Higher-Order Asymptotic Properties of Kernel Density Estimator with Global Plug-In and Its Accompanying Pilot Bandwidth

This study investigates the effect of bandwidth selection via a plug-in method on the asymptotic structure of the nonparametric kernel density estimator. We generalise the result of Hall and Kang (2001) and find that the plug-in method has no effect on the asymptotic structure of the estimator up to the order of $O\{(nh_0)^{-1/2}+h_0^L\}=O(n^{-L/(2L+1)})$ for a bandwidth $h_0$ and any kernel order $L$ when the kernel order for pilot estimation $L_p$ is high enough. We also provide the valid Edgeworth expansion up to the order of $O\{(nh_0)^{-1}+h_0^{2L}\}$ and find that, as long as the $L_p$ is high enough , the plug-in method has an effect from on the term whose convergence rate is $O\{(nh_0)^{-1/2}h_0+h_0^{L+1}\}=O(n^{-(L+1)/(2L+1)})$. In other words, we derive the exact achievable convergence rate of the deviation between the distribution functions of the estimator with a deterministic bandwidth and with the plug-in bandwidth. In addition, we weaken the conditions on kernel order $L_p$ for pilot estimation by considering the effect of pilot bandwidth associated with the plug-in bandwidth. We also show that the bandwidth selection via the global plug-in method possibly has an effect on the asymptotic structure even up to the order of $O\{(nh_0)^{-1/2}+h_0^L\}$. Finally, Monte Carlo experiments are conducted to see whether our approximation improves previous results

Kernel Choice Matters for Boundary Inference using Local Polynomial Density: With Application to Manipulation Testing

Local polynomial density (LPD) estimation has become an essential tool for boundary inference, including manipulation tests for regression discontinuity. It is common sense that kernel choice is not critical for LPD estimation, in analogy to standard kernel smoothing estimation. This paper, however, points out that kernel choice has a severe impact on the performance of LPD, based on both asymptotic and non-asymptotic theoretical investigations. In particular, we show that the estimation accuracy can be extremely poor with commonly used kernels with compact support, such as the triangular and uniform kernels. Importantly, this negative result implies that the LPD-based manipulation test loses its power if a compactly supported kernel is used. As a simple but powerful solution to this problem, we propose using a specific kernel function with unbounded support. We illustrate the empirical relevance of our results with numerous empirical applications and simulations, which show large improvements

Doubly Robust Uniform Confidence Bands for Group-Time Conditional Average Treatment Effects in Difference-in-Differences

We consider a panel data analysis to examine the heterogeneity in treatment effects with respect to a pre-treatment covariate of interest in the staggered difference-in-differences setting of Callaway and Sant'Anna (2021). Under standard identification conditions, a doubly robust estimand conditional on the covariate identifies the group-time conditional average treatment effect given the covariate. Focusing on the case of a continuous covariate, we propose a three-step estimation procedure based on nonparametric local polynomial regressions and parametric estimation methods. Using uniformly valid distributional approximation results for empirical processes and multiplier bootstrapping, we develop doubly robust inference methods to construct uniform confidence bands for the group-time conditional average treatment effect function. The accompanying R package didhetero allows for easy implementation of the proposed methods.Comment: R package: https://tkhdyanagi.github.io/didhetero

Phosphorylation-induced conformation of beta(2)-adrenoceptor related to arrestin recruitment revealed by NMR

The C-terminal region of G-protein-coupled receptors (GPCRs), stimulated by agonist binding, is phosphorylated by GPCR kinases, and the phosphorylated GPCRs bind to arrestin, leading to the cellular responses. To understand the mechanism underlying the formation of the phosphorylated GPCR-arrestin complex, we performed NMR analyses of the phosphorylated beta(2)-adrenoceptor (beta(2)AR) and the phosphorylated beta(2)AR-beta-arrestin 1 complex, in the lipid bilayers of nanodisc. Here we show that the phosphorylated C-terminal region adheres to either the intracellular side of the transmembrane region or lipids, and that the phosphorylation of the C-terminal region allosterically alters the conformation around M215(5.54) and M279(6.41), located on transemembrane helices 5 and 6, respectively. In addition, we found that the conformation induced by the phosphorylation is similar to that corresponding to the beta-arrestin-bound state. The phosphorylation-induced structures revealed in this study propose a conserved structural motif of GPCRs that enables beta-arrestin to recognize dozens of GPCRs.Peer reviewe

Expression of nampt in hippocampal and cortical excitatory neurons is critical for cognitive function

Nicotinamide adenine dinucleotide (NAD(+)) is an enzyme cofactor or cosubstrate in many essential biological pathways. To date, the primary source of neuronal NAD(+) has been unclear. NAD(+) can be synthesized from several different precursors, among which nicotinamide is the substrate predominantly used in mammals. The rate-limiting step in the NAD(+) biosynthetic pathway from nicotinamide is performed by nicotinamide phosphoribosyltransferase (Nampt). Here, we tested the hypothesis that neurons use intracellular Nampt-mediated NAD(+) biosynthesis by generating and evaluating mice lacking Nampt in forebrain excitatory neurons (CaMKIIαNampt(−/−) mice). CaMKIIαNampt(−/−) mice showed hippocampal and cortical atrophy, astrogliosis, microgliosis, and abnormal CA1 dendritic morphology by 2–3 months of age. Importantly, these histological changes occurred with altered intrahippocampal connectivity and abnormal behavior; including hyperactivity, some defects in motor skills, memory impairment, and reduced anxiety, but in the absence of impaired sensory processes or long-term potentiation of the Schaffer collateral pathway. These results clearly demonstrate that forebrain excitatory neurons mainly use intracellular Nampt-mediated NAD(+) biosynthesis to mediate their survival and function. Studying this particular NAD(+) biosynthetic pathway in these neurons provides critical insight into their vulnerability to pathophysiological stimuli and the development of therapeutic and preventive interventions for their preservation

Mossbauer studies on FeSe and FeTe

We carried out 57Fe Mossbauer measurements for FeSe and Fe1.08Te to investigate the magnetic properties. There was no sign of magnetic ordering above 4.2 K for superconducting FeSe. The magnetic sextet corresponding to antiferromagnetic ordering of Fe in low-spin state was observed for non-superconducting Fe1.08Te.Comment: 5 pages, 2 figures, proceedings of M2S conferenc

HIGH-DOSE-RATE AFTERLOADING INTRACAVITARY IRRADIATION AND EXPANDABLE METALLIC BILIARY ENDOPROSTHESIS FOR MALIGNANT BILIARY OBSTRUCTION

A double lumen catheter was developed as an applicator for the remote afterloading system (RALS) of ⁶⁰Co for the intracavitary irradiation of an obstructed common bile duct due to gallbladder cancer in 1 case and by cholangiocarcinoma in 7 cases. This was followed by the biliary endoprosthesis with expandable metallic stents to maintain patency. The mean survival period after treatment was not long (14 weeks). However, removal of the external drainage tube was possible in 7 of the 8 cases, and none of the 8 cases showed dislodgement or deformity of the stent, or obstruction of the bile duct in the stent-inserted area. This combination effectively provided palliation, and has considerable potential for malignant biliary obstruction