Fine recycled concrete aggregate as a material replacement in concrete production

As a fast and rapid growing nation, Malaysia undergoes a lot of development especially in construction field. Most of the building nowadays are being made mainly using concrete as it provides many favorable features such as satisfactory compressive strength, durability, availability, versatility and cost effectiveness. However, in pursuing the development era, sometimes the authorities overlooked about the construction and demolition (C&D) waste that had been created along the development progress. Construction and demolition waste is becoming a vital issue especially to the environmental aspect in many large cities in the world (Chen et al., 2002). Shen [1] describe C&D waste as the waste which generated from renovation, site clearing, demolition, construction, roadwork, land excavation and civil and building construction. Construction and Demolition (C&D) waste constitutes a major portion of total solid waste production in the world, and most of it is used in landfills .

Effect of EGCG on granule cell proliferation in the adult dentate gyrus of the Ts65Dn mouse

poster abstractDown syndrome (DS) is the most common genetic disorder that results in cognitive abnormalities and occurs in approximately 1 in 700 live births. This disorder is caused by an extra copy of human chromosome 21 (Hsa21) which increases the dosage of the genes on that chromosome. Ts65Dn mice, which are the most studied mouse model for DS, are trisomic for segments of mouse chromosome 16 (Mmu16) which contain approximately half the genes found on Hsa21. These mice express some of the physical and behavioral abnormalities associated with DS. Previous research has shown impaired performance of Ts65Dn mice in hippocampaldependent tasks, such as in the radial arm maze task, compared to euploid control mice. Success in such tasks is thought to depend on the ability of the hippocampus to generate granule cells within the dentate gyrus. Young granule cells are highly active after integration and are required for memory formation. Previous research shows that Ts65Dn have a reduction in the formation of granule cells which leads us to hypothesize that Ts65Dn mice will perform worse in the radial arm maze compared to euploid controls. This leads us to conclude that Ts65Dn mice have reduced granule cell proliferation relative to controls. We are investigating the effects of EGCG, a polyphenolic component of green tea, on granule cell proliferation in adult mice. Different pathways are suggested to be effected by EGCG, such as by inhibiting Dyrk1a that is overproduced in DS mice or by up-regulation of the sonic hedgehog receptor Patched. Using BrdU peroxidase immunohistochemistry to label newly generated granule cells in the adult mouse dentate gyrus, we hypothesize that EGCG will increase cell proliferation in the granule cell layer of the dentate gyrus

