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)

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)

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 ...

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)

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)

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)

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)

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.

Contemporary health care often lacks generosity of spirit, even when treatment is most efficient. Too many patients are left unhappy with how they are treated, and too many medical professionals feel estranged from the calling that drew them to medicine. Arthur W. Frank tells the stories of ill people, doctors, and nurses who are restoring generosity to medicine--generosity toward others and to themselves. The Renewal of Generosity evokes medicine as the face-to-face encounter that comes before and after diagnostics, pharmaceuticals, (...) and surgeries. Frank calls upon the Roman emperor Marcus Aurelius, philosopher Emmanuel Levinas, and literary critic Mikhail Bakhtin to reflect on stories of ill people, doctors, and nurses who transform demoralized medicine into caring relationships. He presents their stories as a source of consolation for both ill and professional alike and as an impetus to changing medical systems. Frank shows how generosity is being renewed through dialogue that is more than the exchange of information. Dialogue is an ethic and an ideal for people on both sides of the medical encounter who want to offer more to those they meet and who want their own lives enriched in the process. The Renewal of Generosity views illness and medical work with grace and compassion, making an invaluable contribution to expanding our vision of suffering and healing. (shrink)

Die Idee zu der in diesem Band dokumentierten Tagung ist im Rahmen des disziplinübergreifenden Nachwuchswissenschaftsnetzwerkes THESIS entstanden. Der Dialog über die fachlichen und disziplinären Grenzen hinweg hat bei THESIS seit dessen Gründung im Jahre 1990 stets einen großen Raum eingenommen. Anderen Fächern Respekt und Interesse entgegenzubringen und sich nicht von stereotypen Vorurteilen leiten zu lassen, ist konstitutiver Bestandteil im Selbstverständnis des Netzwerkes. Selbstverständlich gibt es in einem solchen Verbund eine Reihe von Gelegenheiten (darunter auch den einen oder anderen entwicklungsfördernden Konflikt), (...) das eigene Bild vom Anderen und das andere Bild vom Eigenen zur Sprache zu bringen und zu hinterfragen. Auf der Basis dieser bestehenden Kommunikationsstrukturen trafen sich am 11. Oktober 2003 in Göttingen 12 junge Wissenschaftlerinnen und Wissenschaftler zwischen, über und auch auf den Grenzen ihrer eigenen Herkunftsdisziplinen, um den Trendbegriff [alpha]Transdisziplinarität" auf seine Substanz zu prüfen. (shrink)

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

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.

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

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)

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

This article rebuts Ramsey's earlier theory, in 'Universals of Law and of Fact', of how laws of nature differ from other true generalisations. It argues that our laws are rules we use in judging 'if I meet an F I shall regard it as a G'. This temporal asymmetry is derived from that of cause and effect and used to distinguish what's past as what we can know about without knowing our present intentions.

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

A complete collection of Frank Sibley's articles on philosophical aesthetics, this volume includes five, remarkable, hitherto unpublished papers written in Sibley's later years. It addresses many topics, among them the nature of aesthetic qualities versus non-aesthetic qualities, the relation of aesthetic description to aesthetic evaluation, the different levels of evaluation, and the objectivity of aesthetic judgement. The later papers constitute both a significant development of Sibley's individual approach to aesthetics, such as his discussion of the distinction between attributive and (...) predicative uses of adjectives and of the aesthetic significance of tastes and smells, a topic Sibley considered to be much neglected. (shrink)

In At the Will of the Body , Arthur Frank told the story of his own illnesses, heart attack and cancer. That book ended by describing the existence of a "remission society," whose members all live with some form of illness or disability. The Wounded Storyteller is their collective portrait. Ill people are more than victims of disease or patients of medicine they are wounded storytellers. People tell stories to make sense of their suffering when they turn their diseases (...) into stories, they find healing. Drawing on the work of authors such as Oliver Sacks, Anatole Broyard, Norman Cousins, and Audre Lorde, as well as from people he met during the years he spent among different illness groups, Frank recounts a stirring collection of illness stories, ranging from the well-known--Gilda Radner's battle with ovarian cancer--to the private testimonials of people with cancer, chronic fatigue syndrome, and disabilties. Their stories are more than accounts of personal suffering: they abound with moral choices and point to a social ethic. Frank identifies three basic narratives of illness in restitution, chaos, and quest. Restitution narratives anticipate getting well again and give prominence to the technology of cure. In chaos narratives, illness seems to stretch on forever, with no respite or redeeming insights. Quest narratives are about finding that insight as illness is transformed into a means for the ill person to become someone new. (shrink)

