Cardiac myocyte-specific knock-out of calcium-independent phospholipase A2γ (iPLA2γ) decreases oxidized fatty acids during ischemia/reperfusion and reduces infarct size

Calcium-independent phospholipase A(2)γ (iPLA(2)γ) is a mitochondrial enzyme that produces lipid second messengers that facilitate opening of the mitochondrial permeability transition pore (mPTP) and contribute to the production of oxidized fatty acids in myocardium. To specifically identify the roles of iPLA(2)γ in cardiac myocytes, we generated cardiac myocyte-specific iPLA(2)γ knock-out (CMiPLA(2)γKO) mice by removing the exon encoding the active site serine (Ser-477). Hearts of CMiPLA(2)γKO mice exhibited normal hemodynamic function, glycerophospholipid molecular species composition, and normal rates of mitochondrial respiration and ATP production. In contrast, CMiPLA(2)γKO mice demonstrated attenuated Ca(2+)-induced mPTP opening that could be rapidly restored by the addition of palmitate and substantially reduced production of oxidized polyunsaturated fatty acids (PUFAs). Furthermore, myocardial ischemia/reperfusion (I/R) in CMiPLA(2)γKO mice (30 min of ischemia followed by 30 min of reperfusion in vivo) dramatically decreased oxidized fatty acid production in the ischemic border zones. Moreover, CMiPLA(2)γKO mice subjected to 30 min of ischemia followed by 24 h of reperfusion in vivo developed substantially less cardiac necrosis in the area-at-risk in comparison with their WT littermates. Furthermore, we found that membrane depolarization in murine heart mitochondria was sensitized to Ca(2+) by the presence of oxidized PUFAs. Because mitochondrial membrane depolarization and calcium are known to activate iPLA(2)γ, these results are consistent with salvage of myocardium after I/R by iPLA(2)γ loss of function through decreasing mPTP opening, diminishing production of proinflammatory oxidized fatty acids, and attenuating the deleterious effects of abrupt increases in calcium ion on membrane potential during reperfusion

Generic functional modelling of multi-pulse auto-transformer rectifier units for more-electric aircraft applications

The Auto-Transformer Rectifier Unit (ATRU) is one preferred solution for high-power AC/DC power conversion in aircraft. This is mainly due to its simple structure, high reliability and reduced kVA ratings. Indeed, the ATRU has become a preferred AC/DC solution to supply power to the electric environment control system on-board future aircraft. In this paper, a general modelling method for ATRUs is introduced. The developed model is based on the fact that the DC voltage and current are strongly related to the voltage and current vectors at the AC terminals of ATRUs. In this paper, we carry on our research in modelling symmetric 18-pulse ATRUs and develop a generic modelling technique. The developed generic model can study not only symmetric but also asymmetric ATRUs. An 18-pulse asymmetric ATRU is used to demonstrate the accuracy and efficiency of the developed model by comparing with corresponding detailed switching SABER models provided by our industrial partner. The functional models also allow accelerated and accurate simulations and thus enable whole-scale more-electric aircraft electrical power system studies in the future

Concomitant Retrograde Coronary Venous Infusion of Basic Fibroblast Growth Factor Enhances Engraftment and Differentiation of Bone Marrow Mesenchymal Stem Cells for Cardiac Repair after Myocardial Infarction.

AIM: Basic fibroblast growth factor (bFGF) increases the migration and viability of bone marrow mesenchymal stem cells (MSCs) in vitro. Retrograde coronary venous infusion can provide both increased regional bFGF concentrations and homogeneous cell dissemination. We determined whether retrograde delivery of bFGF enhances the potency of transplanted MSCs for cardiac repair in a canine infarct model. METHODS AND RESULTS: Under hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype. A canine infarct model was employed by coronary ligation. One week later, animals were subjected to retrograde infusion of combination bFGF (200ng/mL) and MSCs (1×10(8) cells) (n=5), MSCs (1×10(8) cells, n=5), bFGF (200ng/mL, n=5), or placebo (phosphate-buffered saline, n=3). Four weeks after infusion, only the bFGF+MSCs therapy exhibited significantly increased left ventricular ejection fraction (LVEF) by echocardiography (p CONCLUSIONS: Retrograde coronary venous bFGF infusion augments engraftment and differentiation capacity of transplanted MSCs, recovering cardiac function and preventing adverse remodeling. This novel combined treatment and delivery method is a promising strategy for cardiac repair after ischemic injury

