Search results for: apoptosis induction
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 948

Search results for: apoptosis induction

288 Cytotoxicity of 13 South African Macrofungal Species and Mechanism/s of Action against Cancer Cell Lines

Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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287 Sports and Beauty: Translating the History of Aesthetics into Today’s World of Sports

Authors: Matthew McNees

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An inductive aesthetic approach to sports yields critical and meaningful insight into sports philosophy, sports governance, and sports history. Critical reflection will always remain key to the analysis of the past, present and future of sporting institutions, but a philosophically imaginative method of induction allows certain salient connections to be articulated and potentially implemented between various sporting entities who exist as individuals, particularly between practitioner, owner/manager and observer (‘fan’ or interested party.) By honing in on the concept of beauty in sports, the primary reason for viewership, consumption or engagement with sports comes into focus as an aesthetic concept. While always a subjective or shadowy articulation, an aesthetic state often remains unnecessarily unrevealed due to claims about unconscious states, entire rhetorics (or counter-rhetorics) about beauty, and Misalliance among sporting development systems. Since aesthetics require an inductive state of subjectivity in determining various levels of beauty (which the so-called world of sports often thinks of as morality), the audience for aesthetics in sports also needs an inductive explanation of the concept in which one comes to see a process of viewership at work within themselves that is revealed by a simple need parried outward by a complex process of engagement. The potentially redemptive moment of revelation regarding the beauty of sports and the athlete within these systems creates in the viewer a new space of consciousness where the world of sports discovers some of its longed-for transparency, openness, parity and equity upon which its immediate future depends.

Keywords: aesthetics, governance, history, philosophy

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286 Nasopharyngeal Cancer in Children and Adolescents: Experience of Emir Abdelkader Cancer Center of Oran Algeria

Authors: Taleb L., Benarbia M., Brahmi M., Belmiloud H., Boukerche A.

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Introduction and purpose of the study: Cavum cancer in children and adolescents is rare and represents 8% of all nasopharyngeal cancers treated in our department. Our objective is to study its epidemiological, clinical, therapeutic, and evolutionary particularities. Material and methods: Retrospective study of 39 patients under 20 years old, treated for undifferentiated non-metastatic carcinoma of the nasopharynx at the Emir Abdelkader Cancer Center between 2014 and 2020. Results and statistical analysis: Median age was 14 years [7-19 years], with a sex ratio of 2.9. The median time to diagnosis was 5.6 months [1 to 14 months], the circumstances of the discovery of which were dominated by lymph node syndrome in 43.6% of cases (n=17) followed by a rhinological syndrome in 30.8% of cases (n=13). The tumor stage was T1 for two patients (5.1%), T2 for 8 (20.5%), T3 for 9 (23.1%), T4 for 20 (51.3%), N0 for 2 (5 .1%) N1 for 4 (10.3%), N2 for 28 (71.8%) and N3 for 5 (12.8%). All patients received induction chemotherapy followed by concomitant radiotherapy with cisplatin. The dose of irradiation delivered to the cavum and adenopathies was 66 Gy with fractionation of 2 Gy per session in 69.2% of cases (n=27) and 1.8 Gy in 30.8% of cases (n=12). With a median follow-up of 51 months (15 to 97 months), the locoregional, metastatic, specific, and overall relapse-free survival rates at five years were 91.1%, 73.5%, 66.1%, and 68.4, respectively. Conclusion: Chemotherapy and radiotherapy treatment of cavum cancer in children and adolescents has allowed excellent locoregional control despite the advanced stage of the disease. However, the frequency of metastatic relapses could justify the possible use of systemic maintenance treatment.

Keywords: cancer, nasopharynx, radiotherapy, chemotherapy, survival

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285 The Effect of Different Exercise Intensities on Plasma Endostatin in Healthy Volunteers

Authors: Inayat Shah, Muhammad Omar Malik, Ghareeb Alshuwaier, Ronald H. Baxendale

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Background: The balance between angiogenesis and angiostasis is important in growth and developmental processes in the body. Angiogenic and angiostatic mediators control this balance. Endostatin is one of the prominent angiostatic mediators. The marked angiostatic effect of endostatin includes inhibiting endothelial cell migration, proliferation and apoptosis. Physical activity decreases the risk and development of many angiogenesis related health problems including atherosclerosis and numerous cancers. Physiological influences of different physical activities on plasma endostatin concentration are controversial and not completely clear. Moreover, correlation of physical characteristics and metabolic predictors during physical activity on circulating endostatin is indistinct and poorly speculated. The study aimed to determine the effects of mild, moderate and vigorous exercise on the concentration of endostatin in plasma. Methodology: 22 participants, 16 males (age = 30.6 ± 7.8 years) and 6 females (age = 26.5 ± 5 years) were recruited. Weekly session of different intensities exercise based on the predicted maximum heart of the participants [60%(low), 70% (moderate) and 80% (vigorous)] were carried out. The duration and work rate for each participant was determined through sub-maximal exercise. Standardization of the session was done on total energy expenditure of the participants per session. One pre exercise and two post exercise samples were taken at intervals of 10 and 60 minutes. Results: Pre-exercise mean endostatin was 101 ± 20 ng/dl. Low intensity exercise insignificantly decreased the endostatin concentration in plasma at 10 and 60 minutes 97 ± 20 ng/dl (p= 0.5), 98 ± 23 ng/dl (p= 0.8)). However, moderate (p= 0.022, 0.004) and vigorous intensities (p ≤ 0.001, 0.02) increased the endostatin concentrations significantly at both 10 and 60 minutes intervals respectively. The effects were not significantly influenced by gender, exercise mode (walking vs. running), components of exercise (HR, Speed, Gradients, distance, duration) or metabolism during exercise (VO₂ max, VCO₂, RER, energy expenditure, rate of carbohydrate or fats oxidation). Conclusion: Low intensity exercises did not influence endostatin concentration. However, moderate to high intensity exercises significantly increase endostatin concentration and may have potential benefits.

