Search results for: small cells
5188 Phytolith Analysis of Intrabasaltic Palaeosols (Bole Beds) from the Deccan Volcanic Province of Western India: A Preliminary Study
Authors: Sayyed Mohammed Rafi
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Phytolith studies were carried out for the intrabasaltic bole beds occurring in the western part of the Deccan Volcanic Province. This preliminary study indicates the presence of multiform phytoliths both in red and green boles. Red bole indicates well preserved elongate phytoliths from Acanthaceae plants while bulky Bulliform phytoliths mainly from Pleioblastus/ Andropogonea/reeds plants. Degeneration of few phytoliths from red bole indicates either leaching/etching or some other activity that is responsible for such post-preservation conditions. Phytoliths from the green bole, however, seem to be well preserved as compared to those from the red bole. The phytoliths from green bole are mainly of Festucoid types (especially small square and rectangular types) indicating the presence of Chrysobalanaceae type of vegetation followed by elongate phytoliths from Acanthaceae plant types. The Multiform Trichomes seems to be derived from Panicoid/Andropogonoid/Burseraceae/Fabaceae while Bulliforms from Pleioblastus/Andropogonea/reeds. Presences of silicified woody elements from both red and green boles indicate the presence of dicotyledonous plants which could have been in the form of small shrubs. The degenerated phytoliths in red bole suggest leaching/etching or higher intensity of weathering suggesting the existence of well-drained conditions during its formation that enhanced the leaching activity while the presence of well-preserved phytoliths in green bole point towards the existence of damp and desiccated conditions during its formation. The prevalence of dry condition during red bole formation could suggest their formation under higher temperature as compared to green bole. Based on the phytolith analysis it is too early to comment on the palaeoclimates which could have prevailed during the bole bed formations. However a detailed micromorphological, as well as phytolith analysis of more samples, can throw light on the palaeoenvironmental conditions as well as the biological activity during their formation.Keywords: Deccan volcanic province, intrabasaltic bole beds, palaeoclimate, phytoliths
Procedia PDF Downloads 2415187 Sensory Interventions for Dementia: A Review
Authors: Leigh G. Hayden, Susan E. Shepley, Cristina Passarelli, William Tingo
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Introduction: Sensory interventions are popular therapeutic and recreational approaches for people living with all stages of dementia. However, it is unknown which sensory interventions are used to achieve which outcomes across all subtypes of dementia. Methods: To address this gap, we conducted a scoping review of sensory interventions for people living with dementia. We conducted a search of the literature for any article published in English from 1 January 1990 to 1 June 2019, on any sensory or multisensory intervention targeted to people living with any kind of dementia, which reported on patient health outcomes. We did not include complex interventions where only a small aspect was related to sensory stimulation. We searched the databases Medline, CINHAL, and Psych Articles using our institutional discovery layer. We conducted all screening in duplicate to reduce Type 1 and Type 2 errors. The data from all included papers were extracted by one team member, and audited by another, to ensure consistency of extraction and completeness of data. Results: Our initial search captured 7654 articles, and the removal of duplicates (n=5329), those that didn’t pass title and abstract screening (n=1840) and those that didn’t pass full-text screening (n=281) resulted in 174 articles included. The countries with the highest publication in this area were the United States (n=59), the United Kingdom (n=26) and Australia (n=15). The most common type of interventions were music therapy (n=36), multisensory rooms (n=27) and multisensory therapies (n=25). Seven articles were published in the 1990’s, 55 in the 2000’s, and the remainder since 2010 (n=112). Discussion: Multisensory rooms have been present in the literature since the early 1990’s. However, more recently, nature/garden therapy, art therapy, and light therapy have emerged since 2008 in the literature, an indication of the increasingly diverse scholarship in the area. The least popular type of intervention is a traditional food intervention. Taste as a sensory intervention is generally avoided for safety reasons, however it shows potential for increasing quality of life. Agitation, behavior, and mood are common outcomes for all sensory interventions. However, light therapy commonly targets sleep. The majority (n=110) of studies have very small sample sizes (n=20 or less), an indicator of the lack of robust data in the field. Additional small-scale studies of the known sensory interventions will likely do little to advance the field. However, there is a need for multi-armed studies which directly compare sensory interventions, and more studies which investigate the use of layering sensory interventions (for example, adding an aromatherapy component to a lighting intervention). In addition, large scale studies which enroll people at early stages of dementia will help us better understand the potential of sensory and multisensory interventions to slow the progression of the disease.Keywords: sensory interventions, dementia, scoping review
Procedia PDF Downloads 1375186 The Effect of Traffic Load on the Maximum Response of a Cable-Stayed Bridge under Blast Loads
Authors: S. K. Hashemi, M. A. Bradford, H. R. Valipour
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The Recent collapse of bridges has raised the awareness about safety and robustness of bridges subjected to extreme loading scenarios such as intentional/unintentional blast loads. The air blast generated by the explosion of bombs or fuel tankers leads to high-magnitude short-duration loading scenarios that can cause severe structural damage and loss of critical structural members. Hence, more attentions need to put towards bridge structures to develop guidelines to increase the resistance of such structures against the probable blast. Recent advancements in numerical methods have brought about the viable and cost effective facilities to simulate complicated blast scenarios and subsequently provide useful reference for safeguarding design of critical infrastructures. In the previous studies common bridge responses to blast load, the traffic load is sometimes not included in the analysis. Including traffic load will increase the axial compression in bridge piers especially when the axial load is relatively small. Traffic load also can reduce the uplift of girders and deck when the bridge experiences under deck explosion. For more complicated structures like cable-stayed or suspension bridges, however, the effect of traffic loads can be completely different. The tension in the cables increase and progressive collapse is likely to happen while traffic loads exist. Accordingly, this study is an attempt to simulate the effect of traffic load cases on the maximum local and global response of an entire cable-stayed bridge subjected to blast loadings using LS-DYNA explicit finite element code. The blast loads ranged from small to large explosion placed at different positions above the deck. Furthermore, the variation of the traffic load factor in the load combination and its effect on the dynamic response of the bridge under blast load is investigated.Keywords: blast, cable-stayed bridge, LS-DYNA, numerical, traffic load
