Kidney-specific cadherin (Ksp-cad) recently was proposed to differentiate chromophobe renal cell carcinoma (RCC) from oncocytoma based on a finding of Ksp-cad expression in 97% of chromophobe RCCs ...but only 3% of oncocytomas. However, another study showed no difference in Ksp-cad immunoreactivity between these 2 tumors. We attempted to evaluate Ksp-cad expression in renal tumors using expression microarrays and immunohistochemical analysis. Ksp-cad messenger RNA (mRNA) levels were examined in 158 renal tumors, including 15 chromophobe RCCs and 15 oncocytomas. Immunohistochemical analysis was performed on tissue microarrays containing 125 renal tumors, including 36 chromophobe RCCs and 41 oncocytomas. Ksp-cad mRNA compared with normal kidney tissue was 89% in chromophobe RCC and 64% in oncocytoma. Furthermore, 31 of 36 chromophobe RCCs and 31 of 41 oncocytomas showed Ksp-cad immunoreactivity. Ksp-cad was present in chromophobe RCCs and oncocytomas at mRNA and protein levels, providing strong evidence that Ksp-cad immunohistochemical analysis cannot be used in differentiating these tumors.
By analyzing large quantities of discharges in the unfavorable ion \( \vec B\times \nabla B \) drift direction, the I-mode operation has been confirmed in EAST tokamak. During the L-mode to I-mode ...transition, the energy confinement has a prominent improvement by the formation of a high-temperature edge pedestal, while the particle confinement remains almost identical to that in the L-mode. Similar with the I-mode observation on other devices, the \( E_r \) profiles obtained by the eight-channel Doppler backscattering system (DBS8)\cite{J.Q.Hu} show a deeper edge \( E_r \) well in the I-mode than that in the L-mode. And a weak coherent mode (WCM) with the frequency range of 40-150 kHz is observed at the edge plasma with the radial extend of about 2-3 cm. WCM could be observed in both density fluctuation and radial electric field fluctuation, and the bicoherence analyses showed significant couplings between WCM and high frequency turbulence, implying that the \( E_r \) fluctuation and the caused flow shear from WCM should play an important role during I-mode. In addition, a low-frequency oscillation with a frequency range of 5-10 kHz is always accompanied with WCM, where GAM intensity is decreased or disappeared. Many evidences show that the a low-frequency oscillation may be a novel kind of limited cycle oscillation but further investigations are needed to explain the new properties such as the harmonics and obvious magnetical perturbations.
I super(2)-Amyloid (AI super(2)) plaques in Alzheimer (AD) brains are surrounded by severe dendritic and axonal changes, including local spine loss, axonal swellings and distorted neurite ...trajectories. Whether and how plaques induce these neuropil abnormalities remains unknown. We tested the hypothesis that oligomeric assemblies of AI super(2), seen in the periphery of plaques, mediate the neurodegenerative phenotype of AD by triggering activation of the enzyme GSK-3I super(2), which in turn appears to inhibit a transcriptional program mediated by CREB. We detect increased activity of GSK-3I super(2) after exposure to oligomeric AI super(2) in neurons in culture, in the brain of double transgenic APP/tau mice and in AD brains. Activation of GSK-3I super(2), even in the absence of AI super(2), is sufficient to produce a phenocopy of AI super(2)-induced dendritic spine loss in neurons in culture, while pharmacological inhibition of GSK-3I super(2) prevents spine loss and increases expression of CREB-target genes like BDNF. Of note, in transgenic mice GSK-3I super(2) inhibition ameliorated plaque-related neuritic changes and increased CREB-mediated gene expression. Moreover, GSK-3I super(2) inhibition robustly decreased the oligomeric AI super(2) load in the mouse brain. All these findings support the idea that GSK3I super(2) is aberrantly activated by the presence of AI super(2), and contributes, at least in part, to the neuronal anatomical derangement associated with AI super(2) plaques in AD brains and to AI super(2) pathology itself.
