The progress of the molecular biosciences has been so enormous that a discipline studying how cellular functioning emerges out of the behaviors of their molecular constituents has become reality. Systems biology studies cells as spatiotemporal networks of interacting molecules using an integrative approach of theory , experimental biology , and quantitative network-wide analytical measurement . Its aim is to understand how molecules jointly bring about life. Systems biology is rapidly discovering principles governing the functioning of molecular networks and methods to (...) model and measure them. The application of the conceptual strength of systems sciences such as physics and engineering are opening up new ways of experimentally studying the design and functioning of molecular networks. Typically, in such studies models are used to highlight principles, design experiments, or to act in a predictive mode to specifically modify cellular behavior. In this trend article, theoretical approaches being applied in systems biology will be discussed. A number of books have recently appeared that deal with theoretical aspects of systems biology. In this article they are highlighted to facilitate the communication of systems biology to a broader audience. (shrink)

Microbial systems biology has made enormous advances in relating microbial physiology to the underlying biochemistry and molecular biology. By meticulously studying model microorganisms, in particular Escherichia coli and Saccharomyces cerevisiae, increasingly comprehensive computational models predict metabolic fluxes, protein expression, and growth. The modeling rationale is that cells are constrained by a limited pool of resources that they allocate optimally to maximize fitness. As a consequence, the expression of particular proteins is at the expense of others, causing trade‐offs between cellular objectives (...) such as instantaneous growth, stress tolerance, and capacity to adapt to new environments. While current computational models are remarkably predictive for E. coli and S. cerevisiae when grown in laboratory environments, this may not hold for other growth conditions and other microorganisms. In this contribution, we therefore discuss the relationship between the instantaneous growth rate, limited resources, and long‐term fitness. We discuss uses and limitations of current computational models, in particular for rapidly changing and adverse environments, and propose to classify microbial growth strategies based on Grimes's CSR framework. (shrink)

We will show that there is a strong form of emergence in cell biology. Beginning with C.D. Broad’s classic discussion of emergence, we distinguish two conditions sufficient for emergence. Emergence in biology must be compatible with the thought that all explanations of systemic properties are mechanistic explanations and with their sufficiency. Explanations of systemic properties are always in terms of the properties of the parts within the system. Nonetheless, systemic properties can still be emergent. If the properties of the components (...) within the system cannot be predicted, even in principle, from the behavior of the system’s parts within simpler wholes then there also will be systemic properties which cannot be predicted, even in principle, on basis of the behavior of these parts. We show in an explicit case study drawn from molecular cell physiology that biochemical networks display this kind of emergence, even though they deploy only mechanistic explanations. This illustrates emergence and its place in nature. (shrink)

Systems biology is a vigorous and expanding discipline, in many ways a successor to genomics and perhaps unprecendented in its combination of biology with a ...

After more than a century of research on glycolysis, we have detailed descriptions of its molecular organization, but despite this wealth of knowledge, linking the enzyme properties to metabolic pathway behavior remains challenging. These challenges arise from multi‐layered regulation and the context and time dependence of component functions. However, when viewed as a system that functions according to the principles of supply and demand, a simplifying theoretical framework can be applied to study its regulation logic and to assess the coherence (...) of experimental interpretations. These principles are universally applicable, as they emphasize the common metabolic tasks of glycolysis: the provision of free‐energy carriers, and precursors for biosynthesis and stress‐related compounds. Here we will review the regulation of multi‐tasking by glycolysis and consider how an understanding of this central metabolic pathway can be pursued using general principles, rather than focusing on the biochemical details of constituent components. (shrink)

Biochemistry and molecular biology have been focusing on the structural, catalytic, and regulatory proper- ties of individual macromolecules from the perspective of clarifying the mechanisms of metabolism and gene expression. Complete genomes of ‘primitive’ living organisms seem to be substantially larger than necessary for metabolism and gene expression alone. This is in line with the findings of silent phenotypes for supposedly important genes, apparent redundancy of functions, and variegated networks of signal transduction and transcription factors. Here we propose that evolutionary (...) optimization has been much more intensive than to lead to the bare minima necessary for autonomous life. Much more complex organisms prevail. Much of this complexity arises in the nonlinear interactions between cellular macromolecules and in subtle differences between paralogs (isoenzymes). The complexity can only be understood when analyzed quantitatively, for which quantitative experimentation is needed in living systems that are as simple and manipulatable as possible, yet complex in the above sense. We illustrate this for the glutamine synthetase cascade in Escherichia coli. By reviewing recent molecular findings, we show that this cascade is much more complex than necessary for simple regulation of ammonia assimilation. Simulations suggest that the function of this complexity may lie in quasi-intelligent behavior, including conditioning and learning. (shrink)