Procedia PDF Downloads 3345185 A Technical-Economical Study of a New Solar Tray Distillator
Authors: Abderrahmane Diaf, Assia Cherfa, Lamia Karadaniz
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Multiple tray solar distillation offers an interesting alternative for small-scale desalination and production high quality distilled water at a competitive cost using solar energy. In this work, we present indoor/outdoor trial performance data of our multiple tray solar distillation as well as the results of cost estimation analysis.Keywords: solar desalination, tray distillation, multi-étages solaire, solar distillation
Procedia PDF Downloads 4275184 Dynamics of Soil Fertility Management in India: An Empirical Analysis
Authors: B. Suresh Reddy
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The over dependence on chemical fertilizers for nutrient management in crop production for the last few decades has led to several problems affecting soil health, environment and farmers themselves. Based on the field work done in 2012-13 with 1080 farmers of different size-classes in semi-arid regions of Uttar Pradesh, Jharkhand and Madhya Pradesh states of India, this paper reveals that the farmers in semi-arid regions of India are actively managing soil fertility and other soil properties through a wide range of practices that are based on local resources and knowledge. It also highlights the socio-economic web woven around these soil fertility management practices. This study highlights the contribution of organic matter by traditional soil fertility management practices in maintaining the soil health. Livestock has profound influence on the soil fertility enhancement through supply of organic manure. Empirical data of this study has clearly revealed how farmers’ soil fertility management options are being undermined by government policies that give more priority to chemical fertiliser-based strategies. Based on the findings it is argued that there should be a 'level playing field' for both organic and inorganic soil fertility management methods by promoting and supporting farmers in using organic methods. There is a need to provide credit to farmers for adopting his choice of soil fertility management methods which suits his socio-economic conditions and that best suits the long term productivity of soils. The study suggests that the government policies related to soil fertility management must be enabling, creating the conditions for development based more on locally available resources and local skills and knowledge. This will not only keep Indian soils in healthy condition but also support the livelihoods of millions of people, especially the small and marginal farmers.Keywords: livestock, organic matter, small farmers, soil fertility
Procedia PDF Downloads 1765183 Economic Assessment of the Fish Solar Tent Dryers
Authors: Collen Kawiya
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In an effort of reducing post-harvest losses and improving the supply of quality fish products in Malawi, the fish solar tent dryers have been designed in the southern part of Lake Malawi for processing small fish species under the project of Cultivate Africa’s Future (CultiAF). This study was done to promote the adoption of the fish solar tent dryers by the many small scale fish processors in Malawi through the assessment of the economic viability of these dryers. With the use of the project’s baseline survey data, a business model for a constructed ‘ready for use’ solar tent dryer was developed where investment appraisal techniques were calculated in addition with the sensitivity analysis. The study also conducted a risk analysis through the use of the Monte Carlo simulation technique and a probabilistic net present value was found. The investment appraisal results showed that the net present value was US$8,756.85, the internal rate of return was 62% higher than the 16.32% cost of capital and the payback period was 1.64 years. The sensitivity analysis results showed that only two input variables influenced the fish solar dryer investment’s net present value. These are the dried fish selling prices that were correlating positively with the net present value and the fresh fish buying prices that were negatively correlating with the net present value. Risk analysis results showed that the chances that fish processors will make a loss from this type of investment are 17.56%. It was also observed that there exist only a 0.20 probability of experiencing a negative net present value from this type of investment. Lastly, the study found that the net present value of the fish solar tent dryer’s investment is still robust in spite of any changes in the levels of investors risk preferences. With these results, it is concluded that the fish solar tent dryers in Malawi are an economically viable investment because they are able to improve the returns in the fish processing activity. As such, fish processors need to adopt them by investing their money to construct and use them.Keywords: investment appraisal, risk analysis, sensitivity analysis, solar tent drying
Procedia PDF Downloads 2815182 Non-Native and Invasive Fish Species in Poland
Authors: Tomasz Raczyński
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Non-native and invasive species negatively transform ecosystems. Non-native fish species can displace native fish species through competition, predation, disrupting spawning, transforming ecosystems, or transmitting parasites. This influence is more and more noticeable in Poland and in the world. From December 2014 to October 2020, did catch of fishes by electrofishing method carried on 416 sites in various parts of Poland. Research was conducted in both running and stagnant freshwaters with the predominance of running waters. Only sites where the presence of fish was found were analysed. The research covered a wide spectrum of waters from small mountain streams, through drainage ditches to the largest Polish river - the Vistula. Single sites covered oxbow lakes, small ponds and lakes. Electrofishing was associated with ichthyofauna inventories and was mainly aimed at detecting protected species of fish and lampreys or included in the annexes to the EU Habitats Directive (Council Directive 92/43/EEC on the Conservation of natural habitats and of wild fauna and flora). The results of these catches were analysed for alien and invasive fish species. The analysis of the catch structure shows that in 71 out of 416 research sites was found alien and invasive fish species, belonging to 9 taxa. According to the above, alien species of fish are present in 17% of the study sites. The most frequently observed species was the Prussian carp Carassius gibelio, which was recorded on 43 sites. Stone moroko Pseudorasbora parva was found on 24 sites. Chinese sleeper Perccottus glenii was found on 6 sites, and Bullhead Ameiurus sp. was also found on 6 sites. Western tubenose goby Proterorhinus semilunaris was found at 5 sites and Rainbow trout Oncorhynchus mykiss at 3 sites. Monkey goby Neogobius fluviatilis, Round goby Neogobius melanostomus and Eurasian carp Cyprinus carpio was recorded on 2 sites.Keywords: non-native species, invasive species, fish species, invasive fish species, native fish species
Procedia PDF Downloads 1125181 Lactobacillus rhamnosus GG Increases the Re-Epithelialization Rate of Model Wounds by Stimulating Keratinocyte Migration in Ex-Vivo
Authors: W. Mohammedsaeed, A. J. Mcbain, S. M. Cruickshank, C. A. O’Neill
