Systems biology is today such a widespread discipline that it becomes difficult to propose a clear definition of what it really is. For some, it remains restricted to the genomic field. For many, it designates the integrated approach or the corpus of computational methods employed to handle the vast amount of biological or medical data and investigate the complexity of the living. Although defining systems biology might be difficult, on the other hand its purpose is clear: systems biology, with its (...) emerging subfields systems medicine and systems pharmacology, clearly aims at making sense of complex observations/experimental and clinical datasets to improve our understanding of diseases and their treatments without putting aside the context in which they appear and develop. In this short review, we aim to specifically focus on these new subfields with the new theoretical tools and approaches that were developed in the context of cancer. Systems pharmacology and medicine now give hope for major improvements in cancer therapy, making personalized medicine closer to reality. As we will see, the current challenge is to be able to improve the clinical practice according to the paradigm shift of systems sciences. (shrink)

Building a meaningful model of biological regulatory network is usually done by specifying the components and their interactions, by guessing the values of parameters, by comparing the predicted behaviors to the observed ones, and by modifying in a trial-error process both architecture and parameters in order to reach an optimal fitness. We propose here a different approach to construct and analyze biological models avoiding the trial-error part, where structure and dynamics are represented as formal constraints. We apply the method to (...) Hopfield-like networks, a formalism often used in both neural and regulatory networks modeling. The aim is to characterize automatically the set of all models consistent with all the available knowledge. The available knowledge is formalized into formal constraints. The latter are compiled into Boolean formula in conjunctive normal form and then submitted to a Boolean satisfiability solver. This approach allows to formulate a wide range of queries, expressed in a high level language, and possibly integrating formalized intuitions. In order to explore its potential, we use it to find cycles for 3-nodes networks and to determine the flower morphogenesis regulatory network of Arabidopsis thaliana. Applications of this technique are numerous and concern the building of models from data as well as the design of biological networks possessing specified behaviors. (shrink)

Angiogenesis is a complex morphogenetic process regulated by growth factors, but also by the force balance between endothelial cells traction stresses and extracellular matrix viscoelastic resistance. Studies conducted with in vitro angiogenesis assays demonstrated that decreasing ECM stiffness triggers an angiogenic switch that promotes organization of EC into tubular cords or pseudo-capillaries. Thus, mechano-sensitivity of EC with regard to proteases secretion, and notably matrix metalloproteinases, should likely play a pivotal role in this switching mechanism. While most studies analysing strain regulation (...) of MMPs used cell cultured on stretched membranes, this work focuses on MMP expression during self-assembly of EC into capillary-like structures within fibrin gels, i.e. on conditions that mimics more closely the in vivo cellular mechanical microenvironment. The activity of MMP-2 and MMP-9, two MMPs that have a pivotal role in capillaries formation, has been monitored in pace with the progressive elongation of EAhy926 cells that takes place during the emergence of cellular cords. We found an increase of the zymogen proMMP-2 that correlates with the initial stages of EC cords formation. However, MMP-2 was not detected. ProMMP-9 secretion decreased, with levels of MMP-9 kept at a rather low value. In order to analyse more precisely the observed differences of EAhy926 response on fibrin and plastic substrates, we proposed a theoretical model of the mechano-regulation of proMMP-2 activation in the presence of type 2 tissue inhibitor of MMPs. Using association/dissociation rates experimentally reported for this enzymatic network, the model adequately describes the synergism of proMMP-2 and TIMP-2 strain activation during pseudo-capillary morphogenesis. All together, these results provide a first step toward a systems biology approach of angiogenesis mechano-regulation by cell-generated extracellular stresses and strains. (shrink)

Introduction -- Sanctioning models : theories and their scope -- Methodology for a virtual world -- A tale of two methods -- When theories shake hands -- Models of climate : values and uncertainties -- Reliability without truth -- Conclusion.

