Experimental Study on Dry Friction Damping Characteristics of the Steam Turbine Blade Material with Nonconforming Contacts

An experiment system has been established to study the dry friction damping dynamic characteristics of the steam turbine blade material 1Cr13. The friction dynamic characteristics of the specimens with nonconforming contact surfaces are measured under different parameters. The experiment results are compared with that of the macroslip hysteresis model and the Mindlin microslip friction model in detail. The results show that the experimental result of the tangential contact stiffness is in good agreement with that of the theory result based on the fractal theory and the Hertz contact theory by Jiang et al., 2009. The dimensionless equivalent stiffness and equivalent damping obtained by the macroslip hysteresis model agree well with the experimental results when relative motion is relatively large. However, the results of the macroslip hysteresis model differ a lot from the experimental results when relative motion is relatively small. Compared with the macroslip hysteresis model, the Mindlin microslip friction model can predict the dimensionless equivalent stiffness and equivalent damping accurately during the whole measurement range. The linear regularities of dimensionless equivalent stiffness and equivalent damping are obtained, which decrease the difficulty of building the vibration analysis model of the blade with sufficient accuracy

Transcriptional regulation of PEN-2, a key component of the γ-secretase complex, by CREB

Gamma-secretase, which is responsible for the intramembranous cleavage of Alzheimer's P-amyloid precursor protein (APP), the signaling receptor Notch, and many other substrates, is a multiprotein complex consisting of at least four components: presenilin (PS), nicastrin, APH-1, and PEN-2. Despite the fact that PEN-2 is known to mediate endoproteolytic cleavage of full-length PS and APH-1 and nicastrin are required for maintaining the stability of the complex, the detailed physiological function of each component remain elusive. Unlike that of PS, the transcriptional regulation of PEN-2, APH-1, and nicastrin has not been investigated. Here, we characterized the upstream regions of the human PEN-2 gene and identified a 238-bp fragment located 353 bp upstream of the translational start codon as the key region necessary for the promoter activity. Further analysis revealed a CREB binding site located in the 238-bp region that is essential for the transcriptional activity of the PEN-2 promoter. Mutation of the CREB site abolished the transcriptional activity of the PEN-2 promoter. Electrophoretic mobility shift assays and chromatin immunoprecipitation analysis showed the binding of CREB to the PEN-2 promoter region both in vitro and in vivo. Activation of the CREB transcriptional factor by forskolin dramatically promoted the expression of PEN-2 mRNA and protein, whereas the other components of the gamma-secretase complex remained unaffected. Forskolin treatment slightly increases the secretion of soluble APP alpha and A beta without affecting Notch cleavage. These results demonstrate that expression of PEN-2 is regulated by CREB and suggest that the specific control of PEN-2 expression may imply additional physiological functions uniquely assigned to PEN-2

An analysis of flight Quick Access Recorder (QAR) data and its applications in preventing landing incidents

A long landing is one type of flight incident that will multiply the risk of a runway excursion. It occurs frequently but receives little attention in research due to difficulty in obtaining the real flight data. The aim of this paper is to discover key flight parameter features of long landing incidents by analyzing Quick Access Recorder (QAR) data and put forward prevention measures from the perspective of pilot operation at the same time. First, 73 flight performance parameter variables and 4 operation parameter variables were defined, covering major landing stages from 1500 ft to touchdown. Then 128 cases of selected QAR data were divided into two groups according to the threshold of identifying normal and long landing. Second, each flight parameter variable of these 128 flights was compared between groups and then the logistic and linear regression models were developed respectively to further examine the links between touchdown distance and these flight parameter variables. Third, potential flight operation causing performance difference of long landing incidents was also analyzed. Finally results indicate that the period of 200 ft to touchdown is the key stage of landing and flare is the most critical operation affecting touchdown distance. It is suggested that the pilot should inspect the ratio of descent rate and groundspeed carefully at the height of 50 ft and pilot's faster and steady pulling up columns is probably helpful for an excellent flare and landing. The findings are expected to be applied into flight operation practice for further preventing long landing incidents and even the runway excursion accidents. (C) 2014 Elsevier Ltd. All rights reserved

Estrogen, beta-amyloid metabolism/trafficking, and Alzheimer‘s disease

Estrogen plays key regulatory roles in a variety of biological actions besides its classic function as a sex hormone. Recently, estrogen has been linked to neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). Several lines of evidence support the notion that brain estrogen exerts neuroprotective effects against various types of neurotoxicity in different cellular and animal models. Despite some controversies, estrogen replacement therapy (ERT) at an early stage, especially when given prior to menopause, has been shown to reduce the risk of AD in postmenopausal women. In addition, multiple lines of evidence have proven the neuroprotective effects of estrogen, such as enhancing neurotrophin signaling and synaptic activities pertinent to memory functions and protecting neurons against oxidative injuries and beta-amyloid toxicity; the latter is widely accepted as the prime culprit known to trigger the pathogenesis of AD. Here we will summarize our findings that estrogen decreased generation and secretion of beta-amyloid peptides in cultured cells and primary neurons and that administration of estrogen in estrogen-deprived mice reversed the elevated levels of brain A beta. We will also discuss the molecular and cellular mechanisms underlying estrogen's effects on A beta metabolism, which is highlighted by our demonstration that estrogen increases intracellular trafficking of beta-amyloid precursor protein (beta APP) and hence reduces maximal A beta generation within the traps-Golgi network (TGN), a subcellular compartment in which APP is known to be cleaved by the secretase enzymes to generate A beta

