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BACKGROUND Dementia is a growing public health concern with an estimated prevalence of 50 million people worldwide. Alzheimer's disease (AD) and vascular and frontotemporal dementias (VaD, FTD), share many clinical, genetical, and pathological features making the diagnosis difficult. METHODS In this study, we compared the transcriptome from the frontal cortex of patients with AD, VaD, and FTD to identify dysregulated pathways. RESULTS Upregulated genes in AD were enriched in adherens and tight junctions, mitogen-activated protein kinase, and phosphatidylinositol 3-kinase and protein kinase B/Akt signaling pathways, whereas downregulated genes associated with calcium signaling. Upregulated genes in VaD were centered on infectious diseases and nuclear factor kappa beta signaling, whereas downregulated genes are involved in biosynthesis of amino acids and the pentose phosphate pathway. Upregulated genes in FTD were associated with ECM receptor interactions and the lysosome, whereas downregulated genes were involved in glutamatergic synapse and MAPK signaling. The transcription factor KFL4 was shared among the 3 types of dementia. CONCLUSIONS Collectively, we identified similarities and differences in dysregulated pathways and transcription factors among the dementias. The shared pathways and transcription factors may indicate a potential common etiology, whereas the differences may be useful for distinguishing dementias.Porous asphalt concrete (PAC) has been used to improve the traffic conditions in rainy weather due to its high porosity. Aggregate size and gradation have great impact on the connected pore structure, which ultimately affects the permeability of porous asphalt concrete. In this paper, the topological properties of connective pores including pore area, pore circularity, equivalent pore diameter, and void network of porous asphalt concrete with different nominal maximum aggregate sizes and gradations were analyzed using x-ray computer tomography scans and the image processing technique. It was observed that the maximum aggregate sizes will not have significant effect on the percentage of connected pores to total pores for porous asphalt concrete. Furthermore, the percentage of connected pores to total pores is related to the air void content, but for PAC-13 with 20% target air void content or above, the connectivity does not seem to have a sharp increase. Additionally, porous asphalt concrete with a smaller nominal particle size or lower target air void content seems to generate a more concentrated distribution of Eqdiameter. Moreover, pore circularities for porous asphalt concrete with a maximum aggregate size of 10 mm or above are independent of maximum aggregate sizes. Air void contents ranging from 16% to 21% do not have a significant effect on the voids' circularity. Furthermore, the branching nodes in porous asphalt concrete with a smaller nominal maximum aggregate size or lower target air void content have a more uniform spatial distribution. However, the percentage of cross-linked number to total node raises as the nominal maximum aggregate size or target air void content increases.Newly assembled herpesvirus nucleocapsids traverse the intact nuclear envelope by a vesicle-mediated nucleo-cytoplasmic transport for final virion maturation in the cytoplasm. For this, they bud at the inner nuclear membrane resulting in primary enveloped particles in the perinuclear space (PNS) followed by fusion of the primary envelope with the outer nuclear membrane (ONM). PFI-2 While the conserved viral nuclear egress complex orchestrates the first steps, effectors of fusion of the primary virion envelope with the ONM are still mostly enigmatic but might include cellular proteins like SUN2 or ESCRT-III components. Here, we analyzed the influence of the only known AAA+ ATPases located in the endoplasmic reticulum and the PNS, the Torsins (Tor), on nuclear egress of the alphaherpesvirus pseudorabies virus. For this overexpression of wild type and mutant proteins as well as CRISPR/Cas9 genome editing was applied. Neither single overexpression nor gene knockout (KO) of TorA or TorB had a significant impact. However, TorA/B double KO cells showed decreased viral titers at early time points of infection and an accumulation of primary virions in the PNS pointing to a delay in capsid release during nuclear egress.Vascular calcification is the pathological deposition of calcium/phosphate in the vascular system and is closely associated with cardiovascular morbidity and mortality. Here, we investigated the role of gastrin-releasing peptide (GRP) in phosphate-induced vascular calcification and its potential regulatory mechanism. We found that the silencing of GRP gene and treatment with the GRP receptor antagonist, RC-3095, attenuated the inorganic phosphate-induced calcification of vascular smooth muscle cells (VSMCs). This attenuation was caused by inhibiting phenotype change, apoptosis and matrix vesicle release in VSMCs. Moreover, the treatment with RC-3095 effectively ameliorated phosphate-induced calcium deposition in rat aortas ex vivo and aortas of chronic kidney disease in mice in vivo. Therefore, the regulation of the GRP-GRP receptor axis may be a potential strategy for treatment of diseases associated with excessive vascular calcification.A novel method involving the effect of thermal contact resistance (TCR) was proposed using a plane heat source smaller than the measured samples for improving measurement accuracy of the simultaneous determination of in-plane and cross-plane thermal conductivities and the volumetric heat capacity of anisotropic materials. The heat transfer during the measurement process was mathematically modeled in a 3D Cartesian coordinate system. The temperature distribution inside the sample was analytically derived by applying Laplace transform and the variables separation method. A multiparameter estimation algorithm was developed on the basis of the sensitivity analysis of the parameters to simultaneously estimate the measured parameters. The correctness of the algorithm was verified by performing simulation experiments. The thermophysical parameters of insulating materials were experimentally measured using the proposed method at different temperatures and pressures. Fiber glass and ceramic insulation materials were tested at room temperature.
Read More: https://www.selleckchem.com/products/pfi-2.html
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