Mechanistic models in molecular systems biology are generally mathematical models of the action of networks of biochemical reactions, involving metabolism, signal transduction, and/or gene expression. They can be either simulated numerically or analyzed analytically. Systems biology integrates quantitative molecular data acquisition with mathematical models to design new experiments, discriminate between alternative mechanisms and explain the molecular basis of cellular properties. At the heart of this approach are mechanistic models of molecular networks. We focus on the articulation and development of mechanistic (...) models, identifying five constraints which guide the articulation of models in molecular systems biology. These constraints are not independent of one another, with the result that modeling becomes an iterative process. We illustrate the use of these constraints in the modeling of the mechanism for bistability in the lac operon. (shrink)

Investigations into inter-level relations in computer science, biology and psychology call for an *empirical* turn in the philosophy of mind. Rather than concentrate on *a priori* discussions of inter-level relations between 'completed' sciences, a case is made for the actual study of the way inter-level relations grow out of the developing sciences. Thus, philosophical inquiries will be made more relevant to the sciences, and, more importantly, philosophical accounts of inter-level relations will be testable by confronting them with what really happens (...) in science. Hence, close observation of the ever-changing reduction relations in the developing sciences, and revision of philosophical positions based on these empirical observations, may, in the long run, be more conducive to an adequate understanding of inter-level relations than a traditional *a priori* approach. (shrink)

Schets van een samenwerkingsmodel zoals een neuroloog-psychiater, een psycholoog, een pastor en een verpleegkundige praktiseren in een Vlaamse kliniek.

The biological sciences study (bio)complex living systems. Research directed at the mechanistic explanation of the "live" state truly requires a pluralist research program, i.e. BioComplexity research. The program should apply multiple intra-level and inter-level theories and methodologies. We substantiate this thesis with analysis of BioComplexity: metabolic and modular control analysis of metabolic pathways, emergence of oscillations, and the analysis of the functioning of glycolysis.

Cancers often express hundreds of genes otherwise specific to germ cells, the germline/cancer (GC) genes. Here, we present and discuss the hypothesis that activation of a “germline program” promotes cancer cell malignancy. We do so by proposing four hallmark processes of the germline: meiosis, epigenetic plasticity, migration, and metabolic plasticity. Together, these hallmarks enable replicative immortality of germ cells as well as cancer cells. Especially meiotic genes are frequently expressed in cancer, implying that genes unique to meiosis may play a (...) role in oncogenesis. Because GC genes are not expressed in healthy somatic tissues, they form an appealing source of specific treatment targets with limited side effects besides infertility. Although it is still unclear why germ cell specific genes are so abundantly expressed in cancer, from our hypothesis it follows that the germline's reproductive program is intrinsic to cancer development. (shrink)

In this book, Frank Griffel presents the most comprehensive examination to date of the life and thought of this important figure.

In this book, Frank Griffel presents the most comprehensive examination to date of the life and thought of this important figure.

This note is a postscript to Ramsey's 'Truth and Probability'. It replaces that article's psychological reading of subjective probability with a reading of it as a consistency condition on the theory that we act to maximise expected utility.

How could ectogestative technology disrupt gender roles, parenting practices, and concepts such as ‘birth’, ‘body’, or ‘parent’? In this chapter, we situate this emerging technology in the context of the history of reproductive technologies and analyse the potential social and conceptual disruptions to which it could contribute. An ectogestative device, better known as ‘artificial womb’, enables the extra-uterine gestation of a human being, or mammal more generally. It is currently developed with the main goal of improving the survival chances of (...) extremely premature neonates. We argue that the intended use of the technology in neonatal intensive care units, as an alternative to current incubators (’partial-ectogestation’), challenges concepts such as ‘birth’, ‘fetus’, and ‘neonate’, and has several ethico-legal implications. We moreover address a more futuristic scenario where the entire embryological and fetal development could happen within an artificial womb (’full-ectogestation’). Such a scenario reveals the disruption of gender roles, parenting practices, and concepts such as ‘mother’, ‘father’, and ‘parent’. Both full- and partial-ectogestation would have implications for engineering and design, law-making, ethics, and philosophical anthropology. (shrink)

Amsterdam University Press is a leading publisher of academic books, journals and textbooks in the Humanities and Social Sciences. Our aim is to make current research available to scholars, students, innovators, and the general public. AUP stands for scholarly excellence, global presence, and engagement with the international academic community.

