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To suppress the vibration of a flexible riser system with input saturation and uncertain parameters under the influence of unknown external disturbances, an adaptive fuzzy backstepping boundary control algorithm was designed. First, the backstepping method and Lyapunov function are used to analyze the subsystem and design the virtual control law. On this basis, the adaptive fuzzy system was designed to approximate the unknown nonlinear term in the design process, and the smooth hyperbolic tangent function and the auxiliary system based on Nussbaum function were introduced to limit control input. The stability and uniform boundedness of the closed-loop control system are proved by the Lyapunov stability theory without simplifying or discretizing the infinite dimensional dynamic model. Finally, the effectiveness of the proposed control algorithm is verified by comparing the control effect with proportional–integral–derivative control and the previous adaptive backstepping control by MATLAB simulation. The simulation results show that the proposed control algorithm can overcome the uncertainty of system parameters and effectively suppress the riser vibration under input constraints, and its control effect is better than proportional–integral–derivative control and adaptive backstepping control.

H2O/CO2 co-electrolysis through solid oxide electrolysis cell (SOEC) combined with renewable energy system and Fischer-Tropsch system to produce fuels is a promising way to convert electrical energy into chemical energy. In this work, fuel composition, conversions of H2O and CO2, selectivity to H2, CO and CH4, and yields of H2, CO and CH4 for H2O/CO2 co-electrolysis are investigated based on the thermodynamic equilibrium under the boundary condition without carbon deposition. High selectivity to CH4 can be reached at suitable MH2O/MCO2 ratio and low temperature, while high selectivity to CO and H2 can be reached at high temperature according to the thermodynamic equilibrium results. When the operating temperature of SOEC is low, the conversions of H2O and CO2 cannot reach high due to carbon deposition, which can be improved by increasing MH2O/MCO2 ratio. When the operating temperature of SOEC is high, the conversions of H2O and CO2 can reach high without carbon deposition, which can be higher than 90% at 1073 K according to the thermodynamic equilibrium results. The syngas with different H2/CO ratios for Fischer-Tropsch synthesis of different fuels can be produced by selecting appropriate co-electrolysis condition.

The vibration control of three-dimensional flexible marine riser system with constrained control input is studied in this paper. Combining backstepping method and Lyapunov direct method, an appropriate boundary control which includes smooth hyperbolic tangent function is employed to reduce the vibration of riser system. An auxiliary system which is developed based on Nussbaum function is proposed to tackle with nonlinear constrained input. The closed-loop system is stable ultimately, and the displacement of riser is uniformly bounded which can be proven by Lyapunov synthesis without any discretization or simplification of the dynamic in the time and space. Moreover, the effectiveness of proposed boundary control is illustrated by comparing with SMC (sliding mode control) in the simulation part. The simulation results show that the proposed control can achieve better control performance with a constrained input.

In this paper, fuel composition and efficiency of solid oxide fuel cell with different methanol pretreating technologies are investigated. High concentrations of H2 and CO can be produced by methan...

Natural gas is a cheap and abundant fuel for solid oxide fuel cell (SOFC), generally integrating the SOFC system with methane pre-treating system for improving the stability of SOFC. In this paper, the accurate effects of methane processing strategy on fuel composition, electrical efficiency and thermal efficiency of SOFC are investigated based on the thermodynamic equilibrium. Steam reforming of methane is an endothermic process and can produce 3 mol of H2 and 1 mol of CO from 1 mol of methane, and thus the electrical efficiency of SOFC is high at the same O/C ratio and equivalent fuel utilization, whereas the thermal efficiency is low. On the contrary, partial oxidation of methane is an exothermal process and only produces 2 mol of H2 and 1 mol of CO from 1 mol of methane, and thus the electrical efficiency of SOFC is low at the same O/C ratio and equivalent fuel utilization, whereas the thermal efficiency is high. When the O/C ratio is 1.5, the electrical efficiency of SOFC is 55.3% for steam reforming of methane, while 32.7% for partial oxidation of methane. High electrical efficiency of SOFC can be achieved and carbon deposition can be depressed by selecting suitable O/C ratio from methane pretreatment according to the accurate calculation and analysis of effects of different methane processing strategies on the electrical efficiency and thermal efficiency of SOFC.