Keywords: angiogenesis, exercise, endostatin, physical activity

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284 Evaluation of the Spatial Regulation of Hydrogen Sulphide Producing Enzymes in the Placenta during Labour

Authors: F. Saleh, F. Lyall, A. Abdulsid, L. Marks

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Background: Labour in human is a complex biological process that involves interactions of neurological, hormonal and inflammatory pathways, with the placenta being a key regulator of these pathways. It is known that uterine contractions and labour pain cause physiological changes in gene expression in maternal and fetal blood, and in placenta during labour. Oxidative and inflammatory stress pathways are implicated in labour and they may cause alteration of placental gene expression. Additionally, in placental tissues, labour increases the expression of genes involved in placental oxidative stress, inflammatory cytokines, angiogenic regulators and apoptosis. Recently, Hydrogen Sulphide (H2S) has been considered as an endogenous gaseous mediator which promotes vasodilation and exhibits cytoprotective anti-inflammatory properties. The endogenous H2S is synthesised predominantly by two enzymes: cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). As the H2S pathway has anti-oxidative and anti-inflammatory characteristics thus, we hypothesised that the expression of CBS and CSE in placental tissues would alter during labour. Methods: CBS and CSE expressions were examined in placentas using western blotting and RT-PCR in inner, middle and outer placental zones in placentas obtained from healthy non labouring women who delivered by caesarian section. These were compared with the equivalent zone of placentas obtained from women who had uncomplicated labour and delivered vaginally. Results: No differences in CBS and CSE mRNA or protein levels were found between the different sites within placentas in either the labour or non-labour group. There were no significant differences in either CBS or CSE expression between the two groups at the inner site and middle site. However, at the outer site there was a highly significant decrease in CBS protein expression in the labour group when compared to the non-labour group (p = 0.002). Conclusion: To the best of author’s knowledge, this is the first report to suggest that, CBS is expressed in a spatial manner within the human placenta. Further work is needed to clarify the precise function and mechanism of this spatial regulation although it is likely that inflammatory pathways regulation is a complex process in which this plays a role.

Keywords: anti-inflammatory, hydrogen sulphide, labour, oxidative stress

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283 Analysis of Osmotin as Transcription Factor/Cell Signaling Modulator Using Bioinformatic Tools

Authors: Usha Kiran, M. Z. Abdin

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Osmotin is an abundant cationic multifunctional protein discovered in cells of tobacco (Nicotiana tabacum L. var Wisconsin 38) adapted to an environment of low osmotic potential. It provides plants protection from pathogens, hence placed in the PRP family of proteins. The osmotin induced proline accumulation has been reported in plants including transgenic tomato and strawberry conferring tolerance against both biotic and abiotic stresses. The exact mechanism of induction of proline by osmotin is however, not known till date. These observations have led us to hypothesize that osmotin induced proline accumulation could be due to its involvement as transcription factor and/or cell signal pathway modulator in proline biosynthesis. The present investigation was therefore, undertaken to analyze the osmotin protein as transcription factor /cell signalling modulator using bioinformatics tools. The results of available online DNA binding motif search programs revealed that osmotin does not contain DNA-binding motifs. The alignment results of osmotin protein with the protein sequence from DATF showed the homology in the range of 0-20%, suggesting that it might not contain a DNA binding motif. Further to find unique DNA-binding domain, the superimposition of osmotin 3D structure on modeled Arabidopsis transcription factors using Chimera also suggested absence of the same. We, however, found evidence implicating osmotin in cell signaling. With these results, we concluded that osmotin is not a transcription factor but regulating proline biosynthesis and accumulation through cell signaling during abiotic stresses.

Keywords: osmotin, cell signaling modulator, bioinformatic tools, protein

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282 Upconversion Nanoparticle-Mediated Carbon Monoxide Prodrug Delivery System for Cancer Therapy

Authors: Yaw Opoku-Damoah, Run Zhang, Hang Thu Ta, Zhi Ping Xu

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Gas therapy is still at an early stage of research and development. Even though most gasotransmitters have proven their therapeutic potential, their handling, delivery, and controlled release have been extremely challenging. This research work employs a versatile nanosystem that is capable of delivering a gasotransmitter in the form of a photo-responsive carbon monoxide-releasing molecule (CORM) for targeted cancer therapy. The therapeutic action was mediated by upconversion nanoparticles (UCNPs) designed to transfer bio-friendly low energy near-infrared (NIR) light to ultraviolet (UV) light capable of triggering carbon monoxide (CO) from a water-soluble amphiphilic manganese carbonyl complex CORM incorporated into a carefully designed lipid drug delivery system. Herein, gaseous CO that plays a role as a gasotransmitter with cytotoxic and homeostatic properties was investigated to instigate cellular apoptosis. After successfully synthesizing the drug delivery system, the ability of the system to encapsulate and mediate the sustained release of CO after light excitation was demonstrated. CO fluorescence probe (COFP) was successfully employed to determine the in vitro drug release profile upon NIR light irradiation. The uptake of nanoparticles enhanced by folates and its receptor interaction was also studied for cellular uptake purposes. The anticancer potential of the final lipid nanoparticle Lipid/UCNPs/CORM/FA (LUCF) was also determined by cell viability assay. Intracellular CO release and a subsequent therapeutic action involving ROS production, mitochondrial damage, and CO production was also evaluated. In all, this current project aims to use in vitro studies to determine the potency and efficiency of a NIR-mediated CORM prodrug delivery system.

Keywords: carbon monoxide-releasing molecule, upconversion nanoparticles, site-specific delivery, amphiphilic manganese carbonyl complex, prodrug delivery system.