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Many studies have demonstrated the importance of probiotics and their potential therapeutic effects within the gut. Recently, the possible therapeutic effects of probiotics in other tissues have also begun to be investigated. Comparatively few studies have evaluated the use of topical probiotics in relation to the skin. In this study, we have conducted preliminary investigations into whether a well-known probiotic, Lactobacillus rhamnosus GG (LGG), can increase the rate of re-epithelialization in a model wound. Full-thickness skin was obtained from individuals undergoing elective cosmetic surgery. This skin was wounded using excisional punch and cultured using a serum-free medium, either in the presence or absence of L. rhamnosus GG lysate. Histological staining of the sections was performed with Haematoxylin& Eosin E to quantify “epithelial tongue length”. This is the length of the new epithelial ‘tongue’ that grows and covers the exposed dermis at the inner wound edges. The length of the new epithelial ‘tongue’ was compared in untreated section and section treated with and L. rhamnosus GG made using108CFU/ml bacterial cells. L. rhamnosus GG lysate enhanced significantly the re-epithelialisation of treated wounds compared with that of untreated wounds (P=0.005, n=3). Tongue length, at day 1 was 7.55μm 0.15, at day 3 it was 18.5μm 0.25 and at day 7 was 22.9μm 0.35. These results can be compared with untreated cultures in which tongue length was 3.25μm 0.35, day 3 was 9.65μm 0.25 and day 7 was 13.5μm 0.15 post-wounding. In ex-vivo proliferation and migration cells were measured by determining the expression of nuclear proliferation marker Ki-67 and the expression of Phosphorylated cortactin respectively demonstrated that L. rhamnosus GG significantly increased NHEK proliferation and migration rates relative to controls. However, the dominant mechanism was migration because in ex-vivo skin treated with the L. rhamnosus GG up-regulated the gene expression of the chemokine receptor and ligands CXCR2 and CXCL2 comparing with controls (P=0.02, P=0.03 respectively, n=3). High levels of CXCL2/CXCL2 have already been implicated in multiple aspects of stimulation of wound healing through activation of keratinocyte migration. These data demonstrate that lysates from Lactobacillus rhamnosus GG increase re-epithelialization by stimulation of keratinocyte migration. The current study identifies the partial mechanism that contribute to stimulating the wound-healing process ex vivo in response to L. rhamnosus GG lysate is an increase in the production of CXCL2/ CXCR2 in ex vivo models. The use of probiotic lysates potentially offers new options to develop treatments that could improve wound healing.Keywords: Lactobacillus rhamnosus GG, wounds, migration, lysate
Procedia PDF Downloads 3295180 The Study of Heat and Mass Transfer for Ferrous Materials' Filtration Drying
Authors: Dmytro Symak
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Drying is a complex technologic, thermal and energy process. Energy cost of drying processes in many cases is the most costly stage of production, and can be over 50% of total costs. As we know, in Ukraine over 85% of Portland cement is produced moist, and the finished product energy costs make up to almost 60%. During the wet cement production, energy costs make up over 5500 kJ / kg of clinker, while during the dry only 3100 kJ / kg, that is, switching to a dry Portland cement will allow result into double cutting energy costs. Therefore, to study raw materials drying process in the manufacture of Portland cement is very actual task. The fine ferrous materials drying (small pyrites, red mud, clay Kyoko) is recommended to do by filtration method, that is one of the most intense. The essence of filtration method drying lies in heat agent filtering through a stationary layer of wet material, which is located on the perforated partition, in the "layer-dispersed material - perforated partition." For the optimum drying purposes, it is necessary to establish the dependence of pressure loss in the layer of dispersed material, and the values of heat and mass transfer, depending on the speed of the gas flow filtering. In our research, the experimentally determined pressure loss in the layer of dispersed material was generalized based on dimensionless complexes in the form and coefficients of heat exchange. We also determined the relation between the coefficients of mass and heat transfer. As a result of theoretic and experimental investigations, it was possible to develop a methodology for calculating the optimal parameters for the thermal agent and the main parameters for the filtration drying installation. The comparison of calculated by known operating expenses methods for the process of small pyrites drying in a rotating drum and filtration method shows to save up to 618 kWh per 1,000 kg of dry material and 700 kWh during filtration drying clay.Keywords: drying, cement, heat and mass transfer, filtration method
Procedia PDF Downloads 2625179 Effect of Climate Change on Aridity Index in South Bihar
Authors: Aayush Anant, Roshni Thendiyath
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Aridity impacts on agriculture, as well as ecological, human health, and economic activities. In the present study, the effect of climate change on aridity index has been analysed in South Bihar for the past 30 year period by five types of aridity indices as Lang AI, De-Martonne AI, Erinc AI, Pinna combinative AI and UNEP AI. For the study of aridity index, the analysis of rainfall and temperature is significant. Rainfall was analysed for 30 year period from data of 23 gridded stations in for the period 1991-2020. The results show that rainfall pattern was decreasing with respect to previous decades for majority of stations. Trend of maximum, minimum and mean annual temperature has been observed, which shows increasing trend. Structural breakpoint was observed for mean annual temperature data series in year 2004. In period 1991-2004 mean annual temperature was 25.25 ºC, and in period 2005-2020, mean annual temperature was 25.7 ºC. Average aridity index has been calculated by all the above mentioned methods for whole 30 period. Lang AI shows that eastern part of study area is Humid type, and rest all is semi arid. De-Martonne AI also reveals that east part is humid, but rest of the study area is moist sub humid. According to Erinc AI and Pinna, combinative AI shows that whole south Bihar is dry sub humid and semi dry, respectively. UNEP AI shows most of the part as sub humid, and very small part in west is semi arid, while small part of east is humid. Temporal distribution of all the aridity indices shows a decreasing trend. This indicates a decrease in the humid areas in south Bihar for the selected time period.Keywords: drought, aridity index, climate change, rainfall, temperature
Procedia PDF Downloads 845178 Adverse Curing Conditions and Performance of Concrete: Bangladesh Perspective
Authors: T. Manzur
