Effect of insulin-like growth factor I on HIV type 1 long terminal repeat-driven chloramphenicol acetyltransferase expression

In this study, we have investigated the ability of insulin-like growth factor I (IGF-I) to inhibit HIV long terminal repeat (LTR)-driven gene expression. Using COS 7 cells cotransfected with tat and an HIV LTR linked to a chloramphenicol acetyltransferase (CAT) reporter, we observed that physiological levels of IGF-I (10-9 M) significantly inhibited CAT expression in a concentration- and time-dependent manner. IGF-I did not inhibit C AT expression in COS 7 cells transfected with pSVCAT, and did not affect CAT expression in the absence of cotransfection with tat . Transfection of HIV-1 proviral DNA into COS 7 cells +/- IGF-I resulted in a significant decrease ( p 0.05) in infectious virion production. Both IGF-I and Ro24-7429 inhibited LTR-driven C AT expression, while TNF- alpha -enhanced CAT expression was not affected by IGF-I. On the other hand, a plasmid encoding parathyroid hormone-related peptide exhibited dramatic additivity of inhibition of CAT expression in COS 7 cells. Finally, we show that in Jurkat or U937 cells cotransfected with HIVLTRCAT/tat, IGF-I significantly inhibited CAT expression. Further, interleukin 4 showed in U937 cells inhibition of CAT expression that was not additive to IGF-I induced inhibition. Our data demonstrate that IGF-I can specifically inhibit HIVLTRCAT expression. This inhibition may occur at the level of the tat /TAR interaction. Finally, this IGF-I effect is seen in target cell lines and similar paths of inhibition may be involved in the various cell types employed.

Study of electrical usage and demand at the container terminal

The electrical usage and demand at container terminal were studied for two years. The results provide a technique for calculating the maximum demand at container terminal with a more accurate result, leading to a substantial saving both in capital cost for electrical infrastructure investment and ongoing electricity costs.

cJUN N-terminal kinase (JNK) activation mediates islet amyloid-induced beta cell apoptosis in cultured human islet amyloid polypeptide transgenic mouse islets

Aims/hypothesis

Aggregation of human islet amyloid polypeptide (hIAPP) as islet amyloid is associated with increased beta cell apoptosis and reduced beta cell mass in type 2 diabetes. Islet amyloid formation induces oxidative stress, which contributes to beta cell apoptosis. The cJUN N-terminal kinase (JNK) pathway is a critical mediator of beta cell apoptosis in response to stress stimuli including oxidative stress and exogenous application of hIAPP. We determined whether amyloid formation by endogenous hIAPP mediates beta cell apoptosis through JNK activation and downstream signalling pathways.
Methods

hIAPP transgenic and non-transgenic mouse islets were cultured for up to 144 h in 16.7 mmol/l glucose to induce islet amyloid in the presence or absence of the amyloid inhibitor Congo Red or a cell-permeable JNK inhibitor. Amyloid, beta cell apoptosis, JNK signalling and activation of downstream targets in the intrinsic and extrinsic apoptotic pathways were measured.
Results

JNK activation occurred with islet amyloid formation in hIAPP transgenic islets after 48 and 144 h in culture. Neither high glucose nor the hIAPP transgene alone was sufficient to activate JNK independent of islet amyloid. Inhibition of islet amyloid formation with Congo Red reduced beta cell apoptosis and partially decreased JNK activation. JNK inhibitor treatment reduced beta cell apoptosis without affecting islet amyloid. Islet amyloid increased mRNA levels of markers of the extrinsic (Fas, Fadd) and intrinsic (Bim [also known as Bcl2l11]) apoptotic pathways, caspase 3 and the anti-apoptotic molecule Bclxl (also known as Bcl2l1) in a JNK-dependent manner.
Conclusions/interpretation

Islet amyloid formation induces JNK activation, which upregulates predominantly pro-apoptotic signals in both extrinsic and intrinsic pathways, resulting in beta cell apoptosis.

Terminal sliding mode control strategy design for second-order nonlinear system

This study mainly focuses on the terminal sliding mode control (TSMC) strategy design, including an adaptive terminal sliding mode control (ATSMC) and an exact-estimator-based terminal sliding mode control (ETSMC) for second-order nonlinear dynamical systems. In the ATSMC system, an adaptive bound estimation for the lump uncertainty is proposed to ensure the system stability. On the other hand, an exact estimator is designed for exact estimating system uncertainties to solve the trouble of chattering phenomena caused by a sign function in ATSMC law in despite of the utilization of a fixed value or an adaptive tuning algorithm for the lumped uncertainty bound. The effectiveness of the proposed control schemes can be verified in numerical simulations.

