795 research outputs found

    A Good Quality of Death

    Get PDF

    The experimental study of the relation between the Alpha rhythm of the electroencephalogram and intelligence

    Get PDF
    During in the year 1808, Gall was assessing a person\u27s intellectual attributes by means of bumps in their heads. He held the opinion that an intellectual trait, as well as any other trait, would show the degree of its development by exerting a local pressure, pressing outward and finally appearing as a bump

    Commentaire d\u27Arret: Le Procureur General du Canada c. Patrick Francis Ward

    Get PDF
    The following article is a case comment on Attorney General of Canada v. Patrick Francis Ward, a recent decision of the Federal Court of Appeal. A summary of the facts and issues involved will be provided, followed by an analysis of the majority and dissenting judgments. Particular emphasis will be directed toward the definition of Convention refugee and how the majority decision has dealt with it. This will be contrasted with previous doctrine and jurisprudence. Finally certain problematic aspects of both the majority and dissenting judgments will be examined as well as the possible implications of this case for future refugee claimants in Canada

    Commentaire d\u27Arret: Le Procureur General du Canada c. Patrick Francis Ward

    Get PDF
    The following article is a case comment on Attorney General of Canada v. Patrick Francis Ward, a recent decision of the Federal Court of Appeal. A summary of the facts and issues involved will be provided, followed by an analysis of the majority and dissenting judgments. Particular emphasis will be directed toward the definition of Convention refugee and how the majority decision has dealt with it. This will be contrasted with previous doctrine and jurisprudence. Finally certain problematic aspects of both the majority and dissenting judgments will be examined as well as the possible implications of this case for future refugee claimants in Canada

    Thermodynamic and Kinetic Analysis of Sensitivity Amplification in Biological Signal Transduction

    Get PDF
    Based on a thermodynamic analysis of the kinetic model for the protein phosphorylation-dephosphorylation cycle, we study the ATP (or GTP) energy utilization of this ubiquitous biological signal transduction process. It is shown that the free energy from hydrolysis inside cells, ΔG\Delta G (phosphorylation potential), controls the amplification and sensitivity of the switch-like cellular module; the response coefficient of the sensitivity amplification approaches the optimal 1 and the Hill coefficient increases with increasing ΔG\Delta G. We discover that zero-order ultrasensitivity is mathematically equivalent to allosteric cooperativity. Furthermore, we show that the high amplification in ultrasensitivity is mechanistically related to the proofreading kinetics for protein biosynthesis. Both utilize multiple kinetic cycles in time to gain temporal cooperativity, in contrast to allosteric cooperativity that utilizes multiple subunits in a protein.Comment: 19 pages, 7 figure

    Thresholds, long delays and stability from generalized allosteric effect in protein networks

    Full text link
    Post-transductional modifications tune the functions of proteins and regulate the collective dynamics of biochemical networks that determine how cells respond to environmental signals. For example, protein phosphorylation and nitrosylation are well-known to play a pivotal role in the intracellular transduction of activation and death signals. A protein can have multiple sites where chemical groups can reversibly attach in processes such as phosphorylation or nitrosylation. A microscopic description of these processes must take into account the intrinsic probabilistic nature of the underlying reactions. We apply combinatorial considerations to standard enzyme kinetics and in this way we extend to the dynamic regime a simplified version of the traditional models on the allosteric regulation of protein functions. We link a generic modification chain to a downstream Michaelis-Menten enzymatic reaction and we demonstrate numerically that this accounts both for thresholds and long time delays in the conversion of the substrate by the enzyme. The proposed mechanism is stable and robust and the higher the number of modification sites, the greater the stability. We show that a high number of modification sites converts a fast reaction into a slow process, and the slowing down depends on the number of sites and may span many orders of magnitude; in this way multisite modification of proteins stands out as a general mechanism that allows the transfer of information from the very short time scales of enzyme reactions (milliseconds) to the long time scale of cell response (hours).Comment: 5 figures, submitted to Physica

    Assessment of oxidative metabolism

    Get PDF
    Oxidative metabolism is one of the central physiological processes that regulate multiple functions in a cell including cell death and survival, proliferation, gene transcription, and protein modification. There are multitudes of techniques that are used to evaluate oxidative activity. Here, we summarize how to measure oxidative activity by flow cytometry. This versatile technique allows the evaluation of the level of oxidative activity within heterogeneous populations of cells and in cell culture. Flow cytometry is a quick method that yields highly reproducible results with small sample volumes. Therefore, it is an ideal technique for evaluating changes in oxidative activity in samples from mice

    Validation of protein carbonyl measurement:a multi-centre study

    Get PDF
    Protein carbonyls are widely analysed as a measure of protein oxidation. Several different methods exist for their determination. A previous study had described orders of magnitude variance that existed when protein carbonyls were analysed in a single laboratory by ELISA using different commercial kits. We have further explored the potential causes of variance in carbonyl analysis in a ring study. A soluble protein fraction was prepared from rat liver and exposed to 0, 5 and 15 min of UV irradiation. Lyophilised preparations were distributed to six different laboratories that routinely undertook protein carbonyl analysis across Europe. ELISA and Western blotting techniques detected an increase in protein carbonyl formation between 0 and 5 min of UV irradiation irrespective of method used. After irradiation for 15 min, less oxidation was detected by half of the laboratories than after 5 min irradiation. Three of the four ELISA carbonyl results fell within 95% confidence intervals. Likely errors in calculating absolute carbonyl values may be attributed to differences in standardisation. Out of up to 88 proteins identified as containing carbonyl groups after tryptic cleavage of irradiated and control liver proteins, only seven were common in all three liver preparations. Lysine and arginine residues modified by carbonyls are likely to be resistant to tryptic proteolysis. Use of a cocktail of proteases may increase the recovery of oxidised peptides. In conclusion, standardisation is critical for carbonyl analysis and heavily oxidised proteins may not be effectively analysed by any existing technique
    • …
    corecore