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Concrete is the predominant construction material in Bangladesh. In large projects, stringent quality control procedures are usually followed under the supervision of experienced engineers and skilled labors. However, in the case of small projects and particularly at distant locations from major cities, proper quality control is often an issue. It has been found from experience that such quality related issues mainly arise from inappropriate proportioning of concrete mixes and improper curing conditions. In most cases external curing method is followed which requires supply of adequate quantity of water along with proper protection against evaporation. Often these conditions are found missing in the general construction sites and eventually lead to production of weaker concrete both in terms of strength and durability. In this study, an attempt has been made to investigate the performance of general concreting works of the country when subjected to several adverse curing conditions that are quite common in various small to medium construction sites. A total of six different types of adverse curing conditions were simulated in the laboratory and samples were kept under those conditions for several days. A set of samples was also submerged in normal curing condition having proper supply of curing water. Performance of concrete was evaluated in terms of compressive strength, tensile strength, chloride permeability and drying shrinkage. About 37% and 25% reduction in 28-day compressive and tensile strength were observed respectively, for samples subjected to most adverse curing condition as compared to the samples under normal curing conditions. Normal curing concrete exhibited moderate permeability (close to low permeability) whereas concrete under adverse curing conditions showed very high permeability values. Similar results were also obtained for shrinkage tests. This study, thus, will assist concerned engineers and supervisors to understand the importance of quality assurance during the curing period of concrete.Keywords: adverse, concrete, curing, compressive strength, drying shrinkage, permeability, tensile strength
Procedia PDF Downloads 2025177 Flow Field Optimization for Proton Exchange Membrane Fuel Cells
Authors: Xiao-Dong Wang, Wei-Mon Yan
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The flow field design in the bipolar plates affects the performance of the proton exchange membrane (PEM) fuel cell. This work adopted a combined optimization procedure, including a simplified conjugate-gradient method and a completely three-dimensional, two-phase, non-isothermal fuel cell model, to look for optimal flow field design for a single serpentine fuel cell of size 9×9 mm with five channels. For the direct solution, the two-fluid method was adopted to incorporate the heat effects using energy equations for entire cells. The model assumes that the system is steady; the inlet reactants are ideal gases; the flow is laminar; and the porous layers such as the diffusion layer, catalyst layer and PEM are isotropic. The model includes continuity, momentum and species equations for gaseous species, liquid water transport equations in the channels, gas diffusion layers, and catalyst layers, water transport equation in the membrane, electron and proton transport equations. The Bulter-Volumer equation was used to describe electrochemical reactions in the catalyst layers. The cell output power density Pcell is maximized subjected to an optimal set of channel heights, H1-H5, and channel widths, W2-W5. The basic case with all channel heights and widths set at 1 mm yields a Pcell=7260 Wm-2. The optimal design displays a tapered characteristic for channels 1, 3 and 4, and a diverging characteristic in height for channels 2 and 5, producing a Pcell=8894 Wm-2, about 22.5% increment. The reduced channel heights of channels 2-4 significantly increase the sub-rib convection and widths for effectively removing liquid water and oxygen transport in gas diffusion layer. The final diverging channel minimizes the leakage of fuel to outlet via sub-rib convection from channel 4 to channel 5. Near-optimal design without huge loss in cell performance but is easily manufactured is tested. The use of a straight, final channel of 0.1 mm height has led to 7.37% power loss, while the design with all channel widths to be 1 mm with optimal channel heights obtained above yields only 1.68% loss of current density. The presence of a final, diverging channel has greater impact on cell performance than the fine adjustment of channel width at the simulation conditions set herein studied.Keywords: optimization, flow field design, simplified conjugate-gradient method, serpentine flow field, sub-rib convection
Procedia PDF Downloads 2985176 Influence of Thermal Annealing on Phase Composition and Structure of Quartz-Sericite Minerale
Authors: Atabaev I. G., Fayziev Sh. A., Irmatova Sh. K.
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Raw materials with high content of Kalium oxide widely used in ceramic technology for prevention or decreasing of deformation of ceramic goods during drying process and under thermal annealing. Becouse to low melting temperature it is also used to decreasing of the temperature of thermal annealing during fabrication of ceramic goods [1,2]. So called “Porceline or China stones” - quartz-sericite (muscovite) minerals is also can be used for prevention of deformation as the content of Kalium oxide in muscovite is rather high (SiO2, + KAl2[AlSi3O10](OH)2). [3] . To estimation of possibility of use of this mineral for ceramic manufacture, in the presented article the influence of thermal processing on phase and a chemical content of this raw material is investigated. As well as to other ceramic raw materials (kaoline, white burning clays) the basic requirements of the industry to quality of "a porcelain stone» are following: small size of particles, relative high uniformity of disrtribution of components and phase, white color after burning, small content of colorant oxides or chromophores (Fe2O3, FeO, TiO2, etc) [4,5]. In the presented work natural minerale from the Boynaksay deposit (Uzbekistan) is investigated. The samples was mechanically polished for investigation by Scanning Electron Microscope. Powder with size of particle up to 63 μm was used to X-ray diffractometry and chemical analysis. The annealing of samples was performed at 900, 1120, 1350oC during 1 hour. Chemical composition of Boynaksay raw material according to chemical analysis presented in the table 1. For comparison the composition of raw materials from Russia and USA are also presented. In the Boynaksay quartz – sericite the average parity of quartz and sericite makes 55-60 and 30-35 % accordingly. The distribution of quartz and sericite phases in raw material was investigated using electron probe scanning electronic microscope «JEOL» JXA-8800R. In the figure 1 the scanning electron microscope (SEM) micrograps of the surface and the distributions of Al, Si and K atoms in the sample are presented. As it seen small granular, white and dense mineral includes quartz, sericite and small content of impurity minerals. Basically, crystals of quartz have the sizes from 80 up to 500 μm. Between quartz crystals the sericite inclusions having a tablet form with radiant structure are located. The size of sericite crystals is ~ 40-250 μm. Using data on interplanar distance [6,7] and ASTM Powder X-ray Diffraction Data it is shown that natural «a porcelain stone» quartz – sericite consists the quartz SiO2, sericite (muscovite type) KAl2[AlSi3O10](OH)2 and kaolinite Al203SiO22Н2О (See Figure 2 and Table 2). As it seen in the figure 3 and table 3a after annealing at 900oC the quartz – sericite contains quartz – SiO2 and muscovite - KAl2[AlSi3O10](OH)2, the peaks related with Kaolinite are absent. After annealing at 1120oC the full disintegration of muscovite and formation of mullite phase Al203 SiO2 is observed (the weak peaks of mullite appears in fig 3b and table 3b). After annealing at 1350oC the samples contains crystal phase of quartz and mullite (figure 3c and table 3с). Well known Mullite gives to ceramics high density, abrasive and chemical stability. Thus the obtained experimental data on formation of various phases during thermal annealing can be used for development of fabrication technology of advanced materials. Conclusion: The influence of thermal annealing in the interval 900-1350oC on phase composition and structure of quartz-sericite minerale is investigated. It is shown that during annealing the phase content of raw material is changed. After annealing at 1350oC the samples contains crystal phase of quartz and mullite (which gives gives to ceramics high density, abrasive and chemical stability).Keywords: quartz-sericite, kaolinite, mullite, thermal processing