I argue that to have an attitude is, primarily, (1.) to have a dispositional profile that matches, to an appropriate degree and in appropriate respects, a stereotype for that attitude, typically grounded in folk psychology, and secondarily, (2.) in some cases also to meet further stereotypical attitude-specific conditions. To have an attitude, on the account I will recommend here, is mainly a matter of being apt to interact with the world in patterns that ordinary people would regard as characteristic of (...) having that attitude. I contrast this view with alternative views that treat having an attitude as a matter of possessing some particular internally stored representational content or some other "deep" structural feature. (shrink)

Rationalization, in our intended sense of the term, occurs when a person favors a particular conclusion as a result of some factor (such as self-interest) that is of little justificatory epistemic relevance, if that factor then biases the person’s subsequent search for, and assessment of, potential justifications for the conclusion. Empirical evidence suggests that rationalization is common in people’s moral and philosophical thought. We argue that it is likely that the moral and philosophical thought of philosophers and moral psychologists is (...) also pervaded by rationalization. Moreover, although rationalization has some benefits, overall it would be epistemically better if the moral and philosophical reasoning of people, including professional academics, were not as heavily influenced by rationalization as it likely is. We discuss the significance of our arguments for cognitive management and epistemic responsibility. (shrink)

From the time of Locke, discussions of personal identity have often ignored the question of our basic metaphysical nature: whether we human people are biological organisms, spatial or temporal parts of organisms, bundles of perceptions, or what have you. The result of this neglect has been centuries of wild proposals and clashing intuitions. What Are We? is the first general study of this important question. It beings by explaining what the question means and how it differs from others, such as (...) questions of personal identity and the mind-body problem. It then examines in some depth the main possible accounts of our metaphysical nature, detailing both their theoretical virtues and the often grave difficulties they face. The book does not endorse any particular account of what we are, but argues that the matter turns on more general issues in the ontology of material things. If composition is universal--if any material things whatever make up something bigger--then we are temporal parts of organisms. If things never compose anything bigger, so that there are only mereological simples, then we too are simples--perhaps the immaterial substances of Descartes--or else we do not exist at all (a view Olson takes very seriously). The intermediate view that some things compose bigger things and others do not leads almost inevitably to the conclusion that we are organisms. So we can discover what we are by working out when composition occurs. (shrink)

On an intellectualist approach to belief, the intellectual endorsement of a proposition (such as “The working poor deserve as much respect as the handsomely paid”) is sufficient or nearly sufficient for believing it. On a pragmatic approach to belief, intellectual endorsement is not enough. Belief is behaviorally demanding. To really, fully believe, you must also “walk the walk.” This chapter argues that the pragmatic approach is preferable on pragmatic grounds: It rightly directs our attention to what matters most in thinking (...) about belief. (shrink)

Once again available in paperback, Plato is the first half of Eric Voegelin's Plato and Aristotle, the third volume of his five-volume Order and History, which ...

The view that we are human animals, " animalism ", is deeply unpopular. This paper explains what that claim says and why it is so contentious. It then argues that those who deny it face an awkward choice. They must either deny that there are any human animals, deny that human animals can think, or deny that we are the thinking things located where we are.

In this article I examine several related views expressed by Robin Hendry concerning molecular structure, emergence and chemical bonding. There is a long-standing problem in the philosophy of chemistry arising from the fact that molecular structure cannot be strictly derived from quantum mechanics. Two or more compounds which share a molecular formula, but which differ with respect to their structures, have identical Hamiltonian operators within the quantum mechanical formalism. As a consequence, the properties of all such isomers yield precisely the (...) same calculated quantities such as their energies, dipole moments etc. The only means through which the difference between the isomers can be recovered is to build their structures into the quantum mechanical calculations, something that is carried out by the application of the Born-Oppenheimer approximation. Consequently, it has been argued by many authors that molecular structure is written in ‘by hand’ rather than derived. Robin Hendry is one such author, but he goes a great deal further by proposing that this situation implies the existence of emergence and downward causation. In the current article I argue that there are alternative explanations which render emergence and downward causation redundant. Such an alternative lies in the notion of quantum decoherence and the appeal to work in the foundations of physics, which posits that the various isomers exist as a superposition until their wavefunctions are collapsed either by observation or by interacting with their environment. Hendry also alludes to a debate among chemists as to whether chemical bonds are real or not, in the sense of directional connections between two or more nuclei in any given molecule. I reject this view and propose that the structural and energetic views of chemical bonding, that have been discussed by some philosophers of chemistry including Hendry, do not refer to any essential ontological differences. I agree that chemists view bonding in a more realistic fashion and may consider bonds to be in some senses real, while physicists may consider bonding in more abstract energetic terms. However, I do not believe that such differences in scientific practice and attitudes should be considered to offer a window as to the ontological status of bonding or whether bonding is real. Finally, I discuss the kinetic energy school of chemical bonding which would seem to challenge any notion of bonds as directional entities, since bonding is no longer regarded as being primarily due to the build-up of electron density between nuclei. (shrink)

