We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate (...) assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

The recent genome sequencing of a non‐vertebrate deuterostome, the ascidian tunicate Ciona intestinalis, makes a substantial contribution to the fields of evolutionary and developmental biology.1 Tunicates have some of the smallest bilaterian genomes, embryos with relatively few cells, fixed lineages and early determination of cell fates. Initial analyses of the C. intestinalis genome indicate that it has been evolving rapidly. Comparisons with other bilaterians show that C. intestinalis has lost a number of genes, and that many genes linked together in (...) most other bilaterians have become uncoupled. In addition, a number of independent, lineage‐specific gene duplications have been detected. These new results, although interesting in themselves, will take on a deeper significance once the genomes of additional invertebrate deuterostomes (e.g. echinoderms, hemichordates and amphioxus) have been sequenced. With such a broadened database, comparative genomics can begin to ask pointed questions about the relationship between the evolution of genomes and the evolution of body plans. BioEssays 25:529–532, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

A collection of personal narratives and essays, Living Professionalism is designed to help medical students and residents understand and internalize various aspects of professionalism. These essays are meant for personal reflection and above all, for thoughtful discussion with mentors, with peers, with others throughout the health care provider community who care about acting professionally.

Nature of the problem: Testimony from scientists. Reflex action and theism (1881) by W. James. The organization of thought (1916) by A.N. Whitehead. The changing scientific scene 1900-1950 (1952) by J.B. Conant. A note on methods of analysis (1943) by H.J. Muller. The way things are (1959) by P.W. Bridgman. A definition of style (1948) by J.R. Oppenheimer.--Consequences of the problem: Testimony from artists and writers. Existentialism (1947) by J.-P. Sartre. The testimony of modern art (1957) by W. Barrett. Parts (...) of speech and punctuation (1935) by G. Stein. The waves (1931) by V. Woolf. The imperfect paradise, by W. Stevens. A note on style and the limits of language, by W. Gibson. (shrink)

This collection by some of the leading scholars of Strauss's work is the first devoted to Strauss's thought regarding education. It seeks to address his conception of education as it applies to a range of his most important concepts, such as his views on the importance of revelation, his critique of modern democracy and the importance of modern classical education.

Quaternions consist of a scalar plus a vector and result from multiplication or division of vectors by vectors. Division of vectors is equivalent to multiplication divided by a scalar. Quaternions as used here consist of the scalar product with positive sign plus the vector product with sign determined by the right-hand rule. Units are specified by the multiplication process. Trigonometric functions are quaternions with units that can satisfy Hamilton's requirements. The square of a trigonometric quaternion is a real number provided (...) that the product of the scalar number and the vector is not commutative. Maxwell's electromagnetic equations for empty space can be represented by a single quaternion equation. (shrink)

The texts collected in this volume, which was originally published in 1969, contain Herder's most original and stimulating ideas on politics, history and language. They had for the most part not been previously available in English. In his introduction, Professor Barnard analyses the basic premises of Herder's political thought against the background of the Enlightenment. He examines Herder's concepts of language, community and culture, his theory of historical interaction, and his approach to the problem of change and progress. Finally, he (...) provides a brief comparative analysis of traditionalist thought following the French Revolution, showing how substantive writers like Burke differed from Herder despite the close similarity of political vocabulary. (shrink)