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281 Challenges and Prospects of Digital Economy Development in Georgia

Authors: Gulnaz Erkomaishvili

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Introduction: There are some of the biggest technological shifts happening in the modern world. The introduction of digital technologies, information, and communication services has given rise to unprecedented global socio-political and economic changes. The role of digital technologies in increasing productivity and national competitiveness is increasing. Today, it is used in almost every area of the economy. E-commerce, organizational process in computerized management, and digital infrastructure's pace of growth is remarkably high and is a key instrument of economic development. Methodology: Different research methods are applied in the presented paper; statistical, analysis, synthesis, induction, deduction, comparison ones. Works by local and foreign scientists, Ministry of Economy and Sustainable Development, as well as various organizations' studies and reports were used as a theoretical basis for research and variety of laws, government decrees and orders, and the publications of the National Statistics Office of Georgia were used as an informational basis. Conclusions: The paper deals with the processes and challenges in Georgia in the digital economy. Access to current resources in Georgia and current processes are described. Digital technology for the development of the required environmental conditions is described, how the Internet and communications are available for the population in the regions of Georgia. The pros and cons of the digital economy development and its impact on the country's economy are analyzed. The main difficulties of implementation of the digital economy in Georgia, government involvement, and future action plans are presented.

Keywords: digital economy, digital technologies, internet, communications, economic policy

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280 Autophagy Suppresses Bladder Tumor Formation in a Mouse Orthotopic Bladder Tumor Formation Model

Authors: Wan-Ting Kuo, Yi-Wen Liu, Hsiao-Sheng Liu

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Annual incidence of bladder cancer increases in the world and occurs frequently in the male. Most common type is transitional cell carcinoma (TCC) which is treated by transurethral resection followed by intravesical administration of agents. In clinical treatment of bladder cancer, chemotherapeutic drugs-induced apoptosis is always used in patients. However, cancers usually develop resistance to chemotherapeutic drugs and often lead to aggressive tumors with worse clinical outcomes. Approximate 70% TCC recurs and 30% recurrent tumors progress to high-grade invasive tumors, indicating that new therapeutic agents are urgently needed to improve the successful rate of overall treatment. Nonapoptotic program cell death may assist to overcome worse clinical outcomes. Autophagy which is one of the nonapoptotic pathways provides another option for bladder cancer patients. Autophagy is reported as a potent anticancer therapy in some cancers. First of all, we established a mouse orthotopic bladder tumor formation model in order to create a similar tumor microenvironment. IVIS system and micro-ultrasound were utilized to noninvasively monitor tumor formation. In addition, we carried out intravesical treatment in our animal model to be consistent with human clinical treatment. In our study, we carried out intravesical instillation of the autophagy inducer in mouse orthotopic bladder tumor to observe tumor formation by noninvasive IVIS system and micro-ultrasound. Our results showed that bladder tumor formation is suppressed by the autophagy inducer, and there are no significant side effects in the physiology of mice. Furthermore, the autophagy inducer upregulated autophagy in bladder tissues of the treated mice was confirmed by Western blot, immunohistochemistry, and immunofluorescence. In conclusion, we reveal that a novel autophagy inducer with low side effects suppresses bladder tumor formation in our mouse orthotopic bladder tumor model, and it provides another therapeutic approach in bladder cancer patients.

Keywords: bladder cancer, transitional cell carcinoma, orthotopic bladder tumor formation model, autophagy

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279 Nurses' Knowledge and Attitudes toward the Use of Physical Restraints

Authors: Fatema Salman, Ridha Hammam, Fatima Khairallah, Fatima Aradi, Nafeesa Abdulla, Mohammed Alsafar

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Purpose: This study aims at measuring the extent of nurses’ knowledge and attitudes toward the use of physical restraints in different hospital wards at Salmaniya Medical Complex (SMC). Background: The habitual use of physical restraint is a widespread practice among nurses working in the clinical settings. Restraints inflict many deleterious consequences on patients physically and psychologically which in turn increases their morbidity and mortality risk and jeopardizes care quality. Nurses’ knowledge and attitudes toward physical restraints are crucial determinants of the persistence of this practice. Literature review: the evidence of lack of knowledge among nurses regarding the use of physical restraints is overwhelming in various clinical settings, especially in two main areas which are the negative consequences and the available alternatives to physical restraints. Studies explored nurses’ attitudes toward physical restraints yielded inconsistent findings. Equally comparable, some studies found that nurses hold positive attitudes toward the use of physical restraints while some others reported just the opposite. Methods: Self-administered knowledge and attitudes scales to 106 nurses working in the SMC. Findings: nurses hold the moderate level of knowledge about restraints (M=58%) with weak negative attitudes (M = -20%) toward using it. Significant moderately-strong negative correlation (r= -0.57, r2= 0.32, p= 0.000) was uncovered between nurses knowledge and their attitudes which provided an empirical explanation of this phenomenon (use of physical restraints). Recommendations: Induction of awareness program that especially focuses on the negative consequences and encourages the use of alternatives is an evident need. This effort necessarily should be adjoined with policy and procedure adjustments.

Keywords: attitudes, knowledge, nurses, restraints

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278 Improvement of Microstructure, Wear and Mechanical Properties of Modified G38NiCrMo8-4-4 Steel Used in Mining Industry

Authors: Mustafa Col, Funda Gul Koc, Merve Yangaz, Eylem Subasi, Can Akbasoglu

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G38NiCrMo8-4-4 steel is widely used in mining industries, machine parts, gears due to its high strength and toughness properties. In this study, microstructure, wear and mechanical properties of G38NiCrMo8-4-4 steel modified with boron used in the mining industry were investigated. For this purpose, cast materials were alloyed by melting in an induction furnace to include boron with the rates of 0 ppm, 15 ppm, and 50 ppm (wt.) and were formed in the dimensions of 150x200x150 mm by casting into the sand mould. Homogenization heat treatment was applied to the specimens at 1150˚C for 7 hours. Then all specimens were austenitized at 930˚C for 1 hour, quenched in the polymer solution and tempered at 650˚C for 1 hour. Microstructures of the specimens were investigated by using light microscope and SEM to determine the effect of boron and heat treatment conditions. Changes in microstructure properties and material hardness were obtained due to increasing boron content and heat treatment conditions after microstructure investigations and hardness tests. Wear tests were carried out using a pin-on-disc tribometer under dry sliding conditions. Charpy V notch impact test was performed to determine the toughness properties of the specimens. Fracture and worn surfaces were investigated with scanning electron microscope (SEM). The results show that boron element has a positive effect on the hardness and wear properties of G38NiCrMo8-4-4 steel.