Desensitisation of the human long chain fatty acid receptors FFA1 and FFA4

G protein-coupled receptors (GPCRs) constitute the largest, most ubiquitous and most versatile family of membrane proteins encoded by the human genome. Due to diverse ligands and multiple physiological activities, this set of receptors has frequently been explored as potential drug targets. Deorphanisation of GPCRs successfully identified FFA1 and FFA4 (previously named GPR40 and GPR120) as long chain free fatty acid receptors. With diverse expression patterns and close association to pathophysiology of metabolic diseases, both receptors are being studied to understand both receptor pharmacology and their potential for drug development. Due to the overlap in the activation of FFA1 and FFA4 by endogenous fatty acid ligands, selective synthetic ligands have been developed for these receptors. Using a number of biochemical and biophysical assays, I have characterised TUG-770, TUG-905 and GW-1100 as FFA1 ligands and TUG-891, TUG-1197 and TUG-1275 as FFA4 ligands. TUG-905 was found to be most potent and selective FFA1 agonist and GW-1100 showed insurmountable antagonism at FFA1. At FFA4, TUG-1197 was found to be a highly potent and selective agonist. TUG-1275 showed insurmountable antagonism at FFA4 in β-arrestin2 recruitment, receptor internalisation and inositol monophosphate accumulation studies and showed complete selectivity for hFFA4. Agonist exposure rapidly phosphorylated FFA4 in an agonist-concentration-dependent fashion which was totally blocked by TUG-1275. The protein kinase C activator PMA was also noted to phosphorylate FFAA in a concentration-dependent manner. Thus both homologous and heterologous phosphorylation is involved in FFA4 regulation. The FFA4-agonist TUG-891 produced robust internalisation of FFA4 as detected by each of confocal microscopy, and both cell surface ELISA and biotinylation. PMA was able to internalise FFA4 although it was unable to recruit β-arrestin2 to FFA4 suggesting that this internalisation might not be β-arrestin2-dependent. Constitutive internalisation was seen for FFA1, where the selective FFA1 antagonist GW-1100 had no effect. Repeated agonist-exposure desensitised both FFA1 and FF4 as revealed in single-cell calcium imaging studies. Although there was a small reduction of FFA4-internalisation and a slight elevation of total calcium levels from a single-chronic exposure of agonist, elimination of β-arrestin1/2 from HEK293 cells by genome editing did not significantly change the desensitisation of FFA4 to repeated exposure of agonist and did not prevent agonist-promoted internalisation. These studies indicate that β-arrestins are not the sole factors in desensitisation of human FFA4. Gαq/11 elimination by genome editing completely blocked intracellular calcium mobilisation and accumulation of inositol monophosphates mediated by both FFA1 and FFA4 indicating that Gαq/11 coupling to agonist-activated receptors is essential for this functional signalling outcome via both receptors. FFA4 expressed in Gαq/11-null cells was found to be phosphorylated by agonist, indicating that phosphorylation-mediated desensitisation of this receptor is not dependent on Gαq/11 proteins. FRET and BRET experiments revealed for the first time homo and hetero-oligomerisation of both FFA1 and FFA4. Although ligand regulation of oligomerisation was not investigated these preliminary observations of oligomerisation may help in the future to answer many questions of regulation and desensitisation of these receptors. The selective FFA1 and FFA4 ligands characterised here in this project might be used as tool compounds to further explore the physiology and pharmacology of these therapeutically important receptors

Phase II – Biomechanics of Smooth Muscle Cell Differentiation: Experimental Study Using an Innovative In Vitro Mechanical System

poster abstractSmooth muscle cells (SMCs) controls involuntary contractions and express different genotypic and phenotypic traits on specific organs such as blood vessels, bladder and stomach. However, studies have shown different SMC lineages tend to gradually lose specific characteristics due to a static milieu without exerting forces that they would experience naturally when cultured in vitro. The research provided in vivo conditions are mimicked effectively in vitro by applying controlled mechanical loading, SMCs should express their differentiated characteristics. We have validated an innovative mechanical device that simulates the pulsatile stretching SMCs undergo in their in vivo environment. Using the new system and cell and molecular biology techniques, we are evaluating cell differentiation and strain induced alignment when phenotypically modulated SMCs undergo cyclic mechanical loading at 10 and 20 percent strains, for 4, 6, or 8 hours at physiological frequency. We collected proteins after stretch experiments and analyzed via western blot, α-actin, γ-actin, transgelin, and calponin protein expression changes in: coronary SMCs strained 10% and 20% at 4, 6, and 8 hours, bladder SMCs strained 10% at 4, 6, and 8 hours, and BAECs for varying intensities and durations. In order to improvise the machine capability, LabVIEW code is been developed as the user interface providing advantageous of Graphical Approach instead of Cool Muscle Language code. Developed coding provide a complete coverage of acquisition, analysis, reporting, and display features to create modern applications that can scale as system requirements change over time. The next phase of this experiment enable analysis of gene expression using quantitative RT-PCR (qRT-PCR). This facet of research may prove valuable in the analysis of the effect of mechanical stress on maintaining SMC lineage as well as the study of how pathological stretch conditions affect SMC and endothelial cell gene and protein expressions

Impact of Change in Exchange Rate on Foreign Direct Investment: Evidence from Somalia

