind. (shrink)

The present paper revisits the debate between realists about gravitational energy in GR and anti-realists/eliminativists. I re-assess the arguments underpinning Hoefer’s seminal eliminativist stance, and those of their realist detractors’ responses. A more circumspect reading of the former is proffered that discloses where the so far not fully appreciated, real challenges lie for realism about gravitational energy. I subsequently turn to Lam and Read’s recent proposals for such a realism. Their arguments are critically examined. Special attention is devoted to the (...) adequacy of Read’s appeals to functionalism, imported from the philosophy of mind. (shrink)

In fisheries biology of the late 19th century, the challenges posed to taxonomy by Darwinian theory intersected with attempts to increase the productivity of marine populations. Addressing both discourses, the influential German zoologist Friedrich Heincke developed a set of methods to determine exactly the differences between varieties or races of herring. In taxonomy, his methods contributed to the development of a biological species concept; in fisheries biology, they allowed tracing the herrings' migrations, which ultimately aided in divising schemes for sustainable (...) fisheries. Heincke's use of mathematical statistics, some of them borrowed from anthropometry, served to distinguish his ‚exact’ approach from that of typological taxonomists. Beyond its use as a rhetorical ploy, exactness gained meaning in the epistemic regime of exact reproduction of measurements, which entailed the replication of measurement techniques for the purpose of comparison e.g. of herrings caught at different locations. This exactness was enabled by the formalisation of the process of taxonomic identification. (shrink)

On March, 24, 2020, 818 cases of COVID-19 had been reported in New South Wales, Australia, and new cases were increasing at an exponential rate. In anticipation of resource constraints arising in clinical settings as a result of the COVID-19 pandemic, a working party of ten ethicists was convened at the University of Sydney to draft an ethics framework to support resource allocation decisions. The framework guides decision-makers using a question-and-answer format, in language that avoids philosophical and medical technicality. The (...) working party met five times over the following week and then submitted a draft Framework for consideration by two groups of intensivists and one group of academic ethicists. It was also presented to a panel on a national current affairs programme. The Framework was then revised on the basis of feedback from these sources and made publicly available online on April 3, ten days after the initial meeting. The framework is published here in full to stimulate ongoing discussion about rapid development of user-friendly clinical ethics resources in ongoing and future pandemics. (shrink)

The present paper revisits the debate between realists about gravitational energy in GR and anti-realists/eliminativists. I re-assess the arguments underpinning Hoefer’s seminal eliminativist stance, and those of their realist detractors’ responses. A more circumspect reading of the former is proffered that discloses where the so far not fully appreciated, real challenges lie for realism about gravitational energy. I subsequently turn to Lam and Read’s recent proposals for such a realism. Their arguments are critically examined. Special attention is devoted to the (...) adequacy of Read’s appeals to functionalism, imported from the philosophy of mind. (shrink)

The paper investigates the status of gravitational energy in Newtonian Gravity, developing upon recent work by Dewar and Weatherall. The latter suggest that gravitational energy is a gauge quantity. This is potentially misleading: its gauge status crucially depends on the spacetime setting one adopts. In line with Møller-Nielsen’s plea for a motivational approach to symmetries, we supplement Dewar and Weatherall’s work by discussing gravitational energy–stress in Newtonian spacetime, Galilean spacetime, Maxwell-Huygens spacetime, and Newton–Cartan Theory. Although we ultimately concur with Dewar (...) and Weatherall that the notion of gravitational energy is problematic in NCT, our analysis goes beyond their work. The absence of an explicit definition of gravitational energy–stress in NCT somewhat detracts from the force of Dewar and Weatherall’s argument. We fill this gap by examining the supposed gauge status of prima facie plausible candidates—NCT analogues of gravitational energy–stress pseudotensors, the Komar mass, and the Bel-Robinson tensor. Our paper further strengthens Dewar and Weatherall’s results. In addition, it sheds more light upon the subtle link between sufficiently rich inertial structure and the definability of gravitational energy in NG. (shrink)

After a short sketch of Lowe's account of his four basic categories, I discuss his theory of formal ontological relations and how Lowe wants to account for dispositional predications. I argue that on the ontic level Lowe is a pan-categoricalist, while he is a language dualist and an exemplification dualist with regard to the dispositional/categorical distinction. I argue that Lowe does not present an adequate account of disposition. From an Aristotelian point of view, Lowe conflates dispositional predication with 'hôs epi (...) to poly' statements about what is normally or mostly the case. (shrink)

Super-substantivalism (of the type we’ll consider) roughly comprises two core tenets: (1) the physical properties which we attribute to matter (e.g. charge or mass) can be attributed to spacetime directly, with no need for matter as an extraneous carrier “on top of” spacetime; (2) spacetime is more fundamental than (ontologically prior to) matter. In the present paper, we revisit a recent argument in favour of super-substantivalism, based on General Relativity. A critique is offered that highlights the difference between (various accounts (...) of) fundamentality and (various forms of) ontological dependence. This affords a metaphysically more perspicuous view of what super-substantivalism’s tenets actually assert, and how it may be defended. We tentatively propose a re-formulation of the original argument that not only seems to apply to all classical physics, but also chimes with a standard interpretation of spacetime theories in the philosophy of physics. (shrink)

In recent years, many states in the United States have passed legislation requiring laboratories to report the names of patients with low CD4 cell counts to their state Departments of Health. This name reporting is an integral part of the growing number of “HIV Reporting and Partner Notification Laws” which have emerged in response to recently revised guidelines suggested by the National Centers for Disease Control (CDC). Name reporting for patients with low CD4 cell counts allows for a more accurate (...) tracking of the natural history of HIV disease. However, given that this test is now considered to be an “indicator” of HIV, should it be subject to the same strict consent required for HIV testing? While the CDC has recommended that each state develop its own consent requirements for CD4 cell testing, most states have continued to rely on the presumed consent standards for CD4 cell testing that were in place before the passage of name reporting statutes. This allows physicians who treat patients who refuse HIV testing to order a CD4 cell blood analysis to gather information that is indicative of their patient’s HIV status. This paper examines the ethical and legal issues associated with the practice of “conscientious subversion” as it arises when clinicians use CD4 cell counts as a surrogate for HIV testing. (shrink)

In recent years CL diagrams inspired by Lange’s Cubus Logicus have been used in various contexts of diagrammatic reasoning. However, whether CL diagrams can also be used as a formal system seemed questionable. We present a CL diagram as a formal system, which is a fragment of propositional logic. Syntax and semantics are presented separately and a variant of bitstring semantics is applied to prove soundness and completeness of the system.