Mathematical models of tumour invasion appear as interesting tools for connecting the information extracted from medical imaging techniques and the large amount of data collected at the cellular and molecular levels. Most of the recent studies have used stochastic models of cell translocation for the comparison of computer simulations with histological solid tumour sections in order to discriminate and characterise expansive growth and active cell movements during host tissue invasion. This paper describes how a deterministic approach based on reaction-diffusion models (...) and their generalisation in the mechano-chemical framework developed in the study of biological morphogenesis can be an alternative for analysing tumour morphological patterns. We support these considerations by reviewing two studies. In the first example, successful comparison of simulated brain tumour growth with a time sequence of computerised tomography (CT) scans leads to a quantification of the clinical parameters describing the invasion process and the therapy. The second example considers minimal hypotheses relating cell motility and cell traction forces. Using this model, we can simulate the bifurcation from an homogeneous distribution of cells at the tumour surface toward a nonhomogeneous density pattern which could characterise a pre-invasive stage at the tumour-host tissue interface. (shrink)

How environmental mechanical forces affect cellular functions is a central problem in cell biology. Theoretical models of cellular biomechanics provide relevant tools for understanding how the contributions of deformable intracellular components and specific adhesion conditions at the cell interface are integrated for determining the overall balance of mechanical forces within the cell. We investigate here the spatial distributions of intracellular stresses when adherent cells are probed by magnetic twisting cytometry. The influence of the cell nucleus stiffness on the simulated nonlinear (...) torque-bead rotation response is analyzed by considering a finite element multi-component cell model in which the cell and its nucleus are considered as different hyperelastic materials. We additionally take into account the mechanical properties of the basal cell cortex, which can be affected by the interaction of the basal cell membrane with the extracellular substrate. In agreement with data obtained on epithelial cells, the simulated behaviour of the cell model relates the hyperelastic response observed at the entire cell scale to the distribution of stresses and strains within the nucleus and the cytoskeleton, up to cell adhesion areas. These results, which indicate how mechanical forces are transmitted at distant points through the cytoskeleton, are compared to recent data imaging the highly localized distribution of intracellular stresses. (shrink)

Computational cell models appear as necessary tools for handling the complexity of intracellular cell dynamics, especially calcium dynamics. However, while oscillating intracellular calcium oscillations are well documented and modelled, a simple enough virtual cell taking into account the mechano-chemical coupling between calcium oscillations and cell mechanical properties is still lacking. Considering the spontaneous periodic contraction of isolated cardiac myocytes, we propose here a virtual cardiac cell model in which the cellular contraction is modelled using an hyperelastic description of the cell (...) mechanical behaviour. According to the experimental data, the oscillating cytosolic calcium concentrations trigger the spatio-temporal variation of the anisotropic intracellular stresses. The finite element simulations of the virtual cell deformations are compared to the self-sustained contractions of isolated rat cardiomyocytes recorded by time-lapse video-microscopy. (shrink)

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division (...) and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology. (shrink)

While the control of cell migration by biochemical and biophysical factors is largely documented, a precise quantification of cell migration parameters in different experimental contexts is still questionable. Indeed, these phenomenological parameters can be evaluated from data obtained either at the cell population level or at the individual cell level. However, the range within which both characterizations of cell migration are equivalent remains unclear. We analyse here to which extent both sources of data could be integrated within a unified description (...) of cell migration by considering the motility of the endothelial cell line EAhy926. Using time-lapse video-microscopy and associated analysis of digital image time series, we quantified EAhy926 random motility coefficient, migration speed and trajectory persistence time in two different migration assays: the in vitro wound healing assay, and the cell-populated agarose drop assay. In order to analyse the agreement between independent quantifications of cell motility based either on individual cell analysis or cell population dynamic analysis, a theoretical multi-agents cellular model was developed and discussed as a possible theoretical framework able to unify these multi-scale data. Model simulations especially reveal the potential bias induced by cell proliferation and cell-cell adhesion when cell migration parameters are estimated from the extensively used in vitro wound healing assay. (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)