The purpose of this study is to examine the influence of exchange rate on foreign direct investment in Somali. The study used location theory to analyze the data by applying multiple regression models under OLS method. The results show that the overall model is significant. There is a negative and significant relationship found between exchange rate and FDI, while, a positive and significant relationship is observed between inflation and domestic investment on FDI, and a negative but insignificant relationship is observed between lack of government and FDI.The strength of this research lies in its time limit. The scope of this research was for the less than 50 years ending and including the year 2010. It is not known whether the results would hold if a longer period would have been researched upon. Further it is not possible to tell whether the same findings will hold for the period after 2010. There is need for the government to retain tight monetary and fiscal policies in order to stable exchange rate in the Somalia. Central bank should promote monetary authorities at managing exchange rate effectively to attract foreign direct investors. while utilization location theory, this study contribute significant to the literature by adding new variable to the model lack of government. Keywords- exchange rate, foreign direct investment and Somalia

Targeted elimination of G proteins and arrestins defines their specific contributions to both intensity and duration of G protein-coupled receptor signalling

G protein-coupled receptors (GPCRs) can initiate intracellular signalling cascades by coupling to an array of heterotrimeric G proteins and arrestin adaptor proteins. Understanding the contribution of each of these coupling options to GPCR signalling has been hampered by a paucity of tools to selectively perturb receptor function. Here we employ CRISPR/Cas9 genome editing to eliminate selected G proteins (Gαq and Gα11) or arrestin2 and arrestin3 from HEK293 cells, together with the elimination of receptor phosphorylation sites, to define the relative contribution of G proteins, arrestins and receptor phosphorylation to the signalling outcomes of the free fatty acid receptor 4 (FFA4). A lack of FFA4-mediated elevation of intracellular [Ca2+] in Gαq/Gα11-null cells and agonist-mediated receptor internalization in arrestin2/3-null cells confirmed previously reported canonical signalling features of this receptor, thereby validating the genome-edited HEK293 cells. FFA4-mediated ERK1/2 activation was totally dependent on Gq/11 but intriguingly was substantially enhanced for FFA4 receptors lacking sites of regulated phosphorylation. This was not due to a simple lack of desensitization of Gq/11 signalling because the Gq/11-dependent calcium response was desensitized by both receptor phosphorylation and arrestin-dependent mechanisms whilst a substantially enhanced ERK1/2-response was only observed for receptors lacking phosphorylation sites and not in arrestin2/3-null cells. In conclusion, we validate CRISPR/Cas9 engineered HEK293 cells lacking Gq/11 or arrestin2/3 as systems for GPCR signalling research and employ these cells to reveal a previously unappreciated interplay of signalling pathways where receptor phosphorylation can impact on ERK1/2 signalling through a mechanism that is likely independent of arrestins

Effects of EGCG treatment on deficits in a radial-arm maze spatial pattern separation task in a Down syndrome mouse model

poster abstractDown syndrome (DS) is caused by three copies of human chromosome 21 (Hsa 21) and results in a constellation of phenotypes that include intellectual disability. Ts65Dn mice, the most extensively studied model of DS, have three copies of approximately half the genes on Hsa 21 and display many of the phenotypes associated with DS, including cognitive deficits. DYRK1A is found in three copies in humans with Trisomy 21 and has increased expression in a number of tissues. Dyrk1a is also found in three copies in Ts65Dn mice, and has been shown to be involved in a number of critical pathways including CNS development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol found in green tea, is an inhibitor of Dyrk1a activity. We have previously shown that a three week treatment with EGCG normalizes skeletal abnormalities in Ts65Dn mice. Previous work has found that Ts65Dn mice are significantly impaired in several hippocampal-dependent tasks, including the Morris water maze and novel object recognition. Another hippocampal-dependent process, pattern separation, is the ability to differentiate between similar memories acquired during learning. Distinctive encoding of these similar memories in hippocampal formation is thought to be necessary to distinguish between them. Experimental reductions in adult neurogenesis have produced impairments in pattern separation performance. Given that recent studies in Ts65Dn mice have reported significant reductions in adult hippocampal neurogenesis, we hypothesize that Ts65Dn mice will be impaired in the pattern separation task. Furthermore, we hypothesize that treating Ts65Dn mice with EGCG throughout task learning would improve performance to control levels. A radial arm maze-delayed non-matching-toplace pattern separation task with three different degrees of spatial separation is used. Preliminary data suggests that, in contrast to control mice, Ts65Dn mice do not improve their performance over training

