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Protein phosphatase-1 (PP1) is a ubiquitous enzyme involved in multiple processes inside cells. PP1-disrupting peptides (PDPs) are chemical tools that selectively bind to PP1 and release its activity. To restrict the activity of PDPs to a cellular compartment, we developed PDP-Mem, a cell membrane-targeting PDP. The membrane localization was achieved through the introduction of a palmitoylated lysine. PDP-Mem was shown to activate PP1α in vitro and to localize to the membrane of HeLa Kyoto and U2OS cells. However, in cells, the combination of the polybasic sequence for cell penetration and the membrane targeting palmitoylated lysine activates the MAPK signaling pathway and induces cytoplasmic calcium release independently of PP1 activation. Therefore, when targeting peptides to cellular membranes, undesired effects induced by the targeting sequence and lipid modification need to be considered.

Rapid and convenient wound healing is crucial for reducing potential post-traumatic wound complications. In this study, a temperature-sensitive polymer of poly-(HEMA-co-NIPAM) (PHN) was synthesized by free-radical polymerization, in which the solution quickly underwent a sol-gel transition above 29°C, thus responding to a typical body temperature and facilitating wound sealing. PHN solution incorporated with copper ions (PHN-Cu) not only exhibited excellent antibacterial properties, but also expedited wound closure and facilitated tissue angiogenesis. The in vivo and in vitro experiments showed that the PHN-Cu had a higher wound closure rate and demonstrated an ability to promote skin tissue angiogenesis. Such a versatile, convenient aqueous solution could enable nonprofessionals to promptly treat wounds in a short time after injury, thus providing suitable conditions for later treatment, and can be used as a convenient method to clean wounds.

Protein phosphatase‐1 (PP1)‐disrupting peptides (PDPs) are selective chemical modulators of PP1 that liberate the active PP1 catalytic subunit from regulatory proteins; thus allowing the dephosphorylation of nearby substrates. We have optimized the original cell‐active PDP3 for enhanced stability, and obtained insights into the chemical requirements for stabilizing this 23‐mer peptide for cellular applications. The optimized PDP‐Nal was used to dissect the involvement of PP1 in the MAPK signaling cascade. Specifically, we have demonstrated that, in human osteosarcoma (U2OS) cells, phosphoMEK1/2 is a direct substrate of PP1, whereas dephosphorylation of phosphoERK1/2 is indirect and likely mediated through enhanced tyrosine phosphatase activity after PDP‐mediated PP1 activation. Thus, as liberators of PP1 activity, PDPs represent a valuable tool for identifying the substrates of PP1 and understanding its role in diverse signaling cascades.

Background Disruption of Ca2+ homeostasis is a key pathomechanism in heart failure. CaMKII-dependent hyperphosphorylation of ryanodine receptors in the sarcoplasmic reticulum (SR) increases the arrhythmogenic SR Ca2+ leak and depletes SR Ca2+ stores. The contribution of conversely acting serine/threonine phosphatases [protein phosphatase 1 (PP1) and 2A (PP2A)] is largely unknown. Methods and results Human myocardium from three groups of patients was investigated: (i) healthy controls (non-failing, NF, n = 8), (ii) compensated hypertrophy (Hy, n = 16), and (iii) end-stage heart failure (HF, n = 52). Expression of PP1 was unchanged in Hy but greater in HF compared to NF while its endogenous inhibitor-1 (I-1) was markedly lower expressed in both compared to NF, suggesting increased total PP1 activity. In contrast, PP2A expression was lower in Hy and HF compared to NF. Ca2+ homeostasis was severely disturbed in HF compared to Hy signified by a higher SR Ca2+ leak, lower systolic Ca2+ transients as well as a decreased SR Ca2+ load. Inhibition of PP1/PP2A by okadaic acid increased SR Ca2+ load and systolic Ca2+ transients but severely aggravated diastolic SR Ca2+ leak and cellular arrhythmias in Hy. Conversely, selective activation of PP1 by a PP1-disrupting peptide (PDP3) in HF potently reduced SR Ca2+ leak as well as cellular arrhythmias and, importantly, did not compromise systolic Ca2+ release and SR Ca2+ load. Conclusion This study is the first to functionally investigate the role of PP1/PP2A for Ca2+ homeostasis in diseased human myocardium. Our data indicate that a modulation of phosphatase activity potently impacts Ca2+ cycling properties. An activation of PP1 counteracts increased kinase activity in heart failure and successfully seals the arrhythmogenic SR Ca2+ leak. It may thus represent a promising future antiarrhythmic therapeutic approach.