Keywords: G38NiCrMo8-4-4 steel, boron, heat treatment, microstructure, wear, mechanical properties

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277 Esophageal Premalignant and Malignant Epithelial Lesions: Pathological Characteristics and Value of Cyclooxygenase-2 Expression.

Authors: Hanan Mohamed Abd Elmoneim, Rawan Saleh AlJawi, Razan Saleh AlJawi, Aseel Abdullah AlMasoudi , Zyad Adnan Turkistani, Anas Abdulkarim Alkhoutani , Ohood Musaed AlJuhani , Hanan Attiyah AlZahrani

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Background Esophageal cancer is the eighth most common cancer worldwide. More than 90% of esophageal cancers are either squamous cell carcinoma or adenocarcinoma. Squamous dysplasia is a precancerous lesion for squamous cell carcinoma and Barrett's esophagus is the precancerous lesion for adenocarcinoma. Gastro-esophageal reflux disease (GERD) is the initiation factor for Barrett's esophagus. Cyclooxygenase-2 (COX-2) is a key enzyme in arachidonic metabolism. It appears to play an important role in gastrointestinal carcinogenesis. COX-2 activity may be a potential target for the prevention of cancer progression by selective COX-2 inhibitors, which decrease proliferation and increase apoptosis. Objectives To assess COX-2 expression in premalignant and malignant esophageal epitheliums changes and detect its roles in progression of these lesions. Materials and Methods We analyzed the expression of COX-2 immunohistochemically in 40 esophageal biopsies utilizing the streptavidin-biotin-peroxidase complex method on archival formalin fixed-paraffin embedded blocks. Histopathologically, 17 (42.5%) of cases were non-malignant cases which included GERD, Barrett's esophagus and squamous dysplasia. The malignant cases were 23 (57.5%) squamous cell carcinoma, adenocarcinoma and undifferentiated carcinoma. Results In non-malignant cases 7 (41.2%) out of 17 cases had high COX-2 expression. In squamous cell carcinoma 10 (83.3%) out of 12 cases had high COX-2 expression. The expression of COX-2 was high in all 9 (100%) cases of adenocarcinoma. COX-2 expression is significantly increased (P=0.005 and P=0.0001) in squamous cell carcinoma and adenocarcinoma respectively. There was a significant difference in COX-2 immunoreactivity between malignant and non-malignant lesions (P=0.0003). Conclusion COX-2 is responsible for the progression of esophageal diseases from benign to malignant. We recommend that COX-2 immunohistochemistry should be done routinely for premalignant and malignant esophageal lesions as selective COX-2 inhibitors will be helpful in the treatment. Further studies on molecular and genetic basis of COX-2 expression are needed to unmask its role and relation to progression of esophageal lesions.

Keywords: Cox-2, Esophageal adinocarcinoma, Esophageal squamous cell carcinoma, Immunohistochemistry.

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276 Novel Hybrid Ceramic Nanocomposites Fabricated by Rapid Sintering Technology

Authors: Iftikhar Ahmad, Abulhakim Almajid

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Alumina (Al2O3) is an attractive structural ceramic however; brittleness turns Al2O3 down for advanced applications. Development of multi-phase phase ceramics systems is promising to curtail the brittleness and the incorporation of strong/elastic graphene, as third phase, into dual phase (Al2O3-SiC) is striking for mechanical upgrading purpose. Thin graphene nanosheets (GNS) were prepared by thermal exfoliation process and reinforced into dual phase ceramic system. The hybrid nanocomposite was consolidated by novel HF-IH (high-frequency induction heating) sintering furnace at 1500 °C under 50 MPa in vacuum conditions. Structural features and grain size of the resulting nanocomposite were analyzed by SEM and TEM whilst the mechanical properties were assessed by microhardness and nanoindentation techniques. The fracture toughness of the hybrid nanocomposites was appraised by direct crack measurement method. Electron microscopic investigations confirmed the preparation of thin (< 10 nm) graphene nanosheets (GNS). HF-IH sintering route condensed the three-phase (GNS-Al2O3-SiC) hybrid nanocomposite system to > 99% relative densities. SEM of the hybrid nanocomposites fractured surfaces revealed even distribution of the nanocomposite constituents and changed in fracture-mode. Structurally, 88% grain reduction into hybrid nanocomposite was also obtained. Mechanically, enhanced fracture toughness (50%) and hardness (53%) were also achieved for hybrid nanocomposites were attained against bench marked monolithic Al2O3.

Keywords: alumina, graphene, hybrid nanocomposites, rapid sintering

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275 Perfluoroheptanoic Acid Affects Xenopus Embryo Embryogenesis by Inducing the Phosphorylation of ERK and JNK

Authors: Chowon Kim, Yoo-Kyung Kim, Kyeong Yeon Park, Hyun-Shik Lee

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Perfluoroalkyl compounds (PFCs) are globally distributed synthetic compounds that are known to adversely affect human health. Developmental toxicity assessment of PFCs is important to facilitate the evaluation of their environmental impact. In the present study, we assessed the developmental toxicity and teratogenicity of PFCs with different numbers of carbon atoms on Xenopus embryogenesis. An initial frog embryo teratogenicity assay-Xenopus (FETAX) assay was performed that identified perfluorohexanoic (PFHxA) and perfluoroheptanoic (PFHpA) acids as potential teratogens and developmental toxicants. The mechanism underlying this teratogenicity was also investigated by measuring the expression of tissue-specific biomarkers such as phosphotyrosine‑binding protein, xPTB (liver); NKX2.5 (heart); and Cyl18 (intestine). Whole‑mount in situ hybridization, reverse transcriptase‑polymerase chain reaction (RT-PCR), and histologic analyses detected severe defects in the liver and heart following exposure to PFHxA or PFHpA. In addition, immunoblotting revealed that PFHpA significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), while PFHxA slightly increased these, as compared with the control. These results suggest that PFHxA and PFHpA are developmental toxicants and teratogens, with PFHpA producing more severe effects on liver and heart development through the induction of ERK and JNK phosphorylation.

