Optimization of Forged 42CrMo4 Steel Piston Pin Hole Profile Using Finite Element Method

The fatigue failure of the piston pin hole is considered as a key factor affecting the service life of engines. In this work, the piston pin hole profile was designed as tapered shape following a power law. By combining finite element analysis and hydraulic pulsating fatigue tests, the pin hole profile was optimized. It has been found that the maximum contact pressure on the pin hole surface was reduced by 16,7% with appropriate increasing the radius enlarging rate of the piston pin hole, the maximum tensile stress of the piston pin seat was reduced by 13,1%, and the piston pin seat fatigue safety factor was increased by 41,4%, the piston pin hole fatigue safety factor was increased by 15,9%. The piston pin hole’s hydraulic pulsating fatigue test results were found to be consistent with the FEA results. It could be concluded that appropriate increasing the radius enlarging rate of the pin hole could significantly weaken the fatigue wear of the pin hole, further improving its fatigue resistance

Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5′ flap DNA: basis of interstrand cross-link repair by FAN1

Fanconi anemia (FA) is an autosomal recessive genetic disorder caused by defects in any of 15 FA genes responsible for processing DNA interstrand cross-links (ICLs). The ultimate outcome of the FA pathway is resolution of cross-links, which requires structure-selective nucleases. FA-associated nuclease 1 (FAN1) is believed to be recruited to lesions by a monoubiquitinated FANCI–FANCD2 (ID) complex and participates in ICL repair. Here, we determined the crystal structure of Pseudomonas aeruginosa FAN1 (PaFAN1) lacking the UBZ (ubiquitin-binding zinc) domain in complex with 5′ flap DNA. All four domains of the right-hand-shaped PaFAN1 are involved in DNA recognition, with each domain playing a specific role in bending DNA at the nick. The six-helix bundle that binds the junction connects to the catalytic viral replication and repair (VRR) nuclease (VRR nuc) domain, enabling FAN1 to incise the scissile phosphate a few bases distant from the junction. The six-helix bundle also inhibits the cleavage of intact Holliday junctions. PaFAN1 shares several conserved features with other flap structure-selective nucleases despite structural differences. A clamping motion of the domains around the wedge helix, which acts as a pivot, facilitates nucleolytic cleavage. The PaFAN1 structure provides insights into how archaeal Holliday junction resolvases evolved to incise 5′ flap substrates and how FAN1 integrates with the FA complex to participate in ICL repair

Time-Varying Risk Attitude and Conditional Skewness

Much literature finds that the skewness in the return distribution is negatively correlated with the risk premium coefficient, and speculation is the reason for the skewness in the return distribution. As further research, this paper, first taking up the time-varying property of the risk premium coefficient, proposes a GARCH-M model with a time-varying coefficient of the risk premium for an empirical study of the correlation between the conditional skewness in the return distribution and the time-varying risk attitude. The empirical study indicates that the coefficient of the risk premium varies with the time, and even in a mature market the conditional skewness in the return distribution is negatively correlated with the time-varying coefficient of the risk premium

Time-Varying Risk Attitude and Conditional Skewness

Much literature finds that the skewness in the return distribution is negatively correlated with the risk premium coefficient, and speculation is the reason for the skewness in the return distribution. As further research, this paper, first taking up the time-varying property of the risk premium coefficient, proposes a GARCH-M model with a time-varying coefficient of the risk premium for an empirical study of the correlation between the conditional skewness in the return distribution and the time-varying risk attitude. The empirical study indicates that the coefficient of the risk premium varies with the time, and even in a mature market the conditional skewness in the return distribution is negatively correlated with the time-varying coefficient of the risk premium

Expression and aberrant promoter methylation of Wnt inhibitory factor-1 in human astrocytomas

<p>Abstract</p> <p>Background</p> <p>Wnt inhibitory factor-1(WIF-1) acts as a Wnt-antagonists and tumor suppressor, but hypermethylation of WIF-1 gene promoter and low expression activate Wnt signaling aberrantly and induce the development of various human tumors. With this work we intended to investigate the expression and promoter methylation status of WIF-1 gene in human astrocytomas.</p> <p>Methods</p> <p>The tissue samples consisted of 53 astrocytomas and 6 normal brain tissues. The expression levels of WIF-1 were determined by immunohistochemistry and semiquantitative RT-PCR. The results were analyzed in correlation with clinicopathological data. Methylation status of WIF-1 gene promoter was investigated using methylation specific PCR. The relationship between methylation and expression of the genes was analyzed.</p> <p>Results</p> <p>The average expression levels of WIF-1 protein and mRNA in astrocytomas were decreased significantly compared with normal control tissues. The protein and mRNA expression of WIF-1 gene in astrocytomas was decreased with the increase of pathological grade. Furthermore, WIF-1 promoter methylation was observed by MS-PCR in astrocytomas which showed significant reduction of WIF-1 expression. The WIF-1 promoter hypermethylation was associated with reduced expression of WIF-1 expression.</p> <p>Conclusion</p> <p>Our results demonstrate that the WIF-1 gene is frequently down-regulated or silenced in astrocytomas by aberrant promoter methylation. This may be an important mechanism in astrocytoma carcinogenesis.</p

