Extrapancreatic actions of incretin-based therapies on bone in diabetes mellitus

Diabetes mellitus is correlated with modifications in bone microarchitectural and mechanical strength, leading to increased bone fragility. The incretin hormones, with a classical effect to increase insulin secretion following food ingestion, are now postulated to have important direct effects on bone. As such, glucose-dependent insulinotropic polypeptide (GIP) has dual actions on bone cells; enhancing bone�forming activity of osteoblasts and suppressing bone resorption by osteoclasts. The sister incretin of GIP, glucagon-like peptide-1 (GLP-1), is also suspected to directly influence bone health in a beneficial manner, although mechanism are less clear at present. The physiological actions of incretins are attenuated by dipeptidyl peptidase (DPP-4) activity and it is speculated that introduction of DPP-4 inhibitor may also positively affect quality of the skeleton. As such, this thesis evaluates the potential beneficial effects of a DPP-4 resistant GIP analogue, namely [D-Ala2 ]GIP, on osteoblastic-derived, SaOS-2 cells, and also preliminary in vivo studies on the impact of genetic deficiencies of GIPRs and GLP-1Rs on bone mineral density and content. Further studies characterised the beneficial effects of incretin-based therapies on metabolic control, bone microstructure and bone mechanical integrity in animal models of pharmacologically-, genetically- and environmentally-induced diabetes. GIP and related stable analogue increased bone-forming biomarkers in SaOS-2 cells and importantly, [D-Ala2 ]GIP was shown to be more potent than native GIP. Knockout mouse studies revealed that both GIPR and GLP-1R signaling are important for optimum bone mass. All diabetic mouse models displayed reduced bone mass, altered bone micromorphology and impairment of bone mechanical strength, similar to the human situation, confirming their appropriateness. The incretin-based therapeutics, [D-Ala2 ]GIP and Liraglutide, in streptozotocin-diabetic significantly increased bone matrix properties, indicating recovery of bone strength at the tissue level. The beneficial effects of administration of [D-Ala2 ]GIP�oxyntomodulin on bone health in db/db mice were more prominent as the Oxm analogue did not only improve bone strength at tissue level, but also at whole-bone level. These modifications were independent of metabolic status. Twice-daily Exendin-4 therapy improved glycaemic control and increased work required to resist bone fracture in high-fat fed mice. It was also established that Sitagliptin had neutral effects on bone microstructure and mechanical strength in high-fat mice. In summary, these data demonstrate the negative impact of diabetes mellitus on normal skeleton development and bone quality. Moreover, this thesis highlights the growing potential of incretin-based therapies for ameliorating bone defects and improving the increased fragility fracture risk associated with diabete

A sustainable competitiveness model for strategic alliances: a study of rural entrepreneurs and commercial organisations in Malaysia with special emphasis on Malaysian farmers' organisations

It is evident that strategic alliance route offers Malaysian Farmers’ Organisations a reliable and realistic way forward, towards wealth creation and socio-economic development. It has brought about positive financial rewards to the farmers as well as that of the farmer’s organisations themselves. Statistical significance on effectiveness of the various types of alliance and important control factors of profitable alliance have also been identified. Based on 1991-2004 international strategic alliance development models, a three-stage Dynamic Domestic Sustainable Competitiveness Development Model of Strategic Alliance was developed. It consists of Start-up Period, Adaptation Process and Transformation/termination. With the presence of dynamic business entities, strategic alliance projects inevitably face Competitive Challenge from time to time. A Sustainable Competitiveness Cycle, a product of the Adaptation Process, turns saviour in more ways than one, in a lifespan of an alliance

Malay language as a foreign language and the Singapore’s education system

The paper highlights the impact of the Singapore’s bilingual education policy on the Malay language and how the language has been regarded a foreign language in the Singapore context given the interest of policy makers in the implementation of a new third language policy. The growth can be hampered, however, to some concerns arising from the bilingual policy namely inadequate manpower, teaching materials, lack of resources and opportunities for using the language

