Control of an Underactuated Double-Pendulum Overhead Crane using Improved Model Reference Command Shaping: Design, Simulation and Experiment

This paper presents a new control scheme based on model reference command shaping (MRCS) for an overhead crane, with double-pendulum mechanism effects. The approach has an advantage in achieving an accurate trolley positioning, with low hook and payload oscillations, under various desired trolley positions and parameter uncertainties, without the requirement for measurement or estimation of system parameters. These are challenging in practice. The previously developed MRCS algorithm is improved in order to reduce its design complexity, as well as to ensure that it can be augmented with a feedback controller so that a concurrent controller tuning can be realised. The combined MRCS and feedback controller is used to achieve both, precise trolley positioning, and low hook and payload oscillations. To evaluate the effectiveness and the robustness of the approach, simulations and experiments using a nonlinear model and a laboratory double-pendulum crane are carried out. Under various desired positions and parameter uncertainties that involve varying the cable lengths (payload hoisting) and the payload mass variations, the superiority of the proposed approach is confirmed by achieving higher hook and payload oscillation reductions when compared with a recently proposed feedback controller. In addition, the desired trolley positions are achieved with smoother responses

TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon

Report on the fifth international workshop on the CCN family of genes

The Fifth International Workshop on the CCN Family of Genes was held in Toronto October 18–22, 2008. This bi-annual workshop provides a unique opportunity for the presentation and discussion of cutting edge research in the CCN field. The CCN family members have emerged as extracellular matrix associated proteins which play a crucial role in cardiovascular and skeletal development, fibrosis and cancer. Significant progress has been made in the development of model systems to tease apart the CCN signalling pathways in these systems. Results presented at the conference suggest that targeting these pathways now shows real promise as a therapeutic strategy

Angiogenic output in viral hepatitis, C and B, and HCV-associated hepatocellular carcinoma

Introduction: Angiogenesis is known to play a pivotal role in most of malignancy, including HCC, and in chronic inflammation.Aim: To investigate the angiogenic output in HCV and HBV infection and its implication in the development of HCV associated HCC.Materials and methods: Blood samples were collected and grouped as; HS healthy subjects control group; HCC–HCV; chronic HCV infected patient group (HCV+ve) who are positive for serum anti-HCV antibodies and HCV–RNA; anti-HCV antibody positive and HCV–RNA negative patient group (HCVve); patients with positive HBsAg and HBV-DNA group (HBV+ve); and HBsAg positive and HBV-DNA negative patient group (HBVve). Serum levels of vascular endothelial growth factor, angiopoietin-2, endostatin and angiostatin were assessed in different studied groups.Results: The level of sVEGF was insignificantly elevated in both HCV+ve and HCVve groups when compared with controls, while Ang-2, sES and sAS were significantly elevated in both groups as compared with healthy controls. The studied parameters were significantly elevated in HBV-+ve patients when compared with the control. However, HBVve patients showed significantly elevated levels in sAng-2, sES and sAS when compared with the control while the level of sVEGF was equal to that of controls. In patients with HCC, the studied parameters showed a significant elevation when compared with healthy controls and patients either with HBV or HCV infection except for sAS in the case of HCV-+ve patients and VEGF for HBV-+ve patients who were also higher but not significant.Conclusion: The increased hepatic angiogenesis in chronic HCV and HBV could provide the molecular basis for liver carcinogenesis and contribute to the increased risk of HCC in patients with cirrhosis due to HCV and/or HBV.KEYWORDS Angiogenesis; HCC; HCV; HB

Connective tissue growth factor(CCN2), a pathogenic factor in diabetic nephropathy. What does it do? How does it do it?

Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of matricellular proteins. Its expression is induced by a number of factors including TGF-β. It has been associated with fibrosis in various tissues including the kidney. Diabetic nephropathy (DN) develops in about 30% of patients with diabetes and is characterized by thickening of renal basement membranes, fibrosis in the glomerulus (glomerulosclerosis), tubular atrophy and interstitial fibrosis, all of which compromise kidney function. This review examines changes in CTGF expression in the kidney in DN, the effects they have on glomerular mesangial and podocyte cells and the tubulointerstitium, and how these contribute to driving fibrotic changes in the disease. CTGF can bind to several other growth factors modifying their function. CTGF is also able to interact with receptors on cells, including integrins, tyrosine receptor kinase A (TrkA), low density lipoprotein receptor-related protein (LRP) and heparan sulphate proteoglycans. These interactions, the intracellular signalling pathways they activate, and the cellular responses evoked are reviewed. CTGF also induces the expression of chemokines which themselves have pharmacological actions on cells. CTGF may prompt some responses by acting through several different mechanisms, possibly simultaneously. For example, CTGF is often described as an effector of TGF-β. It can promote TGF-β signalling by binding directly to the growth factor, promoting its interaction with the TGF-β receptor; by triggering intracellular signalling on binding the TrkA receptor, which leads to the transcriptional repression of Smad7, an inhibitor of the TGF-β signalling pathway; and by binding to BMP-7 whose own signalling pathway opposing TGF-β is inhibited, leading to enhanced TGF-β signalling

