Angiogenesis, the generation of new blood vessels from pre‐existing vessels, is an integral component of wound healing, responses to inflammation and other physiologic processes. It is also an essential part of tumor growth; in the absence of new vessel formation, tumors cannot expand beyond a small volume. Although much is known about angiogenesis and its regulation, there is no overall theory that describes or explains this process. It is here suggested that the intracrine hypothesis, which ascribes to certain extracellular signaling (...) peptides (whether hormones, growth factors, DNA‐binding proteins or enzymes) a role in both intracellular biology and extracellular signaling, can contribute to a more general understanding of angiogenesis. Intracrine factors participate in angiogenesis in the following ways: (1) they can act within the cells that synthesized them (type I intracrine action), (2) they can be secreted and then taken up by their cell of synthesis to act intracellularly (type II intracrine action ), or (3) they can be secreted and internalized by a distant target cell (type III intracrine action). The parallels between the intracrine growth factor mechanisms cancer cells employ in stimulating their own growth and the mechanisms operative in endothelial cell proliferation during angiogenesis (“intracrine reciprocity”) are discussed. Collectively, these explorations lead to testable hypotheses regarding the regulation of normal and pathological angiogenesis, and point to similarities between tumor‐induced angiogenesis and tissue differentiation. BioEssays 28: 943–953, 2006. © 2006 Wiley periodicals, Inc. (shrink)

There is evidence that many peptide growth factors and hormones act in the intracellular space after either internalization or retention in their cells of synthesis. These factors, commonly called intracrines, are structurally diverse while sharing some common functional features. Reports of intracellular peptide hormone binding and action are reviewed here. Also, this laboratory has made proposals regarding the origin and actions of intracrines and these areas are further explored. Intracrine interactions and the relationship of intracrines to transcription factors are discussed. (...) The intracellular/intracrine renin–angiotensin system (iRAS) is reviewed to illustrate the intracrine analogue of a well‐established physiological system. The role of intracrine action in metazoan development is also considered. BioEssays 25:401–409, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to (...) existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource providing details on the people, policies, and issues being addressed in association with OBI. (shrink)

An increasing number of people seek medical attention for mild cognitive symptoms at older age, worried that they might develop Alzheimer’s disease. Some clinical practice guidelines suggest offering biomarker testing in such cases, using a brain scan or a lumbar puncture, to improve diagnostic certainty about Alzheimer’s disease and enable an earlier diagnosis. Critics, on the other hand, point out that there is no effective Alzheimer treatment available and argue that biomarker tests lack clinical validity. The debate on the ethical (...) desirability of biomarker testing is currently polarized; advocates and opponents tend to focus on their own line of arguments. In this paper, we show how the method of reflective equilibrium can be used to systematically weigh the relevant arguments on both sides of the debate to decide whether to offer Alzheimer biomarker testing. In the tradition of RE, we reflect upon these arguments in light of their coherence with other argumentative elements, including relevant facts, ethical principles, and theories on societal ideals or relevant concepts, such as autonomy. Our stance in the debate therefore rests upon previously set out in-depth arguments and reflects a wide societal perspective. (shrink)

The discovery and engineering of novel fluorescent proteins (FPs) from diverse organisms is yielding fluorophores with exceptional characteristics for live‐cell imaging. In particular, the development of FPs for fluorescence (or Förster) resonance energy transfer (FRET) microscopy is providing important tools for monitoring dynamic protein interactions inside living cells. The increased interest in FRET microscopy has driven the development of many different methods to measure FRET. However, the interpretation of FRET measurements is complicated by several factors including the high fluorescence background, (...) the potential for photoconversion artifacts and the relatively low dynamic range afforded by this technique. Here, we describe the advantages and disadvantages of four methods commonly used in FRET microscopy. We then discuss the selection of FPs for the different FRET methods, identifying the most useful FP candidates for FRET microscopy. The recent success in expanding the FP color palette offers the opportunity to explore new FRET pairs. (shrink)

Henry Sidgwick remarked in The Methods of Ethics regarding pleasure that the “distinctions of quality that Mill and others urge may … be admitted as grounds of preference, but only in so far as they can be resolved into distinctions of quantity.” Sidgwick had not believed that Mill intended that resolution and commented in his history that “it is hard to see in what sense a man who of two alternative pleasures chooses the less pleasant on the ground of its (...) superiority in quality can be affirmed to take ‘greatest’ happiness or pleasure as his standard of preference.” Though Mill's view has been discussed rather often, the state of the criticism has more or less stabilized with Sidgwick's conclusion. (shrink)

The purpose of this paper is to introduce the multifaceted character of computer outliners and to describe some of their more distinctive features. The author explicates the way outlining processors might be productively employed in teaching philosophy and concludes the paper with a brief discussion on extant outlining software.