The Metaphysical Club, a gathering of intellectuals in the 1870s associated with Harvard, is widely recognized as the crucible where pragmatism, America's distinctively original philosophy, was refined and proclaimed. Louis Menand's bestseller about the group was a dramatic publishing success. However, only three actual members - Oliver Wendell Holmes Jr., Charles S. Peirce, and William James - appear in this book, alongside other thinkers such as John Dewey who were never in the Club. The Real Metaphysical Club tells the full (...) story of how this influential group shifted the course of philosophy in America. In addition to pioneering pragmatism, the group explored radical empiricism and idealism, and formulated personalism and process philosophy, equally important developments. This volume contains thirty-seven important writings dating from 1870 to 1885 by the real members of the Metaphysical Club. The first section centers on pragmatism and science; the second part collects writings of the lawyers; and the third part covers idealist and personalist philosophers. Many of these writings have never been reprinted before, and nothing like this impressive collection has ever been attempted. A general introduction provides a narrative history, and the editors' three introductions to the volume's sections vividly bring to life the intense meetings, sustained debates, and pioneering thought from the Metaphysical Club. (shrink)

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)

The Jewish Philosophy Reader is the first comprehensive anthology of classic writings on Jewish philosophy from the Bible to postmodernism. The Reader is clearly divided into four separate parts: Foundations and First Principles, Medieval and Renaissance Jewish Philosophy, Modern Jewish Thought, and Contemporary Jewish Philosophy. Each part is clearly introduced by the editors. The readings featured are representative writings of each era listed above and are from the following major thinkers: Abrabanel, Baeck, Bergman, Borowitz, Buber, Cohen, Crescas, Fackenheim, Geiger, Gersonides, (...) Goodman, Graetz, Halevi, Hartman, Heschel, Hess, Hirsch, Ibn Ezra, Ibn Gabirol, Ibn Paquda, Kellner, Kook, Krochmal, Leibowitz, Levinas, Maimonides, Maybaum, Mendelssohn, Novak, Philo, Plaskow, Rosenzweig, Saadia, Scholem, Seeskin, Soloveitchik, Spinoza, Strauss, Wolf, Zunz. (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)

English summary: »Selbstbestimmung« is a basic concept in the German ethical discourse, similar to »autonomy«, »liberty«, or »human dignity«. Even though this term is clearly in need of further definition, it has been barely addressed in the theological discourse. The contributions to this volume take a variety of approaches to the question of how we have to understand and interpret the concept of »self-determination« within the framework of theological ethics. In order to achieve this, the authors resort to the orientation (...) and perspectives of reality fostered by reformatory theology. Apart from a fundamental essay that in tracing the different facets of the term »self-determination« refers back to the theology of Martin Luther, the anthology contains a number of contributions from the field of applied ethics. German description: Der Begriff »Selbstbestimmung« gehort zu den Grundbegriffen der Ethik. Er begegnet in vielen aktuellen ethischen Diskursen Ahnlich haufig wie die Begriffe »Autonomie«, »Freiheit« oder »Menschenwuerde«. Trotz eines offensichtlichen Klarungsbedarfs hat sich die Theologie dieses Begriffs bisher noch kaum angenommen. Die Beitrage des vorliegenden Sammelbandes stellen sich in unterschiedlicher Perspektive der Frage, wie das Konzept »Selbstbestimmung« im Rahmen theologischer Ethik verstanden und inhaltlich gefuellt werden kann. Dafuer wird die Orientierungsleistung des von der reformatorischen Theologie gepragten Wirklichkeitsverstandnisses fruchtbar gemacht. Neben einem grundlegenden Aufsatz, der den Begriff »Selbstbestimmung« mit Hilfe von Impulsen aus der Theologie Martin Luthers entfaltet, stehen Aufsatze aus dem Bereich der angewandten Ethik. (shrink)

Frank Ramsey was the greatest of the remarkable generation of Cambridge philosophers and logicians which included G. E. Moore, Bertrand Russell, Ludwig Wittgenstein and Maynard Keynes. Before his tragically early death in 1930 at the age of twenty-six, he had done seminal work in mathematics and economics as well as in logic and philosophy. This volume, with a new and extensive introduction by D. H. Mellor, contains all Ramsey's previously published writings on philosophy and the foundations of mathematics. The (...) latter gives the definitive form and defence of the reduction of mathematics to logic undertaken in Russell and Whitehead's Principia Mathematica; the former includes the most profound and original studies of universals, truth, meaning, probability, knowledge, law and causation, all of which are still constantly referred to, and still essential reading for all serious students of these subjects. (shrink)

This collection introduces the reader to some of the most interesting current work on conditionals. Particular attention is paid to possible world semantics for conditionals, the role of conditional probability in helping us to understand conditionals, implicature and the material conditional, and subjunctive versus indicative conditionals. Contributors include V.H. Dudman, Dorothy Edgington, Nelson Goodman, H.P. Grice, David Lewis, and Robert Stalnaker.