Natural gas is one of the most important fuels for solid oxide fuel cell (SOFC). The relationships among the reactions of methane over the nickel-based anode, fuel compositions, carbon deposition, electromotive force (EMF) and open circuit voltage (OCV) of SOFC are investigated in this work. With the increase of temperature, EMF and OCV of SOFC decrease gradually when the cell uses humidified hydrogen as fuel. Reactivity of methane increases gradually with the increase of temperature, which can affect the EMF and OCV of SOFC. When the humidified mixture of nitrogen and methane is used as the fuel, the EMF and OCV of SOFC increase gradually with the increase of temperature. EMF and OCV of SOFC with humidified mixture of hydrogen and methane (MCH4: MH2: MH2O = 12.2: 85.3: 2.5) as fuel decrease gradually with the increase of temperature when the temperature is lower than 873 K, which is similar to that with humidified hydrogen as fuel. While when the temperature is higher than 923 K, the EMF and OCV of SOFC with humidified mixture of hydrogen and methane as fuel increase gradually with the increase of temperature, which is similar to that with humidified mixture of nitrogen and methane as fuel. OCV of SOFC is mainly affected by thermodynamic equilibriums for methane-fuelled SOFC when the anode activity is high enough, which is close to the EMF calculated according to the thermodynamic equilibriums. While with the increase of carbon deposition, the anode activity decreases apparently and the OCV of SOFC also decreases apparently, which shows that the OCV is affected by the anode activity for methane-fuelled SOFC when the anode activity is low.

Natural gas is one of the most attractive fuels for solid oxide fuel cell (SOFC), while the anode activity for methane fuel has a great influence on the performance and stability of SOFC. Samarium is a good catalyst promoter for methane reforming. In this work, samarium is used to modify nickel catalyst, which results in small nickel oxide particles. The SmNi-YSZ (yttria-stabilized zirconia) anode has smaller particles and better interfacial contact between nickel and YSZ compared with conventional Ni-YSZ anode. The fine structure of SmNi-YSZ anode results in high activity for electrochemical oxidation of hydrogen and low polarization resistance of the cell. The performance of SmNi-YSZ anode cell with humidified methane as fuel is greatly improved, which is similar to that with hydrogen as fuel. The maximum power densities of SmNi-YSZ anode cell are 1.56 W cm−2 for humidified hydrogen fuel and 1.54 W cm−2 for humidified methane fuel at 800 °C. The maximum power density is increased by 221% when samarium is used to modify Ni-YSZ anode for humidified methane fuel at 650 °C. High cell performance results in good stability of SmNi-YSZ anode cell and the cell runs stably for more than 600 min for humidified methane fuel.

This paper investigates a novel adaptive output feedback decentralized control scheme for nonstrict feedback large-scale interconnected systems with time-varying constraints. A decentralized linear state observer is designed to estimate the unmeasurable states of subsystems. Time-varying barrier Lyapunov functions are designed to ensure outputs are not violating constraints. A variable separation approach is applied to deal with the nonstrict feedback problem. Moreover, dynamic surface control and minimal parameter learning technologies are adopted to reduce the computation burden, and there are only two parameters for every subsystem to be updated online. The proof of stability is obtained by the Lyapunov method. Finally, simulation results are given to show the effectiveness of the proposed control scheme.

Calcineurin (CN) controls the immune response by regulating nuclear factor of activated T cells (NFAT). Inhibition of CN function is an effective treatment for immune diseases. The PVIVIT peptide is an artificial peptide based on the NFAT-PxIxIT motif, which exhibits stronger binding to CN. A bioactive peptide (named pep4) that inhibits the CN/NFAT interaction was designed. Pep4 contains a segment of A238L as the linker and the LxVP motif and PVIVIT motif as CN binding sites. Pep4 has strong binding capacity to CN and inhibits CN activity competitively. 11-arginine-modified pep4 (11 R-pep4) inhibits the nuclear translocation of NFAT and reduces the expression of IL-2. 11 R-pep4 improves the pathological characteristics of asthmatic mice to a certain extent. The above results indicated that pep4 is a high-affinity CN inhibitor. These findings will contribute to the discovery of new CN inhibitors and promising immunosuppressive drugs.

Calcineurin is a Ca

A typical three-dimensional flexible marine riser which is described by a distributed parameter system with several partial differential equations and ordinary differential equations is considered in this paper, we are aiming at limiting the top displacement of riser within restricted ranges. Appropriate boundary controls by integrating finite-dimensional backstepping technique with barrier Lyapunov functions are put forwarded to suppress the vibration of flexible riser under the external disturbance. The stability of the closed-loop system with the designed boundary control laws is proved by Lyapunov’s synthetic method without any discretization or simplification of the dynamic in the time and space when the initial conditions are satisfied. Furthermore, in order to illustrate the effectiveness of proposed controls laws, numerical simulation studies are carried.