SCR of NO with C3H6 in the presence of excess O2 over Cu/Ag/CeO2-ZrO2 catalyst

The catalytic activity of a series of CeO2-ZrO2 mixed oxides in the selective catalytic reduction (SCR) of NO by C3H6 at 400'C has been investigated. The NO reduction activity of pure CeO2 is enhanced in the presence of Zr, reaching a maximum NO conversion with CeO2(75)-ZrO2(25) catalyst. Then, the catalytic performances of Cu(4)/Ag(1)/CeO2 and Cu(4)/Ag(1)/CeO2(75)-ZrO2(25) catalysts were compared and the latter showed better activity especially in the low temperature region (250-350 C). The stronger metal-support interaction and higher reducibility shown by the Cu(4)/Ag(1)/CeO2(75)-ZrO2(25) catalyst were believed to enhance its performance compared to Cu(4)/Ag(1)/CeO2 catalyst by activating more C3H6 to selectively reduce NO within this temperature region. Central composite response surface design methodology was employed to study the effect of operating variables such as temperature, NO and C3H6 concentrations on the SCR of NO by C3H6 over Cu(4)/Ag(1)/CeO2(75)-ZrO2(25) catalyst and to determine the optimum value of operating variables for maximum NO conversion. Numerical results indicated that the optimum NO conversion of 82.89% is attained at reaction temperature =415.38 C, NO concentration= 1827.16 ppm and C3H6 concentration = 1908.13 ppm. The addition of water vapor to the reactant significantly decreased the NO conversion over Cu(4)/Ag(1)/CeO2 and Cu(4)/Ag(1)/CeO2 (75)-ZrO2(25), but the inhibition was more pronounced over Cu(4)/Ag(1)/CeO2 catalyst

Effect Of Hydrodynamic Coefficient On Classics Spars Respons

As a floating strucutre ,the motion of spar platform which connected to the sea bottom anchoring is taken into account. The motions are affected by the nevironmental load such as wind,current and wave. The different type of the dynamic response such as heave,surge,pitch,roll and yaw of the classsic spar platform are being analyze

Analytical Model for Outdoor Millimeter Wave Channels using Geometry-Based Stochastic Approach

The severe bandwidth shortage in conventional microwave bands has spurred the exploration of the millimeter wave (MMW) spectrum for the next revolution in wireless communications. However, there is still lack of proper channel modeling for the MMW wireless propagation, especially in the case of outdoor environments. In this paper, we develop a geometry-based stochastic channel model to statistically characterize the effect of all the first-order reflection paths between the transmitter and receiver. These first-order reflections are generated by the single-bounce of signals reflected from the walls of randomly distributed buildings. Based on this geometric model, a closed-form expression for the power delay profile (PDP) contributed by all the first-order reflection paths is obtained and then used to evaluate their impact on the MMW outdoor propagation characteristics. Numerical results are provided to validate the accuracy of the proposed model under various channel parameter settings. The findings in this paper provide a promising step towards more complex and practical MMW propagation channel modeling.Comment: Accepted to appear in IEEE Transactions on Vehicular Technolog

Promoting quality of life through participation in Healthy Cities programme: sharing the experiences of Kuching city

We live in an era where the issue of 'quality of life' is of prime concern with special reference to urban areas in the face of environmental and social deterioration, growing human insecurity and exposure to infectious and high risk diseases; not surprisingly, cities are blamed for the declining quality of life. The declining social and environmental conditions in urban areas warrant the need for swift solutions to be found and concrete measures/actions to be taken to arrest the further worsening of urban conditions. The Healthy Cities Movement was conceived as a result of the growing realization of the gravity of human-induced crisis that has besieged urban dwellers. It is in line with the spirit of Healthy Cities Movement that Kuching agreed to participate in the Healthy City Programme which began in 1995 and ended in 2000. The purpose to be served by this paper is to share the experiences of Kuching city in implementing the programme with a focus on how coordinated local action is achieved through multisectoral approach or 'smart partnership' which in turn engenders collaboration through community participation and inter-agency linkages. The information collated for the purpose of this paper is mostly derived from secondary sources