How diverse is philosophy? In this paper we explore recent data on the racial, ethnic, and gender diversity of philosophy students and faculty in the United States. We have found that women are underrepresented in philosophy at all levels from first-year intention to major through senior faculty. The past four years have seen an increase in the percentage of women philosophy majors at the undergraduate level, but it remains to be seen if this recent increase in the percentage of women (...) will eventually also show at more advanced stages. Temporal trends since 2000 also show substantial increases in the racial and ethnic diversity of philosophy majors at all levels of education from first-year undergraduate through PhD, with substantial declines in the percentage of non-Hispanic White philosophy majors and substantial increases in all other commonly measured racial/ethnic groups except for Native American / Alaska Native. Despite generally increasing diversity, people who identify as Hispanic (any race), or non-Hispanic Native American, Alaska Native, or Black remain substantially underrepresented in philosophy at all levels compared to their presence in the U.S. population, and in some cases also as compared to other majors. (shrink)

One big question in biology is what life is, but another is how life divides into living things. This is the problem of biological individuality. Proposed statements of the problem have been vague and incomplete. And proposed theories of biological individuality are not detailed enough to solve the problem even if they are correct. The root of these troubles is that their authors have not recognized the metaphysical claims presupposed in their statement of the problem. Making these claims explicit will (...) enable us to see better what the problem is and what form a solution to it would need to have. (shrink)

Can large language models produce expert‐quality philosophical texts? To investigate this, we fine‐tuned GPT‐3 with the works of philosopher Daniel Dennett. To evaluate the model, we asked the real Dennett 10 philosophical questions and then posed the same questions to the language model, collecting four responses for each question without cherry‐picking. Experts on Dennett's work succeeded at distinguishing the Dennett‐generated and machine‐generated answers above chance but substantially short of our expectations. Philosophy blog readers performed similarly to the experts, while ordinary (...) research participants were near chance distinguishing GPT‐3's responses from those of an “actual human philosopher”. (shrink)

A core commitment of Bob Hale and Crispin Wright’s neologicism is their invocation of Frege’s Constraint—roughly, the requirement that the core empirical applications for a class of numbers be “built directly into” their formal characterization. According to these neologicists, if legitimate, Frege’s Constraint adjudicates in favor of their preferred foundation—Hume’s Principle—and against alternatives, such as the Dedekind–Peano axioms. In this paper, we consider a recent argument for legitimating Frege’s Constraint due to Hale, according to which the primary empirical application of (...) the naturals is transitive counting, or answering ‘how many’-questions using numerals. We make two claims regarding Hale’s argument. First, it fails to legitimate Frege’s Constraint in virtue of resting on unsupported and highly contentious assumptions. Secondly, even if sound, Hale’s argument would vindicate a version of Frege’s Constraint which fails to adjudicate in favor of Hume’s Principle over alternative characterizations of the naturals. (shrink)

We present evidence that mainstream Anglophone philosophy is insular in the sense that participants in this academic tradition tend mostly to cite or interact with other participants in this academic tradition, while having little academic interaction with philosophers writing in other languages. Among our evidence: In a sample of articles from elite Anglophone philosophy journals, 97% of citations are citations of work originally written in English; 96% of members of editorial boards of elite Anglophone philosophy journals are housed in majority-Anglophone (...) countries; and only one of the 100 most-cited recent authors in the Stanford Encyclopedia of Philosophy spent most of his career in non-Anglophone countries writing primarily in a language other than English. In contrast, philosophy articles published in elite Chinese-language and Spanish-language journals cite from a range of linguistic traditions, as do non-English-language articles in a convenience sample of established European-language journals. We also find evidence that work in English has more influence on work in other languages than vice versa and that when non-Anglophone philosophers cite recent work outside of their own linguistic tradition it tends to be work in English. (shrink)

