Quantile regression with varying coefficients

Quantile regression provides a framework for modeling statistical quantities of interest other than the conditional mean. The regression methodology is well developed for linear models, but less so for nonparametric models. We consider conditional quantiles with varying coefficients and propose a methodology for their estimation and assessment using polynomial splines. The proposed estimators are easy to compute via standard quantile regression algorithms and a stepwise knot selection algorithm. The proposed Rao-score-type test that assesses the model against a linear model is also easy to implement. We provide asymptotic results on the convergence of the estimators and the null distribution of the test statistic. Empirical results are also provided, including an application of the methodology to forced expiratory volume (FEV) data.Comment: Published at http://dx.doi.org/10.1214/009053606000000966 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Claspin and the Activated Form of ATR-ATRIP Collaborate in the Activation of Chk1

Claspin is necessary for the ATR-dependent activation of Chk1 in Xenopus egg extracts containing incompletely replicated DNA. ATR possesses a regulatory partner called ATRIP. We have studied the respective roles of ATR-ATRIP and Claspin in the activation of Chk1. ATR-ATRIP bound well to various DNA templates in Xenopus egg extracts. ATR-ATRIP bound to a single-stranded DNA template was weakly active. By contrast, the ATR-ATRIP complex on a DNA template containing both single- and double-stranded regions displayed a large increase in kinase activity. This observation suggests that ATR-ATRIP normally undergoes activation upon association with specific nucleic acid structures at DNA replication forks. Without Claspin, activated ATR-ATRIP phosphorylated Chk1 weakly in a cell-free reaction. The addition of Claspin to this reaction strongly stimulated the phosphorylation of Chk1 by ATR-ATRIP. Claspin also induced significant autophosphorylation of Chk1 in the absence of ATR-ATRIP. Taken together, these results indicate that the checkpoint-dependent phosphorylation of Chk1 is a multistep process involving activation of the ATR-ATRIP complex at replication forks and presentation of Chk1 to this complex by Claspin

Different Behavior of Magnetic Impurities in Crystalline and Ammorphous States of Superconductors

It has been observed that the effect of magnetic impurities in a superconductor is drastically different depending on whether the host superconductor is in a crystalline or an amorphous state. Based on the recent theory of Kim and Overhauser (KO), it is shown that as the system is getting disordered, the initial slope of the $T_{c}$ depression is decreasing by a factor $\sqrt{\ell/\xi_{0}}$, when the mean free path $\ell$ becomes smaller than the BCS coherence length $\xi_{0}$, which is in agreement with experimental findings. In addition, for a superconductor in a crystalline state in the presence of magnetic impurities the superconducting transition temperature $T_{c}$ drops sharply from about 50% of $T_{c0}$ (for a pure system) to zero near the critical impurity concentration. This {\sl pure limit behavior} was indeed found by Roden and Zimmermeyer in crystalline Cd. Recently, Porto and Parpia have also found the same {\sl pure limit behavior} in superfluid He-3 in aerogel, which may be understood within the framework of the KO theory.Comment: 7 figures, 20 pages, latex, to appear in Superconductor Science and Technolog

Terahertz quantum plasmonics at nanoscales and angstrom scales

Through the manipulation of metallic structures, light-matter interaction can enter into the realm of quantum mechanics. For example, intense terahertz pulses illuminating a metallic nanotip can promote terahertz field-driven electron tunneling to generate enormous electron emission currents in a subpicosecond time scale. By decreasing the dimension of the metallic structures down to the nanoscale and angstrom scale, one can obtain a strong field enhancement of the incoming terahertz field to achieve atomic field strength of the order of V/nm, driving electrons in the metal into tunneling regime by overcoming the potential barrier. Therefore, designing and optimizing the metal structure for high field enhancement are an essential step for studying the quantum phenomena with terahertz light. In this review, we present several types of metallic structures that can enhance the coupling of incoming terahertz pulses with the metals, leading to a strong modification of the potential barriers by the terahertz electric fields. Extreme nonlinear responses are expected, providing opportunities for the terahertz light for the strong light-matter interaction. Starting from a brief review about the terahertz field enhancement on the metallic structures, a few examples including metallic tips, dipole antenna, and metal nanogaps are introduced for boosting the quantum phenomena. The emerging techniques to control the electron tunneling driven by the terahertz pulse have a direct impact on the ultrafast science and on the realization of next-generation quantum devices

Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications.

The hepatic endoplasmic reticulum (ER)-anchored cytochromes P450 (P450s) are mixed-function oxidases engaged in the biotransformation of physiologically relevant endobiotics as well as of myriad xenobiotics of therapeutic and environmental relevance. P450 ER-content and hence function is regulated by their coordinated hemoprotein syntheses and proteolytic turnover. Such P450 proteolytic turnover occurs through a process known as ER-associated degradation (ERAD) that involves ubiquitin-dependent proteasomal degradation (UPD) and/or autophagic-lysosomal degradation (ALD). Herein, on the basis of available literature reports and our own recent findings of in vitro as well as in vivo experimental studies, we discuss the therapeutic and pathophysiological implications of altered P450 ERAD and its plausible clinical relevance. We specifically (i) describe the P450 ERAD-machinery and how it may be repurposed for the generation of antigenic P450 peptides involved in P450 autoantibody pathogenesis in drug-induced acute hypersensitivity reactions and liver injury, or viral hepatitis; (ii) discuss the relevance of accelerated or disrupted P450-ERAD to the pharmacological and/or toxicological effects of clinically relevant P450 drug substrates; and (iii) detail the pathophysiological consequences of disrupted P450 ERAD, contributing to non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) under certain synergistic cellular conditions