2,361 research outputs found

    Corticotropin-releasing hormone exerts direct effects on neuronal progenitor cells: implications for neuroprotection

    Get PDF
    Neurogenesis during embryonic and adult life is tightly regulated by a network of transcriptional, growth and hormonal factors. Emerging evidence indicates that activation of the stress response, via the associated glucocorticoid increase, reduces neurogenesis and contributes to the development of adult diseases.As corticotrophin-releasing hormone (CRH) or factor is the major mediator of adaptive response to stressors, we sought to investigate its involvement in this process. Accordingly, we found that CRH could reverse the damaging effects of glucocorticoid on neural stem/progenitor cells (NS/PCs), while its genetic deficiency results in compromised proliferation and enhanced apoptosis during neurogenesis. Analyses in fetal and adult mouse brain revealed significant expression of CRH receptors in proliferating neuronal progenitors. Furthermore, by using primary cultures of NS/PCs, we characterized the molecular mechanisms and identified CRH receptor-1 as the receptor mediating the neuroprotective effects of CRH. Finally, we demonstrate the expression of CRH receptors in human fetal brain from early gestational age, in areas of active neuronal proliferation. These observations raise the intriguing possibility for CRH-mediated pharmacological applications in diseases characterized by altered neuronal homeostasis, including depression, dementia, neurodegenerative diseases, brain traumas and obesity

    Inconsistency of the MLE for the joint distribution of interval censored survival times and continuous marks

    Full text link
    This paper considers the nonparametric maximum likelihood estimator (MLE) for the joint distribution function of an interval censored survival time and a continuous mark variable. We provide a new explicit formula for the MLE in this problem. We use this formula and the mark specific cumulative hazard function of Huang and Louis (1998) to obtain the almost sure limit of the MLE. This result leads to necessary and sufficient conditions for consistency of the MLE which imply that the MLE is inconsistent in general. We show that the inconsistency can be repaired by discretizing the marks. Our theoretical results are supported by simulations.Comment: 27 pages, 4 figure

    A simple scheme for allocating capital in a foreign exchange proprietary trading firm

    Get PDF
    We present a model of capital allocation in a foreign exchange proprietary trading firm. The owner allocates capital to individual traders, who operate within strict risk limits. Traders specialize in individual currencies, but are given discretion over their choice of trading rule. The owner provides the simple formula that determines position sizes – a formula that does not require estimation of the firm-level covariance matrix. We provide supporting empirical evidence of excess risk-adjusted returns to the firm-level portfolio, and we discuss a modification of the model in which the owner dictates the choice of trading rule

    Stability of an Exciton bound to an Ionized Donor in Quantum Dots

    Full text link
    Total energy, binding energy, recombination rate (of the electron hole pair) for an exciton (X) bound in a parabolic two dimensional quantum dot by a donor impurity located on the z axis at a distance d from the dot plane, are calculated by using the Hartree formalism with a recently developed numerical method (PMM) for the solution of the Schroedinger equation. As our analysis indicates there is a critical dot radius such that for radius less than the critical radius the complex is unstable and with an increase of the impurity distance this critical radius increases. Furthermore, there is a critical value of the mass ratio such that for mass ratio less than the critical value the complex is stable. The appearance of this stability condition depends both on the impurity distance and the dot radius, in a way that with an increase of the impurity distance we have an increase in the maximum dot radius where this stability condition appears. For dot radii greater than this maximum dot radius (for fixed impurity distance) the complex is always stable.Comment: 17 pages, 7 figures Applying a new numerical method which is based on the adiabatic stability of quantum mechanics, we study the stability of an exciton (X) bound in a parabolic two dimensional quantum dot by a donor impurity located on the z axis at a distance d from the dot plan

    Layering and temperature-dependent magnetization and anisotropy of naturally produced Ni/NiO multilayers

    Get PDF
    Ni/NiO multilayers were grown by magnetron sputtering at room temperature, with the aid of the natural oxidation procedure. That is, at the end of the deposition of each single Ni layer, air is let to flow into the vacuum chamber through a leak valve. Then, a very thin NiO layer (~1.2nm) is formed. Simulated x-ray reflectivity patterns reveal that layering is excellent for individual Ni-layer thickness larger than 2.5nm, which is attributed to the intercalation of amorphous NiO between the polycrystalline Ni layers. The magnetization of the films, measured at temperatures 5–300K, has almost bulk- like value, whereas the films exhibit a trend to perpendicular magnetic anisotropy (PMA) with an unusual significant positive interface anisotropy contribution, which presents a weak temperature dependence. The power-law behavior of the multilayers indicates a non-negligible contribution of higher order anisotropies in the uniaxial anisotropy. Bloch-law fittings for the temperature dependence of the magnetization in the spin-wave regime show that the magnetization in the multilayers decreases faster as a function of temperature than the one of bulk Ni. Finally, when the individual Ni-layer thickness decreases below 2nm, the multilayer stacking vanishes, resulting in a dramatic decrease of the interface magnetic anisotropy and consequently in a decrease of the perpendicular magnetic anisotropy

    On the Pulse Intensity Modulation of PSR B0823+26

    Full text link
    We investigate the radio emission behaviour of PSR B0823+26, a pulsar which is known to undergo pulse nulling, using an 153-d intensive sequence of observations. The pulsar is found to exhibit both short (~min) and unusually long-term (~hours or more) nulls, which not only suggest that the source possesses a distribution of nulling timescales, but that it may also provide a link between conventional nulling pulsars and longer-term intermittent pulsars. Despite seeing evidence for periodicities in the pulsar radio emission, we are uncertain whether they are intrinsic to the source, due to the influence of observation sampling on the periodicity analysis performed. Remarkably, we find evidence to suggest that the pulsar may undergo pre-ignition periods of 'emission flickering', that is rapid changes between radio-on (active) and -off (null) emission states, before transitioning to a steady radio-emitting phase. We find no direct evidence to indicate that the object exhibits any change in spin-down rate between its radio-on and -off emission modes. We do, however, place an upper limit on this variation to be <= 6 % from simulations. This indicates that emission cessation in pulsars does not necessarily lead to large changes in spin-down rate. Moreover, we show that such changes in spin-down rate will not be discernible in the majority of objects which exhibit short-term (<= 1 d) emission cessation. In light of this, we predict that many pulsars could exhibit similar magnetospheric and emission properties to PSR B0823+26, but which have not yet been observed.Comment: 13 pages, 11 figures, accepted for publication in MNRAS; 1 reference correcte

    Business experience and start-up size: buying more lottery tickets next time around?

    Get PDF
    This paper explores the determinants of start-up size by focusing on a cohort of 6247 businesses that started trading in 2004, using a unique dataset on customer records at Barclays Bank. Quantile regressions show that prior business experience is significantly related with start-up size, as are a number of other variables such as age, education and bank account activity. Quantile treatment effects (QTE) estimates show similar results, with the effect of business experience on (log) start-up size being roughly constant across the quantiles. Prior personal business experience leads to an increase in expected start-up size of about 50%. Instrumental variable QTE estimates are even higher, although there are concerns about the validity of the instrument
    corecore