Presenilins regulate the cellular level of the tumor suppressor PTEN

Alzheimer's Disease (AD) is characterized by amyloid plaques consisting of beta-amyloid (A beta) peptides and neurofibrillary tangles consisting of hyperphosphorylated tau protein. A beta is proteolytically derived from its precursor protein through cleavages by beta-secretase and beta-secretase complex comprising presenilins (PS, PS1/PS2), nicastrin, APH-1 and PEN-2. PS1 is also known to activate the PI3K/Akt cell survival pathway in ay-secretase-independent manner. The tumor suppressor PTEN, which antagonizes the PI3K/Akt pathway, has increasingly been recognized to play a key role in neural functions and its level found reduced in AD brains. Here, we demonstrate that the protein level of PTEN is dramatically reduced in cultured cells and embryonic tissues deficient in PS, and in the cortical neurons of PS1/PS2 conditional double knockout mice. Restoration of PS in PS-deficient cells reverses the reduction of PTEN. Regulation of PTEN by PS is independent of the PS/gamma-secretase activity since impaired gamma-secretase by the gamma-secretase inhibitor treatment or due to nicastrin deficiency has little effect on the protein level of PTEN. Our data suggest an important role for PS in signaling pathways involving PI3K/Akt and PTEN that are crucial for physiological functions and the pathogenesis of multiple diseases. (c) 2006 Elsevier Inc. All rights reserved

Presenilin/gamma-secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expression

Presenilins (PS, PS1/PS2) are necessary for the proteolytic activity of gamma-secretase, which cleaves multiple type I transmembrane proteins including Alzheimer's beta-amyloid precursor protein (APP), Notch, ErbB4, etc. Cleavage by PS/gamma-secretase releases the intracellular domain (ICD) of its substrates. Notch ICD translocates into the nucleus to regulate expression of genes important for development. However, the patho/physiological role of other ICDs, especially APP ICD (AICD), in regulating gene expression remains controversial because evidence supporting this functionality stems mainly from studies performed under supraphysiological conditions. EGF receptor (EGFR) is up-regulated in a wide variety of tumors and hence is a target for cancer therapeutics. Abnormal expression/activation of EGFR contributes to keratinocytic carcinomas, and mice with reduced PS dosages have been shown to develop skin tumors. Here we demonstrate that the levels of PS and EGFR in the skin tumors of PS1(+/-)/PS2(-/-) mice and the brains of PS1/2 conditional double knockout mice are inversely correlated. Deficiency in PS/gamma-secretase activity or APP expression results in a significant increase of EGFR in fibroblasts. Importantly, we show that AICD mediates transcriptional regulation of EGFR. Furthermore, we provide in vivo evidence demonstrating direct binding of endogenous AICD to the EGFR promoter. Our results indicate an important role of PS/gamma-secretase-generated APP metabolite AICD in gene transcription and in EGFR-mediated tumorigenesis

Association study between X-linked susceptibility genes and clinical features in Chinese female patients with systemic lupus erythematosus

Recent large-scale genetic association studies have identified that several single nucleotide polymorphisms (SNPs) on X chromosome are correlated with risk of systemic lupus erythematosus (SLE) in Chinese population. The aim of this study was to estimate association between these loci and clinical features in female patients with SLE. Six SNPs identified in previous studies were genotyped. Odds ratio (OR) was calculated with adjusting for potential confounding factors. A total of 772 SLE patients were included in the final analysis. The data showed that 3 SNPs (rs5914778, rs3853839 and rs1059702) were marginally associated with several clinical subphenotypes. Furthermore, consistent associations were also found in two independent cohorts. However, the cumulative genetic risk score (GRS) was not associated with clinical manifestations as well as the disease activity index at disease diagnosis. In summary, genetic variants in X-linked genes may be potentially associated with presence of specific clinical feature. Further studies in distinct ethnical populations are required to clarify the association between these loci and presence of SLE clinical features

Block Adjustment without GCPs for Chinese Spaceborne SAR GF-3 Imagery

The Gaofen-3 (GF-3) satellite is the first C-band multi-polarization synthetic aperture radar (SAR) with the ability of high-accuracy mapping in China. However, the Ground Control Points (GCPs) are essential to ensure the accuracy of mapping for GF-3 SAR imagery at present. In this paper, we analyze the error sources that affect the geometric processing and propose a new block adjustment method without GCPs for GF-3 SAR imagery. Firstly, the geometric calibration of GF-3 image is carried out. Secondly, the rational polynomial coefficient (RPC) model is directly generated after the geometric calibration parameters compensation of each image. Finally, we solve the orientation parameters of the GF-3 images through DEM assisted planar block adjustment and conduct ortho-rectification. With two different imaging modes of GF-3 satellite, which include the QPSI and FS2, we carry out the block adjustment without GCPs. Experimental results of testing areas including Wuhan city and Hubei province in China show that the geometric mosaic accuracy and the absolute positioning accuracy of the orthophoto are better than one pixel, which has laid a good foundation for the application of GF-3 image in global high-accuracy mapping