Search results for: accelerated pathways
350 The Retinoprotective Effects and Mechanisms of Fungal Ingredient 3,4-Dihydroxybenzalacetone through Inhibition of Retinal Müller and Microglial Activation
Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao
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Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR
Procedia PDF Downloads 139349 Socio-Economic Impact of Covid-19 in Ethiopia
Authors: Kebron Abich Asnake
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The outbreak of COVID-19 has had far-reaching socio-economic consequences globally, and Ethiopia is no exception. This abstract provides a summary of a research study on the socio-economic impact of COVID-19 in Ethiopia. The study analyzes the health impact, economic repercussions, social consequences, government response measures, and opportunities for post-crisis recovery. In terms of health impact, the research explores the spread and transmission of the virus, the capacity and response of the healthcare system, and the mortality rate, with a focus on vulnerable populations. The economic impact analysis entails investigating the contraction of the GDP, employment and income loss, disruption in key sectors such as agriculture, tourism, and manufacturing, and the specific implications for small and medium-sized enterprises (SMEs), foreign direct investment, and remittances. The social impact section looks at the disruptions in education and the digital divide, food security and nutrition challenges, increased poverty and inequality, gender-based violence, and mental health issues. The research also examines the measures taken by the Ethiopian government, including health and safety regulations, economic stimulus packages, social protection programs, and support for vulnerable populations. Furthermore, the study outlines long-term recovery prospects, social cohesion, and community resilience challenges. It highlights the need to strengthen the healthcare system and finds a balance between health and economic priorities. The research concludes by presenting recommendations for policy-makers and stakeholders, emphasizing opportunities for post-crisis recovery such as diversification of the economy, enhanced healthcare infrastructure, investment in digital infrastructure and technology, and support for domestic tourism and local industries. This research provides valuable insights into the socio-economic impact of COVID-19 in Ethiopia, offering a comprehensive analysis of the challenges faced and potential pathways towards recovery.Keywords: impact, covid, ethiopia, health
Procedia PDF Downloads 81348 Emblica officinalis Fruit Extract Ameliorates Cisplatin-Induced Nephrotoxicity in Experimental Rats
Authors: Prerna Kalra, Surender Singh
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Cisplatin is the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose-dependent nephrotoxicity by generating reactive oxygen species, by stimulating inflammatory and apoptotic pathways. Additional adjuvant therapies to decrease the toxicity of this chemotherapeutic drug are essential. This study was designed to evaluate the protective role of Emblica officinalis Geartn (Indian gooseberry) against cisplatin induced nephrotoxicity. Emblica officinalis was orally administered to Wistar rats (n=6) for 10 days in 50, 100 and 200mg/kg body weight. On day 7, 8mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological and transmission electron microscopy. We found that 200mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen, oxidant stress marker (malondialdehyde) and increased the reduced levels of antioxidant marker (endogenous glutathione and superoxide dismutase). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treating the animals with Emblica officinalis in the treatment group. In ultrastructural changes cisplatin treated group showed the damaged mitochondria (M) with dissolved cristae and large number of lysosomes (L) and vacuole (V) formation in tubular epithelial cells. EOE administered group showed visible cristae formation and sign of autophagy vacuoles at a dose of 200mg/kg. Further in-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as an adjuvant therapy in cisplatin induced nephrotoxicity.Keywords: antioxidant, cisplatin, Emblica officinalis, in silico, nephrotoxicity
Procedia PDF Downloads 291347 A Quasi-Experimental Study of the Impact of 5Es Instructional Model on Students' Mathematics Achievement in Northern Province, Rwanda
Authors: Emmanuel Iyamuremye, Jean François Maniriho, Irenee Ndayambaje
