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1.
Alzheimer disease (AD), while chronic and progressive with an average progression of 7 – 10 years, is both multifactorial
and heterogeneous. Thus, AD offers a large window of opportunity and a large number of therapeutic targets to inhibit it.
The selection of a therapeutic target, however, is one of the biggest challenges in developing a pharmacological treatment
of this multifactorial disease. Inhibition of a pivotal downstream event is likely to benefit more patients than inhibition
of an upstream event in AD pathogenesis. Neurofibrillary degeneration of abnormally hyperphosphorylated tau offers such a
pivotal therapeutic target. Abnormal hyperphosphorylation of tau and not its aggregation into filaments appears to be the
most deleterious step in neurofibrillary degeneration. Tau can be abnormally hyperphosphorylated by downregulation of protein
phosphatase-2A activity or by upregulation of more than one tau kinase. Restoration of the phosphatase activity which is downregulated
in AD brain or inhibition of GSK-3β and cdk5, which are required for AD-type abnormal hyperphosphorylation of tau, are among
the most promising therapeutic strategies. 相似文献
2.
王洁 《高技术通讯(英文版)》2009,15(2):203-207
Accurate performance prediction of Grid workflow activities can help Grid schedulers map activities to appropriate Grid sites.This paper describes an approach based on features-ranked RBF neural network to predict the performance of Grid workflow activities.Experimental results for two kinds of real world Grid workflow activities are presented to show effectiveness of our approach. 相似文献
3.
Waqar?Ahmad YuLin?DengEmail author Bo?Li LiLi?Li Manzoor?Ahamd Zafar?Iqbal Zahida?Parveen 《科学通报(英文版)》2008,53(21):3287-3293
Formaldehyde, a well-known environmental toxic hazard, has been found to produce endogenously via semicarbazide-sensitive amine oxidase-catalyzed oxidative deamination of methylamine. In diabetes, the activity of SSAO has been found to increase with a subsequent increase in endogenous formaldehyde production. It has been postulated that SSAO-induced production of formaldehyde may be involved in the alteration of protein structure, which may subsequently cause protein deposition associated with chronic pathological disorders. Formaldehyde has also been found to react (cross-link) with amino group of the N-terminal amino acid residue and with the side-chains of arginine, cysteine, histidine and lysine residues. Therefore, formaldehyde may be responsible, at least in part, for protein cross-linkage, oxidative stress and cytotoxicity. The cross-linking of formaldehyde with bovine serum albumin was studied using LC-MS and Mascot database. The peptides sequence for control BSA (untreated) digested with trypsin was matched in the online database search query by exporting the MS/MS data to online MASCOT database. In this way, a total of twenty-seven peptides were matched in the database search query. These twenty-seven peptides were then searched manually in all of the tryptic BSA samples treated with different concentrations of FA that were incubated in different time intervals. Six formaldehyde-treated BSA peptides (FKDLGEEHFK, HLVDEPQNLIK, KVPQVSTPTLVEVSR, RPCFSALTPDETYVPK, LVNELTEFAK, DAFLGSFLYEYSR) were found to be the possible markers for formaldehyde-protein/peptides adducts. 相似文献
4.
In this paper, we investigate the performance of a class of M‐estimators for both symmetric and asymmetric conditional heteroscedastic models in the prediction of value‐at‐risk. The class of estimators includes the least absolute deviation (LAD), Huber's, Cauchy and B‐estimator, as well as the well‐known quasi maximum likelihood estimator (QMLE). We use a wide range of summary statistics to compare both the in‐sample and out‐of‐sample VaR estimates of three well‐known stock indices. Our empirical study suggests that in general Cauchy, Huber and B‐estimator have better performance in predicting one‐step‐ahead VaR than the commonly used QMLE. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
5.
M. Iqbal Khan 《Cellular and molecular life sciences : CMLS》1978,34(6):711-712
Summary Lysine content in bread wheat (Triticum aestivum L. m. Thell) was determined by a modified Udy-dye binding method and was compared with that obtained from the amino acid analyzer. The values obtained from the 2 methods were correlated and the co-efficient was found to be +0.91 at 0.450 mg/ml dye concentration. The modified method is quick, less expensive and quite helpful for screening lysine at earlier generation in wheat breeding for improved grain quality content.The author is grateful to Dr V.A. Johnson, University of Nebraska, Lincoln, USA, for supplying wheat cultivars with known protein and lysine values. 相似文献
6.
