LPS is a main causative agent of septic shock. There is a lack of effective therapies. In vitro studies have shown that uptake of apoptotic cells actively inhibits the secretion by activated macrophages (M) of proinflammatory mediators such as TNF- and that such uptake increases the antiinflammatory and immunosuppressive cytokine TGF-. We therefore investigated the protective effect of apoptotic cells against LPS-induced endotoxic shock in mice. The current report is the first study to demonstrate that administration of apoptotic cells can protect mice from LPS-induced death, even when apoptotic cells were administered 24 h after LPS challenge. The beneficial effects of administration of apoptotic cells included 1) reduced circulating proinflammatory cytokines, 2) suppression of polymorphonuclear neutrophil infiltration in target organs, and 3) decreased serum LPS levels. LPS can quickly bind to apoptotic cells

A decisive question in nonparametric smoothing techniques is the choice of the bandwidth or smoothing parameter. The present paper addresses this question when using local polynomial approximations for estimating the regression function and its derivatives. A fully-automatic bandwidth selection procedure has been proposed by Fan and Gijbels (1995a), and the empirical performance of it was tested in detail via a variety of examples. Those experiences supported the methodology towards a great extend. In this paper we establish asymptotic results for the proposed variable bandwidth selector. We provide the rate of convergence of the bandwidth estimate, and obtain the asymptotic distribution of its error relative to the theoretical optimal variable bandwidth. These asymptotic properties give extra support to the proposed bandwidth selection procedure. It is also demonstrated how the proposed selection

In an effort to capture the time variation on the instantaneous return and volatility functions, a family of time-dependent diffusion processes is introduced to model the term structure dynamics. This allows one to examine how the instantaneous return and price volatility change over time and price level. Nonparametric techniques, based on kernel regression, are used to estimate the time-varying coefficient functions in the drift and diffusion. The newly proposed semiparametric model includes most of the well-known short-term interest rate models, such as those proposed by Cox, Ingersoll and Ross (1985) and Chan, Karolyi, Longstaff and Sanders (1992). It can be used to test the goodness-of-fit of these famous time-homogeneous short rate models. The newly proposed method complements the time-homogeneous nonparametric estimation techniques of Stanton (1997) and Fan and Yao (1998), and is shown through

We extend the idea of crossvalidation to choose the smoothing parameters of the double-kernel local linear regression for estimating a conditional density. Our selection rule optimises the estimated conditional density function by minimising the integrated squared error. We also discuss three other bandwidth selection rules, an ad hoc method used by Fan et al. (1996), a bootstrap method of Hall et al. (1999) for bandwidth selection in the estimation of conditional distribution functions, modified by Bashtannyk & Hyndman (2001) to cover conditional density functions, and finally a simple approach proposed by Hyndman & Yao (2002). The performance of the new approach is compared with these three methods by simulation studies, and our method performs outstandingly well. The method is illustrated by an application to estimating the transition density and the Value-at-Risk of treasury-bill data.

In survival analysis, the relationship between a survival time and a covariate is conveniently modeled with the proportional hazards regression model. This model usually assumes that the covariate has a log-linear effect on the hazard function. In this paper we consider the proportional hazards regression model with a nonparametric risk effect. We discuss estimation of the risk function and its derivatives in two cases: when the baseline hazard function is parametrized and when it is not parametrized. In the case of a parametric baseline hazard function, inference is based on a local version of the likelihood function, while in the case of a nonparametric baseline hazard, we use a local version of the partial likelihood. This results in maximum local likelihood estimators and maximum local partial likelihood estimators, respectively. We establish the asymptotic normality of the estimators. It turns out that both methods have