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Mathematics is the foundational enabling discipline that underpins science, technology, and engineering disciplines. Science, technology, engineering, and mathematics (STEM) subjects are foreseen as the engine for socio-economic transformation. Rwanda has done reforms in education aiming at empowering and preparing students for the real world job by providing career pathways in science, technology, engineering, and mathematics related fields. While that considered so, the performance in mathematics has remained deplorable in both formative and national examinations. Therefore, this paper aims at exploring the extent to which the engage, explore, explain, elaborate and evaluate (5Es) instructional model contributing towards students’ achievement in mathematics. The present study adopted the pre-test, post-test non-equivalent control group quasi-experimental design. The 5Es instructional model was applied to the experimental group while the control group received instruction with the conventional teaching method for eight weeks. One research-made instrument, mathematics achievement test (MAT), was used for data collection. A pre-test was given to students before the intervention to make sure that both groups have equivalent characteristics. At the end of the experimental period, the two groups have undergone a post-test to ascertain the contribution of the 5Es instructional model. Descriptive statistics and analysis of covariance (ANCOVA) were used for the analysis of the study. For determining the improvement in mathematics, Hakes methods of calculating gain were used to analyze the pre-test and post-test scores. Results showed that students exposed to 5Es instructional model achieved significantly better performance in mathematics than students instructed using the conventional teaching method. It was also found that 5Es instructional model made lessons more interesting, easy and created friendship among students. Thus, 5Es instructional model was recommended to be adopted as a close substitute to the conventional teaching method in teaching mathematics in lower secondary schools in Rwanda.Keywords: 5Es instructional model, achievement, conventional teaching method, mathematics
Procedia PDF Downloads 103346 Using Structural Equation Modeling to Analyze the Impact of Remote Work on Job Satisfaction
Authors: Florian Pfeffel, Valentin Nickolai, Christian Louis Kühner
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Digitalization has disrupted the traditional workplace environment by allowing many employees to work from anywhere at any time. This trend of working from home was further accelerated due to the COVID-19 crisis, which forced companies to rethink their workplace models. While in many companies, this shift happened out of pure necessity; many employees were left more satisfied with their job due to the opportunity to work from home. This study focuses on employees’ job satisfaction in the service sector in dependence on the different work models, which are defined as a “work from home” model, the traditional “work in office” model, and a hybrid model. Using structural equation modeling (SEM), these three work models have been analyzed based on 13 influencing factors on job satisfaction that have been further summarized in the three groups “classic influencing factors”, “influencing factors changed by remote working”, and “new remote working influencing factors”. Based on the influencing factors on job satisfaction, a survey has been conducted with n = 684 employees in the service sector. Cronbach’s alpha of the individual constructs was shown to be suitable. Furthermore, the construct validity of the constructs was confirmed by face validity, content validity, convergent validity (AVE > 0.5: CR > 0.7), and discriminant validity. Additionally, confirmatory factor analysis (CFA) confirmed the model fit for the investigated sample (CMIN/DF: 2.567; CFI: 0.927; RMSEA: 0.048). The SEM-analysis has shown that the most significant influencing factor on job satisfaction is “identification with the work” with β = 0.540, followed by “Appreciation” (β = 0.151), “Compensation” (β = 0.124), “Work-Life-Balance” (β = 0.116), and “Communication and Exchange of Information” (β = 0.105). While the significance of each factor can vary depending on the work model, the SEM-analysis shows that the identification with the work is the most significant factor in all three work models and, in the case of the traditional office work model, it is the only significant influencing factor. The study shows that employees who work entirely remotely or have a hybrid work model are significantly more satisfied with their job, with a job satisfaction score of 5.0 respectively on a scale from 1 (very dissatisfied) to 7 (very satisfied), than employees do not have the option to work from home with a score of 4.6. This comes as a result of the lower identification with the work in the model without any remote working. Furthermore, the responses indicate that it is important to consider the individual preferences of each employee when it comes to the work model to achieve overall higher job satisfaction. Thus, it can be argued that companies can profit off of more motivation and higher productivity by considering the individual work model preferences, therefore, increasing the identification with the respective work.Keywords: home-office, identification with work, job satisfaction, new work, remote work, structural equation modeling
Procedia PDF Downloads 82345 Reviving Sustainable Architecture in Non-Wester Culture
Authors: Khaled Asfour