Zarnecki JC Leese MR Hathi B Ball AJ Hagermann A Towner MC Lorenz RD McDonnell JA Green SF Patel MR Ringrose TJ Rosenberg PD Atkinson KR Paton MD Banaszkiewicz M Clark BC Ferri F Fulchignoni M Ghafoor NA Kargl G Svedhem H Delderfield J Grande M Parker DJ Challenor PG Geake JE 《Nature》2005,438(7069):792-795
The surface of Saturn's largest satellite--Titan--is largely obscured by an optically thick atmospheric haze, and so its nature has been the subject of considerable speculation and discussion. The Huygens probe entered Titan's atmosphere on 14 January 2005 and descended to the surface using a parachute system. Here we report measurements made just above and on the surface of Titan by the Huygens Surface Science Package. Acoustic sounding over the last 90 m above the surface reveals a relatively smooth, but not completely flat, surface surrounding the landing site. Penetrometry and accelerometry measurements during the probe impact event reveal that the surface was neither hard (like solid ice) nor very compressible (like a blanket of fluffy aerosol); rather, the Huygens probe landed on a relatively soft solid surface whose properties are analogous to wet clay, lightly packed snow and wet or dry sand. The probe settled gradually by a few millimetres after landing. 相似文献
7.
ZnO and Cr-doped ZnO thin films are grown on to glass substrates using reactive electron beam(e-beam) evaporation technique.Variation of structural,morphological,and optical properties with Cr doping is investigated.X-ray diffraction(XRD) studies show that the films are polycrystalline in nature with single phase.Energy dispersive spectroscopy(EDS) results demonstrate that Cr ions are substitutionally incorporated into ZnO.Atomic force microscopy(AFM) reveals that the films present a compact surface and root mean squared(RMS) roughness increased with Cr contents.The optical band gap energy Eg of the films has been determined using Transmission data by spectrophotometer and ellipsometry.The band gap energy found to be decreased with increasing Cr doping concentration.The optical constants(refractive index,extinction coefficient) are calculated using ellipsometry and found to increase with Cr doping concentration. 相似文献
8.
Detecting genetic variants that are highly divergent from a reference sequence remains a major challenge in genome sequencing. We introduce de novo assembly algorithms using colored de Bruijn graphs for detecting and genotyping simple and complex genetic variants in an individual or population. We provide an efficient software implementation, Cortex, the first de novo assembler capable of assembling multiple eukaryotic genomes simultaneously. Four applications of Cortex are presented. First, we detect and validate both simple and complex structural variations in a high-coverage human genome. Second, we identify more than 3 Mb of sequence absent from the human reference genome, in pooled low-coverage population sequence data from the 1000 Genomes Project. Third, we show how population information from ten chimpanzees enables accurate variant calls without a reference sequence. Last, we estimate classical human leukocyte antigen (HLA) genotypes at HLA-B, the most variable gene in the human genome. 相似文献
9.
Structural,morphological, Raman,optical, magnetic,and antibacterial characteristics of CeO<Subscript>2</Subscript> nanostructures
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Fazal Abbas Javed Iqbal Tariq Jan Noor Badshah Qaisar Mansoor Muhammad Ismail 《矿物冶金与材料学报》2016,23(1):102-108
In this study, CeO2 nanostructures were synthesized by a soft chemical method. A hydrothermal treatment was observed to lead to an interesting morphological transformation of the nanoparticles into homogeneous microspheres composed of nanosheets with an average thickness of 40 nm. Structural analysis revealed the formation of a single-phase cubic fluorite structure of CeO2 for both samples. A Raman spectroscopic study confirmed the XRD results and furthermore indicated the presence of a large number of oxygen vacancies in the nanosheets. These oxygen vacancies led to room-temperature ferromagnetism (RTFM) of the CeO2 nanosheets with enhanced magnetic characteristics. Amazingly, the nanosheets exhibited substantially greater antibacterial activity than the nanoparticles. This greater antibacterial activity was attributed to greater exposure of high-surface-energy polar surfaces and to the presence of oxygen vacancies. 相似文献
10.
Lithium-ion full cell with high energy density using nickel-rich LiNi0.8Co0.1Mn0.1O2 cathode and SiO-C composite anode
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A high-energy-density Li-ion battery with excellent rate capability and long cycle life was fabricated with a Ni-rich layered LiNi0.8Mn0.1Co0.1O2 cathode and SiO-C composite anode. The LiNi0.8Mn0.1Co0.1O2 and SiO-C exhibited excellent electrochemical performance in both half and full cells. Specifically, when integrated into a full cell configuration, a high energy density (280 Wh·kg-1) with excellent rate capability and long cycle life was attained. At 0.5C, the full cell retained 80% of its initial capacity after 200 charge/discharge cycles, and 60% after 600 cycles, indicating robust structural tolerance for the repeated insertion/extraction of Li+ ions. The rate performance showed that, at high rate of 1C and 2C, 96.8% and 93% of the initial capacity were retained, respectively. The results demonstrate strong potential for the development of high energy density Li-ion batteries for practical applications. 相似文献