Empirical properties of large covariance matrices

The salient properties of large empirical covariance and correlation matrices are studied for three datasets of size 54, 55 and 330. The covariance is defined as a simple cross product of the returns, with weights that decay logarithmically slowly. The key general properties of the covariance matrices are the following. The spectrum of the covariance is very static, except for the top three to 10 eigenvalues, and decay exponentially fast toward zero. The mean spectrum and spectral density show no particular feature that would separate 'meaningful' from 'noisy' eigenvalues. The spectrum of the correlation is more static, with three to five eigenvalues that have distinct dynamics. The mean projector of rank k on the leading subspace shows that a large part of the dynamics occurs in the eigenvectors. Together, this implies that the reduction of the covariance to a few leading static eigenmodes misses most of the dynamics. Finally, all the analysed properties of the dynamics of the covariance and correlation are similar. This indicates that a covariance estimator correctly evaluates both volatilities and correlations, and separate estimators are not required.Covariance matrix, Correlation, Long memory, Spectrum, Spectral density,

Inhibition of vasopressin action in vascular smooth muscle by the V1 antagonist OPC-21268.

In vascular smooth muscle cells arginine vasopressin acting through the V1 receptor increases intracellular Ca, leading to vasoconstriction. Recent studies have also shown that vasopressin activates mitogen-activated protein kinase (MAP kinase), which may contribute to vasopressin-induced hypertrophy of vascular smooth muscle cells. We examined the ability of an orally active, nonpeptide selective V, antagonist (OPC-21268) to block vasopressin binding and postreceptor signaling in these cells. [H]Vasopressin binding at 2×10 mol/L was half-maximally blocked at 10 mol/L OPC-21268. To compare effects of OPC-21268 on binding and postreceptor signaling, we stimulated cells with 10 mol/L vasopressin. At this vasopressin concentration, half-maximal inhibition of binding occurred at 5×10 mol/L OPC-21268. Half-maximal inhibition of Ca efflux or increases in intracellular free Ca required higher concentrations of antagonist (10 mol/L), and half-maximal inhibition of vasopressin-stimulated MAP kinase was observed only at 10 mol/L OPC-21268. These results indicate that this agent selectively blocks both vasopressin binding and postreceptor signaling in vascular smooth muscle cells. The requirement of higher concentrations of OPC-21268 for blocking increases in intracellular Ca and activation of MAP kinase suggests that binding to a fraction of V1 receptors generates maximal levels of second messengers or the existence of subtypes of the V1 receptor with differential affinity for this antagonist. These data have implications for the clinical use of this compound

Mechanisms of interleukin-10-mediated immune suppression

Specific immune suppression and induction of anergy are essential processes in the regulation and circumvention of immune defence. Interleukin-10 (IL-10), a suppressor cytokine of T-cell proliferative and cytokine responses, plays a key regulatory role in tolerizing exogenous antigens during specific immunotherapy (SIT) of allergy and natural exposure to antigens. Specific T-cell tolerance is directed against the T-cell epitopes of an antigen and characterized by suppressed proliferative and T helper type 1 (Th1) and type 2 (Th2) cytokine responses. IL-10 elicits tolerance in T cells by selective inhibition of the CD28 co-stimulatory pathway and thereby controls suppression and development of antigen-specific immunity. IL-10 only inhibits T cells stimulated by low numbers of triggered T-cell receptors and which therefore depend on CD28 co-stimulation. T cells receiving a strong signal from the T-cell receptor alone, and thus not requiring CD28 co-stimulation, are not affected by IL-10. IL-10 inhibits CD28 tyrosine phosphorylation, the initial step of the CD28 signalling pathway, and consequently the phosphatidylinositol 3-kinase p85 binding to CD28. Together these results demonstrate that IL-10-induced selective inhibition of the CD28 co-stimulatory pathway acts as a decisive mechanism in determining whether a T cell will contribute to an immune response or become anergic