The aim of this paper is to shed light on and develop what I call a phenomenological conception of experiential justification. According to this phenomenological conception, certain experiences gain their justificatory force from their distinctive phenomenology. Such an approach closely connects epistemology and philosophy of mind and has recently been proposed by several authors, most notably by Elijah Chudnoff, Ole Koksvik, and James Pryor. At the present time, however, there is no work that contrasts these different versions of PCEJ. This (...) paper not only bridges this gap, but also reveals problems in current versions of PCEJ. Consequently, I argue for a new version of PCEJ that focuses on what is given within experience and not on how what is given pushes me towards believing something. (shrink)

The aim of this paper is twofold. The first is an interpretative one as I wish to provide a detailed account of Husserl’s conception of experiential justification. Here Ideas I and Introduction to Logic and Theory of Knowledge: Lectures 1906/07 will be my main resources. My second aim is to demonstrate the currency and relevance of Husserl’s conception. This means two things: Firstly, I will show that in current debates in analytic epistemology there is a movement sharing with Husserl the (...) basic idea that certain experiences gain their justificatory force simply from their distinctive phenomenal character. Secondly, I shall reveal the benefits of Husserl’s specific version of this view. Thus, one of my aims is to show that debates in current analytic epistemology could profit from adopting certain Husserlian elements. More precisely, I will defend Husserl’s claim that perceptual experiences are justifiers due to their self-giving phenomenal character as opposed to the currently popular view that it is the phenomenology of pushiness that makes them justifiers. To put it differently, what matters is what is originally given within experience and not how you feel about what is given. (shrink)

The temporal behaviour of the nonlinear compartmental model we have developed for rat calcium metabolism is discussed with respect to the theoretical properties of the self-oscillating autocatalytic subunit around which the model is constructed. Depending on the approximations made, this subunit is described by a minimal two-variable model, SU2, or by a three-variable one, SU3. The diversity of the theoretical dynamic behaviours possible with SU2 is greatly increased with SU3. But the identification of SU3 parameter values in three different experimental (...) situations reveals that biological constraints efficiently preserve a simple circadian rhythm for bone metabolism. This analysis indicates the significant contribution of the available bone crystal pool to the dynamic organization of this tissue, and hence to extracellular calcium homeostasis. (shrink)

The organization of the complex mixed-mode oscillations generated, in a three-dimensional variable space, by an autocatalytic process formalized as a cubic monomial is analyzed. The generation of the temporal patterns is elucidated by complementary approaches dealing with the three-variable differential continuous system itself and with successive discrete applications modelling its first return map. The extent to which the underlying bifurcation structures could constitute a fingerprint of autocatalytic processes is discussed in connection with the modelling of biological systems.

In his influential paper “Grasping the Third Realm,” John Bengson raises the question of how we can non-accidentally grasp abstract facts. What distinguishes successful intuition from hallucinatory intuition? Bengson answers his “non-accidental relation question” by arguing for a constitutive relationship: The intuited object is a literal constituent of the respective intuition. Now, the problem my contribution centers around is that Bengson’s answer cannot be the end of the story. This is because, as Bar Luzon and Preston Werner have recently pointed (...) out, this answer leads to the follow-up question of why certain intuitional experiences are constituted by the facts, but others are not. My objective is to answer this question by specifying precisely what is epistemically defective about intellectual hallucinations. My result is that, in stark contrast to perception, intellectual hallucinations are epistemically defective in the sense that something is overlooked. In successful intuition, by contrast, all relevant possibilities/scenarios are considered/imagined. This has crucial epistemological implications. In particular, I argue that intuitions exhibiting a certain phenomenology cannot fail to successfully grasp abstract facts. I call this the non-accidental correctness thesis, which constitutes the main thesis of this paper. (shrink)