Procedia PDF Downloads 4155175 Using of Bimolecular Fluorescence Complementation (BiFC) Assays to Study Homo and/ or Heterodimerization of Laminin Receptor 37 LRP/ 67 LR with Galectin-3
Authors: Fulwah Alqahtani, Jafar Mahdavi, Lee Weldon, Nick Holliday, Dlawer Ala'Aldeen
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There are two isoforms of laminin receptor; monomeric 37 kDa laminin receptor precursor (37 LRP) and mature 67 kDa laminin receptor (67 LR). The relationship between the 67 LR and its precursor 37 LRP is not completely understood, but previous observations have suggested that 37 LRP can undergo homo- and/or hetero- dimerization with Galectin-3 (Gal-3) to form mature 67 LR. Gal-3 is the only member of the chimera-type group of galectins, and has one C-terminal carbohydrate recognition domain (CRD) that is responsible for binding the ß-galactoside moieties of mono- or oligosaccharides on several host and microbial molecules. The aim of this work was to investigate homo- and hetero-dimerization among the 37 LRP and Gal-3 to form mature 67 LR in mammalian cells using bimolecular fluorescence complementation (BiFC).Keywords: 37 LRP, 67 LR, Gal-3, BiFC
Procedia PDF Downloads 5065174 Multiple Organ Manifestation in Neonatal Lupus Erythematous: Report of Two Cases
Authors: A. Lubis, R. Widayanti, Z. Hikmah, A. Endaryanto, A. Harsono, A. Harianto, R. Etika, D. K. Handayani, M. Sampurna
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Neonatal lupus erythematous (NLE) is a rare disease marked by clinical characteristic and specific maternal autoantibody. Many cutaneous, cardiac, liver, and hematological manifestations could happen with affect of one organ or multiple. In this case, both babies were premature, low birth weight (LBW), small for gestational age (SGA) and born through caesarean section from a systemic lupus erythematous (SLE) mother. In the first case, we found a baby girl with dyspnea and grunting. Chest X ray showed respiratory distress syndrome (RDS) great I and echocardiography showed small atrial septal defect (ASD) and ventricular septal defect (VSD). She also developed anemia, thrombocytopenia, elevated C-reactive protein, hypoalbuminemia, increasing coagulation factors, hyperbilirubinemia, and positive blood culture of Klebsiella pneumonia. Anti-Ro/SSA and Anti-nRNP/sm were positive. Intravenous fluid, antibiotic, transfusion of blood, thrombocyte concentrate, and fresh frozen plasma were given. The second baby, male presented with necrotic tissue on the left ear and skin rashes, erythematous macula, athropic scarring, hyperpigmentation on all of his body with various size and facial haemorrhage. He also suffered from thrombocytopenia, mild elevated transaminase enzyme, hyperbilirubinemia, anti-Ro/SSA was positive. Intravenous fluid, methyprednisolone, intravenous immunoglobulin (IVIG), blood, and thrombocyte concentrate transfution were given. Two cases of neonatal lupus erythematous had been presented. Diagnosis based on clinical presentation and maternal auto antibody on neonate. Organ involvement in NLE can occur as single or multiple manifestations.Keywords: neonatus lupus erythematous, maternal autoantibody, clinical characteristic, multiple organ manifestation
Procedia PDF Downloads 4245173 Aspirin Loaded Poly-L-Lactic Acid Nanofibers and Their Potentials as Small Diameter Vascular Grafts
Authors: Mahboubeh Kabiri, Saba Aslani
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Among various approaches used for the treatment of cardiovascular diseases, the occlusion of the small-diameter vascular graft (SDVG) is still an unresolved problem which seeks further research to address them. Though autografts are now the gold standards to be replaced for blocked coronary arteries, they suffer from inadequate quality and quantity. On the other hand, the major problems of the tissue engineered grafts are thrombosis and intimal hyperplasia. Provision of a suitable spatiotemporal release pattern of anticoagulant agents such as heparin and aspirin can be a step forward to overcome such issues . Herein, we fabricated electrospun scaffolds from FDA (Food and Drug Administration) approved poly-L-lactic acid (PLLA) with aspirin loaded into the nanofibers. Also, we surface coated the scaffolds with Amniotic Membrane lysate as a source for natural elastic polymers and a mimic of endothelial basement membrane. The scaffolds were characterized thoroughly structurally and mechanically for their morphology, fiber orientation, tensile strength, hydrophilicity, cytotoxicity, aspirin release and cell attachment support. According to the scanning electron microscopy (SEM) images, the size of fibers ranged from 250 to 500 nm. The scaffolds showed appropriate tensile strength expected for vascular grafts. Cellular attachment, growth, and infiltration were proved using SEM and MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. Drug-loaded scaffolds showed a sustained release profile of aspirin in 7 days. An enhanced cytocompatibility was observed in AM-coated electrospun PLLA fibers compared to uncoated scaffolds. Our results together indicated that AM lysate coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.Keywords: vascular tissue engineering, vascular grafts, anticoagulant agent, aspirin, amniotic membrane
Procedia PDF Downloads 1665172 Legal Problems with the Thai Political Party Establishment
Authors: Paiboon Chuwatthanakij
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Each of the countries around the world has different ways of management and many of them depend on people to administrate their country. Thailand, for example, empowers the sovereignty of Thai people under constitution; however, our Thai voting system is not able to flow fast enough under the current Political management system. The sovereignty of Thai people is addressing this problem through representatives during current elections, in order to set a new policy for the countries ideology to change in the House and the Cabinet. This is particularly important in a democracy to be developed under our current political institution. The Organic Act on Political Parties 2007 is the establishment we have today that is causing confrontations within the establishment. There are many political parties that will soon be abolished. Many political parties have already been subsidized. This research study is to analyze the legal problems with the political party establishment under the Organic Act on Political Parties 2007. This will focus on the freedom of each political establishment compared to an effective political operation. Textbooks and academic papers will be referenced from studies home and abroad. The study revealed that Organic Act on Political Parties 2007 has strict provisions on the political structure over the number of members and the number of branches involved within political parties system. Such operations shall be completed within one year; but under the existing laws the small parties are not able to participate with the bigger parties. The cities are capable of fulfilling small political party requirements but fail to become coalesced because the current laws won't allow them to be united as one. It is important to allow all independent political parties to join our current political structure. Board members can’t help the smaller parties to become a large organization under the existing Thai laws. Creating a new establishment that functions efficiently throughout all branches would be one solution to these legal problems between all political parties. With this new operation, individual political parties can participate with the bigger parties during elections. Until current political institutions change their system to accommodate public opinion, these current Thai laws will continue to be a problem with all political parties in Thailand.Keywords: coalesced, political party, sovereignty, elections