“The Will to Believe” defines the religious question as forced, living and momentous, but even in this article James asserts that more objective factors are involved. The competing religious hypotheses must both be equally coherent and correspond to experimental data to an equal degree. Otherwise the option is not a live one. “If I say to you ‘Be a theosophist or be a Mohammedan’, it is probably a dead option, because for you neither hypothesis is likely to be alive.” James, (...) WB, p. 3. Analogously, in A Pluralistic Universe James is at pains to convince the reader that his own religious hypothesis is just as “objective,” makes just as much sense, etc. as alternative possibilities: the “only thing I emphatically insist upon is that it [pluralistic pantheism] is a fully coordinate hypothesis with monism. This world may, in the last resort, be a block universe; but on the other hand, it may be a universe only strung along, not rounded in and closed. Reality may exist distributively just as it sensibly seems to, after all. On that possibility I do insist.”William James, A Pluralistic Universe (New York: Longmans, Green, and Co., 1909) p. 328.Here, once again, before the will to believe can be employed, the objective factors of competing hypotheses, their equal coherence and correspondence, must be brought out.When reconstructed, James' overall outlook has a “qausi Kuhnian” taint to it- though obvious differences remain. Much of what goes on in evaluating competing scientific hypotheses is either not forced, or not living, or not momentous, but rather “typical,” “dead,” and “avoidable,” in short very “normal.” But there are moments in the history of science where the decision between hypotheses might well be forced, living and momentous, and sometimes James comes close to recognizing this.Analogously, a good deal of what goes on in religion is not forced, not living or not momentous - in short it is all too “normal”. In The Varieties of Religious Experience for example, James proposes to ignore the institutional branch of the religious domain and to concentrate on personal and psychological factors, his reason being that the institutional aspect concentrates on the routine, the normal. “Worship and sacrifice, procedures for working on the dispositions of the deity, theology and ceremony and ecclesiastical organization, are the essentials of religion in the institutional branch. Were we to limit our view to it, we should have to define religion as an external art, the art of winning the favor of the gods.” James, VRE, p. 29. and again “The word ‘religion,’ as ordinarily used, is equivocal. A survey of history shows us that, as a rule, religious geniuses attract disciples, and produce groups of sympathizers. When these groups get strong enough to ‘organize’ themselves, they become ecclesiastical institutions with corporate ambitions of their own. The spirit of politics and the lust of dogmatic rule are then apt to enter and to contaminate the originally innocent thing; so that when we hear the word ‘religion’ nowadays, we think inevitably of some ‘church’ or other.” Clearly here religion has a normal, i.e. trivial side, just as does science. On the other hand, there are revolutionary moments in religion, such as that of choosing between theism and materialism in Pragmatism, or choosing among theism, monistic pantheism and pluralistic pantheism in A Pluralistic Universe. Such moments involve the will to believe and are clearly more personal than their counterparts in the domain of normal institutionalized religion. Going further, there are no doubt differences of degree between the will to believe decisions in science and the will to believe decisions in religion. These have been explicated in more specific terms by Ian Barbour in his article, “Paradigms in Science and Religion.” ...each of the ‘subjective’ features of science... is more evident in the case of religion: (1) the influence of interpretation on data, (2) the resistance of comprehensive theories of falsification, and (3) the absence of rules for choice among paradigms. Each of the corresponding ‘objective’ features of science is less evident in the case of religion: (1) the presence of common data on which disputants can agree, (2) the cumulative effect of evidence for or against a theory, and (3) the existence of criteria which are not paradigm-dependent. It is clear that in all three respects religion is a more ‘subjective’ enterprise than science. But in each case there is a difference of degree - not an absolute contrast between an ‘objective’ science and a ‘subjective’ religion. Ian Barbour, “Paradigms in Science and Religion,” in Paradigms and Revolutions, edited by Gary Gutting (Notre Dame: University of Notre Dame Press, 1980) pp. 242–43. Barbour correctly notes that the “...choice is not between religion and science, but between theism, pantheism, and naturalism, let us say, as each is expressed in a particular historical tradition. No basic beliefs are capable of demonstrable proof.”Ibid., p. 243. James sometimes comes close to recognizing this but his oscillation on the status of the everyday world of common sense, or the perceptual world, causes him not to see the issue clearly. When the animated world of the perceptual is taken as the all inclusive ‘really real,’ science is viewed as an abstract, second class citizen. But James offers what we would consider a more sophisticated and adequate perspective when he views the world of common sense, having become linguistified, as itself suspicious, and consequently views all three tiers - common sense, scholastic philosophy, and science - as “regional ontologies”, or “language games” in Wittgenstein's terminologySee Ludwig Wittgenstein, Philosophical Investigations, translated by G.E.M. Anscombe (New York: The Macmillan Company, 1953), paragraph 7, paragraph 23. For the notion of “regional ontology” see Edmund Husserl, Ideas, translated by W.R. Boyce Gibson (New York: Collier Books, Macmillan Publishing Company, Inc., 1962) p. 57ff; p. 158ff. - and opposes all three to a more primordial or prereflexive level. When James takes this second approach it is easier to see that the basic distinction he began to make in “The Will to Believe” was between the scientific and religious domain where the will to believe was to be employed, and the domain of “ordinary” religion and science. Finally this position anticipates his ultimate metaphysical outlook, viz. “pure experience” as approachable through language on a series of diverse regional levels, but nonetheless not completely describable within language. It is important to recall that in The Varieties of Religious Experience James distinguishes between the science of religions and what he calls living religion: [T] he science of religions may not be an equivalent for living religion; and if we turn to the inner difficulties of such a science, we see that a point comes when she must drop the purely theoretic attitude, and either let her knots remain uncut, or have them cut by active faith. James, VRE, p. 489. The study of religion, in short is not the activity of religion; the latter is animated, personal, and, we would argue, necessitates a commitment in terms of the will to believe. Once again, however, James hesitates over offering the same two-fold delineation in other areas of science. On the one hand he tells the reader that “science-has ended by utterly repudiating the personal point of view.”Ibid., p. 491. On the other hand, he offers the following comment a few pages later on in a footnote: ...the divorce between scientist facts and religious facts may not necessarily be as eternal as it at first sight seems, nor the personalism and romanticism of the world, as they appeared to primitive thinking, be matters so irrevocably outgrown. The final opinion may, in short, in some manner now impossible to forsee, revert to the more personal style, just as any path of progress may follow a spiral rather than a straight line. If this were so, the rigorously impersonal view of science might one day appear as having been a temporarily useful eccentricity rather than the definitely triumphant position which the sectarian scientist at present so confidently announces it to be.Ibid., p. 501, Footnote. The burden of this paper has been to indicate that when James' two-fold outlook on perception and/or common sense is properly reconstructed, the raproachment between science and religion is not so “impossible to forsee.”. (shrink)