The calcineurin/nuclear factor of activated T cell (CN/NFAT) signaling pathway plays a critical role in the immune response. Therefore, inhibition of the CN/NFAT pathway is an important target for inflammatory disease. The conserved PXIXIT and LXVP motifs of CN substrates and targeting proteins have been recognized. Based on the affinity ability and inhibitory effect of these docking sequences on CN, we designed a bioactive peptide (named pep3) against the CN/NFAT interaction, which has two binding sites derived from the RCAN1-PXIXIT motif and the NFATc1-LXVP motif. The shortest linker between the two binding sites in pep3 is derived from A238L, a physiological binding partner of CN. Microscale thermophoresis revealed that pep3 has two docking sites on CN. Pep3 also has the most potent inhibitory effect on CN. It is suggested that pep3 contains an NFATc1-LXVP–substrate recognition motif and RCAN1-PXIXIT–mediated anchoring to CN. Expression of this peptide significantly suppresses CN/NFAT signaling. Cell-permeable 11-arginine–modified pep3 (11R-pep3) blocks the NFAT downstream signaling pathway. Intranasal administration of the 11R-pep3 peptide inhibits airway inflammation in an ovalbumin-induced asthma model. Our results suggest that pep3 is promising as an immunosuppressive agent and can be used in topical remedies.

Isocitrate dehydrogenase kinase/phosphatase (AceK) is a bifunctional enzyme with both kinase and phosphatase activities that are activated by Mg2+. We have studied the interactions of Mn2+and Mg2+ with AceK using isothermal titration calorimetry (ITC) combined with molecular docking simulations and show for the first time that Mn2+ also activates the enzyme activities. However, Mn2+ and Mg2+ exert their effects by different mechanisms. Although they have similar binding constants (of 1.11 × 105 and 0.98 × 105 M−1, respectively) for AceK and induce conformational changes of the enzyme, they do not compete for the same binding site. Instead Mn2+ appears to bind to the regulatory domain of AceK, and its effect is transmitted to the active site of the enzyme by the conformational change that it induces. The information in this study should be very useful for understanding the molecular mechanism underlying the interaction between AceK and metal ions, especially Mn2+ and Mg2+.

Methane conversion reactions over the LaNi-YSZ and Ni-YSZ anodes, which involve methane decomposition, H2O and CO2 reforming of methane and electrochemical oxidation of H2, CO, C and CH4, are investigated through electrochemical and catalytic performance measurements. The addition of La to the nickel-based anode results in high activity for methane decomposition to hydrogen and carbon deposits. Carbon deposits on the LaNi-YSZ anode as well as on the Ni-YSZ anode could be removed by H2O and CO2, suggesting high reactivity of carbon deposits. The addition of La to the nickel-based anode also enhances the activity for electrochemical oxidation of hydrogen. On the LaNi-YSZ anode, high catalytic activity for methane reforming supplies enough hydrogen for electrochemical oxidation reaction, while high activity for electrochemical oxidation of hydrogen produces enough H2O for methane reforming. High activity for methane reforming and electrochemical oxidation of hydrogen results in the high performance of methane-fueled cell with LaNi-YSZ anode.

Solid oxide fuel cell (SOFC) is one of the most attractive energy conversion systems, while dimethyl ether (DME) is an alternative clean fuel, and thus the application of DME in SOFC has great attraction. Fuel compositions are mainly determined by fuel processing technologies, which can affect the cell efficiency. In this paper, the relationships among fuel composition, oxygen to carbon (O/C) ratio, carbon deposition and cell efficiency are investigated for different DME processing technologies. According to the calculated results, SOFC with steam reforming of DME has the highest efficiency at the same O/C ratio and equivalent fuel utilization, while for catalytic partial oxidation of DME, the cell efficiency decreases rapidly with the increase of O/C ratio. The efficiency of SOFC with CO2 reforming of DME decreases with the increase of O/C ratio, especially at high O/C ratio and low equivalent fuel utilization. When the O/C ratio is 1.5, solid carbon can't be formed, where the cell efficiencies are 51.7% for steam reforming of DME, 42.2% for DME reforming with H2O and O2, 32.7% for catalytic partial oxidation of DME, 49.3% for DME reforming with anode off-gas and 41.4% for CO2 reforming of DME at 80% equivalent fuel utilization.