The purpose of this paper is to introduce the multifaceted character of computer outliners and to describe some of their more distinctive features. The author explicates the way outlining processors might be productively employed in teaching philosophy and concludes the paper with a brief discussion on extant outlining software.

This is a collection of essays touching on four distinct areas of interest to philosophers, lawyers, and political scientists: the philosophical justification for the adversary system; the problems of truth-finding in an adversarial setting; the issue of justice in relation to social policy-making; the right to privacy.

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:A Nietzschean Bestiary: Becoming Animal Beyond Docile and BrutalRobert N. MatuozziA Nietzschean Bestiary: Becoming Animal Beyond Docile and Brutal, edited by Christa Davis Acampora and Ralph R. Acampora ; xxxii & 371 pp. Lanham, MD: Rowman & Littlefield, 2004. $75.00 cloth, $29.95 paper.What if instead of re-reading Nietzsche's corpus, one imagines what it would be like to view his works on the "Nietzsche Network." Imagine a spectator situated (...) in the middle of a vast amphitheatre preparing to watch these simulacra. Gazing up and around a series of giant, flat-screen video monitors arrayed in layers around the interior wall of an amphitheatre, the spectator views and listens to Nietzsche's multi-media texts as, simultaneously, they seductively flash their provocative narratives in flickering streams of high-resolution sounds, words, and images.The Nietzsche Network is a roaring carnival. It consists of colorful, speculative historical dramatizations and equally enticing philosophical tableaux. Dark ambient musical motifs, laced with interludes of explosive, uncontrollable laughter, are a subliminal presence. Lurid detective stories and somber cultural narratives and slashing polemics implicate cultures and ideologies in festivals of cruelty and soul-murder. Poignant genealogical and aphoristic asides on joy [End Page 443] and work and suffering, weird psychological skits starring well-known ensemble casts are accompanied by hoarse oratory, soaring denunciations, and sober etymological digressions. Intermittently, the spectator is startled by abrupt, sometimes strident proclamations, like confessional bulletins shot from nowhere.Nietzsche's siren-like prose exhibits an extraordinary rhetorical range. This is particularly true of the polychromatic works originally published in the gloaming of his career in the period after 1886. Nietzsche's compelling, fluvial style is accounted for in this volume by the kinetic movements of lizards and the halcyon tones of birds, to his study of the ancient Greek and Roman classics (and to the lost musicality of Greek tragedy in particular), and to his emphatic embrace of a kind of plosive, Dionysian philosophical technics.The content of the Nietzsche Network spans thousands of years of human experience and thought. A prequel features a substantial bestiary of traditional animals and emergent biomorphic forms set in a variety of carefully animated zoological dioramas. Among the modernists, has there been another thinker as strangely original and subversive? Allowing for fundamental differences, only Valéry comes to mind. Like the silent, ruminating cow in his "untimely" essay on history, Nietzsche prevents the past from injecting noise into present and future philosophizing. He will be the exemplary philosopher of the other-than-human as he campaigns to re-inscribe human animality into the zoological text of nature. Through explicit pronouncements and in scattered philosophical sorties involving human animality and his (desperate) utopist vision of human perfectibility, Nietzsche attempted to attain—at least conceptually—what Richard Rorty aptly calls the "historical sublime, a future which has broken all relations with the past."This excellent collection of essays on Nietzsche's bestiary demonstrates the surprising persistence of the animal imaginary in his thought. The various pieces also illuminate the multiple thematic and linguistic transformations Nietzsche develops as he enlists animals in his feral, anti-essentialist dialectic on the obscure continuum between "humans," "animals," and "nature." It turns out that a degraded version of Nietzsche's strangest thought experiment on animalism, the übermensch, is perhaps only a few years away from being produced through emerging boutique bioengineering, a prospect that has some commentators on both the left and the right blinking with apprehension. These essays amply demonstrate that Nietzsche's bestial philosophy of human and animal alterity subverts, among other paradigms, the strange Cartesian notion that animals are mechanical automata while humans are transcendental rationalists. As one commentator in this book broadly puts it, Nietzsche shows that the various schemes concocted to put an illusory distance between humans and animals have ended up being an immensely corrupting "pretense" (p. 224).Precursor bestiaries are indicated in this volume, though the medieval tradition originating in the Physiologus is here mostly displaced by a different [End Page 444] menagerie of cultural affiliations. The fabulist Aesop is present, along with Aristotle and Montaigne, though La Fontaine is not, and Pico Mirandola's famous remarks in his Oration on... (shrink)