Shape memory polyurethane microcapsules with active deformation

From smart self-tightening sutures and expandable stents to morphing airplane wings, shape memory structures are increasingly present in our daily life. The lack of methods for synthesizing intricate structures from them on the micron and submicron level, however, is stopping the field from developing. In particular, the methods for the synthesis of shape memory polymers (SMPs) and structures at this scale and the effect of new geometries remain unexplored. Here, we describe the synthesis of shape memory polyurethane (PU) capsules accomplished by interfacial polymerization of emulsified droplets. The emulsified droplets contain the monomers for the hard segments, while the continuous aqueous phase contains the soft segments. A trifunctional chemical cross-linker for shape memory PU synthesis was utilized to eliminate creep and improve the recovery ratios of the final capsules. We observe an anomalous dependence of the recovery ratio with the amount of programmed strain compared to previous SMPs. We develop quantitative characterization methods and theory to show that when dealing with thin-shell objects, alternative parameters to quantify recovery ratios are needed. We show that while achieving 94-99% area recovery ratios, the linear capsule recovery ratios can be as low as 70%. This quantification method allows us to convert from observed linear aspect ratios in capsules to find out unrecovered area strain and stress. The hollow structure of the capsules grants high internal volume for some applications (e.g., drug delivery), which benefit from much higher loading of active ingredients than polymeric particles. The methods we developed for capsule synthesis and programming could be easily scaled up for larger volume applications

Investors’ Risk Preference Characteristics Based on Different Reference Point

Taking the stock market as a whole object, we assume that prior losses and gains are two different factors that can influence risk preference separately. The two factors are introduced as separate explanatory variables into the time-varying GARCH-M (TVRA-GARCH-M) model. Then, we redefine prior losses and gains by selecting different reference point to study investors’ time-varying risk preference. The empirical evidence shows that investors’ risk preference is time varying and is influenced by previous outcomes; the stock market as a whole exhibits house money effect; that is, prior gains can decrease investors’ risk aversion while prior losses increase their risk aversion. Besides, different reference points selected by investors will cause different valuation of prior losses and gains, thus affecting investors’ risk preference

Cardioprotective Effects of Salvianolic Acid A on Myocardial Ischemia-Reperfusion Injury In Vivo and In Vitro

Salvianolic acid A (SAA), one of the major active components of Danshen that is a traditional Chinese medicine, has been reported to possess protective effect in cardiac diseases and antioxidative activity. This study aims to investigate the cardioprotection of SAA in vivo and in vitro using the model of myocardial ischemia-reperfusion in rat and hydrogen peroxide (H2O2)-induced H9c2 rat cardiomyoblasts apoptosis. It was found that SAA significantly limited infarct size of ischemic myocardium when given immediately prior to reperfusion. SAA also significantly suppressed cellular injury and apoptotic cell death. Additionally, the results of western blot and phospho-specific antibody microarray analysis showed that SAA could up-regulate Bcl-2 expression and increase the phosphorylation of proteins such as Akt, p42/p44 extracellular signal-related kinases (Erk1/2), and their related effectors. The phosphorylation of those points was related to suppress apoptosis. In summary, SAA possesses marked protective effect on myocardial ischemia-reperfusion injury, which is related to its ability to reduce myocardial cell apoptosis and damage induced by oxidative stress. The protection is achieved via up-regulation of Bcl-2 expression and affecting protein phosphorylation. These findings indicate that SAA may be of value in cardioprotection during myocardial ischemia-reperfusion injury, which provide pharmacological evidence for clinical application

Effects of a novel pH-sensitive liposome with cleavable esterase-catalyzed and pH-responsive double smart mPEG lipid derivative on ABC phenomenon

Daquan Chen1,2, Wanhui Liu1,2, Yan Shen3, Hongjie Mu1,2, Yanchun Zhang4 , Rongcai Liang1,2, Aiping Wang1,2, Kaoxiang Sun1,2, Fenghua Fu1,2 1School of Pharmacy, Yantai University, Yantai, People&amp;rsquo;s Republic of China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, People&amp;rsquo;s Republic of China; 3College of Pharmacy, China Pharmaceutical University, Nanjing, People&amp;rsquo;s Republic of China; 4College of Pharmacy, Anhui University of Traditional Chinese Medicine, Hefei, People&amp;rsquo;s Republic of China Background: The ABC phenomenon is described as a syndrome of accelerated clearance of polyethylene glycol (PEG)-modified liposomes from the bloodstream when repeatedly injected, with their increased accumulation in the liver and spleen. Methods: To clarify this immune response phenomenon, we evaluated a novel modified pH-sensitive liposome with a cleavable double smart PEG-lipid derivative (mPEG-Hz-CHEMS). Results: The ABC phenomenon in mice was brought about by repeated injection of conventional PEG-PE liposomes and was accompanied by a greatly increased uptake in the liver. However, a slight ABC phenomenon was brought about by repeated injection of mPEG-CHEMS liposomes and was accompanied by only a slightly increased uptake in the liver, and repeated injection of mPEG-Hz-CHEMS liposomes did not induce the ABC phenomenon and there was no increase in liver accumulation. This finding indicates that the cleavable mPEG-Hz-CHEMS derivative could lessen or eliminate the ABC phenomenon induced by repeated injection of PEGylated liposomes. Conclusion: This research has shed some light on a solution to the ABC phenomenon using a cleavable PEG-Hz-CHEMS derivative encapsulated in nanoparticles. Keywords: accelerated blood clearance, double smart, cleavable, mPEG-lipid derivates, pH-sensitive liposom