Properties of glass fiber reinforced self compacting concrete

Self Compacting Concrete (SCC) is able to flow under its own weight and completely fill the formwork, even in the presence of congested reinforcement, without any compaction, while maintaining homogeneity of the concrete. Majority of concrete cast rely on compaction to produce good quality concrete. However, compaction is difficult to be done in conditions where there are dense reinforcement and large casting area. Usage of SCC will overcome the difficult casting conditions and reduce manpower required. Addition of fibers will enhance the tensile and ductile behaviour of concrete with brittle nature. SCC was added with relatively short, discrete, and discontinuous glass fibers to produce Glass Fiber Reinforced Self Compacting Concrete (GFRSCC). The purpose of this study is to investigate the workability and mechanical properties of plain SCC and GFRSCC. Control concrete (NC), plain SCC, and GFRSCC samples were prepared. Water-cement ratio of 0.40 was used for all concrete mixes. The fiber and brand of superplasticizer used were alkaline-resistance glass fiber and Rheobuild 1100, respectively. Three fiber contents of 0.5%, 1.0%, and 1.5% by volume of concrete were utilised in this study. The laboratory testing included slump flow test, L-Box test, sieve segregation resistance test, density test, ultrasonic pulse velocity (UPV) test, compressive strength test, splitting tensile strength test, and flexural strength test. The dosage of superplasticizer required increased as fiber content increased. Plain SCC and GFRSCC were highly workable than NC. The experimental results show that plain SCC exhibited higher compressive strength than NC and GFRSCC. The splitting tensile strength of NC was higher than plain SCC and GFRSCC due to negative effect of superplasticizer added. The flexural strength of NC was slightly higher than plain SCC. All GFRSCC exhibited higher flexural strength than plain SCC. The optimum fiber content was 1.0% by volume of concrete. GFRSCC with 1.0% fiber content developed higher load at first crack and ultimate load than NC and plain SCC slabs

Andrographolide as a template in the synthesis of new anticancer agents with potentially novel molecular targets

Using andrographolide (AGP) as a template, a series of semisynthetic analogues was synthesised for the discovery of new anticancer agent(s) with improved antitumour selectivity and potency. SRJ09, a lead compound displayed remarkable activity in the National Cancer Institute (NCI) of USA in vitro anticancer screen, particularly against breast and colon cancers. The treatment of MCF-7 breast and HCT-116 colon cancer cells with SRJ09 induced a G1 phase cell cycle arrest through the down-regulation of CDK-4 expression with concomitant up-regulation of p21 expression and without affecting the cyclin D1 expression. SRJ09 induced apoptotic cell death in both cells in a p53- and bcl-2-independent manner, implicating extrinsic apoptotic pathway. The compound showed impressive in vivo activity by delaying HCT-116 tumour xenograft growth in nude mice. Recently, a derivative of SRJ09, SRS07 showed vast improvement in the NCI anticancer activity screen compared with the parent compound. Additionally, NCI’s in silico COMPARE and SOM analyses revealed that the new AGP derivatives have potentially novel molecular target(s). These findings although preliminary they are highly suggestive SRS07 have a great potential to be developed into a clinical anticancer agent. This research is funded by the Ministry of Science, Technology and Innovation of Malaysia (MOSTI) under the IRPA and ScienceFund grant schemes

SRJ09, a promising anticancer drug lead: elucidation of mechanisms of antiproliferative and apoptogenic effects and assessment of in vivo antitumor efficacy

