Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis.
In a previous study on matrix-assisted laser desorption ionization (MALDI) of peptides using α-cyano-4-hydroxycinnamic acid (CHCA) as a matrix, we found that the patterns of single-shot spectra obtained under different experimental conditions became similar upon temperature selection. In this paper, we report that absolute ion abundances are also similar in temperature-selected MALDI spectra, even when laser fluence is varied. The result that has been obtained using CHCA and 2,5-dihydroxybenzoic acid as matrices is in disagreement with the hypothesis of laser-induced ionization of matrix as the mechanism for primary ion formation in MALDI. We also report that the total number of ions in such a spectrum is unaffected by the identity, concentration and number of analytes, i.e. it is the same as that in the spectrum of pure matrix. We propose that the generation of gas-phase ions in MALDI can be explained in terms of two thermal reactions, i.e. the autoprotolysis of matrix molecules and the matrix-to-analyte proton transfer, both of which are in quasi-equilibrium in the early matrix plume.
Even though matrix-assisted laser desorption ionization (MALDI) is a powerful technique for mass spectrometry of peptides and proteins, it is not quite useful for their quantification that is one of the outstanding problems in quantitative proteomics. The main difficulty lies in the poor reproducibility of MALDI spectra. In this work, a simple method to circumvent this problem has been developed. The method is based on a previous observation that the reaction quotient for the matrix-to-peptide proton transfer evaluated in temperature-selected MALDI was nearly constant regardless of the peptide concentration in the solid sample. This implied a direct proportionality between the relative abundance of an analyte ion in a temperature-selected MALDI spectrum and the concentration of the corresponding neutral in the solid sample. This relation has been confirmed by calibration curves obtained for some peptides. Another characteristic of the relation is that it holds even when other analytes are present. This has been demonstrated for mixtures containing peptides and proteins. This and the fact that the method does not require the addition of internal standards allow rapid and inexpensive quantification of any analyte amenable to MALDI.
In our previous matrix-assisted laser desorption ionization (MALDI) studies of peptides, we found that their mass spectra were virtually determined by the effective temperature in the early matrix plume, Tearly, when samples were rather homogeneous. This empirical rule allowed acquisition of quantitatively reproducible spectra. A difficulty in utilizing this rule was the complicated spectral treatment needed to get Tearly. In this work, we found another empirical rule that the total number of particles hitting the detector, or TIC, was a good measure of the spectral temperature and, hence, selection of spectra with the same TIC resulted in reproducible spectra. We also succeeded in obtaining reproducible spectra throughout a measurement by controlling TIC near a preset value through feedback adjustment of laser pulse energy. Both TIC selection and TIC control substantially reduced the shot-to-shot spectral variation in a spot, spot-to-spot variation in a sample, and even sample-to-sample variation in MALDI using α-cyano-4-hydroxycinnamic acid or 2,5-dihydroxybenzoic acid as matrix. Based on the utilization of acquired data, TIC control was more efficient than TIC selection by an order of magnitude. Both techniques produced calibration curves with excellent linearity, suggesting their utility in quantification of peptides.
We propose to divide matrix suppression in matrix-assisted laser desorption ionization into two parts, normal and anomalous. In quantification of peptides, the normal effect can be accounted for by constructing the calibration curve in the form of peptide-to-matrix ion abundance ratio versus concentration. The anomalous effect forbids reliable quantification and is noticeable when matrix suppression is larger than 70%. With this 70% rule, matrix suppression becomes a guideline for reliable quantification, rather than a nuisance. A peptide in a complex mixture can be quantified even in the presence of large amounts of contaminants, as long as matrix suppression is below 70%. The theoretical basis for the quantification method using a peptide as an internal standard is presented together with its weaknesses. A systematic method to improve quantification of high concentration analytes has also been developed.
Untreated psychotic symptoms such as Capgras syndrome, living with elderly parents, especially mothers, and conflicts caused by victims' scolding, threatening forced hospitalisation, and forcing medication on the patients are associated with parricide among homicide offenders with schizophrenia.
The current study was designed to investigate the therapeutic effects of Maresin 1 (MAR1) on atherosclerotic response. Human monocytes THP-1 and human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of MAR1 on lipopolysaccharide (LPS)-induced inflammation and apoptosis. In this study, we found that MAR1 induces peroxisome proliferator-activated receptor alpha (PPARα) expression. We also demonstrated that MAR1 suppresses atherosclerotic reactions caused by LPS treatment via a PPARα-dependent pathway. MAR1 treatment inhibited LPS-induced phosphorylation of nuclear factor kappa B (NF-κB) and secretion of pro-inflammatory cytokines in HUVECs and THP-1 cells. In HUVEC cells, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly decreased after MAR1 treatment. Furthermore, LPS-induced endoplasmic reticulum (ER) stress and cell apoptosis was significantly decreased after MAR1 treatment of HUVECs. MAR1 also led to a dose-dependent increase in oxygen-regulated protein 150 (ORP150) expression which is responsible for the inhibition of ER stress. Notably, all of the pro-atherosclerotic effects were completely abrogated by treatment with small interfering (si) RNA targeting PPARα. In conclusion, MAR1 ameliorates LPS-induced atherosclerotic reactions via PPARα-mediated suppression of inflammation and ER stress.
Objectiv e: This study is conducted on the differences between flat and curved displays with respect to location of focused points, posture and satisfaction as well as preferred tilt angles. Background:In order to avoid physical and eye fatigue caused by misplayed sitting posture, many studies have asserted that the display requires appropriate location, size and tilt angle as well as curvature. However, most studies have focused on the work environment and the results are varied in the extent.Method: Eye height data in sitting posture were collected from 30 participants. Participants selected the most comfortable viewing angle within the range from 0°t o 12° while watching videos for both curved and flat display. Then, physical and eye fatigue and overall satisfaction were subjectively evaluated. Lateral diagram describing viewing display condition was set and used to develop linear models for expecting the preferred tilt angle.Results: Due to sitting in the natural viewing posture rather than upright, the eye height is lowered to about 4.6 centimeters, on average, for both displays showing no significant differences. In contrast, preferred angles for the two displays are significantly different and this can be interpreted that curvature vary the points focused. Two linear models as functions of sitting eye height are developed to expect preferred tilt angle for each display. Based on the result of overall satisfaction evaluation, curved display is statistically better than flat display. Conclusion:The results show that flat and curved displays are significantly different expect for the viewing posture. However, reasons for preferring curved display are not accurately factorized and the linear models are limited in the experiment condition such as size of display, distance between display and viewer and other physical environmental factors. Further studies on curved displays under more various conditions are required. Application:This study can contribute to use of the curved display in various way.
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