There is an intensive discussion nowadays about the meaning of effective computability, with implications to the status and provability of the Church-Turing Thesis (CTT). I begin by reviewing what has become the dominant account of the way Turing and Church viewed, in 1936, effective computability. According to this account, to which I refer as the Gandy-Sieg account, Turing and Church aimed to characterize the functions that can be computed by a human computer. In addition, Turing provided a highly convincing argument for CTT by analyzing the processes carried out by a human computer. I then contend that if the Gandy-Sieg account is correct, then the notion of effective computability has changed after 1936. Today computer scientists view effective computability in terms of finite machine computation. My contention is supported by the current formulations of CTT, which always refer to machine computation, and by the current argumentation for CTT, which is different from the main arguments advanced by Turing and Church. I finally turn to discuss Robin Gandy’s characterization of machine computation. I suggest that there is an ambiguity regarding the types of machines Gandy was postulating. I offer three interpretations, which differ in their scope and limitations, and conclude that none provides the basis for claiming that Gandy characterized finite machine computation.
We demonstrate electro-optic spatial two-dimensional mode switching in a bulk sample of potassium lithium tantalate niobate. Spatial confinement, mode coupling, and electro-optic functionality are mediated by two photorefractive needle solitons of opposite electroholographic charges embedded together in their anisotropic lobular structure. (C) 2002 Optical Society of America.
Cities form one of the principal arenas in which globalization processes are manifest. Much of the interest in the urban outcomes of globalization is focused on a limited number of iconic 'global' or 'world' cities. Most places however will never attain that status. They are more likely to play limited and specialized roles in a world economy increasingly dominated by flows. Emerging Nodes in a Global Network looks at the temporal and volatile ways in which two such cities, Frankfurt and Tel Aviv, engage the global economy. The central thesis of the book contends that the current round of globalization is characterized by places selectively functioning as nodes within global networks. Drawing on a combination of qualitative and quantitative empirical studies of leading sectors in Frankfurt and Tel Aviv (financial and business services, high technology, air transportation, tourism and cultural industries), the process of network formation is systematically analyzed and the role of national and regional policy is highlighted. Audience: This book will be of major interest to academics, researchers, practitioners and policy makers in the areas of urban and economic geography, public policy and economic development. It also provides valuable material for government officials and regional and national agencies involved in metropolitan planning and development.
Activation of the epidermal growth factor (EGF) receptor by its ligand, EGF, rapidly enhances receptor internalization and degradation, which desensitizes receptor signaling. In contrast, we have shown previously that exposure to oxidative stress in the form of hydrogen peroxide (H(2)O(2)) activated the EGF receptor but that the levels of activated receptors did not decline, which resulted in prolonged receptor signaling. This study provides mechanistic insights into these different modes of EGF receptor activation. Here we demonstrate that the pattern of receptor tyrosine phosphorylation induced by H(2)O(2) differs from that induced by its ligand, EGF. Importantly, H(2)O(2) generates a receptor with negligible phosphorylation at tyrosine 1045, the major docking site for the ubiquitin ligase c-Cbl. As a result, H(2)O(2)-activated receptors fail to recruit c-Cbl and do not undergo ubiquitination and endocytosis. In summary, H(2)O(2) stimulation results in an activated receptor uncoupled from normal down-regulation, a process that may contribute to oxidant-mediated tumorigenesis.
In this article I attempt to present an explanation that integrates the five features needed for the cognitive (knowledge-yielding) linking of philosophy and literature. These features are, first, explaining how a literary work can support a general claim. Second, explaining what is uniquely gained through concentrating on such support patterns as they appear in aesthetic contexts in particular. Third, explaining how features of aesthetic response are connected with knowledge. Four, maintaining a distinction between manipulation and adequate persuasion. Five, achieving all this without invoking what David Novitz has called “a shamelessly functional and didactic view of literature.” [ABSTRACT FROM AUTHOR]Copyright of Metaphilosophy is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Emerin belongs to the LEM-domain family of nuclear membrane proteins, which are conserved in metazoans from C. elegans to humans. Loss of emerin in humans causes the X-linked form of Emery-Dreifuss muscular dystrophy (EDMD), but the disease mechanism is not understood. We have begun to address the function of emerin in C. elegans, a genetically tractable nematode. The emerin gene (emr-1) is conserved in C. elegans. We detect Ce-emerin protein in the nuclear envelopes of all cell types except sperm, and find that Ce-emerin co-immunoprecipitates with Ce-lamin from embryo lysates. We show for the first time in any organism that nuclear lamins are essential for the nuclear envelope localization of emerin during early development. We further show that four other types of nuclear envelope proteins, including fellow LEM-domain protein Ce-MAN1, as well as Ce-lamin, UNC-84 and nucleoporins do not depend on Ce-emerin for their localization. This result suggests that emerin is not essential to organize or localize the only lamin (B-type) expressed in C. elegans. We also analyzed the RNAi phenotype resulting from the loss of emerin function in C. elegans under laboratory growth conditions, and found no detectable phenotype throughout development. We propose that C. elegans is an appropriate system in which to study the molecular mechanisms of emerin function in vivo.