Philosophers tend to be pretty impressed by human self-knowledge. Descartes (1641/1984) thought our knowledge of our own stream of experience was the secure and indubitable foundation upon which to build our knowledge of the rest of the world. Hume – who was capable of being skeptical about almost anything – said that the only existences we can be certain of are our own sensory and imagistic experiences (1739/1978, p. 212). Perhaps the most prominent writer on self-knowledge in contemporary philosophy is (...) Sydney Shoemaker. The central aim of much of his work has been to show that certain sorts of error are impossible (1963, 1988, 1994). David Chalmers has likewise attempted to show that, for a suitably constrained class of beliefs about one’s own consciousness, error is impossible (2003, sec. 4.1). Even philosophers most of the community thinks of as pessimistic about self-knowledge of consciousness seem to me, really, to be fairly optimistic. Paul Churchland, famous for his disdain of ordinary people’s knowledge about the mind, compares the accuracy of introspection to the accuracy of sense perception – pretty good, presumably, about medium-sized, nearby matters (1985, 1988). Dan Dennett, often cited as a pessimist about introspective report, actually says that we can come close to infallibility when charitably interpreted (2002). The above references concern knowledge of the stream of conscious experience, but philosophers have also tended to be impressed with our self-knowledge of our attitudes, such as our beliefs and desires. Consider this: Although I can be wrong about its being sunny outside, I can’t in the same way be wrong, it seems, about the fact that I think it’s sunny outside. Some.. (shrink)

The advanced division of cognitive labor generates a set of challenges and opportunities for professional philosophers. In this paper, I re-characterize the nature of synthetic philosophy in light of these challenges and opportunities. In part 1, I’ll remind you of the centrality of the division of labor to Plato’s Republic, and why this is especially salient in his banishment of the poets from his Kallipolis. I’ll then focus on the significance of an easily overlooked albeit rather significant character, Damon, mentioned (...) in that dialogue. I’ll argue that if we take the relationship between Socrates and Damon seriously, we’ll notice that in modeling imperfect polities, Plato inscribes Socrates within the advanced division of cognitive labor who defers to Damon as an expert on a key feature of the art of government. In fact, I’ll argue that in Republic, Plato offers us at least two ways to conceptualize philosophy’s relationship to the sciences, and that he alerts us to the social significance of this. In part 2, I’ll re-introduce my conceptualization of synthetic philosophy and restate it. Back in 2019 I published a short paper on it that went viral and was immediately used by others. Reflection on their use instructed me about an ambiguity in my position. Building on the material in parts 1-2, in part 3, I’ll contrast my account with a number of ways that Philip Kitcher has conceptualized synthetic philosophy in order to make more precise the version promoted here. (shrink)

Religious naturalists say all divine or sacred things are natural. A unifying framework is presented for religious naturalism. Nature has five religiously significant levels of organization. These are nature as a whole, the universe, solar system, earth, and body. Each level involves power, cyclicality, complexity, and evolution. These levels take their religious contents from the Zygon group, the World Pantheist Movement, the New Atheists, the New Stoics, and the Burners. Religious naturalists have also taken ideas from the Wicca, the Green (...) Sisters, and the Evolutionary Christians. Rituals can be performed at each level. Linkages between all complex things and the cycles of nature entail a positive soteriology. No gods are involved in this religious naturalism. (shrink)

Trust me: my chair isn't big enough for two. You may doubt that every rational, conscious being is a person; perhaps there are beings that mistakenly believe themselves to be people. If so, read ‘rational, conscious being’ or the like for 'person'.