Propane is a particularly attractive fuel for solid oxide fuel cell (SOFC) because it is cheap, widely available and easily stored with high energy density, while carbon deposition may be a serious problem in direct propane-fueled SOFC, thus efficient propane processing strategy is favored by SOFC. The fuel compositions, efficiency and stability of SOFC may be affected by propane processing strategies apparently. In this paper, the fuel compositions and cell efficiency are investigated for different propane pre-treating techniques. For steam reforming, CO2 reforming and anode off-gas reforming of propane, the decreasing rates of real fuel utilization and cell efficiency are apparently different with the change of equivalent fuel utilization. At high equivalent fuel utilization, the real fuel utilization and cell efficiency decrease slowly with the increase of oxygen to carbon (O/C) ratio. While at low equivalent fuel utilization, the real fuel utilization and cell efficiency decrease rapidly with the increase of O/C ratio. For catalytic partial oxidation of propane, the real fuel utilization and cell efficiency decrease rapidly and the decreasing rate is same at different equivalent fuel utilization with the increase of O/C ratio. Suitable proportions of steam, carbon dioxide and/or oxygen in the feed and efficient propane processing strategy can depress the carbon deposition and improve the cell efficiency.

Isocitrate dehydrogenase kinase/phosphatase (AceK) is a bifunctional enzyme with both kinase and phosphatase activities that are activated by Mg

Isogarcinol, a bioactive polyisoprenylated benzophenone derivative isolated from Garcinia mangostana L., has been shown previously to exert a strong inhibitory effect on calcineurin and is thus a potential oral, low-toxicity immunomodulatory drug. In the present study, enzyme kinetic analysis showed that inhibition of calcineurin by isogarcinol was competitive. Fluorescence spectroscopy indicated that isogarcinol bound to calcineurin. Isothermal titration calorimetry showed that binding was mainly driven by enthalpy, and was exothermic because the enthalpy change exceeded the entropy reduction. The interaction force is either hydrogen bonding or Van der Waals forces. Fluorescence resonance energy transfer and molecular docking experiments indicated that there were two potential binding sites for isogarcinol in the catalytic domain of calcineurin. In summary, isogarcinol binds directly to calcineurin in vitro, unlike the classical calcineurin inhibitors cyclosporin A and tacrolimus.

Inhibitor-resistant TEM (IRT) type β-lactamase mutation is largely known. Therefore, it is of interest to identify new yet improved leads against IRT from traditional Chinese medicine. Hence, we screened more than 10,000 compounds from Chinese medicine (tcm@taiwan database) with mutant molecular IRT models through docking techniques. This exercise identified compounds affeic acid, curcumin, salvianolic acid E, ferulic acid and p-coumaric acid with high binding score with the mutants. This was further validated in vitro where salvianolic acid E combined with cefoperazone and sulbactam effectively inhibit the R244S mutant.

Calcineurin is the only known calmodulin (CaM) activated protein phosphatase, which is involved in the regulation of numerous cellular and developmental processes and in calcium-dependent signal transduction. Although commonly assumed that CaM displaces the autoinhibitory domain (AID) blocking substrate access to its active site, the structural basis underlying activation remains elusive. We have created a fused ternary complex (CBA) by covalently linking three polypeptides: CaM, calcineurin regulatory B subunit (CnB) and calcineurin catalytic A subunit (CnA). CBA catalytic activity is comparable to that of fully activated native calcineurin in the presence of CaM. The crystal structure showed virtually no structural change in the active site and no evidence of CaM despite being covalently linked. The asymmetric unit contains four molecules; two parallel CBA pairs are packed in an antiparallel mode and the large cavities in crystal packing near the calcineurin active site would easily accommodate multiple positions of AID-bound CaM. Intriguingly, the conformation of the ordered segment of AID is not altered by CaM; thus, it is the disordered part of AID, which resumes a regular α-helical conformation upon binding to CaM, which is displaced by CaM for activation. We propose that the structural basis of calcineurin activation by CaM is through displacement of the disordered fragment of AID which otherwise impedes active site access.

This work aims to investigate the role of the loopβ3αC amino acids in the structure and function of isocitrate dehydrogenase kinase/phosphatase (AceK). The results demonstrate that the precise configuration of loopβ3αC is very important for AceK structure and function: structural changes alter the affinity of the enzyme for the isocitrate dehydrogenase (ICDH), which modifies enzyme activity. Intriguingly, D340 is significant for the retention of kinase and phosphatase activities, for the conformational stability of AceK, and for binding ICDH. The deletion △341-345 increases enzyme activity by increasing the maximum velocity and affinity for ICDH. The β3αC loop is thus critical for the structure and function of AceK. This article is protected by copyright. All rights reserved.