In current debates, many philosophers of science have sympathies for the project of introducing a new approach to the scientific realism debate that forges a middle way between traditional forms of scientific realism and anti-realism. One promising approach is perspectivism. Although different proponents of perspectivism differ in their respective characterizations of perspectivism, the common idea is that scientific knowledge is necessarily partial and incomplete. Perspectivism is a new position in current debates but it does have its forerunners. Figures that are (...) typically mentioned in this context include Dewey, Feyerabend, Leibniz, Kant, Kuhn, and Putnam. Interestingly, to my knowledge, there exists no work that discusses similarities to the phenomenological tradition. This is surprising because here one can find systematically similar ideas and even a very similar terminology. It is startling because early modern physics was noticeably influenced by phenomenological ideas. And it is unfortunate because the analysis of perspectival approaches in the phenomenological tradition can help us to achieve a more nuanced understanding of different forms of perspectivism. The main objective of this paper is to show that in the phenomenological tradition one finds a well-elaborated philosophy of science that shares important similarities with current versions of perspectivism. Engaging with the phenomenological tradition is also of systematic value since it helps us to gain a better understanding of the distinctive claims of perspectivism and to distinguish various grades of perspectivism. (shrink)

Solar radiation management (SRM) may help to reduce the negative outcomes of climate change by minimising or reversing global warming. However, many express the worry that SRM may pose a moral hazard, i.e., that information about SRM may lead to a reduction in climate change mitigation efforts. In this paper, we report a large-scale preregistered, money-incentivised, online experiment with a representative US sample (N = 2284). We compare actual behaviour (donations to climate change charities and clicks on climate change petition (...) links) as well as stated preferences (support for a carbon tax and self-reported intentions to reduce emissions) between participants who receive information about SRM with two control groups (a salience control that includes information about climate change generally and a content control that includes information about a different topic). Behavioural choices are made with an earned real-money endowment, and stated preference responses are incentivised via the Bayesian Truth Serum. We fail to find a significant impact of receiving information about SRM and, based on equivalence tests, we provide evidence in favour of the absence of a meaningfully large effect. Our results thus provide evidence for the claim that there is no detectable moral hazard with respect to SRM. [Open access]. (shrink)

A collection of essays investigating key historical and scientific questions relating to the concept of natural purpose in Kant's philosophy of biology.

Quelle politique peut-on faire quand on est un idiot? Loin d'être saugrenue, c'est bien la question qu'on est conduit à se poser inévitablement en lisant l'oeuvre de Gilles Deleuze. L'"idiot" joue, en effet, un rôle incontournable et essentiel dans la philosophie de Deleuze. Il est le personnage conceptuel qui fait tenir cette philosophie dans sa consistance propre. Il se situe à la charnière de l'image de la pensée que le philosophe invoque et suppose plus ou moins implicitement et de la (...) création de concepts qu'il produit explicitement. Aussi, faire de la philosophie, tout comme agir et penser politiquement, c'est toujours une manière de faire l'idiot. Les conséquences de cette approche sont capitales, du fait des questions posées à la réflexion politique classique centrée sur le Droit et l'Etat, du fait aussi des problématiques qui se voient invalidées dans ce champ. La place qui revient au contrôle et au bio-pouvoir, aux zones d'indétermination et aux espaces lisses, permet de prendre une saine distance vis-à-vis de la politique "majoritaire" et de faire apparaître, comme déjà de vieux clichés, bon nombre de thèmes et de concepts revendiqués par les organisations alternatives, mondialistes et subversives récentes. C'est une tout autre idée de la politique, centrée sur les devenirs, que nous invite à méditer la politique deleuzienne de l'idiot. Elle nous ouvre à d'autres espérances, nouvelles, en lien avec un "peuple absent" qui naîtrait avec chaque devenir. (shrink)

This chapter contains section titled: I The Extended Auction II Working in the Peep Show, Flirting in the Square III Insurance Behind a Veil of Ignorance IV Dworkin's Hybrid Scheme V Four Objections to Dworkin VI Ackerman Generalized VII Not Enough Redistribution? VIII Too Much Redistribution? Acknowledgement.