This book brings together a collection of essays written by scholars inspired by Eugene Gendlin's work, particularly those interested in thinking with and beyond Gendlin for the sake of a global community facing significant crises. The contributors take inspiration from Gendlin's philosophy of the implicit, and his theoretical approach to psychology. The essays engage with Gendlin's ideas for our era, including critiques and corrections as well as extrapolations of his work. Gendlin himself worried that knowing about a problem is too (...) often conflated with actions that might lead to change; the essays in this book point to a form of understanding that is activated, an embodied and immediate way of thinking about today's problems. Throughout the volume, the contributors creatively engage with Gendlin's work and its applicability to the complex, pressing crises of our time: the Covid-19 pandemic, environmental/climate issues, racism, sexism, economic inequality, and other factors threatening human persons and communities. Gendlin's theoretical approach to psychology is naturally interdisciplinary, making this book an essential read for anyone interested in moving to the boundaries where psychology meets philosophy, theology, art, environmental studies, science, and technology, and much more. (shrink)

The prosaic content of these sayings is that events change from future to present and from present to past. Your next birthday is in the future, but with the passage of time it draws nearer and nearer until it is present. 24 hours later it will be in the past, and then lapse forever deeper into history. And things get older: even if they don’t wear out or lose their hair or change in any other way, their chronological age is (...) always increasing. These changes are universal and inescapable: no event could ever fail to be first future, then present, then past, and no persisting thing can avoid growing older. We call this process time’s passage. (shrink)

Whether firms can be said to be moral agents and to have the capacity for moral responsibility has significant practical consequences. In most legal systems in the world, business firms are recognized as persons with the ability to own property, to maintain and defend lawsuits, and to self-organize governance structures. To recognize that these business persons can also act morally or immorally as organizations, however, would justify the imposition of other legal constraints and normative expectations on organizations. In the criminal (...) law, for example, the idea that an organized firm may itself have criminal culpability is accepted in many countries (such as the United States) but rejected in others (such as Germany). This book collects new contributions by leading business scholars in business ethics, philosophy, and related disciplines to extend our understanding of the moral responsibility of firms. (shrink)

In this collection of new and previously published essays, noted philosopher Eric Schliesser offers new interpretations of the signifance of Isaac Newton's metaphysics on his physics and the subsequent development of philosophy more broadly. In particular, he explores the rich resonances between Newton's and Spinoza's metaphysics. The volume includes a substantive introduction, new chapters on Newton's modal metaphysics and his theology, and two postscripts in whichSchliesser responds to some of his most important critics, including Katherine Brading, Andrew Janiak, Hylarie (...) Kochiras, Steffen Ducheyne, and Adwait Parker. The collection provides new and varied analyses on familiar focuses of Newton's work, adding important perspectives to the recent revival ofinterest in Spinoza's metaphysics. (shrink)

A chronological approach that examines the progression of Levinas's deliberations on time over six decades, thus providing new insights about aspects of Levinasian thought that have consistently troubled readers, including the differences between Levinas's early and later writings, his controversial invocation of the feminine, and the blurry line between philosophy and religion in his work"--Provided by publisher.

With The Perils of Global Legalism, Eric A. Posner explains that such views demonstrate a dangerously naive tendency toward legalism—an idealistic belief that ...

The idea that there is incommensurability in science has been controversial since its popularization by Thomas Kuhn and Paul Feyerabend. While incommensurability in science does have significant implications for understanding science and its development, much of the controversy about incommensurability appears to be at least in part due to a lack of clarity about exactly what is being claimed, what that claim implies, and how the claim is justified. This can easily be seen in recent literature, which has continued to (...) struggle to delineate a coherent account of incommensurability in science, with some opponents attempting to undercut its legitimacy entirely, and others attempting to accept it in some weakened form, so as to downplay its significance for our understanding of science. For this reason, a clear, precise and unambiguous statement of incommensurability, its causes, consequences and implications may help to demystify something that has proven to be especially difficult to pin down. The remainder of the paper attempts to explain much of the confusion surrounding incommensurability on the basis of metaincommensurability, in an attempt to expose the exact nature of the relationship between incommensurability and scientific realism more clearly. (shrink)

"Jazz, the wound" : negative identity, culture, and the shadow of race -- America, or the stranger -- Negative identities of the subject in wartime America -- Critical theory goes to war : the critique of positive identity and positive science -- Negative modeling : objectivity, normativity, and the refusal of the universal -- Subject/object and disciplinarity.