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Going for LEED certification is the latest concern in Egyptian practice that only materialized during the last 4 years. Egyptian Consultant Group (ECG) together with Credit Agricole had the vision to design a headquarters (Cairo) that delivers a serious sustainable design. The bank is a strong advocator of “green banking” and supports renewable energy and energy saving projects. Their HQ in Cairo has passed all the hurdles to become the first platinum LEED certificate holder in Egypt. With this design Egyptian practice has finally re-engaged in a serious way with its long-standing traditions in sustainable architecture. Perhaps the closest to our memory is the medieval houses of Cairo. Few centuries later these qualities disappeared with the advent of Modern Movement that focused more on standard modernist image making than real localized quality of living environments. The first person to note this disappearance was Hassan Fathy half a century ago. Despite international applaud for his efforts he had no effect on prevailing local practice that continued senselessly adopting recycled modernist templates. The Egyptian society was not ready to accept any reference to historic architecture. Disciples of Hassan Fathy, few decades later sought, of tackling the lack of interest in green architecture in a different way. Mohamed Awad introduced in his design sustainable ideals inspired from traditional architecture rather than recycling directly historic forms and images. Despite success, this approach did not go far enough to influence the prevailing practice. Since year 2000 Egyptian economy was ebbing and flowing dramatically. This staggering fluctuation coupled by energy crisis has disillusioned architects and clients on the issue of modern image making. No more shining architecture under the sun with high running cost of fossil fuel. They sought of adopting contemporary green measures that offer pleasant living while saving on energy. A revival is on its way but is very slow and timid. The paper will present this problem of reviving sustainable architecture. How this process can be accelerated in order to give stronger impact on current practice will be addressed through the works of Mario Cucinella and Norman Foster.Keywords: LEED certification, Hasan Fathy, Medieval architecture, Mario Cucinella, Norman Foster
Procedia PDF Downloads 491344 AI Predictive Modeling of Excited State Dynamics in OPV Materials
Authors: Pranav Gunhal., Krish Jhurani
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This study tackles the significant computational challenge of predicting excited state dynamics in organic photovoltaic (OPV) materials—a pivotal factor in the performance of solar energy solutions. Time-dependent density functional theory (TDDFT), though effective, is computationally prohibitive for larger and more complex molecules. As a solution, the research explores the application of transformer neural networks, a type of artificial intelligence (AI) model known for its superior performance in natural language processing, to predict excited state dynamics in OPV materials. The methodology involves a two-fold process. First, the transformer model is trained on an extensive dataset comprising over 10,000 TDDFT calculations of excited state dynamics from a diverse set of OPV materials. Each training example includes a molecular structure and the corresponding TDDFT-calculated excited state lifetimes and key electronic transitions. Second, the trained model is tested on a separate set of molecules, and its predictions are rigorously compared to independent TDDFT calculations. The results indicate a remarkable degree of predictive accuracy. Specifically, for a test set of 1,000 OPV materials, the transformer model predicted excited state lifetimes with a mean absolute error of 0.15 picoseconds, a negligible deviation from TDDFT-calculated values. The model also correctly identified key electronic transitions contributing to the excited state dynamics in 92% of the test cases, signifying a substantial concordance with the results obtained via conventional quantum chemistry calculations. The practical integration of the transformer model with existing quantum chemistry software was also realized, demonstrating its potential as a powerful tool in the arsenal of materials scientists and chemists. The implementation of this AI model is estimated to reduce the computational cost of predicting excited state dynamics by two orders of magnitude compared to conventional TDDFT calculations. The successful utilization of transformer neural networks to accurately predict excited state dynamics provides an efficient computational pathway for the accelerated discovery and design of new OPV materials, potentially catalyzing advancements in the realm of sustainable energy solutions.Keywords: transformer neural networks, organic photovoltaic materials, excited state dynamics, time-dependent density functional theory, predictive modeling
Procedia PDF Downloads 118343 Field Study of Chlorinated Aliphatic Hydrocarbons Degradation in Contaminated Groundwater via Micron Zero-Valent Iron Coupled with Biostimulation
Authors: Naijin Wu, Peizhong Li, Haijian Wang, Wenxia Wei, Yun Song