We showed previously that calcineurin B subunit (CnB) protein activates innate immune cells including macrophages, monocytes and dendritic cells and acts as an adjuvant of a model antigen (ovalbumin) and a recombinant pneumolysin antigen, but the detailed mechanism is not clear and whether it can serve as an adjuvant of a commercial HBV vaccine is unknown. Here, we report that CnB promotes inflammatory cytokines production, splenocytes proliferation and NK lytic activity, and that CnB-induced inflammatory cytokines (IFN-γ, IL-6, TNF-α) production is dependent on integrin αM. Animal experiments demonstrate that CnB markedly increases the total anti-HBs antibodies in a dose and time dependent manner. Furthermore, CnB increases both anti-HBs IgM and anti-HBs IgG titers and changes the balance of IgG2a and IgG1. Combined use of CnB and CpG induces more cytokines production in splenocytes, as well as more anti-HBs antibodies production in vivo. These results reveal a probable mechanism of CnB-induced inflammatory cytokines production and further demonstrate that CnB is a novel and effective adjuvant of Engerix-B ® HBV vaccine.

Calcineurin B subunit (CnB) is the regulatory subunit of calcineurin (Cn), a Ca(2+)/calmodulin-dependent serine/threonine protein phosphatase. It has been reported that mice deleting the CnB gene lose nearly all Cn activity and show poor tolerance to cardiac stress; CnB gene expression is downregulated in the hearts of rats that have suffered ischemia/reperfusion (I/R) injury. Therefore, we wonder whether injection of exogenous CnB protein can prevent the rats from suffering I/R injury. In cardiomyocytes, fluorogenic labeling shows that exogenous CnB quickly enters the cell. Pretreatment of cardiomyocytes with CnB reduces apoptosis in response to hypoxia/reoxygenation injury (an in vitro model mimicking ischemia/reperfusion injury), and CsA reverses this effect by inhibiting Cn activity. Furthermore, CnB upregulates Bcl-2 and Bcl-XL expression in the process of hypoxia/reoxygenation injury, which may contribute to protecting cardiomyocytes against apoptosis. In vivo experiments shows that pretreatment with CnB improves cardiac contractile function and reduces the frequency of arrhythmias induced by global I/R injury. These findings reveal a novel function for CnB protein in cardiac stress response and suggest a possible application of CnB in coronary disease therapy.

International audience; Debio 025 is a cyclosporin A (CsA) analogue that interferes strongly with the hepatitis C viral life cycle. Compared to CsA, Debio 025 has an additional methyl group at position 3 of the cyclic undecapeptide and an N-ethylvaline instead of an N-methylleucine at position 4. Unlike CsA, Debio 025 lacks immunosuppressive activity in vitro and in vivo. We show here that, in vitro, the cyclophilin A (CypA)-Debio 025 complex cannot interact any longer with calcineurin (CaN), a determinant for the immunosuppressive activity of CsA. We further use NMR spectroscopy to investigate at the molecular level the interaction of Debio 025 with CypA and thereby understand the basis for this loss of CaN interaction. NMR data and molecular modeling indicate that Debio 025 optimally interacts with CypA, which underlies the anti-HCV properties of Debio 025. However, the interaction between CaN and the CypA-Debio 025 complex is impeded by sterical hindrance of the CaN with the side chain of its Val4 residue. This is in sharp contrast with the case for the CypA-CsA-CaN ternary complex, where the Leu4 side chain can enter a hydrophobic cavity at the CaN interface. The structure of the CypA-Debio 025 complex thus provides a rational explanation for the non-immunosuppressive character of Debio 025.

Chlorogenic acid (CHA) has been proved to be an activator of calcineurin (CN) in our previous research. In this study, the activation of single chain calcineurin (BA) by CHA, their interaction and concomitant changes in protein conformation were studied using fluorescence and Fourier transform infrared spectroscopy. Evidence is present that binding of CHA to CN is responsible for the stimulation of enzyme and results in structural changes. Aromatic residues reorient into new environments upon binding of CHA, the binding constant for the reaction was (2.76 ± 0.64) × 10 4 M −1 by one binding site, which indicated that CHA bound to BA statically and the change of secondary structure was mainly due to reduced α-helical content and increased β-turns. The results obtained in this study should be useful for understanding the molecular mechanisms underlying the interactions between CN and its activators.

In this study, an electrochemical method to assay calcineurin activity is proposed. Although the enzyme could not exhibit electron transfer reactivity and the catalytic reaction of the substrate could not give any electrochemical wave, p-nitrophenol as the catalytic reaction production could be oxidized at the calcineurin/Triton X-100 film modified electrode to exhibit useful wave that might be employed to assay the enzyme activity. The effect of Ni(2+) and Zn(2+) on calcineurin was also investigated. Whereas Ni(2+) was confirmed to be able to enhance the enzymatic activity, Zn(2+) was found to be an inhibitor to calcineurin.