The stimulus responsible for inducing hepatocytes to enter the cell cycle following partial hepatectomy (PHx) remains to be identified. One suggested candidate is the change in hepatocyte membrane ...potential (PD) that occurs immediately following PHx. To test this possibility, we monitored changes in hepatocyte PD and immediate‐early proto‐oncogene expression in rats pretreated with saline or gamma aminobutyric acid (GABA), an amino‐acid neurotransmitter that hyperpolarizes isolated hepatocytes. Intraperitoneal injections of saline or GABA (500 μg/g body weight) were administered to adult, male Sprague‐Dawley rats 1 hour prior to 70% PHx. Rats were sacrificed and the livers excised at various times until 180 minutes post‐PHx for messenger RNA (mRNA) and protein analyses. In additional groups of saline‐ and GABA‐treated rats, PD changes were recorded continuously from −260 to 180 minutes post‐PHx. Serum GABA concentrations were determined by ion‐exchange chromatography with orthopthaldehyde fluorescence detection. Hepatocyte PD's were recorded in situ by intracellular microelectrodes with an Axoprobe‐1A amplifier. Steady‐state levels of c‐fos, c‐jun, jun‐B, and c‐myc transcripts and proteins were documented by Northern blots of poly(A)‐enriched RNA derived from resected livers and Western blots of total nuclear protein, respectively. Serum GABA concentrations remained unchanged in saline‐treated controls but increased 10‐ to 20‐fold above baseline values in GABA‐treated rats. In saline‐treated controls, hepatocyte depolarization occurred immediately and was maintained throughout the 180 minutes post‐PHx period (PD pre‐PHx, −36.8 ± 5.1; 15 minutes post‐PHx, −27.5 ± 5.7; and 180 minutes post‐PHx, −28.3 ± 4.4 mV, mean ± SD); whereas in GABA‐treated rats, hepatocyte PD remained unchanged (‐37.0 ± 1.1; −36.4 ± 3.1 and −39.2 ± 2.7 mV, respectively). Despite abrogation of hepatocyte PD changes, proto‐oncogene mRNA and protein levels in saline‐ and GABA‐treated rats were either similar or, in the case of c‐fos and c‐jun, increased five‐ to sevenfold in GABA‐treated rats. The results of this study indicate the following: 1) hepatocytes depolarize immediately post‐PHx and remain depolarized throughout the priming phase of the cell cycle; 2) elevated serum GABA concentrations prevent PHx‐induced hepatocyte depolarization; and 3) depolarization is not the stimulus responsible for priming hepatocytes into replicative competence.
Artificial Neural Networks (ANNs) with Extended Delta-Bar-Delta (EDBD) back propagation learning algorithm have been developed to predict the standard enthalpy and entropy of 87 acyclic alkanes. ...Molecular weight, boiling point and density of the compounds were used as input parameters. The network's architecture and parameters were optimized to give maximum performances. The best network was a 3-6-2 ANN, and the optimum learning epoch was about 1320. The results show that the maximum relative errors of enthalpy and entropy are less than 3%. They reveal that the performances of ANNs for predicting the enthalpy and entropy of alkanes are satisfying.
Gas chromatographic retention indices of nitrogen-containing polycyclic aromatic compounds (N-PACs) have been predicted by quantitative structure–property relationship (QSPR) analysis based on ...heuristic method (HM) implemented in CODESSA. In order to indicate the influence of different molecular descriptors on retention indices and well understand the important structural factors affecting the experimental values, three multivariable linear models derived from three groups of different molecular descriptors were built. Moreover, each molecular descriptor in these models was discussed to well understand the relationship between molecular structures and their retention indices. The proposed models gave the following results: the square of correlation coefficient,
R
2, for the models with one, two and three molecular descriptors was 0.9571, 0.9776 and 0.9846, respectively.
Gas chromatography–mass spectrometry (GC–MS) coupled with chemometric resolution upon two-dimensional data was proposed as a method for the analysis of volatile components in a traditional Chinese ...medicinal preparation peptic powder which contains
Rhizoma Atractylodis,
Pericarpium Citri Reticulatae,
Cortex Magnoliae Officinalis and
Radix Glycyrrhizae. Ninety-three components were separated and 65 of them were qualitatively and quantitatively analyzed which represented about 90.28% of the total content. With the help of chemometric resolution, the data were resolved into a pure chromatogram and a mass spectrum of each chemical component. The accuracy of qualitative and quantitative results was greatly improved by using the two-dimensional comprehensive information of chromatograms and mass spectra. The example showed that chemometric resolution could greatly enhance separation ability. This makes it possible to analyze complicated practical systems like traditional Chinese medicinal preparations with the help of coupled instruments and chemometric resolution methods.
The support vector machine (SVM) and the heuristic method (HM) were used to develop the non-linear and linear models between the retention time (RT) and five molecular descriptors of 149 volatile ...organic compounds (VOCs). Descriptors calculated from the molecular structures alone were used to represent the characteristics of compounds. The five molecular descriptors selected by the heuristic method in CODESSA were used as inputs for SVM. The results obtained by SVM were compared with those obtained by the heuristic method. The mean squared errors (MSE) in RT predictions for the whole data set given by HM and SVM were 1.270 and 0.844, respectively, which shows the performance of SVM model is better than that of the HM model. The prediction results are in very good agreement with the experimental values. This paper provided a new and effective method for predicting the chromatography retention index.
The retention factor (log
k) in the biopartitioning micellar chromatography (BMC) of 79 heterogeneous pesticides was studied by quantitative structure–property relationships (QSPR) method. Heuristic ...method (HM) and support vector machine (SVM) method were used to build linear and nonlinear models, respectively. Compared the results of these two methods, those obtained by the SVM model are much better. For the test set, a predictive correlation coefficient (
R) of 0.9755 and root-mean-square (RMS) error of 0.1403 were obtained. The proposed QSPR models, both by HM and SVM, contain the same descriptors that agree with the classical Abraham parameters of well-known linear solvation energy relationships (LSER).
By employing a novel low-temperature synthetic pathway, highly ordered cubic mesoporous materials with hitherto the largest pores (up to 27 nm) and unit cells (up to 44 nm) have been successfully ...obtained.
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