Procedia PDF Downloads 3175171 Biohydrogen and Potential Vinegar Production from Agricultural Wastes Using Thermotoga neopolitana
Authors: Nidhi Nalin
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This study is theoretical modelling of the fermentation process of glucose in agricultural wastes like discarded peaches to produce hydrogen, acetic acid, and carbon dioxide using Thermotoga neopolitana bacteria. The hydrogen gas produced in this process can be used in hydrogen fuel cells to generate power, and the fermented broth with acetic acid and salts could be utilized as salty vinegar if enough acetic acid is produced. The theoretical modelling was done using SuperPro software, and the results indicated how much sugar (discarded peaches) is required to produce both hydrogen and vinegar for the process to be profitable.Keywords: fermentation, thermotoga, hydrogen, vinegar, biofuel
Procedia PDF Downloads 1575170 Chloride Ion Channels Play a Role in Mediating Immune Response during Pseudomonas aeruginosa Infection
Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo
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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa
Procedia PDF Downloads 1785169 Oxidation Behavior of Ferritic Stainless Steel Interconnects Modified Using Nanoparticles of Rare-Earth Elements under Operating Conditions Specific to Solid Oxide Electrolyzer Cells
Authors: Łukasz Mazur, Kamil Domaradzki, Bartosz Kamecki, Justyna Ignaczak, Sebastian Molin, Aleksander Gil, Tomasz Brylewski
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The rising global power consumption necessitates the development of new energy storage solutions. Prospective technologies include solid oxide electrolyzer cells (SOECs), which convert surplus electrical energy into hydrogen. An electrolyzer cell consists of a porous anode, and cathode, and a dense electrolyte. Power output is increased by connecting cells into stacks using interconnects. Interconnects are currently made from high-chromium ferritic steels – for example, Crofer 22 APU – which exhibit high oxidation resistance and a thermal expansion coefficient that is similar to that of electrode materials. These materials have one disadvantage – their area-specific resistance (ASR) gradually increases due to the formation of a Cr₂O₃ scale on their surface as a result of oxidation. The chromia in the scale also reacts with the water vapor present in the reaction media, forming volatile chromium oxyhydroxides, which in turn react with electrode materials and cause their deterioration. The electrochemical efficiency of SOECs thus decreases. To mitigate this, the interconnect surface can be modified with protective-conducting coatings of spinel or other materials. The high prices of SOEC components -especially the Crofer 22 APU- have prevented their widespread adoption. More inexpensive counterparts, therefore, need to be found, and their properties need to be enhanced to make them viable. Candidates include the Nirosta 4016/1,4016 low-chromium ferritic steel with a chromium content of just 16.3 wt%. This steel's resistance to high-temperature oxidation was improved by depositing Gd₂O₃ nanoparticles on its surface via either dip coating or electrolysis. Modification with CeO₂ or Ce₀.₉Y₀.₁O₂ nanoparticles deposited by means of spray pyrolysis was also tested. These methods were selected because of their low cost and simplicity of application. The aim of this study was to investigate the oxidation kinetics of Nirosta 4016/1,4016 modified using the afore-mentioned methods and to subsequently measure the obtained samples' ASR. The samples were oxidized for 100 h in the air as well as air/H₂O and Ar/H₂/H₂O mixtures at 1073 K. Such conditions reflect those found in the anode and cathode operating space during real-life use of SOECs. Phase and chemical composition and the microstructure of oxidation products were determined using XRD and SEM-EDS. ASR was measured over the range of 623-1073 K using a four-point, two-probe DC technique. The results indicate that the applied nanoparticles improve the oxidation resistance and electrical properties of the studied layered systems. The properties of individual systems varied significantly depending on the applied reaction medium. Gd₂O₃ nanoparticles improved oxidation resistance to a greater degree than either CeO₂ or Ce₀.₉Y₀.₁O₂ nanoparticles. On the other hand, the cerium-containing nanoparticles improved electrical properties regardless of the reaction medium. The ASR values of all surface-modified steel samples were below the 0.1 Ω.cm² threshold set for interconnect materials, which was exceeded in the case of the unmodified reference sample. It can be concluded that the applied modifications increased the oxidation resistance of Nirosta 4016/1.4016 to a level that allows its use as SOEC interconnect material. Acknowledgments: Funding of Research project supported by program "Excellence initiative – research university" for the AGH University of Krakow" is gratefully acknowledged (TB).Keywords: cerium oxide, ferritic stainless steel, gadolinium oxide, interconnect, SOEC
Procedia PDF Downloads 885168 Comparative Study of Two New Configurations of Solar Photovoltaic Thermal Collectors
Authors: K. Touafek, A. Khelifa, E. H. Khettaf, A. Embarek
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Hybrid photovoltaic thermal (PV/T) solar system comprises a solar collector which is disposed on photovoltaic solar cells. The disadvantage of a conventional photovoltaic cell is that its performance decreases as the temperature increases. Indeed, part of the solar radiation is converted into electricity and is dissipated as heat, increasing the temperature of the photovoltaic cell with respect to the ambient temperature. The objective of this work is to study experimentally and implement a hybrid prototype to evaluate electrical and thermal performance. In this paper, an experimental study of two new configurations of hybrid collectors is exposed. The results are given and interpreted. The two configurations of absorber studied are a new combination with tubes and galvanized tank, the other is a tubes and sheet.Keywords: experimental, photovoltaic, solar, temperature
Procedia PDF Downloads 4925167 Assessment of Waste Management Practices in Bahrain
Authors: T. Radu, R. Sreenivas, H. Albuflasa, A. Mustafa Khan, W. Aloqab
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The Kingdom of Bahrain, a small island country in the Gulf region, is experiencing fast economic growth resulting in a sharp increase in population and greater than ever amounts of waste being produced. However, waste management in the country is still very basic, with landfilling being the most popular option. Recycling is still a scarce practice, with small recycling businesses and initiatives emerging in recent years. This scenario is typical for other countries in the region, with similar amounts of per capita waste being produced. In this paper, we are reviewing current waste management practices in Bahrain by collecting data published by the Government and various authors, and by visiting the country’s only landfill site, Askar. In addition, we have performed a survey of the residents to learn more about the awareness and attitudes towards sustainable waste management strategies. A review of the available data on waste management indicates that the Askar landfill site is nearing its capacity. The site uses open tipping as the method of disposal. The highest percentage of disposed waste comes from the building sector (38.4%), followed by domestic (27.5%) and commercial waste (17.9%). Disposal monitoring and recording are often based on estimates of weight and without proper characterization/classification of received waste. Besides, there is a need for assessment of the environmental impact of the site with systematic monitoring of pollutants in the area and their potential spreading to the surrounding land, groundwater, and air. The results of the survey indicate low awareness of what happens with the collected waste in the country. However, the respondents have shown support for future waste reduction and recycling initiatives. This implies that the education of local communities would be very beneficial for such governmental initiatives, securing greater participation. Raising awareness of issues surrounding recycling and waste management and systematic effort to divert waste from landfills are the first steps towards securing sustainable waste management in the Kingdom of Bahrain.Keywords: landfill, municipal solid waste, survey, waste management