SRJ09 (3,19-(2-bromobenzylidene)andrographolide), a semisynthetic andrographolide (AGP) derivative, was shown to induce G1 cell cycle arrest and eventually apoptosis in breast and colon cancer cell lines. The present investigation was carried out to elucidate the mechanisms cell cycle arrest and apoptosis and evaluate the in vivo antitumor activity of SRJ09. The in vitro growth inhibitory properties of compounds were assessed in colon (HCT-116) and breast (MCF-7) cancer cell lines. Immunoblotting was utilized to quantitate the protein levels in cells. The gene expressions were determined using reverse transcriptase PCR (RT-PCR). Pharmacokinetic investigation was carried out by determining SRJ09 levels in plasma of Balb/C mice using HPLC. In vivo antitumor activity was evaluated in athymic mice carrying HCT-116 colon tumor xenografts. SRJ09 displayed improved in vitro activity when compared with AGP by producing rapid cell killing effect in vitro. Its activity was not compromised in MES-SA/Dx5 multidrug resistant (MDR) cells expressing p-glycoprotein. Cells treated with SRJ09 (0.1⿿10 μM) displayed increased p21 protein level, which corresponded with gene expression. Whereas CDK4 protein level and gene expression was suppressed. The treatment did not affect cyclin D1. Changes of these proteins paralleled G1 cell cycle arrest in both cell lines as determined by flow cytometry. Induction of apoptosis by SRJ09 in HCT-116 cells which occurred independent of p53 and bcl-2 was inhibited in the presence of caspase 8 inhibitor, implicating the extrinsic apoptotic pathway. A single dose (100 mg/kg, i.p) of SRJ09 produced a plasma concentration range of 12⿿30.4 μM. At 400 mg/kg (q4dX3), it significantly retarded growth of tumor xenografts. The antitumor activity of SRJ09 is suggested mediated via the induction of p21 expression and suppression of CDK-4 expression without affecting cyclin D1 to trigger G1 arrest leading to apoptosis

DDX3X loss is an adverse prognostic marker in diffuse large B-cell lymphoma and is associated with chemoresistance in aggressive non-Hodgkin lymphoma subtypes.

Funder: addenbrooke's charitable trust, cambridge university hospital

Nonvirally Modified Autologous Primary Hepatocytes Correct Diabetes and Prevent Target Organ Injury in a Large Preclinical Model

BACKGROUND: Current gene- and cell-based therapies have significant limitations which impede widespread clinical application. Taking diabetes mellitus as a paradigm, we have sought to overcome these limitations by ex vivo electrotransfer of a nonviral insulin expression vector into primary hepatocytes followed by immediate autologous reimplantation in a preclinical model of diabetes. METHODS AND RESULTS: In a single 3-hour procedure, hepatocytes were isolated from a surgically resected liver wedge, electroporated with an insulin expression plasmid ex vivo and reimplanted intraparenchymally under ultrasonic guidance into the liver in each of 10 streptozotocin-induced diabetic Yorkshire pigs. The vector was comprised of a bifunctional, glucose-responsive promoter linked to human insulin cDNA. Ambient glucose concentrations appropriately altered human insulin mRNA expression and C-peptide secretion within minutes in vitro and in vivo. Treated swine showed correction of hyperglycemia, glucose intolerance, dyslipidemia and other metabolic abnormalities for > or = 47 weeks. Metabolic correction correlated significantly with the number of hepatocytes implanted. Importantly, we observed no hypoglycemia even under fasting conditions. Direct intrahepatic implantation of hepatocytes did not alter biochemical indices of liver function or induce abnormal hepatic lobular architecture. About 70% of implanted hepatocytes functionally engrafted, appeared histologically normal, retained vector DNA and expressed human insulin for > or = 47 weeks. Based on structural tissue analyses and transcriptome data, we showed that early correction of diabetes attenuated and even prevented pathological changes in the eye, kidney, liver and aorta. CONCLUSIONS: We demonstrate that autologous hepatocytes can be efficiently, simply and safely modified by electroporation of a nonviral vector to express, process and secrete insulin durably. This strategy, which achieved significant and sustained therapeutic efficacy in a large preclinical model without adverse effects, warrants consideration for clinical development especially as it could have broader future applications for the treatment of other acquired and inherited diseases for which systemic reconstitution of a specific protein deficiency is critical