Post-Translational Modification of PTEN Protein: Quantity and Activity

Post-translational modifications play crucial roles in regulating protein functions and stabilities. PTEN is a critical tumor suppressor involved in regulating cellular proliferation, survival, and migration processes. However, dysregulation of PTEN is common in various human cancers. PTEN stability and activation/suppression have been extensively studied in the context of tumorigenesis through inhibition of the PI3K/AKT signaling pathway. PTEN undergoes various post-translational modifications, primarily including phosphorylation, acetylation, ubiquitination, SUMOylation, neddylation, and oxidation, which finely tune its activity and stability. Generally, phosphorylation modulates PTEN activity through its lipid phosphatase function, leading to altered power of the signaling pathways. Acetylation influences PTEN protein stability and degradation rate. SUMOylation has been implicated in PTEN localization and interactions with other proteins, affecting its overall function. Neddylation, as a novel modification of PTEN, is a key regulatory mechanism in the loss of tumor suppressor function of PTEN. Although current therapeutic approaches focus primarily on inhibiting PI3 kinase, understanding the post-translational modifications of PTEN could help provide new therapeutic strategies that can restore PTEN’s role in PIP3-dependent tumors. The present review summarizes the major recent developments in the regulation of PTEN protein level and activity. We expect that these insights will contribute to better understanding of this critical tumor suppressor and its potential implications for cancer therapy in the future

Suppress vibration on robotic polishing with impedance matching

Installing force-controlled end-effectors on the end of industrial robots has become the mainstream method for robot force control. Additionally, during the polishing process, contact force stability has an important impact on polishing quality. However, due to the difference between the robot structure and the force-controlled end-effector, in the polishing operation, direct force control will have impact during the transition from noncontact to contact between the tool and the workpiece. Although impedance control can solve this problem, industrial robots still produce vibrations with high inertia and low stiffness. Therefore, this research proposes an impedance matching control strategy based on traditional direct force control and impedance control methods to improve this problem. This method's primary purpose is to avoid force vibration in the contact phase and maintain force-tracking performance during the dynamic tracking phase. Simulation and experimental results show that this method can smoothly track the contact force and reduce vibration compared with traditional force control and impedance control

A Survey on Dropout Methods and Experimental Verification in Recommendation

Overfitting is a common problem in machine learning, which means the model too closely fits the training data while performing poorly in the test data. Among various methods of coping with overfitting, dropout is one of the representative ways. From randomly dropping neurons to dropping neural structures, dropout has achieved great success in improving model performances. Although various dropout methods have been designed and widely applied in past years, their effectiveness, application scenarios, and contributions have not been comprehensively summarized and empirically compared by far. It is the right time to make a comprehensive survey. In this paper, we systematically review previous dropout methods and classify them into three major categories according to the stage where dropout operation is performed. Specifically, more than seventy dropout methods published in top AI conferences or journals (e.g., TKDE, KDD, TheWebConf, SIGIR) are involved. The designed taxonomy is easy to understand and capable of including new dropout methods. Then, we further discuss their application scenarios, connections, and contributions. To verify the effectiveness of distinct dropout methods, extensive experiments are conducted on recommendation scenarios with abundant heterogeneous information. Finally, we propose some open problems and potential research directions about dropout that worth to be further explored.Comment: 26 page

THUIR at the NTCIR-16 WWW-4 Task

The THUIR team participates in the English subtask of the NTCIR-16 We Want Web with CENTRE(WWW-4) task. This paper elaborates on our methods and discusses the experimental results. We adopt three methods, namely learning-to-rank models, a pre-trained language model tailored for information retrieval, and BERT with prompt learning. Experimental results demonstrate the importance of designing pre-training task specifically for information retrieval. Results also suggest the relatively simple prompt method cannot effectively improve the ranking performance.conference pape

Arabidopsis IAR4 Modulates Primary Root Growth Under Salt Stress Through ROS-Mediated Modulation of Auxin Distribution

High salinity is one of the major environmental stresses that plants encounter. Roots are the initial and direct organs to perceive the signal. However, how plant roots perceive and respond to salinity at the molecular and physiological levels is still poorly understood. Here, we report that IAA-CONJUGATE-RESISTANT 4 (IAR4) plays a key role in primary root growth under salt stress conditions. Mutation of IAR4 led to increased sensitivity to salt stress conditions, with strongly inhibited primary root growth and reduced survival rate in two iar4 mutant alleles. iar4 mutants accumulated greater Na+ and exhibited a greater Na+/K+ ratio under NaCl treatment. In addition, more reactive oxygen species (ROS) accumulated in the iar4 mutants due to reduced ROS scavenging. NaCl treatment greatly suppressed the expression levels of ProPIN1:PIN1-GFP, ProPIN2:PIN2-GFP, ProPIN3:PIN3-GFP, and ProDR5:GFP, and suppressed root meristem activity in iar4. GSH or auxin treatment greatly recovered the PIN expression, auxin distribution and primary root growth in the iar4 mutants, suggesting ROS is a vital mediator between salt stress and auxin response. Our data support a model in which IAR4 integrates ROS and auxin pathways to modulate primary root growth under salinity stress conditions, by regulation of PIN-mediated auxin transport