The transformation of macrophages into lipid‐loaded foam cells is a critical early event in the pathogenesis of atherosclerosis. Both receptor‐mediated uptake of modified LDL, mediated primarily by scavenger receptors‐A (SR‐A) and CD36 along with other proteins such as lipoprotein lipase (LPL), and macropinocytosis contribute to macrophage foam cell formation. The signaling pathways that are involved in the control of foam cell formation are not fully understood. In this study, we have investigated the role of phosphoinositide 3‐kinase (PI3K) in relation to foam cell formation in human macrophages. The pan PI3K inhibitor LY294002 attenuated the uptake of modified LDL and macropinocytosis, as measured by Lucifer Yellow uptake, by human macrophages. In addition, the expression of SR‐A, CD36 and LPL was attenuated by LY294002. The use of isoform‐selective PI3K inhibitors showed that PI3K‐β, ‐γ and ‐δ were all required for the expression of SR‐A and CD36 whereas only PI3K‐γ was necessary in the case of LPL. These studies reveal a pivotal role of PI3K in the control of macrophage foam cell formation and provide further evidence for their potential as therapeutic target against atherosclerosis. 相似文献
Recent work in the literature has shown weighted variants of the classic portmanteau test for time series can be more powerful in many situations. In this article, we study the asymptotic distribution of weighted sums of the squared residual autocorrelations where both the sample size n and maximum lag of the statistic m grow large. Several weighting schemes are introduced, including a data‐adaptive statistic in which the weights are determined by a function of the sample partial autocorrelations. These statistics can provide more power than other portmanteau tests found in the literature and are much less sensitive to the choice of the maximum correlation lag. The efficacy of the proposed methods is further demonstrated through an analysis of Australian red wine sales. 相似文献
The aims of the current study were to synthesize new responsive polymeric microgels with embedded silver nanoparticles and then to employ these particles as catalyst for reduction reactions. To these ends, stimuli‐responsive microgels from PNIPAAm and the chitosan derivative were firstly synthesized by free radical precipitation polymerization. Then, silver nanoparticles were synthesized inside these microgel networks by in situ reduction of AgNO3. These microgels were temperature/pH sensitive with a phase transition temperature of 32–35 °C in water at pH = 3 and 8, respectively. The catalytic activity of the Ag nanoparticles for the reduction of 4‐nitrophenol can be tuned through the swelling or collapse of the responsive microgel network hosting the active nanoparticles.
The targeting of bioactive molecules and probes to mitochondria can be achieved by coupling to the lipophilic triphenyl phosphonium (TPP) cation, which accumulates several hundred-fold within mitochondria in response to the mitochondrial membrane potential (Δψm). Typically, a simple alkane links the TPP to its “cargo”, increasing overall hydrophobicity. As it would be beneficial to enhance the water solubility of mitochondria-targeted compounds we explored the effects of replacing the alkyl linker with a polyethylene glycol (PEG). We found that the use of PEG led to compounds that were readily taken up by isolated mitochondria and by mitochondria inside cells. Within mitochondria the PEG linker greatly decreased adsorption of the TPP constructs to the matrix-facing face of the mitochondrial inner membrane. These findings will allow the distribution of mitochondria-targeted TPP compounds within mitochondria to be fine-tuned. 相似文献
A lithium-ion positive electrode is proposed that contains both high energy density and efficient pulse power capability, even at low state-of-charge (SOC). The pulse power capability at low SOC is attractive for applications, such as plug-in hybrid electric vehicles (PHEVs), which require pulse power operation over the entire useable SOC window. A lithium- and manganese-rich transition-metal layered-oxide (LMR-NMC), also classified as a layered-layered oxide material, is blended with a lithium iron phosphate (LFP) to achieve a potentially low-cost, high-performance electrode. The LMR-NMC material provides high energy by delivering cathode material gravimetric energy densities greater than 890 Wh kg−1. The pulse power capability of this material at low SOC is greatly improved by incorporating a modest quantity of LFP. The LFP serves as an internal redox couple to charge and discharge the more rate-limited LMR-NMC material at moderate to low SOCs. 相似文献
Hand scaling is a physically demanding task responsible for numerous overexertion injuries in underground mining. Scaling requires the miner to use a long pry bar to remove loose rock, reducing the likelihood of rock fall injuries. The experiments described in this article simulated “rib” scaling (scaling a mine wall) from an elevated bucket to examine force generation and electromyographic responses using two types of scaling bars (steel and fiberglass-reinforced aluminum) at five target heights ranging from floor level to 176 cm. Ten male and six female subjects were tested in separate experiments. Peak and average force applied at the scaling bar tip and normalized electromyography (EMG) of the left and right pairs of the deltoid and erectores spinae muscles were obtained. Work height significantly affected peak prying force during scaling activities with highest force capacity at the lower levels. Bar type did not affect force generation. However, use of the lighter fiberglass bar required significantly more muscle activity to achieve the same force. Results of these studies suggest that miners scale points on the rock face that are below their knees, and reposition the bucket as often as necessary to do so. 相似文献