Animal research suggests that central serotonergic neurons are involved in behavioral suppression, particularly anxiety-related inhibition. The hypothesis linking decreased serotonin transmission to reduced anxiety as the mechanism in the anxiolytic activity of benzodiazepines conflicts with most clinical observations. Serotonin antagonists show no marked capacity to alleviate anxiety. On the other hand, clinical signs of reduced serotonergic transmission (low 5-HIAA levels in the cerebrospinal fluid) are frequently associated with aggressiveness, suicide attempts, and increased anxiety. The target article attempts to reconcile such (...) human and animal findings by investigating whether anxiety reduction or increased impulsivity is more Likely to account for animal behavioral changes associated with decreased serotonergic transmission. The effects of manipulating central serotonin in experimental anxiety paradigms in animals (punishment, extinction, novelty) are reviewed and compared with the effects of antianxiety drugs. Anxiety seems neither necessary nor sufficient to induce control by serotonergic neurons on behavior. Further evidence suggests that behavioral effects of anxiolytics thought to be mediated by decreases in anxiety are not caused by the ability of these drugs to reduce serotonin transmission. Blockade of serotonin transmission, especially at the level of the substantia nigra, results in a shift of behavior toward facilitation of responding. This behavioral shift is particularly marked when there is competition between acting and restraining response tendencies and when obstacles prevent the immediate attainment of an anticipated reward. It is proposed that serotonergic neurons are involved not only in behavioral arousal but also in enabling the organism to arrange or tolerate delay before acting. Decreases in serotonin transmission seem to be associated with the increased performance of behaviors that are usually suppressed, though not necessarily because of the alleviation of anxiety, which might contribute to the suppression. (shrink)

The relevance of nonlinear dynamics to calcium metabolism led us to reevaluate the role of Ca-regulating hormones in Ca homeostasis. We suggest that, firstly, the main Ca metabolic functions in rat-bone and gut - are organized as dynamic entities able to generate various temporal expressions, including self-oscillating patterns and, secondly, Ca homeostasis results from interaction between both metabolic and hormonal oscillators. Following this schema, a major role for the hormonal system, with its circadian pattern, could be to act directly on (...) metabolic functions or indirectly through feeding behaviour, in order to optimize, coordinate and synchronize the Ca fluxes at ECF level. (shrink)

The once-lost introduction to the philosophy of science by Philipp Frank (1884-1966), a leading member of the Vienna circle of philosophers and biographer of Albert Einstein.

The conception of social justice presented and defended in Philippe Van Parijs, "Real Freedom for All" entails, among other implication, the justification of an unconditional basic income. It was the subject of seven critical comments that forms issue 22 and part of 23 of ANALYSE & KRITIK. In this article, Van Parijs offers a comprehensive reply.

An introduction to semantics for the general reader. How things mean, from animal communication to music.

This chapter introduces time travel into the Star Wars lore. Time travel stories in which the past is changed are in danger of being inconsistent or plagued by paradoxes. In famous time travel stories such as Back to the Future, the protagonist travels to the past, changes the past, and then returns to a present quite different from the one they left. In contemporary philosophy of time, there are three main approaches to this question: presentism, eternalism, and the growing block (...) universe. Time travel works by entering a place, the World Between Worlds, that connects different points in time and space. In terms of modern physics, the portals in the World Between Worlds may be understood as traversable wormholes. The nature of time and the possibility of time travel have attracted and captivated humanity for centuries. (shrink)

Philipp Mayring und Norbert Rath greifen zentrale Fragen der heutigen Zeit auf: Was ist Glück? Woher kommt Glück? Wie kann man Glück erreichen? Zunächst geht es um klassische philosophische Ansätze – was verstehen antike Denker wie Demokrit, Platon, Aristoteles und Epikur sowie neuzeitliche Philosophen wie Montaigne, Kant, Hegel, Nietzsche, Freud und Adorno darunter? Es zeigt sich die Historizität der Glückskonzepte und die Notwendigkeit einer Kritik am »falschen« Glück. Psychologische Konzepte von Glück sind ebenso schillernd. Sie untersuchen empirisch, wie subjektive Glücksgefühle (...) zustande kommen, welche emotionalen, kognitiven und handlungsbezogenen Prozesse ihnen zu Grunde liegen und in welchen Situationen sich Menschen glücklich fühlen. Auch hier erscheint ein kritischer Standpunkt notwendig: Kritik an unterschiedlichen Glücksdefinitionen, Kritik an Erhebungsinstrumenten und Kritik an der Instrumentalisierung und Kommerzialisierung von Forschungsergebnissen. Gerade im Blick auf eine neuerdings weit verbreitete Positive Psychologie besteht ein Ideologieverdacht: Könnte es sich hier um kaum einlösbare Versprechungen einer affirmativen psychologischen Glücksforschung handeln? Philipp Mayring und Norbert Rath gehen diesen Fragen im Dialog zwischen Philosophie und Psychologie nach. Trotz der unterschiedlichen Herangehensweisen und Perspektiven der beiden Autoren zeigen sich erstaunliche Übereinstimmungen hinsichtlich einer kritischen Theorie des Glücks. (shrink)