Famously Ryle imagined a visitor who has seen the colleges, departments, and libraries of a university but still wonders where the university is. The visitor fails to realize that the university consists of these organizational units. In this paper I ask what exactly the relation is between institutional entities such as universities and the entities they are composed of. I argue that the relation is constitution, and that it can be illuminated in terms of constitutive rules. The understanding of the (...) ontology of institutions that constitutive rules provide, however, is incomplete. In order to capture the practical significance of institutions, I introduce the notion of a status rule. Status rules concern the normative powers of institutions. The status account of institutions defended here is used to solve the problem of freestanding status terms: it turns out to be rather difficult to identify the entities of which statuses such as corporations and electronic money are composed. Unable to solve this problem, Searle concludes that they are created out of thin air. I criticize this claim and argue that these statuses are imposed on persons. (shrink)

How should we react to the contention that there is empirical evidence showing that many judge Gettier cases to be cases of knowledge, contrary to the verdict of most analytical philosophers about these cases? I argue that there is no single answer to this question. The discussion is set inside a view about how to view the role and significance of intuitive responses to some of philosophy's famous thought experiments. One take-home message is that experimental philosophy and conceptual analysis are (...) not as far apart as is often thought. (shrink)

Historicism -- Time -- Interpretation -- Representation -- Reference -- Truth -- Meaning -- Presence -- Experience (I) -- Experience (II) -- Subjectivity -- Politics.

Talkers are recognized more accurately if they are speaking the listeners’ native language rather than an unfamiliar language. This “language familiarity effect” has been shown not to depend upon comprehension and must instead involve language sound patterns. We further examine the level of sound-pattern processing involved, by comparing talker recognition in foreign languages versus two varieties of English, by English speakers of one variety, English speakers of the other variety, and non-native listeners. All listener groups performed better with native than (...) foreign speech, but no effect of language variety appeared: Native listeners discriminated talkers equally well in each, with the native variety never outdoing the other variety, and non-native listeners discriminated talkers equally poorly in each, irrespective of the variety's familiarity. The results suggest that this talker recognition effect rests not on simple familiarity, but on an abstract level of phonological processing. (shrink)

We enter here upon a history of conversational traffic between the respective departments of philosophy and law in the old academy of liberalism, where lawyers hear much from philosophers, yes-and philosophers hear from lawyers, too, in what has fruitfully been a both-ways exchange. Our philosophical protagonist is John Rawls. This book comprises a study of the rise and workings, within the Rawlsian political-liberal philosophy, of the idea of a country's higher-legal constitution as a public platform for the justification of political (...) coercion. A study of Rawls on constitutionalism can help us, I believe, in scoping out and managing a cluster of constitutional lawyers' debates-interminable ones, it seems, in the constitutional-democratic precincts of our times-that I will catalogue soon below. But conversely, I believe, those seeking the best and truest readings of Rawls might have something to learn from the controversies of the lawyers. My approach to Rawls has accordingly been that of a critically leavened (while no doubt broadly sympathetic) exegesis, while with the legal-discursive materials I take more of a diagnostic turn. My hope is that a treatment of these two discourses in relation to each other will prove an aid to both political-philosophical and legal-practical reflection. (shrink)

The present study seeks to lay out the most basic elements of the ontology of classical Aš‘arite theology. In several cases this requires a careful examination of the traditional and the formal lexicography of certain key expressions. The topics primarily treated are: how they understood “Being/ existence” and “being/existent” and essential natures; the systematic exploitation of the equivocities of certain expressions within a general context in which other than words there are no universals proves to be elegant as well as (...) insightful; the basic categories of primary entities: independant beings and nonindependant beings, created and uncreated, the equivocity of “being/existent” as predicated of contingent entities on the one hand and of God and His attributes on the other, and certain problems that arise because of the rigid application of the system's underlying analytic principles. Nous essayons ici de presenter les éléments fondamentaux de l'ontologie de l'aš‘arisme classique. Pour quelques expressions, il a fallu examiner la lexicographie et ordinaire et technique pour bien comprendre leur emploi et leur signification. Les sujets examinés sont: le sens de “Etre/existence” et de “être/existant” et le concept de réalité essentielle; l'emploi nuancé des équivocités de quelques expressions dans un contexte où les seuls universaux sont des mots, emploi qui se révèle philosophiquement élégant; les catégories fondamentales des êtres: êtres indépendants et êtres non-indépendants, soit créés soit incréés, l'équivocité de “être/existant” dit des êtres contingents d'une part, de Dieu et ses attributs d'autre part, et enfin quelques difficultiés qui résultent de l'application rigide des principes analytiques du système. (shrink)

