The intelligibility of motion and construction: Descartes’ early mathematics and metaphysics, 1619-1637

I argue for an interpretation of the connection between Descartes’ early mathematics and metaphysics that centers on the standard of geometrical intelligibility that characterizes Descartes’ mathematical work during the period 1619 to 1637. This approach remains sensitive to the innovations of Descartes’ system of geometry and, I claim, sheds important light on the relationship between his landmark Geometry (1637) and his first metaphysics of nature, which is presented in Le monde (1633). In particular, I argue that the same standard of clear and distinct motions for construction that allows Descartes to distinguish ‘geometric’ from ‘imaginary’ curves in the domain of mathematics is adopted in Le monde as Descartes details God’s construction of nature. I also show how, on this interpretation, the metaphysics of Le monde can fruitfully be brought to bear on Descartes’ attempted solution to the Pappus problem, which he presents in Book I of the Geometry. My general goal is to show that attention to the standard of intelligibility Descartes invokes in these different areas of inquiry grants us a richer view of the connection between his early mathematics and philosophy than an approach that assumes a common method is what binds his work in these domains together.     

The concept of transition and its role in Leibniz’s and Whitehead’s metaphysics of motion

Leibniz’s and Whitehead’s analyses of motion are at the heart of their metaphysical schemes. These schemes are to be considered as two blueprints of a similar metaphysical intuition that emerged during two breakthrough eras, that is, the 17th century and the beginning of the 20th century, and retained the Aristotelian idea that existence requires an active principle. The two philosophers’ attempts to elucidate this idea in the context of their analyses of motion still interact with central, longstanding questions in philosophy, in particular that concerning the ontological status of change. For both thinkers, the phenomenon of motion is an example par excellence, of the metaphysically fundamental principle of action that is required for change in the world. I focus on Leibniz’s and Whitehead’s similar understanding of the concept of transition that is inserted as an essential constitutive component of motion and ensures its status as something real.     

The birth of classical genetics as the junction of two disciplines: Conceptual change as representational change

The birth of classical genetics in the 1910's was the result of the junction of two modes of analysis, corresponding to two disciplines: Mendelism and cytology. The goal of this paper is to shed some light on the change undergone by the science of heredity at the time, and to emphasize the subtlety of the conceptual articulation of Mendelian and cytological hypotheses within classical genetics. As a way to contribute to understanding how the junction of the two disciplines at play gave birth to a new way of studying heredity, my focus will be on the forms of representation used in genetics research at the time. More particularly, I will study the design and development, by Thomas H. Morgan's group, of the technique of linkage mapping, which embodies the integration of the Mendelian and cytological forms of representation. I will show that the design of this technique resulted in a genuine conceptual change, which should be described as a representational change, rather than merely as the introduction of new hypotheses into genetics.     

The annexins: spatial and temporal coordination of signaling events during cellular stress

Annexins are a family of structurally related, Ca²⁺-sensitive proteins that bind to negatively charged phospholipids and establish specific interactions with other lipids and lipid microdomains. They are present in all eukaryotic cells and share a common folding motif, the “annexin core”, which incorporates Ca²⁺- and membrane-binding sites. Annexins participate in a variety of intracellular processes, ranging from the regulation of membrane dynamics to cell migration, proliferation, and apoptosis. Here we focus on the role of annexins in cellular signaling during stress. A chronic stress response triggers the activation of different intracellular pathways, resulting in profound changes in Ca²⁺ and pH homeostasis and the production of lipid second messengers. We review the latest data on how these changes are sensed by the annexins, which have the ability to simultaneously interact with specific lipid and protein moieties at the plasma membrane, contributing to stress adaptation via regulation of various signaling pathways.     

Changes in calpastatin localization and expression during calpain activation: a new mechanism for the regulation of intracellular Ca<Superscript>2+</Superscript>-dependent proteolysis

The amount of calpastatin directly available in cytosol is under the control of [Ca²⁺] and [cyclic AMP]. Prolonged calpain activation also promotes degradation of calpastatin. The fluctuation of calpastatin concentration in cell soluble fraction is accompanied by an initial decrease in calpastatin gene expression, followed by a fivefold increase in its expression when the inhibitor protein is degraded. This process can be conceptualized as a mechanism to regulate calpastatin availability in the cell. This conclusion is supported by the fact that calpain, the other component of this proteolytic system, undergoes changes in its levels of expression in a much more limited manner. Furthermore, this process can be observed both in cells exposed to different natural stimuli, or in other cell lines. Modification of calpastatin gene expression might represent a new tool for the in vivo control of the regulatory machinery required for the modulation of Ca²⁺-dependent proteolysis.Received 18 July 2003; received after revision 3 September 2003; accepted 23 September 2003     

