23 research outputs found

    Does a Computer have an Arrow of Time?

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    In [Sch05a], it is argued that Boltzmann's intuition, that the psychological arrow of time is necessarily aligned with the thermodynamic arrow, is correct. Schulman gives an explicit physical mechanism for this connection, based on the brain being representable as a computer, together with certain thermodynamic properties of computational processes. [Haw94] presents similar, if briefer, arguments. The purpose of this paper is to critically examine the support for the link between thermodynamics and an arrow of time for computers. The principal arguments put forward by Schulman and Hawking will be shown to fail. It will be shown that any computational process that can take place in an entropy increasing universe, can equally take place in an entropy decreasing universe. This conclusion does not automatically imply a psychological arrow can run counter to the thermodynamic arrow. Some alternative possible explana- tions for the alignment of the two arrows will be briefly discussed.Comment: 31 pages, no figures, publication versio

    Genetic Ablation of Phosphatidylinositol Transfer Protein Function in Murine Embryonic Stem Cells

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    Phosphatidylinositol transfer proteins (PITPs) regulate the interface between signal transduction, membrane-trafficking, and lipid metabolic pathways in eukaryotic cells. The best characterized mammalian PITPs are PITPα and PITPβ, two highly homologous proteins that are encoded by distinct genes. Insights into PITPα and PITPβ function in mammalian systems have been gleaned exclusively from cell-free or permeabilized cell reconstitution and resolution studies. Herein, we report for the first time the use of genetic approaches to directly address the physiological functions of PITPα and PITPβ in murine cells. Contrary to expectations, we find that ablation of PITPα function in murine cells fails to compromise growth and has no significant consequence for bulk phospholipid metabolism. Moreover, the data show that PITPα does not play an obvious role in any of the cellular activities where it has been reconstituted as an essential stimulatory factor. These activities include protein trafficking through the constitutive secretory pathway, endocytic pathway function, biogenesis of mast cell dense core secretory granules, and the agonist-induced fusion of dense core secretory granules to the mast cell plasma membrane. Finally, the data demonstrate that PITPα-deficient cells not only retain their responsiveness to bulk growth factor stimulation but also retain their pluripotency. In contrast, we were unable to evict both PITPβ alleles from murine cells and show that PITPβ deficiency results in catastrophic failure early in murine embryonic development. We suggest that PITPβ is an essential housekeeping PITP in murine cells, whereas PITPα plays a far more specialized function in mammals than that indicated by in vitro systems that show PITP dependence

    Mouse genetics and metabolic mouse phenotyping.

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    The mouse is widely considered as a toolbox for modeling human diseases: mice are easy to handle and breed, there exist inbred strains, and the mouse genome sequence is available. Mutant mouse lines can be generated by different technologies, and standardized phenotyping of these mutant mouse lines produces a huge amount of valuable data. Useful resources for the scientific community are archives of mutant lines and strains as well as databases delivering information about the mouse lines and their availability. The phenotypic characterization of mutant mouse lines is the bottleneck within the pipeline from the generation via phenotyping to archiving of mutant mouse lines. Mouse clinics generate large data sets by the standardized, comprehensive phenotypic characterization of mutant mouse lines. There is a portfolio of phenotyping protocols available for a broad spectrum of disease areas that is considered as an international standard. For the investigation of human diseases like diabetes, obesity or the metabolic syndrome, metabolic tests to analyze mutant mouse lines become increasingly important. In this respect, challenge experiments have become the major focus to induce disease phenotypes in mutant mice that would remain undiscovered without the environmental challenges. These experimental setups reflect human conditions, where genetic predisposition and the environmental factors originating from different life style act together and enhance each other
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