The Cell Ontology (CL) is designed to provide a standardized representation of cell types for data annotation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL’s utility for cross-species data integration. To address this problem, we developed a method for the ontological representation of cells and applied this method to develop a (...) dendritic cell ontology (DC-CL). DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. 104. Barry Smith, “Toward a Realistic Science of Environments”, Ecological Psychology, 2009, 21 (2), April-June, 121-130. Abstract: The perceptual psychologist J. J. Gibson embraces a radically externalistic view of mind and action. We have, for Gibson, not a Cartesian mind or soul, with its interior theater of contents and the consequent problem of explaining how this mind or soul and its psychological environment can succeed in grasping physical objects external to itself. Rather, we have a perceiving, acting organism, whose perceptions and actions are always already tuned to the parts and moments, the things and surfaces, of its external environment. We describe how on this basis Gibson sought to develop a realist science of environments which will be ‘consistent with physics, mechanics, optics, acoustics, and chemistry’. (shrink)

This essay is written on the following premises and argues for them. “Enlightenment” is a word or signifier, and not a single or unifiable phenomenon which it consistently signifies. There is no single or unifiable phenomenon describable as “the Enlightenment,” but it is the definite article rather than the noun which is to be avoided. In studying the intellectual history of the late seventeenth century and the eighteenth, we encounter a variety of statements made, and assumptions proposed, to which the (...) term “Enlightenment” may usefully be applied, but the meanings of the term shift as we apply it. The things are connected, but not continuous; they cannot be reduced to a single narrative; and we find ourselves using the word “Enlightenment” in a family of ways and talking about a family of phenomena, resembling and related to one another in a variety of ways that permit of various generalizations about them. We are not, however, committed to a single root meaning of the word “Enlightenment,” and we do not need to reduce the phenomena of which we treat to a single process or entity to be termed “the” Enlightenment. It is a reification that we wish to avoid, but the structure of our language is such that this is difficult, and we will find ourselves talking of “the French” or “the Scottish,” “the Newtonian” or the “the Arminian” Enlightenments, and hoping that by employing qualifying adjectives we may constantly remind ourselves that the keyword “Enlightenment” is ours to use and should not master us. (shrink)

The first English translation of Fichte’s second set of 1804 lectures on the Wissenschaftslehre.

Unlike most other sciences, psychology has no true core theory to guide a coherent research programme. It does have James J Gibson’s ecological approach to visual perception, however, which we suggest should serve as an example of the benefits a good theory brings to psychological research. Here we focus on an example of how the ecological approach has served as a guide to discovery, shaping and constraining a recent hypothesis about how humans perform coordinated rhythmic movements (Bingham 2004a, b). (...) Early experiments on this task were framed in a dynamic pattern approach. This phenomenological, behavioural framework (e.g. Jeka & Kelso 1989) classifies the behaviour of complex action systems in terms of the key order parameters, and describes the dynamical stability of the system as it responds to perturbations. Dynamical systems, however, while a valuable toolkit, is not a theory of behaviour, and this style of research is unable to successfully predict data it is not explicitly designed to fit. More recent work by Bingham & colleagues has used dynamical systems to formalise hypotheses derived from Gibson’s ecological approach to perception and action, with a particular emphasis on perceptual information. The resulting model (Bingham 2001, 2004a, b; Snapp-Childs et al. 2011) has had great success with both the phenomena it was designed to explain as well as a wide range of empirical results from a version of the task it is not specifically designed to explain (specifically, learning a novel coordination). This model and the research programme that produced it stand as an example of the value of theory driven research, and we use it to illustrate the contemporary importance the ecological approach has for psychology. (shrink)

In recent work, Adlam (2022b), Chen & Goldstein (2022), and Meacham (2023) have defended accounts of laws that take laws to be primitive global constraints. A major advantage of these accounts is that they’re able to accommodate the many different kinds of laws that appear in physical theories. In this paper I’ll present these three accounts, highlight their distinguishing features, and note some key differences that might lead one to favor one of these accounts over the others. I’ll conclude by (...) briefly discussing a version of a “constraint” account that I think is especially attractive. (shrink)