Keywords: PFCs, ERK, JNK, xenopus

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274 Viability Study of the Use of Solar Energy for Water Heating in Homes in Brazil

Authors: Elmo Thiago Lins Cöuras Ford, Valentina Alessandra Carvalho do Vale

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The sun is an inexhaustible source and harnessing its potential both for heating and for power generation is one of the most promising and necessary alternatives, mainly due to environmental issues. However, it should be noted that this has always been present in the generation of energy on the planet, only indirectly, as it is responsible for virtually all other energy sources, such as: Generates the evaporation source of the water cycle, which allows the impoundment and the consequent generation of electricity (hydroelectricity); Winds are caused by large-scale atmospheric induction caused by solar radiation; Oil, coal and natural gas were generated from waste plants and animals that originally obtained the energy needed for its development of solar radiation. Thus, the idea of using solar energy for practical purposes for the benefit of man is not new, as it accompanies the story since the beginning of time, which means that the sun was always of utmost importance in the design of shelters, or homes is, constructed by taking into consideration the use of sunlight, practicing what was being lost through the centuries, until a time when the buildings started to be designed completely independent of the sun. However, the climatic rigors still needed to be fought, only artificially and today seen as unsustainable, with additional facilities fueled by energy consumption. This paper presents a study on the feasibility of using solar energy for heating water in homes, developing a simplified methodology covering the mode of operation of solar water heaters, solar potential existing alternative systems of Brazil, the international market, and barriers encountered.

Keywords: solar energy, solar heating, solar project, water heating

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273 Circular Labour Migration and Its Consequences in Georgia

Authors: Manana Lobzhanidze

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Introduction: The paper will argue that labor migration is the most important problem Georgia faces today. The structure of labor migration by age and gender of Georgia is analyzed. The main driving factors of circular labor migration during the last ten years are identified. While studying migration, it is necessary to discuss the interconnection of economic, social, and demographic features, also taking into consideration the policy of state regulations in terms of education and professional training. Methodology: Different research methods are applied in the presented paper: statistical, such as selection, grouping, observation, trend, and qualitative research methods, namely; analysis, synthesis, induction, deduction, comparison ones. Main Findings: Labour migrants are filling the labor market as a low salary worker. The main positive feedback of migration from developing countries is poverty eradication, but this process is accompanied by problems, such as 'Brain Drain'. The country loses an important part of its intellectual potential, and it is invested by households or state itself. Conclusions: Labor migration is characterized to be temporary, but socio-economic problems of the country often push the labor migration in the direction of longterm and illegal migration. Countries with developed economies try to stricter migration policy and fight illegal migration with different methods; circular migration helps solve this problem. Conclusions and recommendations are included about circular labor migration consequences in Georgia and its influence on the reduction of unemployment level.

Keywords: migration, circular labor migration, labor migration employment, unemployment

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272 Design-Analysis and Optimization of 10 MW Permanent Magnet Surface Mounted Off-Shore Wind Generator

Authors: Mamidi Ramakrishna Rao, Jagdish Mamidi

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With advancing technology, the market environment for wind power generation systems has become highly competitive. The industry has been moving towards higher wind generator power ratings, in particular, off-shore generator ratings. Current off-shore wind turbine generators are in the power range of 10 to 12 MW. Unlike traditional induction motors, slow-speed permanent magnet surface mounted (PMSM) high-power generators are relatively challenging and designed differently. In this paper, PMSM generator design features have been discussed and analysed. The focus attention is on armature windings, harmonics, and permanent magnet. For the power ratings under consideration, the generator air-gap diameters are in the range of 8 to 10 meters, and active material weigh ~60 tons and above. Therefore, material weight becomes one of the critical parameters. Particle Swarm Optimization (PSO) technique is used for weight reduction and performance improvement. Four independent variables have been considered, which are air gap diameter, stack length, magnet thickness, and winding current density. To account for core and teeth saturation, preventing demagnetization effects due to short circuit armature currents, and maintaining minimum efficiency, suitable penalty functions have been applied. To check for performance satisfaction, a detailed analysis and 2D flux plotting are done for the optimized design.

Keywords: offshore wind generator, PMSM, PSO optimization, design optimization

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271 Development and Efficacy Assessment of an Enteric Coated Porous Tablet Loaded with F4 Fimbriae for Oral Vaccination against Enterotoxigenic Escherichia coli Infections

Authors: Atul Srivastava, D. V. Gowda

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Enterotoxigenic Escherichia coli (ETEC) infection is one of the major causes contributing to the development of diarrhoea in adults and children in developing countries. To date, no preventive/treatment strategy showed promising results, which could be due to the lack of potent vaccines, and/or due to the development of resistance of ETEC to antibiotics. Therefore, in the present investigation, a novel porous Sodium Alginate (SA) tablet formulation loaded with F4 fimbriae antigen was developed and tested for efficacy against ETEC infections in piglet models. Pre-compression parameters of the powder mixes and post compression parameters of tablets have been evaluated and results were found to be satisfactory. Loading of F4 fimbrial antigens in to the tablets was achieved by inducing pores in the tablets via the sublimation of camphor followed by incubation with purified F4 fimbriae. The loaded tablets have been coated with Eudragit L100 to protect the F4 fimbriae from (a) highly acidic gastric environment; (b) proteolytic cleavage by pepsin; and (c) to promote subsequent release in the intestine. Evaluation of developed F4 fimbrial tablets in a Pig model demonstrated induction of mucosal immunity, and a significant reduction of F4+ E. coli in faeces. Therefore, F4 fimbriae loaded porous tablets could be a novel oral vaccination candidate to induce mucosal and systemic immunity against ETEC infections.