Our intention here is to present the essential character of classical, sunnī kalām within a strictly formal perspective and to set out its basic aspects. It was conceived by the mutakallimīn as a rational, conceptual, and critical science and, although kalām differed in a number of basic concepts and constructs and in its analytic system, the topical organisation of the major compendia parallels that of metaphysics as understood in the contemporary Aristotelian tradition. The debates between kalām and falsafa need to (...) be examined within this context. Kalām, however, is theological in the strict sense of the term and it is as such that its problematic and its procedures are primarily to be understood. Thus seen, the object of kalām is to rationalise the cognitive content presented to Believers in the symbolic language of the koranic revelation. It has, then, four principal tasks, sc, to conceptualise, to order, to explain, and where possible to justify the primary doctrines of the community whose belief is held to be normative. Within this framework the differences that characterise the major schools as such and the various tendencies of individual masters within each school may readily be brought to light. On se propose ici de présenter, d'un point de vue strictement formel, la nature du kālam classique sunnite et d'identifier ses caractéristiques principales. II avait été conçu par les mutakallimin comme une science rationelle, conceptuelle et critique. L'organisation des matières dans ses traités reprend celle de la métaphysique dans la tradition aristotélicienne de l'époque, bien que le kalām s'en distingue par plusieurs de ses structures et concepts fondamentaux, ainsi que par son système analytique. C'est dans ce contexte qu'il faut considérer les debats qui s'instaurèrent entre kalām et falsafa. Le kalām, cependant, est d'ordre strictement théologique et c'est principalement dans ce cadre qu'il faut comprendre sa problématique et ses procédures. Le kalām a pour fonction de rationaliser le contenu cognitif offert aux croyants dans le langage symbolique de la révélation coranique. Il en résulte quatre tâches principales; il s'agit de conceptualiser, ordonner, expliquer et, dans le mesure du possible, justifier les doctrines principales reconnues par la communauté faisant référence en matière de croyance. Dans ce cadre, il sera possible de mettre en lumière les différences entre les principales écoles, ainsi que les tendances qui distinguent certains de leurs grands maîtres respectifs. (shrink)

This is a comprehensive study of the far-reaching changes that led to a re-shaping of the philosophical discourse in Islam during the sixth/twelfth century. Whereas earlier Western scholars thought that Islam's engagement with the tradition of Greek philosophy ended during that century, more recent analyses suggest its integration into the genre of rationalist Muslim theology (kalam). This book proposes a third view about the fate of philosophy in Islam. It argues that in addition to this integration, Muslim theologians picked up (...) the discourse of philosophy in Islam (falsafa) and began to produce books on philosophy. Written by the same authors, books in these two genres, kalām and philosophy, argue for opposing teachings on the nature of God, the world's creation, and on the afterlife. This study explains the emergence of a new genre of philosophical books called "hikma" that stand opposed to Islamic theology and at the same wishes to complement it. Offering a detailed history of philosophy in Iraq, Iran, and Central Asia during the sixth/twelfth century together with an analysis of the circumstances of practicing philosophy during this time, this study can show how reports of falsafa, written by major Muslim theologians such as al-Ghazali (d. 505/1111), developed step-by-step into critical assessments of philosophy that try to improve philosophical teachings, and eventually become fully fledged philosophical summas in the work of Fakhr al-Din al-Razi (d. 606/1210). The book ends in a discussion of the different methods of kalam and hikma and the coherence and ambiguity of a Muslim post-classical philosopher's œuvre. (shrink)

Sohn-Rethel’s great idea was to ‘socialise’ Kant’s transcendental subject by combining it with Marx’s commodity-form. In so doing, he took on three challenges simultaneously: a) the timeless validity of modern natural science; b) the social genesis of empirically pure forms of cognition; and c) socialisation occurring through a purely social synthesis. However, Sohn-Rethel construed Marx’s value-form analysis as an empirical exchange of commodities and held that such exchange performs a real abstraction – in this way, he laboured under the very (...) semblance that money engenders at the surface of society by virtue of its function qua means of exchange. This semblance can be rendered transparent by, on the one hand, explaining value in terms of capitalist valorisation rather than as a product of abstraction, and, on the other, developing money as the measure and form of this valorisation. (shrink)

Als »Subjektphilosophie« hat man das neuzeitliche Denken insgesamt charakterisiert. Diese Auszeichnung verdankt das Subjekt der verwegenen Hoffnung, es eigne sich zum ultimativen Prinzip der Wissensbegründung. Das Interesse an einer Aufklärung seiner Struktur wurde dadurch jedoch in den Hintergrund gedrängt. Diese Struktur steht im Zentrum von Manfred Franks jüngstem Buch, das einen Blick auf die moderne Geschichte der Subjekttheorien mit Analysen der inneren Beschaffenheit und der Zeitlichkeit des Subjekts sowie seines Verhältnisses zur Intersubjektivität und einer Auseinandersetzung mit klassischen und neuesten analytischen (...) Theoriebildungen verbindet. Dem Begriff der Präreflexivität kommt dabei die Schlüsselrolle zu. (shrink)

The article argues that universals of law, i.e. the laws of nature, are the general axioms of a deductive system of all knowledge, and their deductive consequences. Universals of fact are generalisations deducible from these together with particular facts.