Robust fault-tolerant leader-follower control of four-wheel-steering mobile robots using terminal sliding mode

This paper addresses the actuator failure compensation problem of non-linear fourwheel-steering mobile robots based on vehicle kinematics, undergoing both known and unknown failures causing degenerated steering performance or wheels stuck at some observable angles. Terminal sliding mode control technique is used to guarantee the tracking stability infinite time with the presence of actuator fault. Simulation results are given to illustrate the effectiveness of the proposed control scheme. © Institution of Engineers Australia 2012.

Reperfusion-induced myocardial dysfunction is prevented by endogenous annexin-A1 and its N-terminal-derived peptide Ac-ANX-A12-26

BACKGROUND AND PURPOSE : Annexin-A1 (ANX-A1) is an endogenous, glucocorticoid-regulated anti-inflammatory protein. The N-terminal-derived peptide Ac-ANX-A12–26 preserves cardiomyocyte viability, but the impact of ANX-A1-peptides on cardiac contractility is unknown. We now test the hypothesis that ANX-A1 preserves post-ischaemic recovery of left ventricular (LV) function.

EXPERIMENTAL APPROACH : Ac-ANX-A12–26 was administered on reperfusion, to adult rat cardiomyocytes as well as hearts isolated from rats, wild-type mice and mice deficient in endogenous ANX-A1 (ANX-A1–/–). Myocardial viability and recovery of LV function were determined.

KEY RESULTS: Ischaemia–reperfusion markedly impaired both cardiomyocyte viability and recovery of LV function by 60%. Treatment with exogenous Ac-ANX-A12–26 at the onset of reperfusion prevented cardiomyocyte injury and significantly improved recovery of LV function, in both intact rat and wild-type mouse hearts. Ac-ANX-A12–26 cardioprotection was abolished by either formyl peptide receptor (FPR)-nonselective or FPR1-selective antagonists, Boc2 and cyclosporin H, but was relatively insensitive to the FPR2-selective antagonist QuinC7. ANX-A1-induced cardioprotection was associated with increased phosphorylation of the cell survival kinase Akt. ANX-A1−/− exaggerated impairment of post-ischaemic recovery of LV function, in addition to selective LV FPR1 down-regulation.

CONCLUSIONS AND IMPLICATIONS : These data represent the first evidence that ANX-A1 affects myocardial function. Our findings suggest ANX-A1 is an endogenous regulator of post-ischaemic recovery of LV function. Furthermore, the ANX-A1-derived peptide Ac-ANX-A12–26 on reperfusion rescues LV function, probably via activation of FPR1. ANX-A1-based therapies may thus represent a novel clinical approach for the prevention and treatment of myocardial reperfusion injury.

Exact-estimator-based terminal sliding mode control system design

This paper investigates an estimator-based terminal sliding mode control system. An exact estimator is proposed to exactly estimate the unknown uncertainties in finite time. The output of the exact estimator is used to design a continuous chattering free terminal sliding mode control. The time taken for the closed-loop system to reach zero tracking error is proven to be finite. Experiment results are presented, using a real time digital-signal-processor (DSP) based electromagnetic levitation system to implement the control performance.

A non-fullerene electron acceptor based on central carbazole and terminal diketopyrrolopyrrole functionalities for efficient, reproducible and solution-processable bulk-heterojunction devices

A novel, solution-processable non-fullerene electron acceptor, 6,6′-((9-(heptadecan-9-yl)-9H-carbazole-2,7-diyl)bis(thiophene-5,2-diyl))bis(2,5-bis(2-ethylhexyl)-3-(thiophen-2-yl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione) (coded as N7), based on central carbazole and terminal diketopyrrolopyrrole building blocks was designed, synthesized and characterized. N7 displayed excellent solubility, thanks to its design allowing incorporation of numerous lipophilic chains, thermal stability, and afforded a 2.30% power conversion efficiency with a high open-circuit voltage (1.17 V) when tested with the conventional donor polymer poly(3-hexylthiophene) in solution-processable bulk-heterojunction devices. To our knowledge, not only is N7 the first reported chromophore based on carbazole and diketopyrrolopyrrole functionalities but the open-circuit voltage reported here is among the highest values for a single junction bulk-heterojunction device that has been fabricated using a simple device architecture, with reproducible outcomes and with no special treatment.

Rock slope stability analyses using extreme learning neural network and terminal steepest descent algorithm

The analysis of rock slope stability is a classical problem for geotechnical engineers. However, for practicing engineers, proper software is not usually user friendly, and additional resources capable of providing information useful for decision-making are required. This study developed a convenient tool that can provide a prompt assessment of rock slope stability. A nonlinear input-output mapping of the rock slope system was constructed using a neural network trained by an extreme learning algorithm. The training data was obtained by using finite element upper and lower bound limit analysis methods. The newly developed techniques in this study can either estimate the factor of safety for a rock slope or obtain the implicit parameters through back analyses. Back analysis parameter identification was performed using a terminal steepest descent algorithm based on the finite-time stability theory. This algorithm not only guarantees finite-time error convergence but also achieves exact zero convergence, unlike the conventional steepest descent algorithm in which the training error never reaches zero.