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This article investigates the estimation and inference of quantile impulse response functions. We propose a new estimation method using the idea of local projections by Jordà (2005). We establish consistency and asymptotic normality of the estimator, thereby enabling asymptotic inference. We also consider the confidence interval construction based on the stationary bootstrap and prove its consistency. Confirmatory simulation results and empirical practices on value-at-risk dynamics are provided. [ABSTRACT FROM AUTHOR]

We propose a novel conditional quantile prediction method based on complete subset averaging (CSA) for quantile regressions. All models under consideration are potentially misspecified, and the dimension of regressors goes to infinity as the sample size increases. Since we average over the complete subsets, the number of models is much larger than the usual model averaging method which adopts sophisticated weighting schemes. We propose to use an equal weight but select the proper size of the complete subset based on the leave-one-out cross-validation method. Building upon the theory of Lu and Su (2015, Journal of Econometrics 188, 40–58), we investigate the large sample properties of CSA and show the asymptotic optimality in the sense of Li (1987, Annals of Statistics 15, 958–975) We check the finite sample performance via Monte Carlo simulations and empirical applications. [ABSTRACT FROM AUTHOR]

This paper presents the structural performance of jacketed concrete columns subjected to cyclic lateral loading using ultrahigh-performance fiber-reinforced concrete (UHPFRC) with various advantages as construction materials of high strength and durability with self-compacting. The UHPFRC jacketing with/without textile reinforcement for concrete columns for the seismic retrofitting demonstrates its strengthening efficiency and reduction of jacket thickness through the experimental program in this study. Especially, textile-reinforced UHPFRC (TR-UHPFRC) jacketing has enhanced ductility compared with that of UHPFRC jacketing by changing critical failure crack patterns in jackets. The satisfactory interface shear strength between UHPFRC jackets and substrate concrete of columns was confirmed by a series of slant shear test programs provided that required roughness on substrate with moisture were prepared according to current design guidelines. This study also investigates the effects of discontinuity of tension forces in jackets at the floor level of columns on shear load paths, which are intended to alleviate jacketing construction for columns in existing buildings as a member intervention technique. Shears and axial forces induced in jacketed columns under lateral loading are mainly resisted by compression forces in diagonal struts through the jacket with substrate concrete columns and are explained by arch actions for enhancement of shear strength after jacketing. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy is a feature of aging (termed sarcopenia) and various diseases, such as cancer and kidney failure. Effective drug treatment options for muscle atrophy are lacking. The tapeworm medication, niclosamide is being assessed for repurposing to treat numerous diseases, including end-stage cancer metastasis and hepatic steatosis. In this study, we investigated the potential of niclosamide as a repurposing drug for muscle atrophy. In a myotube atrophy model using the glucocorticoid, dexamethasone, niclosamide did not prevent the reduction in myotube diameter or the decreased expression of phosphorylated FOXO3a, which upregulates the ubiquitin-proteasome pathway of muscle catabolism. Treatment of normal myotubes with niclosamide did not activate mTOR, a major regulator of muscle protein synthesis, and increased the expression of atrogin-1, which is induced in catabolic states. Niclosamide treatment also inhibited myogenesis in muscle precursor cells, enhanced the expression of myoblast markers Pax7 and Myf5, and downregulated the expression of differentiation markers MyoD, MyoG and Myh2. In an animal model of muscle atrophy, niclosamide did not improve muscle mass, grip strength or muscle fiber cross-sectional area. Muscle atrophy is also feature of cancer cachexia. IC50 analyses indicated that niclosamide was more cytotoxic for myoblasts than cancer cells. In addition, niclosamide did not suppress the induction of iNOS, a key mediator of atrophy, in an in vitro model of cancer cachexia and did not rescue myotube diameter. Overall, these results suggest that niclosamide may not be a suitable repurposing drug for glucocorticoid-induced skeletal muscle atrophy or cancer cachexia. Nevertheless, niclosamide may be employed as a compound to study mechanisms regulating myogenesis and catabolic pathways in skeletal muscle. [ABSTRACT FROM AUTHOR]

