3,030 research outputs found

    Expedient and Monotone Learning Rules

    Get PDF
    This paper considers learning rules for environments in which little prior and feedback information is available to the decision-maker. Two properties of such learning rules, absolute expediency and monotonicity, are studied. The paper provides some necessary and some sufficient conditions for these properties. A number of examples show that there is quite a large variety of learning rules which have these properties. It is also shown that all learning rules that have these properties are, in some sense, related to replicator dynamics of evolutionary game theory.Absolute expediency, monotonicity, learning rule, decision making

    The role of signal transducer and activator of transcription-3 (STAT-3) in ischaemic and pharmacological postconditioning

    Get PDF
    Includes abstract. Includes bibliographical references (leaves 131-147)

    Comparing Platforms for C. elegans Mutant Identification Using High-Throughput Whole-Genome Sequencing

    Get PDF
    Whole-genome sequencing represents a promising approach to pinpoint chemically induced mutations in genetic model organisms, thereby short-cutting time-consuming genetic mapping efforts.We compare here the ability of two leading high-throughput platforms for paired-end deep sequencing, SOLiD (ABI) and Genome Analyzer (Illumina; "Solexa"), to achieve the goal of mutant detection. As a test case we used a mutant C. elegans strain that harbors a mutation in the lsy-12 locus which we compare to the reference wild-type genome sequence. We analyzed the accuracy, sensitivity, and depth-coverage characteristics of the two platforms. Both platforms were able to identify the mutation that causes the phenotype of the mutant C. elegans strain, lsy-12. Based on a 4 MB genomic region in which individual variants were validated by Sanger sequencing, we observe tradeoffs between rates of false positives and false negatives when using both platforms under similar coverage and mapping criteria.In conclusion, whole-genome sequencing conducted by either platform is a viable approach for the identification of single-nucleotide variations in the C. elegans genome

    Patient-Specific Patellofemoral Arthroplasty

    Get PDF

    Differential effects of nanoselenium doping on healthy and cancerous osteoblasts in coculture on titanium

    Get PDF
    In the present study, selenium (Se) nanoclusters were grown through heterogeneous nucleation on titanium (Ti) surfaces, a common orthopedic implant material. Normal healthy osteoblasts (bone-forming cells) and cancerous osteoblasts (osteosarcoma) were cultured on the Se-doped surfaces having three different coating densities. For the first time, it is shown that substrates with Se nanoclusters promote normal osteoblast proliferation and inhibit cancerous osteoblast growth in both separate (mono-culture) and coculture experiment. This study suggests that Se surface nanoclusters can be properly engineered to inhibit bone cancer growth while simultaneously promoting the growth of normal bone tissue

    Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose antigen induction of apoptosis of effector CTL

    Get PDF
    Experimental data suggest that negative selection of thymocytes can occur as a result of supraoptimal antigenic stimulation. It is unknown, however, whether, such mechanisms are at work in mature CD8+ T lymphocytes. Here, we show that CD8+ effector cytotoxic T lymphocytes (CTL) are susceptible to proliferative inhibition by high dose peptide antigen, leading to apoptotic death mediated by TNF-α release. Such inhibition is not reflected in the cytolytic potential of the CTL, since concentrations of antigen that are inhibitory for proliferation promote efficient lysis of target cells. Thus, although CTL have committed to the apoptotic pathway, the kinetics of this process are such that CTL function can occur before death of the CTL. The concentration of antigen required for inhibition is a function of the CTL avidity, in that concentrations of antigen capable of completely inhibiting high avidity CTL maximally stimulate low avidity CTL. Importantly, the inhibition can be detected in both activated and resting CTL. Blocking studies demonstrate that the CD8 molecule contributes significantly to the inhibitory signal as the addition of anti-CD8 antibody restores the proliferative response. Thus, our data support the model that mature CD8+ CTL can accommodate an activation signal of restricted intensity, which, if surpassed, results in deletion of that cell

    The crystal structure of JNK from Drosophila melanogaster reveals an evolutionarily conserved topology with that of mammalian JNK proteins

    Get PDF
    Pairwise sequence alignment of mammalian JIP1 and Drosophila melanogaster APLIP1 [UniProt:Q9UQF2 and UniProt:Q9W0K0, respectively]. (DOCX 24 kb
    corecore