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)

Frank E. Zachos offers a comprehensive review of one of today's most important and contentious issues in biology: the species problem. After setting the stage with key background information on the topic, the book provides a brief history of species concepts from antiquity to the Modern Synthesis, followed by a discussion of the ontological status of species with a focus on the individuality thesis and potential means of reconciling it with other philosophical approaches. More than 30 different species concepts (...) found in the literature are presented in an annotated list, and the most important ones, including the Biological, Genetic, Evolutionary and different versions of the Phylogenetic Species Concept, are discussed in more detail. Specific questions addressed include the problem of asexual and prokaryotic species, intraspecific categories like subspecies and Evolutionarily Significant Units, and a potential solution to the species problem based on a hierarchical approach that distinguishes between ontological and operational species concepts. A full chapter is dedicated to the challenge of delimiting species by means of a discrete taxonomy in a continuous world of inherently fuzzy boundaries. Further, the book outlines the practical ramifications for ecology and evolutionary biology of how we define the species category, highlighting the danger of an apples and oranges problem if what we subsume under the same name ("species") is in actuality a variety of different entities. A succinct summary chapter, glossary and annotated list of references round out the coverage, making the book essential reading for all biologists looking for an accessible introduction to the historical, philosophical and practical dimensions of the species problem. (shrink)

How important is luck in economic success? No question more reliably divides conservatives from liberals. As conservatives correctly observe, people who amass great fortunes are almost always talented and hardworking. But liberals are also correct to note that countless others have those same qualities yet never earn much. In recent years, social scientists have discovered that chance plays a much larger role in important life outcomes than most people imagine. In Success and Luck, bestselling author and New York Times economics (...) columnist Robert Frank explores the surprising implications of those findings to show why the rich underestimate the importance of luck in success--and why that hurts everyone, even the wealthy. Frank describes how, in a world increasingly dominated by winner-take-all markets, chance opportunities and trivial initial advantages often translate into much larger ones--and enormous income differences--over time; how false beliefs about luck persist, despite compelling evidence against them; and how myths about personal success and luck shape individual and political choices in harmful ways. But, Frank argues, we could decrease the inequality driven by sheer luck by adopting simple, unintrusive policies that would free up trillions of dollars each year--more than enough to fix our crumbling infrastructure, expand healthcare coverage, fight global warming, and reduce poverty, all without requiring painful sacrifices from anyone. If this sounds implausible, you'll be surprised to discover that the solution requires only a few, uncontroversial steps. Compellingly readable, Success and Luck shows how a more accurate understanding of the role of chance in life could lead to better, richer, and fairer economies and societies. (shrink)

In this study, the author shows new entry points to the dialogue between Kant and Heidegger. Schalow takes up the question: "Why should a philosopher like Kant, for whom language seemed to be almost inconsequential, become the crucial counter point for a thinker like Heidegger to develop a novel way to understand and express the most perennial of all philosophical concepts, namely, 'being' as such?" This approach allows for addressing issues which are normally relegated to the periphery of the exchange (...) between Heidegger and Kant, including spatiality and embodiment, nature and art, religion and politics. (shrink)

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.

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)

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)

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 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.

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)

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)

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)

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

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)

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)

John Dewey's Experience and Education is an important book, but first-time readers of Dewey's philosophy can find it challenging and not meaningfully related to the contemporary landscape of education. Jeff Frank's Teaching in the Now aims to reanimate Dewey's text--for first-time readers and anyone who teaches the text or is interested in appreciating Dewey's continuing significance--by focusing on Dewey's thinking on preparation. Frank, through close readings of Dewey, asks readers to wonder: How much of what we justify as (...) preparation in education is actually necessary? That is, every time we catch ourselves telling a student--you need to learn this in order to do something else--we need to stop and reflect. We need to reflect, because when we always justify the present moment of a student's education in terms of what will happen in the future, we may lose out on the ability to engage students' attention and interest now, when it matters. Dewey asks his readers to trust that the best way to prepare students for an engaging and productive future is to create the most engaging and productive present experience for students. We learn to live fully in the future, only by practicing living fully in the present. Although it can feel scary to stop thinking of the work of education in terms of preparation, when educators reclaim the present for students, new opportunities--for teachers, students, schools, democracy, and education--emerge. Teaching in the Now explores these opportunities in impassioned and engaging prose that makes Experience and Education come alive for readers new to Dewey or who have taught and read him for many years. (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.

This chapter contains section titled: The Conundrum of Canada/Quebec The Landscape Some Questions of Methodology In Defense of a National Orientation Multiculturalism The (Anglophone) Canadian Nation “Tri”‐Nationalism Actors Political Theory.

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