Application of Box-Behnken Design for Ultrasound- Assisted Extraction and Recycling Preparative HPLC for Isolation of Anthraquinones from Cassia singueana

Introduction – Cassia singueana Del. (Fabaceae) is a rare medicinal plant used in the traditional medicine preparations to treat various ailments. The root of C. singueana is a rich source of anthraquinones that possess anticancer, antibacterial and antifungal properties. Objective – The objective of this study was to develop ultrasound-assisted extraction (UAE) method for achieving a high extraction yield of anthraquinones using the response surface methodology (RSM), Box-Behnken Design (BBD), and a recycling preparative HPLC protocol for isolation of anthraquinones from C. singueana. Methodology – Optimisation of UAE was performed using the Box-Behnken experimental design. Recycling preparative HPLC was employed to isolate anthraquinones from the root extract of C. singueana. Results - The BBD was well-described by a quadratic polynomial model (R2 = 0.9751). The predicted optimal UAE conditions for a high extraction yield were obtained at: extraction time 25.00 min, temperature 50C and solvent-sample ratio of 10 mL/g. Under the predicted conditions, the experimental value (1.65 ± 0.07%) closely agreed to the predicted yield (1.64%). The obtained crude extract of C. singueana root was subsequently purified to afford eight anthraquinones. Conclusion - The extraction protocol described here is suitable for large-scale extraction of anthraquinones from plant extracts

CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis

CTGF is a secreted matricellular protein with very complex biology. It has been shown to modulate many signaling pathways leading to cell adhesion and migration, angiogenesis, myofibroblast activation, and extracellular matrix deposition and remodeling, which together lead to tissue remodeling and fibrosis. It has been reported in the literature that inhibition of CTGF expression by siRNA prevents CCl4-induced liver fibrosis and can reverse fibrosis when administered after significant collagen deposition is observed. A monoclonal antibody to CTGF that is currently in clinical development (FG-3019) has demonstrated the ability to reverse vascular stiffening and improve cardiac function in a rat model of diabetic complications. FG-3019 has also exhibited activity in a murine radiation-induced pulmonary fibrosis model. When FG-3019 was administered to mice after a significant radiation-induced increase in lung density could be observed by CT imaging, the density of the lungs was observed to decrease over the period during which the antibody was administered and to remain stable after therapy had ceased. When considered together, these data indicate that inhibition of CTGF can prevent and reverse the process of fibrosis

Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis

Background. Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. Aim:To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. Patients: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. Methods: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. Results: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (< 2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. Conclusion: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance. Copyright (c) 2006 S. Karger AG, Basel

Regulation of pro-inflammatory and pro-fibrotic factors by CCN2/CTGF in H9c2 cardiomyocytes

Connective tissue growth factor (CTGF), also known as CCN2, is implicated in fibrosis through both extracellular matrix (ECM) induction and inhibition of ECM degradation. The role of CTGF in inflammation in cardiomyocytes is unknown. In some mesenchymal cell systems, CTGF mediates effects through TGF-β or tyrosine kinase cell surface receptor, TrkA, signalling. In this study, cellular mechanisms by which CTGF regulates pathways involved in fibrosis and inflammation were explored. Murine H9c2 cardiomyocytes were treated with recombinant human (rh)CTGF and ECM formation gene expression: fibronectin, collagen type -I and -III and ECM degradation genes: TIMP-1, TIMP-2 and PAI-1 were found to be induced. CTGF treatment also increased pro-inflammatory cytokines TNF-α, IL-6, MCP-1 and IL-8. CTGF upregulated TGF-β1 mRNA and rapidly induced phosphorylation of TrkA. The CTGF-induced pro-fibrotic and pro-inflammatory effects were blocked by anti-TGF-β neutralizing antibody and Alk 5 inhibitor (SB431542). A specific blocker of TrkA activation, k252a, also abrogated CTGF-induced effects on fibrosis and gene expresison of MCP-1 and IL-8, but not TNF-α or IL-6. Collectively, this data implicates CTGF in effects on pro-fibrotic genes and pro-inflammatory genes via TGF-β pathway signalling and partly through TrkA