Peut-on définir un "sens" musical? Quelle est la part d'intuition, de spontanéité, et celle de la technique, des règles, des systèmes dans la création? Pionnier de la musique électroacoustique en temps réel, Philippe Manoury nous fait entrer au coeur du processus de composition, montrant par exemple comment faire interagir les techniques numériques et les instruments acoustiques (y compris la voix) pour créer de nouvelles formes musicales et interroger sans cesse la matière sonore elle-même."--Page 4 of cover.

Die vorliegende Studie ist die erste umfassende Darstellung, die Kierkegaards Verfahren einer indirekten Mitteilung als hermeneutischen Schl ssel zu seinem Gesamtwerk entfaltet. Erkenntnisleitend ist das philosophische Interesse, die indirekte Mitteilung als Kierkegaards denkerische Methode und als das bestimmende Strukturprinzip seiner Existenzphilosophie zu begreifen. Indirekte Mitteilung meint nicht blo eine u erliche Form maieutischer und existenzieller Kommunikation, sie ist vielmehr zugleich eine Theorie ber die Grenze von Sprache und Begriff. Zudem ist die perspektivisch gebrochene, experimentalphilosophische Methode ein Gegenentwurf zur geschlossenen Form (...) des Systems. Hierin zeigt sich Kierkegaards geschichtliche Zwischenstellung in der Umbruchskonstellation von Idealismus und Moderne: Er st t sich im Ganzen vom Systemdenken Schellings und Hegels ab und weist voraus auf die Experimentalphilosophie Nietzsches und das Differenzdenken Derridas. Die Studie ist in dreierlei Hinsicht strukturiert: Systematisch wird die indirekte Methode als ein gegen sich selbst arbeitendes, prinzipiell unabgeschlossenes Verfahren bestimmt; geschichtlich wird sie vor dem Hintergrund der Tradition der Ironie und weiterer paradoxaler Begriffskonstellationen entfaltet; werkgeschichtlich-exegetisch werden Kierkegaards weit verzweigte Reflexionen ber den Begriff der indirekten Methode rekonstruiert, ihre Praxis und Durchf hrung anhand ausgew hlter Werke exemplarisch herausgearbeitet. (shrink)

This is the outline : I - Quelques étapes aux avancées significatives II - La pensée chrétienne et le hasard d’ignorance III - De quelques difficultés de raisonner sur le probable IV - Téléologie et évolutionnisme V - Où est l’« étage » qui permette de parler d’indépendance ? VI. Qu’y a-t-il à la base de nos concepts d’ordre ? VII - Quelle place pour le hasard ? VIII. Le hasard appréhendé de dos ?

Cet ouvrage s'intéresse aux lieux laissés vacants, avec le projet de débusquer le sens caché que recouvre leur mise à l'écart du jeu social. Il aborde leur "renaturation", qui leur confère une valeur mémorielle, ainsi que leur réaménagement ou leur restauration. Autrement dit, il s'essaie à décrypter le jeu subtil de l'oubli et de la mémoire qui s'y joue, entre enfouissement et résurgence. Parmi ces lieux, l'auteur examine particulièrement les friches et étudie celles-ci sous leurs multiples facettes : en référence (...) à leur statut, qu'on les qualifie de rurales, urbaines, industrielles, militaires, touristiques, même si le plus souvent elles sont tout cela à la fois ; en rapport à leur durée, variable, car il en est d'immémoriales mais aussi d'éphémères, d'involontaires et de circonstanciées ; et au regard de leur finalité, au moment où elles sont réappropriées par des activités patrimoniales, touristiques... L'idée ici soutenue serait que les espaces délaissés deviennent des lieux de mémoire par le biais de leur réappropriation patrimoniale, dès lors qu'une recherche identitaire s'accommode de leur mise en tourisme. La friche est donc présentée ici comme un fondement de l'illusion mémorielle, une nostalgie du rétro? (shrink)