For the detection of incipient bearing faults, formulating decoupling noise reduction of vibration signal and fault enhancement strategy is the key to overcoming noise interference and recovering periodic pulses from the original signal. This paper's method of achieving the above diagnosis is based on adaptive chirp mode decomposition (ACMD) and parametric optimized minimum noise amplitude deconvolution (POMNAD). Firstly, ACMD is used to reduce the influence of noise components. Secondly, MNAD, which has an outstanding ability to recover periodic pulses from the original signal, is performed on the noise-reduced component. However, practical applications have consistently shown that the fault characteristic frequency (FCF) parameter of MNAD must be selected adaptively to ensure MNAD works at its best. To solve the parameter setting problem, POMNAD is proposed in this paper. Taking the Gini index of the squared envelope spectrum (GISES) as the fitness function, and iteratively searching through the gray wolf optimization (GWO) algorithm, POMNAD can adaptively obtain the optimal FCF parameter of the filter. After ACMD and POMNAD, the envelope analysis is performed to determine the fault condition. Simulation and experiment indicate that the proposed method correctly detects the incipient fault of rolling bearings.
Electrophoresis is one of the most widely used analytical tools for the quantification of the charged conditions on the surface of fine particles including biological entities. Although it has been studied extensively in the past, relevant results for the case when the dispersion medium is non-Newtonian are very limited. This may occur, for example, when the concentration of the dispersed phase is not low, which is not uncommon in practice. Here, the electrophoresis of a concentrated spherical dispersion in a Carreau fluid is analyzed theoretically under the conditions of low electric potential and weak external applied electrical field. A pseudospectral method coupled with a Newton−Raphson iteration procedure is used to solve the electrokinetic equations describing the phenomenon under consideration. We conclude that the more significant the shear thinning effect of the fluid, the larger the mobility, and this phenomenon is pronounced for the case when the double layer surrounding a particle is thin. We show that if the double layer is thin and the effect of shear thinning is significant, a second vortex can be observed in the neighborhood of a particle.
Pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) are required for host defense against pathogens. Although PTI and ETI are intimately connected, the underlying molecular mechanisms remain elusive. In this study, we demonstrate that flg22 priming attenuates Pseudomonas syringae pv. tomato DC3000 (Pst) AvrRpt2-induced hypersensitive cell death, resistance, and biomass reduction in Arabidopsis. Mitogen-activated protein kinases (MAPKs) are key signaling regulators of PTI and ETI. The absence of MPK3 and MPK6 significantly reduces pre-PTI-mediated ETI suppression (PES). We found that MPK3/MPK6 interact with and phosphorylate the downstream transcription factor WRKY18, which regulates the expression of AP2C1 and PP2C5, two genes encoding protein phosphatases. Furthermore, we observed that the PTI-suppressed ETI-triggered cell death, MAPK activation, and growth retardation are significantly attenuated in wrky18/40/60 and ap2c1 pp2c5 mutants. Taken together, our results suggest that the MPK3/MPK6-WRKYs-PP2Cs module underlies PES and is essential for the maintenance of plant fitness during ETI.
We have developed a simple method for the selective colorimetric detection of aqueous mercuric (Hg2+), silver (Ag+), and lead (Pb2+) ions by using label-free gold nanoparticles (Au NPs) and alkanethiols. The degree of alkanethiol-induced aggregation of the Au NPs decreases in the order of 6-mercaptohexanol (6-MH) ∼ 4-mercaptobutanol (4-MB) > 11-mercaptoundecanol (11-MU) > 2-mercaptoethanol (2-ME). The specific and strong interactions of these alkanethiols with Au NPs and heavy metal ions enabled us to develop label-free assays for the sensitive and selective detection of Hg2+ ions using the 4-MB/Au NPs probe, as well as Ag+ and Pb2+ ions using the 2-ME/Au NPs probe. The presence of strong Hg2+-S bonds alleviated the extent of 4-MB-induced aggregation of the Au NPs, resulting in a declining ratio of the extinction coefficients at 650 to 520 nm (Ex650/520, a measure of the molar ratio of the aggregated to the dispersed Au NPs) of the Au NP solution. In contrast, the presence of Ag+, Cu2+, and Pb2+ ions led to a severe aggregation of the Au NPs, mediated by the deposition of these ions on the surfaces of the Au NPs in the 2-ME/Au NPs system. In the presence of masking agents [ethylenediaminetetraacetic acid (EDTA), Na2S], the 2-ME/Au NP-EDTA and 2-ME/Au NP-Na2S sensors permitted the selective detection of Ag+ and Pb2+ ions, respectively, at concentrations down to the nanomolar range. This cost-effective process also allowed the rapid and simple determination of the concentrations of heavy metal ions in real environmental samples (river water and Montana soil). These alkanethiol/Au NP-based sensor probes enabled us to detect three different heavy metal ions, and we feel confident that, because of the simplicity, rapidity, and cost-effectiveness of these analyses, such systems demonstrate great potential for the practical detection of heavy metal ions in real samples.
Glioblastoma (GBM), classified as a grade IV glioma, is a rapidly growing, aggressive, and most commonly occurring tumor of the central nervous system. Despite the therapeutic advances, it carries an ominous prognosis, with a median survival of 14.6 months after diagnosis. Accumulating evidence suggests that cancer stem cells in GBM, termed glioma stem cells (GSCs), play a crucial role in tumor propagation, treatment resistance, and tumor recurrence. GSCs, possessing the capacity for self-renewal and multilineage differentiation, are responsible for tumor growth and heterogeneity, leading to primary obstacles to current cancer therapy. In this respect, increasing efforts have been devoted to the development of anti-GSC strategies based on targeting GSC surface markers, blockage of essential signaling pathways of GSCs, and manipulating the tumor microenvironment (GSC niches). In this review, we will discuss the research knowledge regarding GSC-based therapy and the underlying mechanisms for the treatment of GBM. Given the rapid progression in nanotechnology, innovative nanomedicines developed for GSC targeting will also be highlighted from the perspective of rationale, advantages, and limitations. The goal of this review is to provide broader understanding and key considerations toward the future direction of GSC-based nanotheranostics to fight against GBM.