The study discusses how some challenges from a small sample fatigue test can be analysed statistically and resolved. In terms of data dispersion, fatigue data are initially processed by confidence, and then, the fatigue life curve is replaced by the parabolic reliability approximation. Fatigue data under various reliability levels are obtained. Instead of the traditional single S–N curve, the mean value curve and mean square deviation curve of the S–N curve are computed based on the processed fatigue data. The S–N curve with reliability is deduced by applying quantile theory. The S–N curve is improved by considering the effects of low-amplitude load strengthening. The benefits of the modification are visible in the comparison of the fatigue life before and after low-amplitude load strengthening. Copyright © 2016 John Wiley & Sons, Ltd.

The differential is an important part of a driveline, and differential performance is related to the handling and stability performance of a vehicle. Thus, a differential with sound design structure and reasonable form and size parameters could lead to satisfactory driving performance. In this work, we analyze and evaluate the reliability of the key parts of a differential system. Firstly, each of key parts is regarded as a subsystem of a differential system, so the subsystem reliability models are obtained. A system reliability model is built based on the paths of the forces from the differential system, and system reliability is calculated. Secondly, according to the result of the analysis of system reliability and the use of the six sigma method, 45 steel or 1Cr18Ni9Ti utilized as the material for the worm shaft, system reliability is analyzed and discussed separately. Then, the reliability of the key parts and the overall system reliability increase with the low load strengthening characteristic of the material. Finally, according to the analysis and discussion, the level of system reliability matches that required for differential systems, and the cost is also considerably reduced, as demonstrated using the stress–strength interference and low-load strengthening models. These results provide a theoretical basis for the improvement of the design of Torsen differentials. Similar methods can be used to develop automobile subsystems in the future. Copyright © 2015 John Wiley & Sons, Ltd.

SiOCN ceramics are formed by the thermal decomposition of a polyvinylsilazane precursor in the presence of a dicumyl peroxide (DP) thermal initiator with different concentrations. The SiOCN ceramics pyrolyzed at 1000°C with different concentrations of DP are characterized with X-ray diffraction, transmission electron microscope, electron paramagnetic resonance, and UV-visible spectroscopy. We find that the structure and optical band gap of the SiOCN ceramics can be changed by altering the concentration of DP. There is a critical concentration, at which the structural and optical behavior varied in different ways as a function of the concentration of DP. The detailed mechanism is discussed.

Ankylosing spondylitis (AS) is a common chronic inflammatory rheumatic disease. Early and accurate detection is essential for effective disease treatment. Recently, research has focused on genomics and proteomics. However, the associated metabolic variations, especially fatty acid profiles, have been poorly discussed. In this study, the gas chromatography–mass spectrometry (GC-MS) approach and multivariate statistical analysis were used to investigate the metabolic profiles of serum free fatty acids (FFAs) and esterified fatty acids (EFAs) in AS patients. The results showed that significant differences in most of the FFA (C12:0, C16:0, C16:1, C18:3, C20:4, C20:5, C22:5 and C22:6) and EFA (C12:0, C16:1, C18:0, C18:1, C18:2, C18:3, C20:4 and C22:6) concentrations were found between the AS patients and healthy controls (p

Insulin-like growth factor-1 (IGF-1) is a brain-specific multifunctional protein involved in neuronal polarity and axonal guidance. Mature IGF-1 triggers three enzymes, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and phosphoinositide phospholipase C-γ (PLC-γ), which are its predominant downstream regulators. The PI3K-AKT signaling pathway is upstream of the mammalian target of rapamycin (mTOR), which is of great importance in the induction of autophagy. However, whether the neuroprotective effect of IGF-1 against excitotoxicity is mediated by autophagy through the PI3K/AKT/mTOR pathway remains to be elucidated. The induction of autophagy following NMDA treatment was determined by microtubule-associated protein light chain 3 (LC3) conversion and the result of this autophagy was assessed by monitoring the cleavage of caspase 3 in cultured hippocampal neurons. Cell viability was determined using MTT and LDH assay, and PI-staining was used to estimate the fate of autophagy and the protective effect of IGF-1. In addition, IGF-1 was found to decrease autophagy induced by NMDA using transmission electron microscopy and MDC staining. The protective effect of IGF-1 against autophagy was accompanied with up-regulation of phospho-AKT (p-AKT) and phospho-mTOR (p-mTOR), which was blocked by the inhibitor of PI3K. At the same time, the activation of NR2B resulting in the down-regulation of p-AKT and p-mTOR was blocked by IGF-1. Together, these data suggest that NMDA induces the autophagy, followed by apoptosis in cultured hippocampal neurons, and that IGF-1 can block this effect via inhibition of NR2B receptors and activation of the PI3K-AKT-mTOR pathway.