Keywords: porous tablets, sublimation, f4 fimbriae, eudragit l100, vaccination

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270 Impact of Microbial Pathogen on Aquatic Environment

Authors: Muhammad Younis Laghari

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Global climate change has had many effects on the aquatic environment, and the major issue is pollution. Along with the other pollutants, there are a significant number of human microbial pathogens that pollute the water bodies. Another concern about the water quality is that the major aquatic resources bring water-borne pathogens and other related diseases. These resources include industrial effluent, untreated domestic sewage, acid mine drainage, etc. However, these water discharges through various routes may have treatment to eliminate the pathogenic microbes. Therefore, it is essential to control the leakage from sewer systems, residential discharge, and agricultural run-off. These pathogenic microbes have been implicated in the lives of water health (fishes), which is harmful and causes diseases. Mostly, the mortality of aquatic species results because of catastrophic floods due to poor water waste treatment and sanitation that introduce pathogenic bacteria into rivers. Pathogens survive in rivers and remain poorly known but essential to control water-borne diseases. The presence of bacteria in watercourses is diverse and constitutes a complicated subject. Many species are autochthonous and play an important role in aquatic ecosystems, while many others arise from untreated or poorly treated waste from industrial and domestic sources. Further, more investigation is required to know the induction of water-borne pathogens in various water resources and the potential impacts of water resource development on pathogen contamination.

Keywords: microbial pathogens, contamination, water resources, river water body

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269 Improving the Employee Transfer Experience within an Organization

Authors: Drew Fockler

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This research examines how to improve an employee’s experience when transferring between departments within an organization. This research includes a historical review of a Canadian retail organization. Based on this historical review, gaps are identified between current and future visions to show where problems with existing training and development practices need to be resolved to reduce front-line employee turnover within an organization. The strategies within this paper support leaders through the LEAD: Listen, Explore, Act and Develop, Change Management Model. The LEAD Change Management Model supports the change process. This research proposes three possible solutions to improve an employee who is transferring between departments. The best solution to resolve the problem of improving an employee moving between departments experience is creating a Training Manager position within the retail store. A Training Manager position could support both employees and leadership with training and development of staff who are moving between departments. Within this research, an implementation plan using the TransX Model was created. The TransX Model is a hybrid of Leader-Member Exchange Theory and Transformational Leadership Theory to facilitate this organizational change within an organization by creating a common vision. Finally, this research provides the next steps as well as future considerations to enhance the training manager role within an organization.

Keywords: employee transfers, employee engagement, human resources, employee induction, TransX model, lead change management model

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268 Fault Analysis of Ship Power System Comprising of Parallel Generators and Variable Frequency Drive

Authors: Umair Ashraf, Kjetil Uhlen, Sverre Eriksen, Nadeem Jelani

Abstract:

Although advancement in technology has increased the reliability and ease of work in ship power system, but these advancements are also adding complexities. Ever increasing non linear loads, like power electronics (PE) devices effect the stability of the system. Frequent load variations and complex load dynamics are due to the frequency converters and motor drives, these problem are more prominent when system is connected with the weak grid. In the ship power system major consumers are thruster motors for the propulsion. For the control operation of these motors variable frequency drives (VFD) are used, mostly VFDs operate on nominal voltage of the system. Some of the consumers in ship operate on lower voltage than nominal, these consumers got supply through step down transformers. In this paper the vector control scheme is used for the control of both rectifier and inverter, parallel operation of the synchronous generators is also demonstrated. The simulation have been performed with induction motor as load on VFD and parallel RLC load. Fault analysis has been performed first for the system which do not have VFD and then for the system with VFD. Three phase to the ground, single phase to the ground fault were implemented and behavior of the system in both the cases was observed.

Keywords: non-linear load, power electronics, parallel operating generators, pulse width modulation, variable frequency drives, voltage source converters, weak grid

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267 RNA Antisense Coat Protein Showing Promising Effects against Cotton Leaf Curl Disease in Pakistani Cotton

Authors: Zunnu Raen Akhtar

Abstract:

Cotton Leaf Curl Disease (CLCuD) is from Gemini virus and is transmitted through whiteflies in cotton. Transgenic cotton containing Antisense Coat Protein (ACP) has been found to show better results against CLCuD in cotton. In current research, Antisense Coat Protein was inserted in cotton plants to observe resistance developed in the cotton plants against CLCuD. T1 generation of plants were observed for its expression in plants. Tests were carried out to observe the expression of Antisense Coat Protein using Polymerase Chain Reaction (PCR) technique and by southern blotting. Whiteflies showing positive Cotton Leaf Curl Virus (CLCV) were reared and released in bioassay on ACP expressing cotton plants under laboratory as well as confined semi-field conditions. Results confirmed the expression of AC protein in PCR and southern blotting. Further laboratory results showed that cotton plants expressing AC protein showed rare incidence of CLCuD infection as compared to control. In the confined semi-field, similar results were observed in AC protein expressing cotton as compared to control. These results explicitly show that ACP can help to tackle the CLCuD issue in the future and further studies on biochemical processes involved in these plants and effects of ACP induction on non-target organisms should also be studied for eco-system.