It is widely assumed that selection history accounts of function can support a fully reductive naturalization of functional properties. I argue that this assumption is false. A problem with the alternative causal role account of function in this context is that it invokes the teleological notion of a goal in analysing real function. The selection history account, if it is to have reductive status, must not do the same. But attention to certain cases of selection history in biology, specifically those (...) involving meiotic drive, shows that selection historical explanations are available in the case of items without any plausible function. Making contributions to goals, here fitness, must be introduced as an additional constraint in the analysis, either explicitly, or implicitly by appeal to individual functions or the selection-of/selection-for distinction. (shrink)

Two ideas govern the organisation of this collection. It is suggested that medieval philosophy is best studied as an interactive debate between thinkers of different times, and also the importance of the Ancient Greek philosophers in this field.

This book presents selections from the political and social thought of the ancient West from the early sixth century BCE up to the early years of the Roman Empire and includes not only the classic philosophers, Plato, Aristotle, and Cicero, but a number of dramatists and historians as well. The range of topics these writings treat run from class conflict, through the perils of democracy and the horrors of tyranny, to the place of women in politics, while the styles range (...) from the deeply dramatic of Sophocles' Antigone and the bawdy satire of Aristophanes' Assemblywomen to Plato's Socratic dialogue Republic and Aristotle's scientific treatise Politics. The translations have been chosen, and sometimes modified, for clarity and readability, and are accompanied by introductions which set forth the historical context and trace the general lines of thought the readings develop. Frequent notes explain references to ancient lore unfamiliar to many readers. Questions for discussion accompany each reading. (shrink)

In this important collection, the editors argue that medieval philosophy is best studied as an interactive discussion between thinkers working on very much the same problems despite being often widely separated in time or place. Each section opens with at least one selection from a classical philosopher, and there are many points at which the readings chosen refer to other works that the reader will also find in this collection. There is a considerable amount of material from central figures such (...) as Augustine, Abelard, Duns Scotus, and William of Ockham, as well as extensive texts from thinkers in the medieval Islamic world. Each selection is prefaced by a brief introduction by the editors, providing a philosophical and religious background to help make the material more accessible to the reader. This edition, updated throughout, contains a substantial new chapter on medieval psychology and philosophy of mind, with texts from authors not previously represented such as John Buridan and Peter John Olivi. (shrink)

In this book, Della Rocca traces out the conceptual links between key concepts and principles of Spinoza's system bearing on representation and the mind-body problem. In the course of doing so, he presents and defends a number of new, interesting theses about Spinoza's thought on these matters. The arguments are presented with impressive clarity and in great detail. All in all, the book is a significant contribution to the literature on Spinoza's metaphysics and epistemology, and should be read by anyone (...) with a serious interest in its historical subject or in the two perennial philosophical problems on which it focuses. (shrink)

From the neurophysiological perspective, thinking in dreaming and the quality of dream thought have been considered hallucinatory, bizarre, illogical, improbable, or even impossible. This empirical phenomenological research concentrates on testing whether dream thought can be defined as rational in the sense of an intervening mental process between sensory perception and the creation of meaning, leading to a conclusion or to taking action. From 10 individual dream journals of male participants aged 22–59 years and female participants aged 25–49 years, we delimited (...) four dreams per journal and randomly selected five thought units from each dream for scoring. The units provided a base for testing a hypothesis that the thought processes of dream construction are rational. The results support the hypothesis and demonstrate that eight fundamental rational thought processes can be applied to the dreaming process. (shrink)