Propagation of Measurement-While-Drilling Mud Pulse during High Temperature Deep Well Drilling Operations

Signal attenuates while Measurement-While-Drilling (MWD) mud pulse is transmited in drill string during high temperature deep well drilling. In this work, an analytical model for the propagation of mud pulse was presented. The model consists of continuity, momentum, and state equations with analytical solutions based on the linear perturbation analysis. The model can predict the wave speed and attenuation coefficient of mud pulse. The calculated results were compared with the experimental data showing a good agreement. Effects of the angular frequency, static velocity, mud viscosity, and mud density behavior on speed and attenuation coefficients were included in this paper. Simulated results indicate that the effects of angular frequency, static velocity, and mud viscosity are important, and lower frequency, viscosity, and static velocity benefit the transmission of mud pulse. Influenced by density behavior, the speed and attenuation coefficients in drill string are seen to have different values with respect to well depth. For different circulation times, the profiles of speed and attenuation coefficients behave distinctly different especially in lower section. In general, the effects of variables above on speed are seen to be small in comparison

Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144634/1/aji12860_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144634/2/aji12860.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144634/3/aji12860-sup-0001-Supinfo.pd

Propofol inhibits myocardial injury induced by microvesicles derived from hypoxia-reoxygenated endothelial cells via lncCCT4-2/CCT4 signaling

Abstract Background Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. Methods Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. Results In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. Conclusions Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis

Phosphoinositide Binding to the Substrate Regulates Susceptibility to Proteolysis by Calpain*

Calpain-mediated proteolysis regulates cytoskeletal dynamics and is altered during aging and the progression of numerous diseases or pathological conditions. Although several cytoskeletal proteins have been identified as substrates, how localized calpain activity is regulated and the mechanisms controlling substrate recognition are not clear. In this study, we report that phosphoinositide binding regulates the susceptibility of the cytoskeletal adhesion protein α-actinin to proteolysis by calpains 1 and 2. At first, α-actinin did not appear to be a substrate for calpain 2; however, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding to α-actinin resulted in nearly complete proteolysis of the full-length protein, producing stable breakdown products. Calpain 1 was able to cleave α-actinin in the absence of phosphoinositide binding; however, PtdIns(3,4,5)P3 binding increased the rate of proteolysis, and phosphatidylinositol 4,5-diphosphate (PtdIns(4,5)P2) binding significantly inhibited cleavage. Phosphoinositide binding appeared to regulate calpain proteolysis of α-actinin by modulating the exposure of a highly sensitive cleavage site within the calponin homology 2 domain. In U87MG glioblastoma cells, which contain elevated levels of PtdIns(3,4,5)P3, α-actinin colocalized with calpain within dynamic actin cytoskeletal structures. Furthermore, proteolysis of α-actinin producing stable breakdown products was observed in U87MG cells treated with calcium ionophore to activate the calcium-dependent calpains. Additional evidence of PtdIns(3,4,5)P3-mediated calpain proteolysis of α-actinin was observed in rat embryonic fibroblasts. These results suggest that PtdIns(3,4,5)P3 binding is a critical determinant for α-actinin proteolysis by calpain. In conclusion, phosphoinositide binding to the substrate is a potential mechanism for regulating susceptibility to proteolysis by calpain