Institutions are normative social structures that are collectively accepted. In his book Making the Social World, John R. Searle maintains that these social structures are created and maintained by Status Function Declarations. The article’s author criticizes this claim and argues, first, that Searle overestimates the role that language plays in relation to institutions and, second, that Searle’s notion of a Status Function Declaration confuses more than it enlightens. The distinction is exposed between regulative and constitutive rules as being primarily a (...) linguistic one: whereas deontic powers figure explicitly in regulative rules, they feature only implicitly in constitutive rules. Furthermore, he contends that Searle’s collective acceptance account of human rights cannot adequately account for the fact that people have these rights even when they are not recognized. Finally, It is argued that a conception of collective intentionality that involves collective commitment is needed in order to do justice to the normative dimension of institutions. (shrink)

In modern democracies, moral experts play an increasingly important role in law-making. Apart from the question of which competences characterize moral experts, their influence on the legitimacy of democratic procedures must be discussed. On the one hand, the contribution of moral experts promises to improve the quality of decision making. On the other hand, however, moral experts cannot claim to represent the will of the people. In this essay, at first a concept of the moral expert will be sketched which (...) does without the assumption of a privileged access to 'moral truths'. Then a procedural understanding of democratic legitimacy without epistemic components will be defended. Finally there will be a distinction between the purely consultative and the quasi-legislative tasks of ethics committees. Whereas councelling by moral experts does not influence the legitimacy of democratic procedures, giving them quasilegislative functions is connected to risks in this respect. (shrink)

First published in 2000. Routledge is an imprint of Taylor & Francis, an informa company.

We will show that there is a strong form of emergence in cell biology. Beginning with C.D. Broad's classic discussion of emergence, we distinguish two conditions sufficient for emergence. Emergence in biology must be compatible with the thought that all explanations of systemic properties are mechanistic explanations and with their sufficiency. Explanations of systemic properties are always in terms of the properties of the parts within the system. Nonetheless, systemic properties can still be emergent. If the properties of the components (...) within the system cannot be predicted, even in principle, from the behavior of the system's parts within simpler wholes then there also will be systemic properties which cannot be predicted, even in principle, on basis of the behavior of these parts. We show in an explicit case study drawn from molecular cell physiology that biochemical networks display this kind of emergence, even though they deploy only mechanistic explanations. This illustrates emergence and its place in nature. (shrink)

Institutions are normative social structures that are collectively accepted. In his book Making the Social World, John R. Searle maintains that these social structures are created and maintained by Status Function Declarations. The article’s author criticizes this claim and argues, first, that Searle overestimates the role that language plays in relation to institutions and, second, that Searle’s notion of a Status Function Declaration confuses more than it enlightens. The distinction is exposed between regulative and constitutive rules as being primarily a (...) linguistic one: whereas deontic powers figure explicitly in regulative rules, they feature only implicitly in constitutive rules. Furthermore, he contends that Searle’s collective acceptance account of human rights cannot adequately account for the fact that people have these rights even when they are not recognized. Finally, It is argued that a conception of collective intentionality that involves collective commitment is needed in order to do justice to the normative dimension of institutions. (shrink)

Skill or control is commonly regarded as a necessary condition for intentional action. This received wisdom is challenged by experiments conducted by Joshua Knobe and Thomas Nadelhoffer, which suggest that moral considerations sometimes trump considerations of skill and control. I argue that this effect (as well as the Knobe effect) can be explained in terms of the role normative reasons play in the concept of intentional action. This explanation has significant advantages over its rivals. It involves at most a conservative (...) extension rather than a radical revision of what we tend to believe about intentional action, and it fits better with the way we conceive of the relation between intentional action and moral responsibility. (shrink)

This paper seeks to provide a basis for a fruitful correspondence between the projects of Nietzsche and Merleau-Ponty. It argues that both philosophers are committed to an ontology of relation and they both regards any terms to these relations as being hypostases of a horizontal movement. This commits them to very parallel views of history, politics, and perception.

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