Agent Causation: Before and After the Ontological Turn

Imagine Ludwig has a cup of tea for breakfast. He\ud pours it; he eats his egg until it seems to him that the tea\ud should have the right temperature; he moves his hand to\ud the cup, puts his fingers at the handle, and then, careful\ud not to spill anything, he does something with his arm;\ud namely, he raises it, and if all goes well he then drinks the\ud tea without burning his lips.\ud The rising of Ludwig"s arm surely has a cause. But\ud what is the cause? Defenders of agent causation, such as\ud Thomas Reid (1788), Richard Taylor (1966), Roderick\ud Chisholm (1976a), and many more recent authors (see\ud Swinburne 1997, ch. 5; Thorp 1980; Meixner 1999; Clarke\ud 1996; O'Connor 2000) have argued that the rising of\ud Ludwig"s arm is caused by Ludwig himself. Some events\ud are caused, not by other events, but by concrete things, by\ud substances, more specifically by intentional agents

A Dual Receptor Crosstalk Model of G-Protein-Coupled Signal Transduction

Macrophage cells that are stimulated by two different ligands that bind to G-protein-coupled receptors (GPCRs) usually respond as if the stimulus effects are additive, but for a minority of ligand combinations the response is synergistic. The G-protein-coupled receptor system integrates signaling cues from the environment to actuate cell morphology, gene expression, ion homeostasis, and other physiological states. We analyze the effects of the two signaling molecules complement factors 5a (C5a) and uridine diphosphate (UDP) on the intracellular second messenger calcium to elucidate the principles that govern the processing of multiple signals by GPCRs. We have developed a formal hypothesis, in the form of a kinetic model, for the mechanism of action of this GPCR signal transduction system using data obtained from RAW264.7 macrophage cells. Bayesian statistical methods are employed to represent uncertainty in both data and model parameters and formally tie the model to experimental data. When the model is also used as a tool in the design of experiments, it predicts a synergistic region in the calcium peak height dose response that results when cells are simultaneously stimulated by C5a and UDP. An analysis of the model reveals a potential mechanism for crosstalk between the Gαi-coupled C5a receptor and the Gαq-coupled UDP receptor signaling systems that results in synergistic calcium release

Self-Consciousness in Cognitive Systems

Beckermann A. Self-Consciousness in Cognitive Systems. In: Kanzian C, Quitterer J, Runggaldier E, eds. Persons: an Interdisciplinary Approach; Proceedings of the 25th International Wittgenstein Symposium 11th to 17th August Kirchberg am Wechsel (Austria). Contributions of the Austrian Ludwig Wittgenstein Society ; 10. Wien: öbv & hpt; 2003: 72-86

On the structure of the amino-terminal domain ED 1 of the B2 receptor

Receptors for kinins are classified into B 1 (Menke et al., 1994) and B2 (McEachern et al., 1991) sub- types. Both receptors belong to the seven transmembrane domain (TMD) receptor family which activate trimeric G-proteins. The cDNAs coding for the rat (McEachern et al., 1991), the human (Hess et al., 1992; Eggerickx et al., 1992) and the mouse (Yokoyama et al., 1994) B2 receptors contain several in-frame methionine codons which could be used as an initiation site for translation; however, none of them conforms to the 'canonical' consensus sequence often preceding the initiation codon (Kozak, 1989). On the basis of sequence similarity studies the third in-frame AUG of the human B2 receptor mRNA, starting at nucleotide 223 of clone CCD-16- 2, was assumed to be the preferred start codon (Hess et al., 1992). The underlying gene of the human B2 receptor consists of three exons interrupted by two introns (Ma et al., 1994): exon-1 is non-coding, the first two in-frame AUG codons are located on exon-2, and the third in-frame AUG is located on exon-3 together with the seven transmembrane spanning sequence segments. There is no evidence for alternative splicing of the human B2 receptor pre-mRNA (Kammerer et al., 1995). To clarify which in-frame AUG serves as the translation initiation codon, we have isolated the B2 receptor protein and determined its amino-terminal sequence (Abd Alia et al., in preparation). The sequence data indicate that the B2 receptor mRNA from human foreskin fibroblasts is translated from the first in-frame initiator AUG codon. We report here that the extra segment of 27 amino acid residues which precedes the predicted amino-terminus of the receptor protein does not significantly alter the binding characteristics of the receptor