CCL2 mitigates cyclic AMP-suppressed Th2 immune response in human dendritic cells Keywords: allergic rhinitis; cAMP; CCL2; dendritic cells; Gnas CD11c mice EN allergic rhinitis cAMP CCL2 dendritic cells Gnas CD11c mice 1 4 4 07/29/20 20200801 NES 200801 Allergic rhinitis (AR) is a Th2-type chronic inflammatory disease of the nasal mucosa, characterized by symptoms including rhinorrhea, obstruction, and sneezing. However, CCL7 mRNA in AR MDDCs was not different from that in control MDDCs (Figure S4), suggesting that decreased cAMP levels in AR DCs induce the Th2 immune response through upregulation of CCL2. [Extracted from the article]

We develop the limit theory of the quantilogram and cross-quantilogram under long memory. We establish the sub-root-n central limit theorems for quantilograms that depend on nuisance parameters. We propose a moving block bootstrap (MBB) procedure for inference and establish its consistency, thereby enabling a consistent confidence interval construction for the quantilograms. The newly developed reduction principles for the quantilograms serve as the main technical devices used to derive the asymptotics and establish the validity of MBB. We report some simulation evidence that our methods work satisfactorily. We apply our method to quantile predictive relations between financial returns and long-memory predictors. [ABSTRACT FROM AUTHOR]

Background: A20 protein has ubiquitin-editing activities and acts as a key regulator of inflammation and immunity. Previously, our group showed that A20 promotes tumor metastasis through multi-monoubiquitylation of SNAIL1 in basal-like breast cancer. Here, we investigated survival outcomes in patients with breast cancer according to A20 expression. Patients and methods: We retrospectively collected tumor samples from patients with breast cancer. Immunohistochemistry (IHC) with an A20-specific antibody was performed, and survival outcomes were analyzed. Results: A20 expression was evaluated in 442 patients. High A20 expression was associated with advanced anatomical stage and young age. High A20 expression showed significantly inferior recurrence-free-survival and overall-survival (P<0.001 and P<0.001, respectively). Multivariate analysis showed that A20 was an independent prognostic marker for RFS (HRs: 2.324, 95% CIs: 1.446–3.736) and OS (HRs: 2.629, 95% CIs: 1.585–4.361). In human epidermal growth factor receptor 2 (HER2)-positive and triple negative breast cancer (TNBC) subtypes, high A20 levels were associated with poor OS. Conclusion: We found that A20 expression is a poor prognostic marker in breast cancer. The prognostic impact of A20 was pronounced in aggressive tumors, such as HER2-positive and TNBC subtypes. Our findings suggested that A20 may be a valuable target in patients with aggressive breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: Autophagy begins with the formation of autophagosomes, a process that depends on the activity of the serine/threonine kinase ULK1 (hATG1). Although earlier studies indicated that ULK1 activity is regulated by dynamic polyubiquitination, the deubiquitinase involved in the regulation of ULK1 remained unknown. In this study, we demonstrate that ubiquitin‐specific protease 20 (USP20) acts as a positive regulator of autophagy initiation through stabilizing ULK1. At basal state, USP20 binds to and stabilizes ULK1 by removing the ubiquitin moiety, thereby interfering with the lysosomal degradation of ULK1. The stabilization of basal ULK1 protein levels is required for the initiation of starvation‐induced autophagy, since the depletion of USP20 by RNA interference inhibits LC3 puncta formation, a marker of autophagic flux. At later stages of autophagy, USP20 dissociates from ULK1, resulting in enhanced ULK1 degradation and apoptosis. Taken together, our findings provide the first evidence that USP20 plays a crucial role in autophagy initiation by maintaining the basal expression level of ULK1. [ABSTRACT FROM AUTHOR]