Effects of Asiatic Acid on Neurite Outgrowth in Neuro-2a Cells

Recently, medicinal plants from ancient Ayurvedic medicine have provided clues to the discovery of novel therapeutics for various diseases. In Ayurvedic medicine, a common Indian plant, Centella asiatica is highly regarded as a rasayana or nerve tonic. The Centella extract is used to ward off age-related dementia and to increase memory and intelligence. The mechanism by which Centella improves memory and learning and reduces the risk of dementia is unclear. We recently tested the effects of asiatic acid, the main active component of Centella, on neuronal growth. We hypothesized that asiatic acid will promote neuronal growth and neurite network formation. To test this hypothesis, we examined the effects of asiatic acid on neuronal growth in murine neuroblastoma cells, Neuro2a. Neuro2a cells were cultured for 24 hours in DMEM medium containing 10 mM glucose and 10% FBS in six-well plates at a concentration of 200,000 cells/well. The cells were further cultured for 72 hours in DMEM containing 10 mM glucose and with either 1 μM asiatic acid in ethanol or ethanol alone (vehicle). Cells were photographed, and neurite outgrowth quantified using NeuronJ software. The results revealed that asiatic acid treatment significantly increased the percentage of cells bearing neurites as compared to neurons grown in medium alone. In addition, asiatic acid treatment increased neurite extension and combined length of neurites. To investigate the impact of asiatic acid on bioenergetics in Neuro2a cells, we first analyzed the electron transport chain of the mitochondria via respirometry. The respiration rates of Neuro2a cells cultured in medium containing asiatic acid was significantly (p\u3c 0.05) higher than cells grown in medium containing vehicle alone. Also, western blot analyses were used to examine if asiatic acid could increase the mitochondrial complex. The result showed that Asiatic acid increased complex 1, 2, 3, and 4. In addition, we examined if asiatic acid would increase oxidative phosphorylation instead of glycolysis that results in lactate production. The results indicated that Neuro2a cells treated for 24 hours with 1 μM of asiatic acid induced less lactate as compared to Neuro2a with ethanol alone (vehicle). Also, the MTT assay was used to detect the viable cells in Neuro2a cells treated with either 1 μM asiatic acid or ethanol alone (vehicle) for two days. The result shows that Neuro2a cells treated with asiatic acid showed increased cell viability as compared to Neuro2a exposed to ethanol alone. Finally, the effect of asiatic acid on cell proliferation was examined using standard trypan blue staining. The data revealed that doubling time was significantly slower in cells cultured in presence of asiatic acid as compared to cells grown in vehicle (ethanol) alone (p\u3c 0.05). Together these results suggest that asiatic acid is neurotrophic. This effect may explain the beneficial role of Centella asiatica extract on learning and memory and in preventing neurological disorders

Liquefaction of empty palm fruit bunch (EPFB) in alkaline hot compressed water

Effect of alkalis (NaOH, KOH and K2CO3) on liquefaction of EPFB (emptypalmfruitbunch) biomass liquefaction was investigated under subcritical water conditions in a batch reactor operating at 270 °C and 20 bars for a period of 20 min. Catalytic performance and suitable biomass to water ratio that supported higher EPFB conversion, liquid hydrocarbons yield and lignin degradations were screened. Analytical results indicate that maximum of 68 wt% liquids were produced along with 72.4 wt% EPFB mass conversions and 65.6 wt% lignin degradation under 1.0 M K2CO3/2:10 (biomass/water) conditions. In comparison, the experiments that were performed in the absence of alkalis yielded only 30.4 wt% liquids, converted 36 wt% EPFB and degraded 24.3 wt% lignin. Furthermore, biomass to water ratios >2:10 decreased both solid mass conversion and liquid hydrocarbons' yield. The reactivity of the alkalis was in the order of K2CO3 > KOH > NaOH. The liquid compositions were dominantly phenols and esters; the highest value of phenol (60.1 wt% of liquid yield) was achieved in the case of K2CO3 (1.0 M) with 5 g EPFB/25 ml water ratio while 1.0 M NaOH yielded maximum esters (86.4 wt% of liquid yield). The alkali promoted process assisted with hotwater treatments seemed promising for production of bio-oils from EPFB