Study of the density, spatial distribution, and molecular interactions of receptors on the cell membrane provides the knowledge required to understand cellular behavior and biological functions, as well as to discover, design, and screen novel therapeutic agents. However, the mapping of receptor distribution and the monitoring of ligand-receptor interactions on live cells in a spatially and temporally ordered manner are challenging tasks. In this paper, we apply fluorescence correlation spectroscopy (FCS) to map receptor densities on live cell membranes by introducing fluorescently marked aptamer molecules, which specifically bind to certain cell-surface receptors. The femtoliter-sized (0.4 fL) observation volume created by FCS allows fluorescent-aptamer detection down to 2 molecules and appears to be an ideal and highly sensitive biophysical tool for studying molecular interactions on live cells. Fluorophore-labeled aptamers were chosen for receptor recognition because of their high binding affinity and specificity. Aptamer sgc8, generated for specific cell recognition by a process called cell systematic evolution of ligands by exponential enrichment, was determined by FCS to have a binding affinity in the picomolar range (dissociation constant K(d)=790+/-150 pM) with its target membrane receptor, human protein tyrosine kinase-7 (PTK7), a potential cancer biomarker. We then constructed a cellular model and applied this aptamer-receptor interaction to estimate receptor densities and distributions on the cell surface. Specifically, different expression levels of PTK7 were studied by using human leukemia CCRF-CEM cells (1300+/-190 receptors microm(-2)) and HeLa cervical cancer cells (550+/-90 receptors microm(-2)). Competition studies with excess nonlabeled aptamers and proteinase treatment studies proved the validity of the density-estimation approach. With its intrinsic advantages of direct measurement, high sensitivity, fast analysis, and single-cell measurement, this FCS density-estimation approach holds potential for future applications in molecular-interaction studies and density estimations for subcellular structures and membrane receptors.
Hydrogen peroxide attracts a great interest due to its important role in food, pharmaceutical, and clinical applications. Hydrogen peroxide is also a by-product in many enzyme catalytic reactions, such as glucose oxidase, lactate oxidase, cholesterol oxidase, alcohol oxidase, urate oxidase, aldehyde oxidase, and oxalate oxidase, which are implemented to detect glucose, lactic acid, cholesterol, ethanol, urea, formaldehyde, and oxalate, respectively. These biomolecules are significant markers in many biologically metabolic reactions. In our study, we present a cholesterol sensor based on a high sensitivity hydrogen peroxide sensor with ultra-low detection limit. The sensor can directly test the sample and only need very small amount of sample. And because of the simple structural design and fabrication, the sensor can be used as a cheap, efficient, and portable sensor system. The HRP-modified resistive sensors based on n-alkylated polyaniline(PANI) detect hydrogen peroxide in solution with very high sensitivity, ultra-low limit, and short response time. The sensitivity is higher than that of other sensing methods, such as electrochemical sensors or transistor sensors. The detection limit of PANI sensor is 0.7 nM. It is three orders smaller than that of other common methods with detection limit around 1 μM. To the best of our knowledge, it is the lowest detection limit that has ever been reported. And we combine the hydrogen peroxide sensor with cholesterol oxidase to build up the cholesterol sensor. In our study, the PANI layer and gold electrodes were deposited on silicon nitride substrate, and the PANI was applied to fabricate a thin film between two electrodes. Then the PANI layer was sultonated by propane sultone and modified with HRP. After that, the device was combined with dialysis membrane which was modified with cholesterol oxidase. During the measurement, the sensor was operated at 100mV and different concentrations of cholesterol PBS solutions (pH=7.0) were dropped on it. The cholesterol reacted with the cholesterol oxidase and created hydrogen peroxide on the PANI thin film (Figure 1). The current change was measured when the hydrogen peroxide reacted with the HRP immobilized PANI thin film. According to regular cholesterol level in human blood, we tested the cholesterol solution from 100 mg/dl to 400 mg/dl ,and we get a very good linear result (Figure 2). In summary, the cholesterol sensor can provide a more exact cholesterol concentration detection. The simple process for the sensor fabrication also allows the sensor to be cheap, disposable and combinable with other sensors to build up sensing system. This work was partially supported by National Science Council grant (No.99B20495A & 101-2221-E-007-102-MY3) and by the research grant (100N2049E1) at National Tsing Hua University.
A near-infrared light-responsive drug delivery platform based on Au-Ag nanorods (Au-Ag NRs) coated with DNA cross-linked polymeric shells was constructed. DNA complementarity has been applied to develop a polyacrylamide-based sol-gel transition system to encapsulate anticancer drugs into the gel scaffold. The Au-Ag NR-based nanogels can also be readily functionalized with targeting moieties, such as aptamers, for specific recognition of tumor cells. When exposed to NIR irradiation, the photothermal effect of the Au-Ag NRs leads to a rapid rise in the temperature of the surrounding gel, resulting in the fast release of the encapsulated payload with high controllability. In vitro study confirmed that aptamer-functionalized nanogels can be used as drug carriers for targeted drug delivery with remote control capability by NIR light with high spatial/temporal resolution.
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