Procedia PDF Downloads 1625166 Sustainable Crop Mechanization among Small Scale Rural Farmers in Nigeria: The Hurdles
Authors: Charles Iledun Oyewole
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The daunting challenge that the ‘man with the hoe’ is going to face in the coming decades will be complex and interwoven. With global population already above 7 billion people, it has been estimated that food (crop) production must more than double by 2050 to meet up with the world’s food requirements. Nigeria population is also expected to reach over 240 million people by 2050, at the current annual population growth of 2.61 per cent. The country’s farming population is estimated at over 65 per cent, but the country still depends on food importation to complement production. The small scale farmer, who depends on simple hand tools: hoes and cutlasses, remains the centre of agricultural production, accounting for 90 per cent of the total agricultural output and 80 per cent of the market flow. While the hoe may have been a tool for sustainable development at a time in human history, this role has been smothered by population growth, which has brought too many mouths to be fed (over 170 million), as well as many industries to fuel with raw materials. It may then be argued that the hoe is unfortunately not a tool for the coming challenges and that agricultural mechanization should be the focus. However, agriculture as an enterprise is a ‘complete wheel’ which does not work when broken, particularly, in respect to mechanization. Generally, mechanization will prompt increase production, where land is readily available; increase production, will require post-harvest handling mechanisms, crop processing and subsequent storage. An important aspect of this is readily available and favourable markets for such produce; fuel by good agricultural policies. A break in this wheel will lead to the process of mechanization crashing back to subsistence production, and probably reversal to the hoe. The focus of any agricultural policy should be to chart a course for sustainable mechanization that is environmentally friendly, that may ameliorate Nigeria’s food and raw material gaps. This is the focal point of this article.Keywords: Crop production, Farmer, Hoes, Mechanization, Policy framework, Population, Growth, Rural areas
Procedia PDF Downloads 2275165 Associations between Physical Activity and Risk Factors for Type II Diabetes in Prediabetic Adults
Authors: Rukia Yosuf
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Diabetes is a national healthcare crisis related to both macrovascular and microvascular complications. We hypothesized that higher levels of physical activity are associated with lower total and visceral fat mass, lower systolic blood pressure, and increased insulin sensitivity. Participant inclusion criteria: 21-50 years old, BMI ≥ 30 kg/m2, hemoglobin A1C 5.7-6.4, fasting glucose 100-125 mg/dL, and HOMA IR ≥ 2.5. Exclusion criteria: history of diabetes, hypertension, HIV, renal disease, hearing loss, alcoholic intake over four drinks daily, use of organic nitrates or PDE5 inhibitors, and decreased cardiac function. Total physical activity was measured using accelerometers, body composition using DXA, and insulin resistance via fsIVGTT. Clinical and biochemical cardiometabolic risk factors, blood pressure and heart rate were obtained using a calibrated sphygmomanometer. Anthropometric measures, fasting glucose, insulin, lipid profile, C-reactive protein, and BMP were analyzed using standard procedures. Within our study, we found correlations between levels of physical activity in a heterogeneous group of prediabetic adults. Patients with more physical activity had a higher degree of insulin sensitivity, lower blood pressure, total visceral adipose tissue, and overall lower total mass. Total physical activity levels showed small, but significant correlations with systolic blood pressure, visceral fat, lean mass and insulin sensitivity. After normalizing for the race, age, and gender using multiple regression, these associations were no longer significant considering our small sample size. More research into prediabetes will decrease the population of diabetics overall. In the future, we could increase sample size and conduct cross sectional and longitudinal studies in various populations with prediabetes.Keywords: diabetes, kidney disease, nephrology, prediabetes
Procedia PDF Downloads 1885164 The Antagonistic/Synergistic Effect of Probiotic Yeast Saccharomyces boulardii on Candida glabrata Adhesion
Authors: Zorica Tomičić, Ružica Tomičić, Peter Raspor
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Growing resistance of pathogenic yeast Candida glabrata to many classes of antifungal drugs has stimulated efforts to discover new agents to combat a rising number of invasive C. glabrata infections, which deserves a great deal of concern due to the high mortality rate in immunocompromised populations. One promising strategy is the use of probiotic microorganisms, which, when administered in adequate amounts, confers a health benefit. A selected number of probiotic organisms, Saccharomyces boulardii among them, have been tested as potential biotherapeutic agents. The aim of this study was to investigate the effect of the probiotic yeast S. boulardii on the adhesion of clinical isolates of C. glabrata at different temperatures, pH values, and in the presence of three clinically important antifungal drugs, such as fluconazole, itraconazole and amphotericin B. The method used to assess adhesion was crystal violet staining. The selection of antimycotics concentrations used in the adhesion assay was based on minimum inhibitory concentrations (MICs) obtained by the preliminarily performed microdilution modification of the Reference method for broth dilution antifungal susceptibility testing of yeast (Clinical and Laboratory Standards Institute (CLSI), standard M27-A2). the results showed that despite the nonadhesiveness of S. boulardii cells, probiotic yeast significantly suppressed the adhesion of C. glabrata strains. Besides, at specific strain ratios, a slight stimulatory effect was observed in some C. glabrata strains, which highlights the importance of strain specificity and opens up further research interests. When environmental conditions are considered, temperature and pH significantly influenced co-culture adhesion of C. glabrata and S. boulardii. The adhesion of C. glabrata strains was relatively equally reduced over all tested temperature range (28°C, 37°C, 39°C and 42°C) in the presence of S. boulardii cells, while the adhesion of a few C. glabrata strains were significantly stimulated at 28°C and suppressed at 42°C. Further, the adhesion was highly dependent on pH, with the highest adherence at pH 4 and lowest at pH 8.5. It was observed that S. boulardii did not manage to suppress the adhesion of C. glabrata strains at high pH. Antimycotics on the other hand showed a greater impact, since S. boulardii failed to affect co-culture adhesion at higher antimycotics concentrations. As expected, exposure to various concentrations of amphotericin B significantly reduced the adherence ability of C.glabrata strains both in a single culture and co-culture with S. boulardii. Therefore, it can be speculated that S. boulardii could substitute the effect of antimycotics in a range concentrations and with specific type of strains. This would certainly change the view on the treatment of yeast infections in the future.Keywords: adhesion, antimycotics, candida glabrata, saccharomyces boulardii