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Chlorinated aliphatic hydrocarbons (CAHs) pollution poses a severe threat to human health and is persistent in groundwater. Although chemical reduction or bioremediation is effective, it is still hard to achieve their complete and rapid dechlorination. Recently, the combination of zero-valent iron and biostimulation has been considered to be one of the most promising strategies, but field studies of this technology are scarce. In a typical site contaminated by various types of CAHs, basic physicochemical parameters of groundwater, CAHs and their product concentrations, and microbial abundance and diversity were monitored after a remediation slurry containing both micron zero-valent iron (mZVI) and biostimulation components were directly injected into the aquifer. Results showed that groundwater could form and keep low oxidation-reduction potential (ORP), a neutral pH, and anoxic conditions after different degrees of fluctuations, which was benefit for the reductive dechlorination of CAHs. The injection also caused an obvious increase in the total organic carbon (TOC) concentration and sulfate reduction. After 253 days post-injection, the mean concentration of total chlorinated ethylene (CEE) from two monitoring wells decreased from 304 μg/L to 8 μg/L, and total chlorinated ethane (CEA) decreased from 548 μg/L to 108 μg/L. Occurrence of chloroethane (CA) suggested that hydrogenolysis dechlorination was one of the main degradation pathways for CEA, and also hints that biological dechlorination was activated. A significant increase of ethylene at day 67 post-injection indicated that dechlorination was complete. Additionally, the total bacterial counts increased by 2-3 orders of magnitude after 253 days post-injection. And the microbial species richness decreased and gradually changed to anaerobic/fermentative bacteria. The relative abundance of potential degradation bacteria increased corresponding to the degradation of CAHs. This work demonstrates that mZVI and biostimulation can be combined to achieve the efficient removal of various CAHs from contaminated groundwater sources.Keywords: chlorinated aliphatic hydrocarbons, groundwater, field study, zero-valent iron, biostimulation
Procedia PDF Downloads 165342 Use of Activated Carbon from Olive Stone for CO₂ Capture in Porous Mortars
Authors: A. González-Caro, A. M. Merino-Lechuga, D. Suescum-Morales, E. Fernández-Ledesma, J. R. Jiménez, J. M. Fernández-Rodríguez
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Climate change is one of the most significant issues today. Since the 19th century, the rise in temperature has not only been due to natural change, but also to human activities, which have been the main cause of climate change, mainly due to the burning of fossil fuels such as coal, oil and gas. The boom in the construction sector in recent years is also one of the main contributors to CO₂ emissions into the atmosphere; for example, for every tonne of cement produced, 1 tonne of CO₂ is emitted into the atmosphere. Most of the research being carried out in this sector is focused on reducing the large environmental impact generated during the manufacturing process of building materials. In detail, this research focuses on the recovery of waste from olive oil mills. Spain is the world's largest producer of olive oil, and this sector generates a large amount of waste and by-products such as olive pits, “alpechín” or “alpeorujo”. This olive stone by means of a pyrosilisis process gives rise to the production of active carbon. The process causes the carbon to develop many internal spaces. This study is based on the manufacture of porous mortars with Portland cement and natural limestone sand, with an addition of 5% and 10% of activated carbon. Two curing environments were used: i) dry chamber, with a humidity of 65 ± 10% and temperature of 21 ± 2 ºC and an atmospheric CO₂ concentration (approximately 0.04%); ii) accelerated carbonation chamber, with a humidity of 65 ± 10% and temperature of 21 ± 2 ºC and an atmospheric CO₂ concentration of 5%. In addition to eliminating waste from an industry, the aim of this study is to reduce atmospheric CO₂. For this purpose, first, a physicochemical and mineralogical characterisation of all raw materials was carried out, using techniques such as fluorescence and X-ray diffraction. The particle size and specific surface area of the activated carbon were determined. Subsequently, tests were carried out on the hardened mortar, such as thermogravimetric analysis (to determine the percentage of CO₂ capture), as well as mechanical properties, density, porosity, and water absorption. It was concluded that the activated carbon acts as a sink for CO₂, causing it to be trapped inside the voids. This increases CO₂ capture by 300% with the addition of 10% activated carbon at 7 days of curing. There was an increase in compressive strength of 17.5% with the CO₂ chamber after 7 days of curing using 10% activated carbon compared to the dry chamber.Keywords: olive stone, activated carbon, porous mortar, CO₂ capture, economy circular
Procedia PDF Downloads 63341 Efficient Field-Oriented Motor Control on Resource-Constrained Microcontrollers for Optimal Performance without Specialized Hardware
Authors: Nishita Jaiswal, Apoorv Mohan Satpute