Invertebrates and in Drosophila, lamins and lamin-associated proteins are primary targets for cleavage by caspases. Eliminating mammalian lamins causes apoptosis, whereas expressing mutant lamins that cannot be cleaved by caspase-6 delay apoptosis. Caenorhabditis elegans has a single lamin protein, Ce-lamin, and a caspase, CED-3, that is responsible for most if not all somatic apoptosis. In this study we show that in C. elegans embryos induced to undergo apoptosis Ce-lamin is degraded surprisingly late. In such embryos CED-4 translocated to the nuclear envelope but the cytological localization of Ce-lamin remained similar to that in wild-type embryos. TUNEL labeling indicated that Ce-lamin was degraded only after DNA is fragmented. Ce-lamin, Ce-emerin, or Ce-MAN1 were not cleaved by recombinant CED-3, showing that these lamina proteins are not substrates for CED-3 cleavage. These results suggest that lamin cleavage probably is not essential for apoptosis in C. elegans.
Repression or overexpression of ferritin accelerated or retarded cell cycling respectively, via changes in the cellular labile iron pool (LIP). A rise in LIP is caused by ferritin repression enhanced growth, induced by H-ras, and reverted growth arrest is induced by dominant negative H-ras. The studies indicate that repression of ferritin expression provides a mechanism by which certain oncogenes lead to cell growth stimulation.
Five polycyclic aromatic hydrocarbons of the C-26 series having similar bonding structure yield dianions upon reduction with lithium metal. Anisotropy changes, revealed from an advanced charge distribution analysis performed on these dianions, show a correlation to the bonding structure of the dianions. Electron counting and orbital considerations rationalize this correlation in terms of aromatic/anti-aromatic behaviour that is mixed into the character of the aromatic PAH upon reduction. Predictions made regarding relative stability based on this correlation were successfully tested against calculation and experiment. The anisotropy change is suggested as a valid index for the reduction-induced change in the aromatic character of PAHs, which is applicable for both aromatic and anti-aromatic changes.
Anterior-posterior patterning of the embryo requires the activity of multiple homeobox genes among them Hox, caudal (Cdx, Xcad) and Otx2. During early gastrulation, Otx2 and Xcad2 establish a cross-regulatory network, which is an early event in the anterior-posterior patterning of the embryo. As gastrulation proceeds and the embryo elongates, a new domain forms, which expresses neither, Otx2 nor Xcad2 genes. Early transcription of the Xenopus Gbx2 homologue, Xgbx2a, is spatially restricted between Otx2 and Xcad2. When overexpressed, Otx2 and Xcad2 repress Xgbx2a transcription, suggesting their role in setting the early Xgbx2a expression domain. Homeobox genes have been shown to play crucial roles in the specification of the vertebrate brain. The border between the transcription domains of Otx2 and Gbx2 is the earliest known marker of the region where the midbrain/hindbrain boundary (MHB) organizer will develop. Xgbx2a is a negative regulator of Otx2 and a weak positive regulator of Xcad2. Using obligatory activator and repressor versions of Xgbx2a, we demonstrate that, during early embryogenesis, Xgbx2a acts as a transcriptional repressor. In addition, taking advantage of hormone-inducible versions of Xgbx2a and its antimorph, we show that the ability of Xgbx2a to induce head malformations is restricted to gastrula stages and correlates with its ability to repress Otx2 during the same developmental stages. We therefore suggest that the earliest known step of the MHB formation, the establishment of Otx2/Gbx2 boundary, takes place via mutual inhibitory interactions between these two genes and this process begins as early as at midgastrulation.
Theodore Sider distinguishes two notions of global supervenience: strong global supervenience and weak global supervenience. He then discusses some applications to general metaphysical questions. Most interestingly, Sider employs the weak notion in order to undermine a familiar argument against coincident distinct entities. In what follows, I reexamine the two notions and distinguish them from a third, intermediate, notion (“intermediate global supervenience”). I argue that (a) weak global supervenience is not an adequate notion of dependence; (b) weak global supervenience does not capture certain assumptions about coincidence relations; (c) these assumptions are better accommodated by the stronger notion of intermediate global supervenience; (d) intermediate global supervenience, however, may not be an adequate notion of dependence; and (e) strong global supervenience is an adequate notion of dependence. It also fits in with anti-individualism about the mental. It does not, however, serve to rebut arguments against coincident entities.