Procedia PDF Downloads 685163 Robust Single/Multi bit Memristor Based Memory
Authors: Ahmed Emara, Maged Ghoneima, Mohamed Dessouky
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Demand for low power fast memories is increasing with the increase in IC’s complexity, in this paper we introduce a proposal for a compact SRAM based on memristor devices. The compact size of the proposed cell (1T2M compared to 6T of traditional SRAMs) allows denser memories on the same area. In this paper, we will discuss the proposed memristor memory cell for single/multi bit data storing configurations along with the writing and reading operations. Stored data stability across successive read operation will be illustrated, operational simulation results and a comparison of our proposed design with previously conventional SRAM and previously proposed memristor cells will be provided.Keywords: memristor, multi-bit, single-bit, circuits, systems
Procedia PDF Downloads 3745162 The Strategic Roles of Women in Small Family Businesses: Evidence from Two Emerging Economies in West Africa
Authors: Bamidele Wale-Oshinowo, Doris Akyere Boateng, Lebura Sorbarikor
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Women play significant roles when it comes to the survival of family businesses; however, their efforts are less acknowledged across the developing world. In the case where these businesses are started by husbands, women in many instances work as hard as the men to build up the business. In spite of this, the benefits women receive are not equal to their inputs. For instance, the profits accruing from ownership of these businesses are mainly enjoyed by husbands, as they are deemed to be the legal owners of family businesses in most developing economies. Though the number of women involvement in the ownership, management, and direction of family businesses keeps increasing over the years, their efforts sometimes are ‘invisible’ and not rewarded. Using a phenomenological approach, this study purposively selected 20 businesswomen each from Ghana and Nigeria for in-depth interviews on the different roles they play in ensuring the success of their family businesses (FBs). This study also explored the challenges and opportunities that these women have within their family businesses. Among the major findings of this study is the important strategic direction that women give in terms of providing both tangible and intangible resources such as transfer of transit knowledge to the next generation. Women were also found to play a significant role in the implementation of entrepreneurial orientation within small family businesses in Ghana and Nigeria. However, the study revealed that women experience various challenges as stakeholders in family businesses, among which are: work-life balance issues, succession issues, and culture-related presuppositions about gender roles both within the business and in their families. In the light of the study’s findings, critical recommendations made include encouraging founders and/or owners of family businesses to create a conducive and viable platform for women to grow into key leadership positions within Family businesses; doing this would impact strongly on the growth rate of these form of businesses within the African Region.Keywords: emerging economies, control, management, resources, strategy, women
Procedia PDF Downloads 3625161 Identification, Synthesis, and Biological Evaluation of the Major Human Metabolite of NLRP3 Inflammasome Inhibitor MCC950
Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson
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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3
Procedia PDF Downloads 2535160 Energy System Analysis Using Data-Driven Modelling and Bayesian Methods
Authors: Paul Rowley, Adam Thirkill, Nick Doylend, Philip Leicester, Becky Gough
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The dynamic performance of all energy generation technologies is impacted to varying degrees by the stochastic properties of the wider system within which the generation technology is located. This stochasticity can include the varying nature of ambient renewable energy resources such as wind or solar radiation, or unpredicted changes in energy demand which impact upon the operational behaviour of thermal generation technologies. An understanding of these stochastic impacts are especially important in contexts such as highly distributed (or embedded) generation, where an understanding of issues affecting the individual or aggregated performance of high numbers of relatively small generators is especially important, such as in ESCO projects. Probabilistic evaluation of monitored or simulated performance data is one technique which can provide an insight into the dynamic performance characteristics of generating systems, both in a prognostic sense (such as the prediction of future performance at the project’s design stage) as well as in a diagnostic sense (such as in the real-time analysis of underperforming systems). In this work, we describe the development, application and outcomes of a new approach to the acquisition of datasets suitable for use in the subsequent performance and impact analysis (including the use of Bayesian approaches) for a number of distributed generation technologies. The application of the approach is illustrated using a number of case studies involving domestic and small commercial scale photovoltaic, solar thermal and natural gas boiler installations, and the results as presented show that the methodology offers significant advantages in terms of plant efficiency prediction or diagnosis, along with allied environmental and social impacts such as greenhouse gas emission reduction or fuel affordability.Keywords: renewable energy, dynamic performance simulation, Bayesian analysis, distributed generation
Procedia PDF Downloads 4975159 Bio-Functional Polymeric Protein Based Materials Utilized for Soft Tissue Engineering Application
Authors: Er-Yuan Chuang
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Bio-mimetic matters have biological functionalities. This might be valuable in the development of versatile biomaterials. At biological fields, protein-based materials might be components to form a 3D network of extracellular biomolecules, containing growth factors. Also, the protein-based biomaterial provides biochemical and structural assistance of adjacent cells. In this study, we try to prepare protein based biomaterial, which was harvested from living animal. We analyzed it’s chemical, physical and biological property in vitro. Besides, in vivo bio-interaction of the prepared biomimetic matrix was tested in an animal model. The protein-based biomaterial has degradability and biocompatibility. This development could be used for tissue regenerations and be served as platform technologies.Keywords: protein based, in vitro study, in vivo study, biomaterials
Procedia PDF Downloads 190