Keywords: cotton, white flies, antisense coat protein, CLCV

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266 One-Step Synthesis and Characterization of Biodegradable ‘Click-Able’ Polyester Polymer for Biomedical Applications

Authors: Wadha Alqahtani

Abstract:

In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

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265 Determination of Biological Efficiency Values of Some Pesticide Application Methods under Second Crop Maize Conditions

Authors: Ali Bolat, Ali Bayat, Mustafa Gullu

Abstract:

Maize can be cultivated both under main and second crop conditions in Turkey. Main pests of maize under second crop conditions are Sesamia nonagrioides Lefebvre (Lepidoptera: Noctuidae) and Ostrinia nubilalis Hübner (Lepidoptera: Crambidae). Aerial spraying applications to control these two main maize pests can be carried out until 2006 in Turkey before it was banned due to environmental concerns like drifting of sprayed pestisides and low biological efficiency. In this context, pulverizers which can spray tall maize plants ( > 175 cm) from the ground have begun to be used. However, the biological efficiency of these sprayers is unknown. Some methods have been tested to increase the success of ground spraying in field experiments conducted in second crop maize in 2008 and 2009. For this aim, 6 spraying methods (air assisted spraying with TX cone jet, domestic cone nozzles, twinjet nozzles, air induction nozzles, standard domestic cone nozzles and tail booms) were used at two application rates (150 and 300 l.ha-1) by a sprayer. In the study, biological efficacy evaluations of each methods were measured in each parcel. Biological efficacy evaluations included counts of number of insect damaged plants, number of holes in stems and live larvae and pupa in stems of selected plants. As a result, the highest biological efficacy value (close to 70%) was obtained from Air Assisted Spraying method at 300 l / ha application volume.

Keywords: air assisted sprayer, drift nozzles, biological efficiency, maize plant

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264 Absence of Malignancy in Oral Epithelial Cells from Individuals Occupationally Exposed to Organic Solvents Working in the Shoe Industry

Authors: B. González-Yebra, B. Flores-Nieto, P. Aguilar-Salinas, M. Preciado Puga, A. L. González Yebra

Abstract:

The monitoring of populations occupationally exposed to organic solvents has been an important issue for several shoe factories for years since the International Agency for Research on Cancer (IARC) has advised on the potential carcinogenic risk of chemicals related to occupations. In order to detect if exposition to organic solvents used in some Mexican shoe factories contributes to oral carcinogenesis, we performed monitoring in three factories. Occupational exposure was determined by using monitors 3M. Organic solvents were assessed by gas chromatography. Then, we recruited 30 shoe workers (30.2 ± 8.4 years) and 10 unexposed subjects (43.3 ± 11.2 years) for the micronuclei (MN) test and immunodetection of some cancer biomarkers (ki-67, p16, caspase-3) in scraped oral epithelial cells. Monitored solvents detected were acetone, benzene, hexane, methyl ethyl ketone, and toluene in acceptable levels according to Official Mexican Norm. We found by MN test higher incidence of nuclear abnormalities (karyorrhexis, pycnosis, karyolysis, condensed chromatin, and macronuclei) in the exposed group than the non-exposed group. On the other hand, we found, a negative expression for Ki-67 and p16 in exfoliated epithelial cells from exposed and non-exposed to organic solvents subjects. Only caspase-3 shown positive patter of expression in 9/30 (30%) exposed subjects, and we detected high karyolysis incidence in caspase-3 subjects (p = 0.021). The absence of expression of proliferation markers p16 and ki-67 and presence of apoptosis marker caspase-3 are indicating the absence of malignancy in oral epithelial cells and low risk for oral cancer. It is a fact that the MN test is a very effective method to detect nuclear abnormalities in exfoliated buccal cells from subjects that have been exposed to organic solvents in the shoe industry. However, in order to improve this tool and predict cancer risk is it is mandatory to implement complementary tests as other biomarkers that can help to detect malignancy in individuals occupationally exposed.

Keywords: biomarkers, oral cancer, organic solvents, shoe industries

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263 Supply Chain Coordination under Carbon Trading Mechanism in Case of Conflict

Authors: Fuqiang Wang, Jun Liu, Liyan Cai

Abstract:

This paper investigates the coordination of the conflicting two-stage low carbon supply chain consisting of upstream and downstream manufacturers. The conflict means that the upstream manufacturer takes action for carbon emissions reduction under carbon trading mechanism while the downstream manufacturer’s production cost rises. It assumes for the Stackelberg game that the upstream manufacturer plays as a leader and the downstream manufacturer does as a follower. Four kinds of the situation of decentralized decision making, centralized decision-making, the production cost sharing contract and the carbon emissions reduction revenue sharing contract under decentralized decision making are considered. The backward induction approach is adopted to solve the game. The results show that the more intense the conflict is, the lower the efficiency of carbon emissions reduction and the higher the retail price is. The optimal investment of the decentralized supply chain under the two contracts is unchanged and still lower than that of the centralized supply chain. Both the production cost sharing contract and the carbon emissions reduction revenue sharing contract cannot coordinate the supply chain, because that the sharing cost or carbon emissions reduction sharing revenue will transfer through the wholesale price mechanism. As a result, it requires more complicated contract forms to coordinate such a supply chain.

Keywords: cap-and-trade mechanism, carbon emissions reduction, conflict, supply chain coordination

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262 Utilization of CD-ROM Database as a Storage and Retrieval System by Students of Nasarawa State University Keffi

Authors: Suleiman Musa

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The utilization of CD-ROM as a storage and retrieval system by Nasarawa State University Keffi (NSUK) Library is crucial in preserving and dissemination of information to students and staff. This study investigated the utilization of CD-ROM Database storage and retrieval system by students of NUSK. Data was generated using structure questionnaire. One thousand and fifty two (1052) respondents were randomly selected among post-graduate and under-graduate students. Eight hundred and ten (810) questionnaires were returned, but only five hundred and ninety three (593) questionnaires were well completed and useful. The study found that post-graduate students use CD-ROM Databases more often than the under-graduate students in NSUK. The result of the study revealed that knowledge about CD-ROM Database 33.22% got it through library staff. 29.69% use CD-ROM once a month. Large number of users 45.70% purposely uses CD-ROM Databases for study and research. In fact, lack of users’ orientation amount to 58.35% of problems faced, while 31.20% lack of trained staff make it more difficult for utilization of CD-ROM Database. Major numbers of users 38.28% are neither satisfied nor dissatisfied, while a good number of them 27.99% are satisfied. Then 1.52% is highly dissatisfied but could not give reasons why. However, to ensure effective utilization of CD-ROM Database storage and retrieval system by students of NSUK, the following recommendations are made: effort should be made to encourage under-graduate in using CD-ROM Database. The institution should conduct orientation/induction course for students on CD-ROM Databases in the library. There is need for NSUK to produce in house databases on their CD-ROM for easy access by users.

