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)

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)

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

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)

Collected for the first time in a single volume are essays which examine the developments in three fundamental biological disciplines - embryology, evolutionary biology, and genetics. These disciplines were in conflict for much of the twentieth century and the essays in this collection examine key methodological problems within these disciplines and the difficulties faced in overcoming the conflicts between them. Burian skilfully weaves together historical appreciation of the settings within which scientists work, substantial knowledge of the biological problems at stake (...) and the methodological and philosophical issues faced in integrating biological knowledge drawn from disparate sources. The final chapter describes what recent findings in development biology and genetics can tell us about the history and development of animals. Written in a clear, accessible style this collection should appeal to students and professionals in philosophy of science, and the philosophy and history of biology. (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)

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 ...

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)

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)

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)

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)

"Ce livre propose une enquête philosophique explorant le rapport à la mort dans nos sociétés. C’est une invitation à penser les liens humains à la fin de la vie. On évoque les liens intimes, mais également les liens sociaux encadrés par la loi. Dans un tel contexte, comment discerner les raisons anciennes et nouvelles convenant au bien de la cité? L’ouvrage s’adresse aux accompagnants en soins palliatifs. Il concerne également toute personne soucieuse pour elle-même et ses proches de réfléchir à (...) son voyage au bout de la vie. Nous sommes mortels, nous le savons et le fil de nos existences provoque des occasions de nous le rappeler. Dans la solitude de mourir s’inscrit l’appel à la compassion. Ainsi, pour les Grecs de l’Antiquité, l’image de la cigogne symbolisait la prise en charge des vieux par les jeunes, un signe de l’amitié politique. L’émergence de la culture palliative est intimement liée aux changements qui ont affecté l’évolution récente de la vie démocratique. Cette culture est née et s’est développée dans des circonstances politiques particulières. À l’observer, on peut déchiffrer certains codes de notre vie civique, ses aspirations, mais aussi ses ambiguïtés. Louis-André Richard propose d’examiner les questions actuelles en compagnie de Platon, d’Aristote, d’Augustin ou de Tocqueville. Grâce à eux, la philosophie, symbolisée par la sagesse de Minerve, est mise à contribution pour explorer la genèse et les métamorphoses de concepts comme la dignité et l’autonomie. Comment se déploie la dynamique de la raison et de la liberté à l’heure de notre mort? Tel est l’enjeu pour les roseaux pensants que nous sommes. Si notre frêle espèce appelle à la sollicitude de la cigogne, elle ne saurait négliger de convoquer aussi la sagesse de Minerve."--Résumé de l'éditeur. (shrink)

Les périodes de confinement sont des moments éprouvants. On a la sensation de perdre nos repères. Nous nous sentons déboussolés. On peut cependant saisir l’occasion de faire le point. Sous le regard de la réflexion philosophique, ce petit livre est une tentative pour éviter de perdre le nord. L’auteur propose de courtes réflexions puisées à même la littérature philosophique. Sans prétention, il s’agit de fournir des pistes rendant intelligibles nos conditions d’êtres confinés.

Despite wide acceptance that the attributes of living creatures have appeared through a cumulative evolutionary process guided chiefly by natural selection, many human activities have seemed analytically inaccessible through such an approach. Prominent evolutionary biologists, for example, have described morality as contrary to the direction of biological evolution, and moral philosophers rarely regard evolution as relevant to their discussions. -/- The Biology of Moral Systems adopts the position that moral questions arise out of conflicts of interest, and that moral systems (...) are ways of using confluences of interest at lower levels of social organiation to deal with conflicts of interest at higher levels. Moral systems are described as systems of indirect reciprocity: humans gain and lose socially and reproductively not only by direct transactions, but also by the reputations they gain from the everyday flow of social interactions. -/- The author develops a general theory of human interests, using senescence and effort theory from biology, to help analye the patterning of human lifetimes. He argues that the ultimate interests of humans are reproductive, and that the concept of morality has arisen within groups because of its contribution to unity in the context, ultimately, of success in intergroup competition. He contends that morality is not easily relatable to universals, and he carries this argument into a discussion of what he calls the greatest of all moral problems, the nuclear arms race. (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)

When making decisions, people naturally face uncertainty about the potential consequences of their actions due in part to limits in their capacity to represent, evaluate or deliberate. Nonetheless, they aim to make the best decisions possible. In Decision Theory with a Human Face, Richard Bradley develops new theories of agency and rational decision-making, offering guidance on how 'real' agents who are aware of their bounds should represent the uncertainty they face, how they should revise their opinions as a result (...) of experience and how they should make decisions when lacking full awareness of, or precise opinions on relevant contingencies. He engages with the strengths and flaws of Bayesian reasoning, and presents clear and comprehensive explorations of key issues in decision theory, from belief and desire to semantics and learning. His book draws on philosophy, economics, decision science and psychology, and will appeal to readers in all of these disciplines. (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)