Bovine serum albumin/poly(acrylic acid), BSA/PAA, nano-scaled particles were produced by noncovalent bonds induced self-assembly method at acid pH area. Proper conditions during preparation process, such as pH value, BSA/PAA weight ratio(WR), PAA molecular weight, were researched by studying the hydrodynamic diameter, polydispersity index, and ζ potential of the nanoparticles. Complex formation between BSA and PAA was studied by FT-IR, AFM, and TEM. BSA chains are supposed to be partly trapped in the nanoparticles core after interaction with PAA because of the electrostatic attractions and hydrogen bonds interactions between BSA and PAA, while the rest of the BSA chains should form the shell of the nanoparticles. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Nanosized carbon clusters self-formed in polymer-derived ceramics (named free carbon) play a key role in determining the properties of the materials. However, it is difficult to quantitatively measure the concentration of the free carbon. Lack of this information restricts the understanding of the properties of the materials. In this paper, we report a Raman spectroscopy-based quantitative method to measure the free carbon concentration by using silicon as an external reference. We demonstrate that the technique provides a simple and reliable way for the carbon content quantification.

The electron transport behavior of polymer-derived amorphous silicon oxycarbonitride ceramics is studied by measuring their temperature-dependent electrical conductivities. The experimental results are analyzed using theoretical models. The results reveal that the materials exhibit three conduction mechanisms: conduction in extended states, conduction in band tails, and conduction in localized states. Particularly, it is found that in a low-temperature regime, the conduction of the materials follows a band tail hopping mechanism, rather than the previously assumed variable range hopping mechanism. The results also reveal that energy gaps such as EC−EF and EC−EA decrease with increasing pyrolysis temperature.

The electric conductivity of polymer-derived silicon carbonitrides made from a polysilazane modified with different amounts of thermal initiator is measured at room temperature. It is found that the thermal initiator has a significant effect on the electric conductivity, which first increases and then decreases with increasing thermal initiator concentration. The highly conductive sample exhibits a very high piezoresistive coefficient and weak temperature dependence as compared with the low conductive samples. The microstructures of the materials are characterized using a Raman spectroscope. Based on these results, two conducting mechanisms are identified: the highly conductive sample is dominated by the tunneling-percolation mechanism, while the low conductive samples are dominated by matrix phases. The effect of the thermal initiator on the development of the microstructures of the materials is discussed.

A finite element model is presented for mixed lubrication of journal-bearing systems operating in adverse conditions. The asperity effects on contact and lubrication at large eccentricity ratios are modelled. The elastic deformation due to both hydrodynamic and contact pressure, and the cavitation of the lubricant film are considered in the model system. Two verification problems with both theoretical and experimental comparisons are given to show the effectiveness of this model. Finally, a new example is presented which discusses the influence of waviness depth, secondary roughness, external force and shaft speed on the mixed lubrication. Copyright © 2004 John Wiley & Sons, Ltd.

Three amorphous silicon oxycarbonitrides are prepared by thermal decomposition of a polymeric precursor at different temperatures. The optical absorption spectra of these materials are measured over a wide range of excitation energies from 0.4 to 5.0 eV. The spectra are analyzed using theoretical models. Two absorption transitions are identified between the deep defect energy level and the delocalized conduction band and between the two delocalized bands. It is found that the band gaps measured decrease with increasing pyrolysis temperature. The results obtained are discussed.

In this paper, we report the growth of bamboo-like silicon-doped boron nitride nanotubes via catalyst-assisted pyrolysis of a boron-containing polymeric precursor. The morphologies and structures of the nanotubes were characterized using electron microscopy and Raman spectroscopy. Two types of nanotubes are observed, one from a base-growth mode and the other from a tip-growth mode. The type II nanotubes contain encapsulated catalytic nanoparticles at the tip of every compartment. This unique structure is a promising candidate for applications in many nanodevices.

The optical properties of heavily Al-doped single-crystal Si3N4 nanobelts are investigated by measuring their absorption, photoluminescence, and photoluminescence excitation spectra. The results suggest that the doped Si3N4 exhibit two absorptions at 2.5 and 4.2 eV, instead of absorption at 5.0 eV in the pure Si3N4. The doped nanobelts show light emissions in a range of 1.4 to 3.6 eV, which is red-shifted as compared with that of pure Si3N4 nanobelts. These results are ascribed to the unique doping mechanism of Al, which generates two types of defects.