Dom Deschamps représente un aspect des Lumières encore souvent méconnu. Il est un penseur tout à fait à part, dans son temps : à la fois défenseur d'une métaphysique rigoureuse et auteur d'un système logique proche du matérialisme. On l'a tantôt présenté comme un "antécédent de l'hégélianisme", tantôt comme un utopiste, tantôt comme un précurseur du socialisme, tantôt encore comme le Maître des maîtres du soupçon. Ce livre cherche d'abord à saisir la pensée de Dom Deschamps dans son contexte historique (...) et dans ses rapports, parfois complexes, à ses contemporains les plus illustres (Diderot, Voltaire, Rousseau, etc.) puis à présenter quelques-uns des éléments clés du système lui-même avant de questionner le destin de l'oeuvre. Dom Deschamps nous invite à un voyage inédit dans la pensée des Lumières françaises. Il nous permet d'orienter notre regard sur cette face cachée et de découvrir une métaphysique matérialiste inédite dans l'histoire de la philosophie. (shrink)

In advocating Bayesian Enlightenment as a solution to Bayesian Fundamentalism, Jones & Love (J&L) rule out a broader critique of rationalist approaches to cognition. However, Bayesian Fundamentalism is merely one example of the more general phenomenon of Rationalist Fundamentalism: the tendency to characterize human judgments as rational and optimal in a post hoc manner, after the empirical data are already known.

From Clouds to Corsair: Kierkegaard, Aristophanes, and Socrates -- The pure fool and the knight of faith: Wolfram's Parzival and the stages of existence -- From romantic aesthete to Christian analogue: Don Quixote's sallies in Kierkegaard's authorship -- Saying not quite "everything just as it is": Shakespeare on life's way -- "Sorrow's changeling": irony, humor, and laughter in Kierkegaard and Carlyle.

Eric Voegelin (1901-1985) was one of the most original philosophers of our time, working throughout his life to account for the endemic political violence of the twentieth century, in an effort variously referred to as a philosophy of politics, history, or consciousness. Drawing from the University of Missouri Press's thirty-four-volume edition of his collected works, Charles Embry and Glenn Hughes have assembled a selection of Voegelin's representative writings, satisfying the need for a single volume that can serve as a (...) general introduction to his philosophy. The selection demonstrates the range and creativity of Voegelin's thought, including writings that show his thinking as it developed historically in his long search for order in human society. (shrink)

We review and present a new meta‐analysis of research suggesting that ethicists in the United States appear to behave no morally better overall than do non‐ethicist professors. Measures include: returning library books, peer evaluation of overall moral behavior, voting participation, courteous and discourteous behavior at conferences, replying to student emails, paying conference registration fees and disciplinary society dues, staying in touch with one's mother, charitable giving, organ and blood donation, vegetarianism, and honesty in responding to survey questions. One multi‐measure study (...) found ethicists tending to embrace more stringent moral views, especially about meat eating and charitable donation. The same multi‐measure study found ethicists and other professors to show similarly small‐to‐medium correlations between their expressed normative attitudes and their self‐reported or directly measured behavior. (shrink)

Although this article uses Obergefell v Hodges (2015) as its frame, it aims to bring out some distinctive features of Justice Kennedy’s jurisprudence of dignity more broadly. There are two reasons why such an investigation is important. The first is important to those interested in the legal case. Indeed, in Dobbs v Jackson Women’s Health (2022), the Court now argues that the relevant ‘test’ for determining whether a right is protected under the Due Process Clause is whether the right is (...) found to be ‘deeply rooted’ in the nation’s history and tradition. This article aims to critique this decision, as well as originalist approaches to constitutional interpretation more broadly, and seeks to resurrect and reconstruct Kennedy’s jurisprudence of dignity that has undergirded (sometimes quietly) the expansion of civil rights protections to the LGBTQ+ community. The second reason this investigation is important is of interest to philosophers and legal historians. Dignity is a notoriously elusive concept, and much ink has been spilt trying to sort out the precise nature of its content and its boundaries. This article brings together the many (seemingly disparate) uses of dignity found across cases involving gay rights, abortion, and foreign sovereign immunity, and argues Kennedy effectively weaves these uses together in ways that may sharpen our understanding of dignity in both the philosophical and legal literatures. (shrink)