Estimating False Discovery Proportion Under Arbitrary Covariance Dependence

Multiple hypothesis testing is a fundamental problem in high dimensional inference, with wide applications in many scientific fields. In genome-wide association studies, tens of thousands of tests are performed simultaneously to find if any SNPs are associated with some traits and those tests are correlated. When test statistics are correlated, false discovery control becomes very challenging under arbitrary dependence. In the current paper, we propose a novel method based on principal factor approximation, which successfully subtracts the common dependence and weakens significantly the correlation structure, to deal with an arbitrary dependence structure. We derive an approximate expression for false discovery proportion (FDP) in large scale multiple testing when a common threshold is used and provide a consistent estimate of realized FDP. This result has important applications in controlling FDR and FDP. Our estimate of realized FDP compares favorably with Efron (2007)'s approach, as demonstrated in the simulated examples. Our approach is further illustrated by some real data applications. We also propose a dependence-adjusted procedure, which is more powerful than the fixed threshold procedure.Comment: 51 pages, 7 figures. arXiv admin note: substantial text overlap with arXiv:1012.439

Intense Pulsed Light Therapy

Intense pulsed light (IPL) is one of the most effective nonablative approaches to treat skin photoaging. The broad range of wavelengths (500–1200 nm) emitted from IPL devices effectively target both melanin and hemoglobin in the skin. Numerous trials show the effectiveness and compatibility of IPL devices in a variety of skin conditions, especially in cosmetic indications such as hypertrichosis and telangiectasias. Compared with the wide clinical use of IPL, the biochemical and molecular mechanism is not clear. Both in vivo and in vitro studies demonstrate that IPL could increase the production of extracellular matrix, promote the proliferation of fibroblasts, and increase the secretion of TGF-β and matrix metalloproteinases, which play important roles in the photorejuvenation effects of IPL. However, investigations regarding the detailed underlying mechanism are necessary

Size and Location Diagnosis of Rolling Bearing Faults: An Approach of Kernel Principal Component Analysis and Deep Belief Network

Diagnosing incipient faults of rotating machines is very important for reducing economic losses and avoiding accidents caused by faults. However, diagnoses of locations and sizes of incipient faults are very difficult in a noisy background. In this paper, we propose a fault diagnosis method that combines kernel principal component analysis (KPCA) and deep belief network (DBN) to detect sizes and locations of incipient faults on rolling bearings. Effective information of raw vibration signals processed by KPCA method is used as input signals of the DBN of which weights of the first RBM are initialized by contribution rates of principal components. A DBN with complex structures can be cut into a briefer network by KPCA-DBN model. That model reduces network structure and increases convergence rate. As a result, an average test accuracy by KPCA-DBN can reach 99.1% for identification of 12 labels including incipient faults and the training time is 28s which is half of that by DBN model. The average accuracy of rolling bearing location detection nearly gets to 100% and the average accuracy of fault size detection is above 99%. Compared with SVM, BP, CNN, Deep EMD-PCA (Empirical Mode Decomposition-Principal Component Analysis), CNN-SVM and DBN, it is found that training time can be shortened and detection accuracy can be improved by KPCA-DBN model. The proposed method is beneficial to realize sizes and locations detection of incipient faults online

BMPRIA mediated signaling is essential for temporomandibular joint development in mice

The central importance of BMP signaling in the development and homeostasis of synovial joint of appendicular skeleton has been well documented, but its role in the development of temporomandibular joint (TMJ), also classified as a synovial joint, remains completely unknown. In this study, we investigated the function of BMPRIA mediated signaling in TMJ development in mice by transgenic loss-of- and gain-of-function approaches. We found that BMPRIA is expressed in the cranial neural crest (CNC)-derived developing condyle and glenoid fossa, major components of TMJ, as well as the interzone mesenchymal cells. Wnt1-Cre mediated tissue specific inactivation of BmprIa in CNC lineage led to defective TMJ development, including failure of articular disc separation from a hypoplastic condyle, persistence of interzone cells, and failed formation of a functional fibrocartilage layer on the articular surface of the glenoid fossa and condyle, which could be at least partially attributed to the down-regulation of Ihh in the developing condyle and inhibition of apoptosis in the interzone. On the other hand, augmented BMPRIA signaling by Wnt1-Cre driven expression of a constitutively active form of BmprIa (caBmprIa) inhibited osteogenesis of the glenoid fossa and converted the condylar primordium from secondary cartilage to primary cartilage associated with ectopic activation of Smad-dependent pathway but inhibition of JNK pathway, leading to TMJ agenesis. Our results present unambiguous evidence for an essential role of finely tuned BMPRIA mediated signaling in TMJ development