Judicial review by constitutional courts is often presented as a necessary supplement to democracy. This book questions its effectiveness and legitimacy. Drawing on the republican tradition, Richard Bellamy argues that the democratic mechanisms of open elections between competing parties and decision-making by majority rule offer superior and sufficient methods for upholding rights and the rule of law. The absence of popular accountability renders judicial review a form of arbitrary rule which lacks the incentive structure democracy provides to ensure rulers (...) treat the ruled with equal concern and respect. Rights based judicial review undermines the constitutionality of democracy. Its counter-majoritarian bias promotes privileged against unprivileged minorities, while its legalism and focus on individual cases distort public debate. Rather than constraining democracy with written constitutions and greater judicial oversight, attention should be paid to improving democratic processes through such measures as reformed electoral systems and enhanced parliamentary scrutiny. (shrink)

This book argues that a plausible account of emergence requires replacing the traditional assumption that what primarily exists are particular entities with generic processes. Traversing contemporary physics and issues of identity over time, it then proceeds to develop a metaphysical taxonomy of emergent entities and of the character of human life.

Few philosophers have left a legacy like that of Gottfried Wilhelm Leibniz. He has been credited not only with inventing the differential calculus, but also with anticipating the basic ideas of modern logic, information science, and fractal geometry. He made important contributions to such diverse fields as jurisprudence, geology and etymology, while sketching designs for calculating machines, wind pumps, and submarines. But the common presentation of his philosophy as a kind of unworldly idealism is at odds with all this bustling (...) practical activity. In this book Richard. T. W. Arthur offers a fresh reading of Leibniz’s philosophy, clearly situating it in its scientific, political and theological contexts. He argues that Leibniz aimed to provide an improved foundation for the mechanical philosophy based on a new kind of universal language. His contributions to natural philosophy are an integral part of this programme, which his metaphysics, dynamics and organic philosophy were designed to support. Rather than denying that substances really exist in space and time, as the idealist reading proposes, Leibniz sought to provide a deeper understanding of substance and body, and a correct understanding of space as an order of situations and time as an order of successive things. This lively and approachable book will appeal to students of philosophy, as well as anyone seeking a stimulating introduction to Leibniz's thought and its continuing relevance. (shrink)

In this ground breaking and controversial work Richard Bentall shatters the myths that surround madness. He shows there is no reassuring dividing line between mental health and mental illness.

In Liberalism and Pluralism, Richard Bellamy explores the challenges posed by conflicting values, interests and identities to liberal democracy. Conventional liberal thought is no longer suited to the complex, plural societies of today. By analyzing the three major strands of liberal thought as represented by Hayek, Rawls and Walzer, the author reveals how standard liberalism has tried to circumvent unstable settlements. This book establishes a more satisfactory alternative: namely, negotiated compromise.

In this third edition of "John Locke", the text is divided into three parts. The first is biographical, giving an account of the development of Locke's mind. The second expounds the teaching of the "Essay", and relates this to its background; while the third deals with Locke's teaching in political theory, moral philosophy, education, and religion. -- From publisher's description.

Ethics and the Clinical Encounter explores the moral dimensions of clinical medicine and the phenomenon of illness, to determine what ethics must be in order to be fully responsive to clinical encounters. Written in a lively and conversational style with minimal technical terminology, and enhanced by actual experience or real clinical situations, this volume lays out a clinical ethics methodology both in practical and theoretical terms. Here's what the experts had to say: Professor Zaner has provided us with a remarkably (...) lucid and trenchant discussion of the interface of philosophy and the field of medicine. He brings into play an extraordinary range of historial knowledge, extensive observations based on firsthand experience with medical practices, and an acute sense of philosophical argumentation. This is a work that will be an exemplary and indispensable text in the philosophy of medicine for years to come. -- Calvin Schrag... it is a highly original contribution usable in a number of fields.... It really has no competition.... The genius of Zaner's approach is to ground ethics from the 'bottom up' and to direct us to the concrete particulars of therapeutic encounters wherein lie moral and ethical matters... meaty, challenging, and ultimately rewarding.... -- Paul R. Dokecki Richard M. Zaner founded the Center for Clinical and Research Ethics at Vanderbilt University Medical Center. Having established Vanderbilt's first Hospital Ethics Committee (1985), he served as co-chair of VUMC's Ethics Committee since its inception in 1990. Zaner has published five original books, edited ten, and translated four more, and has published more than 100 sections of books and professional journals. (shrink)

Parfit's On What Matters offers a rousing defence of non-naturalist normative realism against pressing metaphysical and epistemological objections. He addresses skeptical arguments based on (i) the causal origins of our normative beliefs, and (ii) the appearance of pervasive moral disagreement. In both cases, he concedes the first step to the skeptic, but draws a subsequent distinction with which he hopes to stem the skeptic's advance. I argue, however, that these distinctions cannot bear the weight that Parfit places on them. A (...) successful moral epistemology must take a harder line with the skeptic, insisting that moral knowledge can be had by those with the right kind of psychology -- no matter the evolutionary origin of the psychology, nor whether we can demonstrate its reliability over the alternatives. (shrink)