The Determinants of Foreign Direct Investment in Somalia

This study examines determinants of foreign direct investment in Somalia, measured foreign direct investment inflow (FDI). Used time series data obtained from World Bank and SESRIC for a period of 41 years that is 1970 to 2010. Augmented Dickey-Fuller (ADF) test was used for the unit root test and ordinary Least Square statistical technique was used to assess the degree of influence the variables have on each other. The results show a negative and significant relationship in exchange rate and FDI, while, a positive and significant relationship is observed between inflation, external debt and domestic investment of FDI. Also a negative but insignificant relationship is observed between lack of government and gross domestic product FDI. Therefore, there is need for the government to retain tight monetary and fiscal policies in order to attract foreign direct investment. This study therefore recommends that central bank of Somalia should control the fluctuations of the exchange rate in order to increase the FDI. Since the inflation is higher, the study also recommends having a good government to recover the financial institutions that manage the monetary policy of Somalia. Keywords: Exchange rate, foreign direct investments, Somalia. JEL Classifications: F21, F3

ETS1 induction by the microenvironment promotes ovarian cancer metastasis through focal adhesion kinase

Metastatic colonization involves paracrine/juxtacrine interactions with the microenvironment inducing an adaptive response through transcriptional regulation. However, the identities of transcription factors (TFs) induced by the metastatic microenvironment in ovarian cancer (OC) and their mechanism of action is poorly understood. Using an organotypic 3D culture model recapitulating the early events of metastasis, we identified ETS1 as the most upregulated member of the ETS family of TFs in metastasizing OC cells as they interacted with the microenvironment. ETS1 was regulated by p44/42 MAP kinase signaling activated in the OC cells interacting with mesothelial cells at the metastatic site. Human OC tumors had increased expression of ETS1, which predicted poor prognosis. ETS1 regulated OC metastasis both in vitro and in mouse xenografts. A combination of ChIP-seq and RNA-seq analysis and functional rescue experiments revealed FAK as the key transcriptional target and downstream effector of ETS1. Taken together, our results indicate that ETS1 is an essential transcription factor induced in OC cells by the microenvironment, which promotes metastatic colonization though the transcriptional upregulation of its target FAK

Antimicrobial compounds from Calophyllum canum

Calophyllum species have been used in traditional medicine for its therapeutic properties in many tropical climate counteries. Calopyllum canum locally known as bintagor merah has been isolated and tested for its antimcirobial activity. Stembarks of C. canum were extracted by soxhlet extraction with n-hexane, ethyl acetate and then methanol, successively. The antimictovial activity was carried out by disc difussion method and determination of MIC and MBC values. n-Hexane extracts was active against S.aureus and B.subtili, while methanol extract inhibited the growuth of S.aureus, B.subtilis and E.coli. Ethyl acetate extract was also active against S.aureus and B.subtilis. Both n-haxena and methanol extracts were furhter subjected to column chramotography by guiding of its antimicrobial actvity. Four compounds were sucesfully isolated.; two (D1 and D2) from n-hexane extract and two from methanol (CCM1 and CCM2). The compondsD1 and d2 were active against S.aureus and B. anthracis. While CCM1 and CCM2 were active against S.aureus. Furhter research need to be done to identify the structure of the active compounds and investigate their mood of action