Microstructure evolution and electrochemical properties of TiO 2 /Ti-35Nb-2Ta-3Zr micro/nano-composites fabricated by friction stir processing

Forming stable anti-corrosion surface layer and homogenized microstructure on the surface of material has become a major challenge in developing biomedical β titanium alloy. In the study, TiO 2 /Ti-35Nb-2Ta-3Zr anti-corrosion micro/nano-composites with different amount of TiO 2 particles were successfully fabricated by one-pass friction stir processing (FSP). The composition, microstructure and electrochemical properties of the material are characterized systematically. In particular, compact passive oxide films formed on surface of the material after electrochemical corrosion are elaborated from constituent, thickness and structural characteristics. Furthermore, the relationship between various FSP parameters, microstructure presented and corresponding corrosion resistance has been discussed in detail. The results show that TiO 2 /Ti-35Nb-2Ta-3Zr micro/nano-composite layers possess massive uniform β grains with homogeneous dispersive oxygen on the surface. Nanocrystallines surrounded by amorphous phases and α″ martensite accompanied with dislocations are discovered. TiO 2 /Ti-35Nb-2Ta-3Zr micro/nano-composite layers present outstanding corrosion resistance. More TiO 2 added and higher rotation speed promotes the optimization in corrosion resistance forming more compact passive films. The study displays the potential of a new micro/nano-composite with outstanding surface microstructure and corrosion resistance that serves better as a biomedical implant. © 2019 Elsevier Lt

Quercetin protects cadmium-induced renal injuries in mice by inhibiting cell pyroptosis

The toxic heavy metal cadmium (Cd) has a significant impact on kidney health. Documents manifested that non-toxic flavonoid quercetin can reduce Cd-induced kidney damage by reducing oxidative stress and inhibiting apoptosis, while the effect of quercetin on Cd-induced renal cell pyroptosis has not been elucidated. In this study, we established a model of Cd poisoning treated with quercetin both in vitro and in vivo. Results revealed that quercetin effectively reversed the decrease in Cd-induced cell viability. Furthermore, Cd increased blood urea nitrogen while reducing GPX and SOD levels, caused histopathological injuries in kidney with a significantly elevated cell pyroptosis characterized by enhanced levels of proteins representing assembly (NLRP3) and activation (pro IL-1β, cleaved IL-1β, and IL-18) of NLRP3 inflammasome as well as pyroptosis executor (pro caspase-1, cleaved caspase-1). However, quercetin administration alleviated kidney injuries above by decreasing cell pyroptosis. Overall, it suggests that kidney cells are susceptible to pyroptotic cell death due to Cd exposure; while quercetin exhibits protective effects through cell pyroptosis inhibition

Altered FGF Signaling Pathways Impair Cell Proliferation and Elevation of Palate Shelves

In palatogenesis, palatal shelves are patterned along the mediolateral axis as well as the anteroposterior axis before the onset of palatal fusion. Fgf10 specifically expressed in lateral mesenchyme of palate maintains Shh transcription in lateral epithelium, while Fgf7 activated in medial mesenchyme by Dlx5, suppressed the expansion of Shh expression to medial epithelium. How FGF signaling pathways regulate the cell behaviors of developing palate remains elusive. In our study, we found that when Fgf8 is ectopically expressed in the embryonic palatal mesenchyme, the elevation of palatal shelves is impaired and the posterior palatal shelves are enlarged, especially in the medial side. The palatal deformity results from the drastic increase of cell proliferation in posterior mesenchyme and decrease of cell proliferation in epithelium. The expression of mesenchymal Fgf10 and epithelial Shh in the lateral palate, as well as the Dlx5 and Fgf7 transcription in the medial mesenchyme are all interrupted, indicating that the epithelial-mesenchymal interactions during palatogenesis are disrupted by the ectopic activation of mesenchymal Fgf8. Besides the altered Fgf7, Fgf10, Dlx5 and Shh expression pattern, the reduced Osr2 expression domain in the lateral mesenchyme also suggests an impaired mediolateral patterning of posterior palate. Moreover, the ectopic Fgf8 expression up-regulates pJak1 throughout the palatal mesenchyme and pErk in the medial mesenchyme, but down-regulates pJak2 in the epithelium, suggesting that during normal palatogenesis, the medial mesenchymal cell proliferation is stimulated by FGF/Erk pathway, while the epithelial cell proliferation is maintained through FGF/Jak2 pathway