We attempt to extend the nominalistic project initiated in Hartry Field's Science Without Numbers to modern physical theories based in differential geometry.

I argue that it may well be the case that space and time do not consist of points, indeed that they have no smallest parts. I examine two different approaches to such pointless spaces : a topological approach and a measure theoretic approach. I argue in favor of the measure theoretic approach.

An introduction to informal logic, critical thinking and rhetoric utilizing actual public discourse .

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Happiness in Premodern Judaism: Virtue, Knowledge, and Well-BeingDaniel H. FrankHava Tirosh-Samuelson. Happiness in Premodern Judaism: Virtue, Knowledge, and Well-Being. Cincinnati: Hebrew Union College Press, 2003. Pp. xi + 596. Cloth, $50.00.Franz Rosenzweig tried hard to convince the neoKantian Hermann Cohen of the merits of Zionism and the normalization it would bring to Jews and Jewish life. His attempt met with this response from Cohen: "Oho! So the gang (...) now wants to be happy, does it?" For those ignorant of the history of Jewish philosophy, one might imagine that Jewish philosophers, no less than their non-philosophical kinsmen, were so weighed down by the burdens of history and persecution that happiness could play no role in their theorizing. But happiness plays a key role in the history of Jewish moral and political philosophy, especially in the premodern period. Even Spinoza, the last of the medievals and the first of the moderns, the great critic of the rabbinic tradition and of Maimonides in particular, is concerned in his Ethics with identifying those activities that together constitute human well-being and the good life. Only lately, since the Enlightenment and Kant, has non-eudaimonism been a live option for Jewish thinkers. Only with the rise of (modern) Orthodoxy, and its predilection for construing goodness as rectitude and rule-following, has eudaimonism fallen out of favor. But with Tirosh-Samuelson's weighty volume on happiness in premodern Judaism, there can be no excuse in the future to imagine that all Jews are, or must be, closet Kantians, strict deontologists. To think otherwise seems to come close to taking on the classical (anti-Semitic) dichotomy of legalistic Judaism vs. spiritual Christianity. In it own way, Happiness in Premodern Judaism is a critique of such a one-sided, monochromatic view of Judaism, whether from the Christian or even from the Jewish side.Tirosh-Samuelson writes explicitly as an intellectual historian, rather than as a philosopher. She understands herself and her project as one that presents just the facts, without evaluating them. While one may cavil at a lost opportunity, in the present case this would be churlish, given the enormous erudition on display. After an introductory chapter outlining the foundational moral theories of Plato, Aristotle, and the Hellenistic philosophers, the text presents the (Greek-inspired) areteic wisdom literature of the Second Temple period, the teleological theocentrism of the rabbis, the Greco-Arabic Islamicate culture that nurtured Jewish philosophers from Saadia in the tenth century to Maimonides in the twelfth, the rabbinic and kabbalistic critiques of the philosophical ideal of happiness commencing [End Page 338] with the translation (into Hebrew) of Maimonides' Guide of the Perplexed at the beginning of the thirteenth century, and finally, very important and the focus of much recent scholarly work, the transformation of Jewish eudaimonism through direct contact with Christian Scholasticism and later with the humanist Renaissance. All in all, a millennium and a half of Jewish intellectual history is presented in a sober and scholarly way.Not surprisingly Maimonides plays a pivotal role in the story that Tirosh-Samuelson relates. A Janus-like figure, he represents the culmination and height of accommodation with Greek and Greco-Arabic philosophical culture. However, with the gradual worsening of the socio-economic condition of European Jewry in the thirteenth century, his accommodationism seemed traitorous, and as a result generations of thinkers, mystics and philosophers alike, strove to critically distance themselves from Maimonidean Aristotelianism. Tirosh-Samuelson is admirably clear in pointing out that such anti-Maimonidean tendencies are ill-characterized as anti-philosophical. Hasdai Crescas in the late-fourteenth and early-fifteenth centuries launched a massive critique of Maimonides' physics, metaphysics, and moral philosophy, but did so in as rigorous a manner as any philosopher would. The picture that enfolds over the course of the text is one of vigorous dialectic between partisans of 'alien' (Greek) wisdom and those who viewed such wisdom with considerable suspicion. Such a dialectic parallels, not surprisingly, developments in Christian philosophy.The trajectory of the story of premodern Jewish musings on happiness is from the centrality of reason and intellect, and the contemplative activity that is reason's preeminent actuality, to the primacy... (shrink)