Keywords: utilization, CD-ROM databases, storage, retrieval, students

Procedia PDF Downloads 420
261 Performance of BLDC Motor under Kalman Filter Sensorless Drive

Authors: Yuri Boiko, Ci Lin, Iluju Kiringa, Tet Yeap

Abstract:

The performance of a BLDC motor controlled by the Kalman filter-based position-sensorless drive is studied in terms of its dependence on the system’s parameters' variations. The effects of system’s parameters changes on the dynamic behavior of state variables are verified. Simulated is a closed-loop control scheme with a Kalman filter in the feedback line. Distinguished are two separate data sampling modes in analyzing feedback output from the BLDC motor: (1) equal angular separation and (2) equal time intervals. In case (1), the data are collected via equal intervals Δθ of rotor’s angular position θᵢ, i.e., keeping Δθ=const. In case (2), the data collection time points tᵢ are separated by equal sampling time intervals Δt=const. Demonstrated are the effects of the parameters changes on the sensorless control flow, in particular, reduction of the torque ripples, switching spikes, torque load balancing. It is specifically shown that an efficient suppression of commutation induced torque ripples is achievable selection of the sampling rate in the Kalman filter settings above certain critical value. The computational cost of such suppression is shown to be higher for the motors with lower induction values of the windings.

Keywords: BLDC motor, Kalman filter, sensorless drive, state variables, torque ripples reduction, sampling rate

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260 Computational Fluid Dynamic Modeling of Mixing Enhancement by Stimulation of Ferrofluid under Magnetic Field

Authors: Neda Azimi, Masoud Rahimi, Faezeh Mohammadi

Abstract:

Computational fluid dynamics (CFD) simulation was performed to investigate the effect of ferrofluid stimulation on hydrodynamic and mass transfer characteristics of two immiscible liquid phases in a Y-micromixer. The main purpose of this work was to develop a numerical model that is able to simulate hydrodynamic of the ferrofluid flow under magnetic field and determine its effect on mass transfer characteristics. A uniform external magnetic field was applied perpendicular to the flow direction. The volume of fluid (VOF) approach was used for simulating the multiphase flow of ferrofluid and two-immiscible liquid flows. The geometric reconstruction scheme (Geo-Reconstruct) based on piecewise linear interpolation (PLIC) was used for reconstruction of the interface in the VOF approach. The mass transfer rate was defined via an equation as a function of mass concentration gradient of the transported species and added into the phase interaction panel using the user-defined function (UDF). The magnetic field was solved numerically by Fluent MHD module based on solving the magnetic induction equation method. CFD results were validated by experimental data and good agreements have been achieved, which maximum relative error for extraction efficiency was about 7.52 %. It was showed that ferrofluid actuation by a magnetic field can be considered as an efficient mixing agent for liquid-liquid two-phase mass transfer in microdevices.

Keywords: CFD modeling, hydrodynamic, micromixer, ferrofluid, mixing

Procedia PDF Downloads 175
259 The Impact of Intestinal Ischaemia-Reperfusion Injury upon the Biological Function of Mesenteric Lymph

Authors: Beth Taylor, Kojima Mituaki, Atsushi Senda, Koji Morishita, Yasuhiro Otomo

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Intestinal ischaemia-reperfusion injury drives systemic inflammation and organ failure following trauma/haemorrhagic shock (T/HS), through the release of pro-inflammatory mediators into the mesenteric lymph (ML). However, changes in the biological function of ML are not fully understood, and therefore, a specific model of intestinal ischaemia-reperfusion injury is required to obtain ML for the study of its biological function upon inflammatory cells. ML obtained from a model of intestinal ischaemia-reperfusion injury was used to assess biological function upon inflammatory cells and investigate changes in the biological function of individual ML components. An additional model was used to determine the effect of vagal nerve stimulation (VNS) upon biological function. Rat ML was obtained by mesenteric lymphatic duct cannulation before and after occlusion of the superior mesenteric artery (SMAO). ML was incubated with human polymorphonuclear neutrophils (PMNs), monocytes and lymphocytes, and the biological function of these cells was assessed. ML was then separated into supernatant, exosome and micro-vesicle components, and biological activity was compared in monocytes. A model with an additional VNS phase was developed, in which the right cervical vagal nerve was exposed and stimulated, and ML collected for comparison of biological function with the conventional model. The biological function of ML was altered by intestinal ischaemia-reperfusion injury, increasing PMN activation, monocyte activation, and lymphocyte apoptosis. Increased monocyte activation was only induced by the exosome component of ML, with no significant changes induced by the supernatant or micro-vesicle components. VNS partially attenuated monocyte activation, but no attenuation of PMN activation was observed. Intestinal ischaemia-reperfusion injury induces changes in the biological function of ML upon both innate and adaptive inflammatory cells, supporting the role of intestinal ischaemia-reperfusion injury in driving systemic inflammation following T/HS. The exosome component of ML appears to be critical to the transport of pro-inflammatory mediators in ML. VNS partially attenuates changes in innate inflammatory cell biological activity observed, presenting possibilities for future novel treatment development in multiple organ failure patients.

Keywords: exosomes, inflammation, intestinal ischaemia, mesenteric lymph, vagal stimulation

Procedia PDF Downloads 112