Multiple-Robot Systems for USAR: Key Design Attributes and Deployment Issues

The interaction between humans and robots is undergoing an evolution. Progress in this evolution means that humans are close to robustly deploying multiple robots. Urban search and rescue (USAR) can benefit greatly from such capability. The review shows that with state of the art artificial intelligence, robots can work autonomously but still require human supervision. It also shows that multiple robot deployment (MRD) is more economical, shortens mission durations, adds reliability as well as addresses missions impossible with one robot and payload constraints. By combining robot autonomy and human supervision, the benefits of MRD can be applied to USAR while at the same time minimizing human exposure to danger. This is achieved with a single-human multiple-robot system (SHMRS). However, designers of the SHMRS must consider key attributes such as the size, composition and organizational structure of the robot collective. Variations in these attributes also induce fluctuations in issues within SHMRS deployment such as robot communication and computational load as well as human cognitive workload and situation awareness (SA). Research is essential to determine how the attributes can be manipulated to mitigate these issues while meeting the requirements of the USAR mission

Properties of glass fibre reinforced self compacting concrete

Self Compacting Concrete (SCC) is a concrete that is able to flow under its own weight and completely fill the formwork, even in the presence of congested reinforcement, without any compaction, while maintaining homogeneity of the concrete. The elimination of compaction for SCC is beneficial in solving difficult casting conditions and reduction in manpower required. SCC was added with relatively short, discrete, and discontinuous glass fibers to produce Glass Fiber Reinforced Self Compacting Concrete (GFRSCC). Water-cement (w/c) ratio of 0.40 was used in concrete mix proportions. The fiber used was alkaline-resistance glass fiber. Three volume percentages of fiber were added to the mix, i.e. 0.5%, 1.0%, and 1.5% by volume of concrete. Workability and mechanical properties of the concrete were evaluated. SCC and GFRSCC were highly workable than normal concrete (NC). The dosage of superplasticizer required increment as fiber content increase. SCC exhibits higher compressive strength than NC and GFRSCC. Inclusion of fibers does not give positive effect to the compressive strength of GFRSCC. The splitting tensile strength of NC was higher than SCC and GFRSCC due to the negative influence of superplasticizer added. Results indicated that the flexural strength of NC was slightly higher than SCC. The flexural strength of GFRSCC was higher than SCC. The optimum fiber content for GFRSCC, determined during the study was 1.0% by volume of concrete. GFRSCC slab developed higher first crack load and ultimate load compared to NC and SCC slabs

Degradation of Bacterial Quorum Sensing Signaling Molecules by the Microscopic Yeast Trichosporon loubieri Isolated from Tropical Wetland Waters

Proteobacteria produce N-acylhomoserine lactones as signaling molecules, which will bind to their cognate receptor and activate quorum sensing-mediated phenotypes in a population-dependent manner. Although quorum sensing signaling molecules can be degraded by bacteria or fungi, there is no reported work on the degradation of such molecules by basidiomycetous yeast. By using a minimal growth medium containing N-3-oxohexanoylhomoserine lactone as the sole source of carbon, a wetland water sample from Malaysia was enriched for microbial strains that can degrade N-acylhomoserine lactones, and consequently, a basidiomycetous yeast strain WW1C was isolated. Morphological phenotype and molecular analyses confirmed that WW1C was a strain of Trichosporon loubieri. We showed that WW1C degraded AHLs with N-acyl side chains ranging from 4 to 10 carbons in length, with or without oxo group substitutions at the C3 position. Re-lactonisation bioassays revealed that WW1C degraded AHLs via a lactonase activity. To the best of our knowledge, this is the first report of degradation of N-acyl-homoserine lactones and utilization of N-3-oxohexanoylhomoserine as carbon and nitrogen source for growth by basidiomycetous yeast from tropical wetland water; and the degradation of bacterial quorum sensing molecules by an eukaryotic yeast