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The increasing demand for efficient, cost-effective motor control systems in the automotive industry has driven the need for advanced, highly optimized control algorithms. Field-Oriented Control (FOC) has established itself as the leading approach for motor control, offering precise and dynamic regulation of torque, speed, and position. However, as energy efficiency becomes more critical in modern applications, implementing FOC on low-power, cost-sensitive microcontrollers pose significant challenges due to the limited availability of computational and hardware resources. Currently, most solutions rely on high-performance 32-bit microcontrollers or Application-Specific Integrated Circuits (ASICs) equipped with Floating Point Units (FPUs) and Hardware Accelerated Units (HAUs). These advanced platforms enable rapid computation and simplify the execution of complex control algorithms like FOC. However, these benefits come at the expense of higher costs, increased power consumption, and added system complexity. These drawbacks limit their suitability for embedded systems with strict power and budget constraints, where achieving energy and execution efficiency without compromising performance is essential. In this paper, we present an alternative approach that utilizes optimized data representation and computation techniques on a 16-bit microcontroller without FPUs or HAUs. By carefully optimizing data point formats and employing fixed-point arithmetic, we demonstrate how the precision and computational efficiency required for FOC can be maintained in resource-constrained environments. This approach eliminates the overhead performance associated with floating-point operations and hardware acceleration, providing a more practical solution in terms of cost, scalability and improved execution time efficiency, allowing faster response in motor control applications. Furthermore, it enhances system design flexibility, making it particularly well-suited for applications that demand stringent control over power consumption and costs.Keywords: field-oriented control, fixed-point arithmetic, floating point unit, hardware accelerator unit, motor control systems
Procedia PDF Downloads 14340 New Experiences into Pancreatic Disease Science
Authors: Nadia Akbarpour
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Pancreatic ductal adenocarcinoma is a forceful and obliterating illness, which is portrayed by intrusiveness, fast movement, and significant protection from treatment. Advances in neurotic arrangement and malignant growth hereditary qualities have worked on our illustrative comprehension of this infection; be that as it may, significant parts of pancreatic disease science remain ineffectively comprehended. A superior comprehension of pancreatic disease science should lead the way to more viable medicines. In the course of the most recent couple of years, there have been significant advances in the sub-atomic and organic comprehension of pancreatic malignancy. This included comprehension of the genomic intricacy of the illness, the job of pancreatic malignant growth undifferentiated organisms, the importance of the growth microenvironment, and the one-of-a-kind metabolic transformation of pancreas disease cells to acquire supplements under hypoxic climate. Endeavors have been made towards the advancement of the practical answer for its treatment with compelled achievement due to its complicated science. It is grounded that pancreatic malignancy undifferentiated cells (CSCs), yet present in a little count, contribute extraordinarily to PC inception, movement, and metastasis. Standard chemo and radiotherapeutic choices, notwithstanding, grow general endurance, the connected aftereffects are a huge concern. In the midst of the latest decade, our understanding with regards to atomic and cell pathways engaged with PC and the job of CSCs in its movement has expanded massively. By and by, the center is to target CSCs. The natural items have acquired a lot of thought as of late as they, generally, sharpen CSCs to chemotherapy and target atomic flagging engaged with different cancers, including PC. Some arranged investigations have demonstrated promising outcomes recommending that assessments in this course bring a ton to the table for the treatment of PC. Albeit preclinical investigations uncovered the significance of natural items in lessening pancreatic carcinoma, restricted examinations have been led to assess their part in centers. The current survey gives another knowledge to late advances in pancreatic malignancy science, treatment, and the current status of natural items in its expectation.Keywords: pancreatic, genomic, organic, cancer
Procedia PDF Downloads 138339 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
Procedia PDF Downloads 176338 Trans-Activator of Transcription-Tagged Active AKT1 Variants for Delivery to Mammalian Cells
Authors: Tarana Siddika, Ilka U. Heinemann, Patrick O’Donoghue