<Emphasis Type="Italic">The Art of War:</Emphasis> Innate and adaptive immune responses

Research over the last several years has greatly advanced our understanding of the mechanisms by which the immune system functions. There exist two main branches of immunity, termed innate and adaptive immunity. Innate immunity uses the genetic memory of germline-encoded receptors to recognize the molecular patterns of common pathogens. Adaptive immunity, akin to somatic memory, is a complex system by which the body learns to recognize a pathogens unique antigens and builds an antigen specific response to destroy it. The effective development of the overall immune response depends on careful interplay and regulation between innate and adaptive immunity. Here we review our current understanding of how these integrated systems distinguish targets against which a response is appropriate and neutralize potentially pathogenic challenges.Received 8 May 2003; accepted 2 June 2003     

Newton–Cartan theory and teleparallel gravity: The force of a formulation

It is well-known that Newtonian gravity, commonly held to describe a gravitational force, can be recast in a form that incorporates gravity into the geometry of the theory: Newton–Cartan theory. It is less well-known that general relativity, a geometrical theory of gravity, can be reformulated in such a way that it resembles a force theory of gravity; teleparallel gravity does just this. This raises questions. One of these concerns theoretical underdetermination. I argue that these theories do not, in fact, represent cases of worrying underdetermination. On close examination, the alternative formulations are best interpreted as postulating the same spacetime ontology. In accepting this, we see that the ontological commitments of these theories cannot be directly deduced from their mathematical form. The spacetime geometry involved in a gravitational theory is not a straightforward consequence of anything internal to that theory as a theory of gravity. Rather, it essentially relies on the rest of nature (the non-gravitational interactions) conspiring to choose the appropriate set of inertial frames.     

The E-site story: the importance of maintaining two tRNAs on the ribosome during protein synthesis

In the sixties James Watson suggested a twosite model for the ribosome comprising the P site for the peptidyl transfer RNA (tRNA) before peptide-bond formation and the A site, where decoding takes place according to the codon exposed there. In the eighties a third tRNA binding site was detected, the E site, which was specific for deacylated tRNA and turned out to be a universal feature of ribosomes. However, despite having three tRNA binding sites, only two tRNAs occupy the ribosome at a time during protein synthesis: at the A and P sites before translocation (PRE state) and at the P and E sites after translocation (POST state). The importance of having two tRNAs in the POST state has been revealed during the last 25 years, showing that the E site contributes two fundamental features: (i) the fact that incorporation of a wrong amino acid is not harmful for the cell (only 1 in about 400 misincorporations destroys the function of a protein) stems from the presence of an E-tRNA; (ii) maintenance of the reading frame is one of the most remarkable achievements of the ribosome, essential for faithful translation of the genetic information. The presence of the POST state E-tRNA prevents loss of the reading frame. Received 14 March 2006; received after revision 8 June 2006; accepted 4 August 2006     

The electrons of the dinosaurs and the center of the Earth: comments on D.D. Turner’s ‘The past vs. the tiny: historical science and the abductive arguments for realism’

Turner [The past vs. the tiny: Historical science and the abductive arguments for realism. Studies in History and Philosophy of Science 35A (2004) 1] claims that the arguments in favor of realism do not support with the same force both classes of realism, since they supply stronger reasons for experimental realism than for historical realism. I would like to make two comments, which should be seen as amplifications inspired by his proposal, rather than as a criticism. First, it is important to highlight that Turner’s distinction between ‘tiny’ and ‘past unobservables’ is neither excluding nor exhaustive. Second, even if we agreed with everything that Turner says regarding the arguments for realism and their relative weight in order to justify the experimental or historical version, there is an aspect that Turner does not consider and that renders historical realism less problematic than experimental realism.     

The concentration of ammonia in the excreta of sixth instar larvae ofLamida moncusalis Walker (Pyralidae: Lepidoptera) during development

Summary The concentration of ammonia in the fresh and dry excreta ofLamida moncusalis Walker was determined. It was found that a large quantity of ammonia was lost from the excreta on drying. Ammonia is one of the major excretory products of the larva.5 September 1986Acknowledgment. We thank the State Committee on Science, Technology and Environment, Kerala, for the financial assistance.