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Protein kinase B (AKT1) is a serine/threonine kinase and central transducer of cell survival pathways. Typical approaches to study AKT1 biology in cells rely on growth factor or insulin stimulation that activates AKT1 via phosphorylation at two key regulatory sites (Threonine308, Serine473), yet cell stimulation also activates many other kinases and fails to differentiate the effect of the two main activating sites of AKT1 on downstream substrate phosphorylation and cell growth. While both AKT1 activating sites are associated with disease and used as clinical markers, in some cancers, high levels of Threonine308 phosphorylation are associated with poor prognosis while in others poor survival correlates with high Serine473 levels. To produce cells with specific AKT1 activity, a system was developed to deliver active AKT1 to human cells. AKT1 phospho-variants were produced from Escherichia coli with programmed phosphorylation by genetic code expansion. Tagging of AKT1 with an N-terminal cell penetrating peptide tag derived from the human immunodeficiency virus trans-activator of transcription (TAT) helped to enter AKT1 proteins in mammalian cells. The TAT-tag did not alter AKT1 kinase activity and was necessary and sufficient to rapidly deliver AKT1 protein variants that persisted in human cells for 24 h without the need to use transfection reagents. TAT-pAKT1T308, TAT-pAKT1S473 and TAT-pAKT1T308S473 proteins induced selective phosphorylation of the known AKT1 substrate GSK-3αβ, and downstream stimulation of the AKT1 pathway as evidenced by phosphorylation of ribosomal protein S6 at Serine240/244 in transfected cells. Increase in cell growth and proliferation was observed due to the transfection of different phosphorylated AKT1 protein variants compared to cells with TAT-AKT1 protein. The data demonstrate efficient delivery of AKT1 with programmed phosphorylation to human cells, thus establishing a cell-based model system to investigate signaling that is dependent on specific AKT1 activity and phosphorylation.Keywords: cell penetrating peptide, cell signaling, protein kinase b (AKT1), phosphorylation
Procedia PDF Downloads 118337 Identification of the Expression of Top Deregulated MiRNAs in Rheumatoid Arthritis and Osteoarthritis
Authors: Hala Raslan, Noha Eltaweel, Hanaa Rasmi, Solaf Kamel, May Magdy, Sherif Ismail, Khalda Amr
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Introduction: Rheumatoid arthritis (RA) is an inflammatory, autoimmune disorder with progressive joint damage. Osteoarthritis (OA) is a degenerative disease of the articular cartilage that shows multiple clinical manifestations or symptoms resembling those of RA. Genetic predisposition is believed to be a principal etiological factor for RA and OA. In this study, we aimed to measure the expression of the top deregulated miRNAs that might be the cause of pathogenesis in both diseases, according to our latest NGS analysis. Six of the deregulated miRNAs were selected as they had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis.Methods: Eighty cases were recruited in this study; 45 rheumatoid arthiritis (RA), 30 osteoarthiritis (OA) patients, as well as 20 healthy controls. The selection of the miRNAs from our latest NGS study was done using miRwalk according to the number of their target genes that are members in the KEGG RA pathway. Total RNA was isolated from plasma of all recruited cases. The cDNA was generated by the miRcury RT Kit then used as a template for real-time PCR with miRcury Primer Assays and the miRcury SYBR Green PCR Kit. Fold changes were calculated from CT values using the ΔΔCT method of relative quantification. Results were compared RA vs Controls and OA vs Controls. Target gene prediction and functional annotation of the deregulated miRNAs was done using Mienturnet. Results: Six miRNAs were selected. They were miR-15b-3p, -128-3p, -194-3p, -328-3p, -542-3p and -3180-5p. In RA samples, three of the measured miRNAs were upregulated (miR-194, -542, and -3180; mean Rq= 2.6, 3.8 and 8.05; P-value= 0.07, 0.05 and 0.01; respectively) while the remaining 3 were downregulated (miR-15b, -128 and -328; mean Rq= 0.21, 0.39 and 0.6; P-value= <0.0001, <0.0001 and 0.02; respectively) all with high statistical significance except miR-194. While in OA samples, two of the measured miRNAs were upregulated (miR-194 and -3180; mean Rq= 2.6 and 7.7; P-value= 0.1 and 0.03; respectively) while the remaining 4 were downregulated (miR-15b, -128, -328 and -542; mean Rq= 0.5, 0.03, 0.08 and 0.5; P-value= 0.0008, 0.003, 0.006 and 0.4; respectively) with statistical significance compared to controls except miR-194 and miR-542. The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Conclusion: Five of the studied miRNAs were greatly deregulated in RA and OA, they might be highly involved in the disease pathogenesis and so might be future therapeutic targets. Further functional studies are crucial to assess their roles and actual target genes.Keywords: MiRNAs, expression, rheumatoid arthritis, osteoarthritis
Procedia PDF Downloads 79336 Fabric-Reinforced Cementitious Matrix (FRCM)-Repaired Corroded Reinforced Concrete (RC) Beams under Monotonic and Fatigue Loads
Authors: Mohammed Elghazy, Ahmed El Refai, Usama Ebead, Antonio Nanni
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Rehabilitating corrosion-damaged reinforced concrete (RC) structures has been accomplished using various techniques such as steel plating, external post-tensioning, and external bonding of fiber reinforced polymer (FRP) composites. This paper reports on the use of an innovative technique to strengthen corrosion-damaged RC structures using fabric-reinforced cementitious matrix (FRCM) composites. FRCM consists of dry-fiber fabric embedded in cement-based matrix. Twelve large-scale RC beams were constructed and tested in flexural monotonic and fatigue loads. Prior to testing, ten specimens were subjected to accelerated corrosion process for 140 days leading to an average mass loss in the tensile steel bars of 18.8 %. Corrosion was restricted to the main reinforcement located in the middle third of the beam span. Eight corroded specimens were repaired and strengthened while two virgin and two corroded-unrepaired/unstrengthened beams were used as benchmarks for comparison purpose. The test parameters included the FRCM materials (Carbon-FRCM, PBO-FRCM), the number of FRCM plies, the strengthening scheme, and the type of loading (monotonic and fatigue). The effects of the pervious parameters on the flexural response, the mode of failure, and the fatigue life were reported. Test results showed that corrosion reduced the yield and ultimate strength of the beams. The corroded-unrepaired specimen failed to meet the provisions of the ACI-318 code for crack width criteria. The use of FRCM significantly increased the ultimate strength of the corroded specimen by 21% and 65% more than that of the corroded-unrepaired specimen. Corrosion significantly decreased the fatigue life of the corroded-unrepaired beam by 77% of that of the virgin beam. The fatigue life of the FRCM repaired-corroded beams increased to 1.5 to 3.8 times that of the corroded-unrepaired beam but was lower than that of the virgin specimen. The specimens repaired with U-wrapped PBO-FRCM strips showed higher fatigue life than those repaired with the end-anchored bottom strips having similar number of PBO-FRCM-layers. PBO-FRCM was more effective than Carbon-FRCM in restoring the fatigue life of the corroded specimens.Keywords: corrosion, concrete, fabric-reinforced cementitious matrix (FRCM), fatigue, flexure, repair
Procedia PDF Downloads 296335 The Development of the First Inter-Agency Residential Rehabilitation Service for Gambling Disorder with Complex Clinical Needs
Authors: Dragos Dragomir-Stanciu, Leon Marsh
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Background As a response to the gaps identified in recent research in the provision of residential care to address co-occurring health needs, including mental health problems and complexities Gamble Aware has facilitated the possibility to provide a new service which would extend the NGTS provision of residential rehabilitation for gambling disorder with complex and co-morbid presentation. Gordon Moody, together with Adferiad have been successful in securing the tender for this service and this presentation aims to introduce FOLD, the resulting model of treatment developed for the delivery of the service. Setting As a partnership, we have come together to coproduce a model which allows us to share our clinical and industry knowledge and build on our reputations as trusted treatment providers. The presentation will outline our expertise share in development of a unified approach to recovery-oriented models of care, clinical governance, risk assessment and management and aftercare and continuous recovery. We will also introduce our innovative specialist referral portal which will offer referring partners the ability to include the service user in planning their own recovery journey. Outcomes Our collaboration has resulted in the development of the FOLD model which includes three agile and flexible treatment packages aimed at offering the most enhanced and comprehensive treatment in UK, to date, for those most affected by gambling harm. The paper will offer insight into each treatment package and all recovery model stages involved, as well as into the partnership work with NGST providers, local mental health and social care providers and lived experience organisation that will enable us to offer support to more 100 people a year who would otherwise get “lost in the system”. Conclusion FOLD offers a great opportunity to develop, implement and evaluate a new, much needed, whole-person and whole-system approach to counter gambling related harms.Keywords: gambling treatment, partnership working, integrated care pathways, NGTS, complex needs
Procedia PDF Downloads 134334 Characterization, Replication and Testing of Designed Micro-Textures, Inspired by the Brill Fish, Scophthalmus rhombus, for the Development of Bioinspired Antifouling Materials
Authors: Chloe Richards, Adrian Delgado Ollero, Yan Delaure, Fiona Regan
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Growing concern about the natural environment has accelerated the search for non-toxic, but at the same time, economically reasonable, antifouling materials. Bioinspired surfaces, due to their nano and micro topographical antifouling capabilities, provide a hopeful approach to the design of novel antifouling surfaces. Biological organisms are known to have highly evolved and complex topographies, demonstrating antifouling potential, i.e. shark skin. Previous studies have examined the antifouling ability of topographic patterns, textures and roughness scales found on natural organisms. One of the mechanisms used to explain the adhesion of cells to a substrate is called attachment point theory. Here, the fouling organism experiences increased attachment where there are multiple attachment points and reduced attachment, where the number of attachment points are decreased. In this study, an attempt to characterize the microtopography of the common brill fish, Scophthalmus rhombus, was undertaken. Scophthalmus rhombus is a small flatfish of the family Scophthalmidae, inhabiting regions from Norway to the Mediterranean and the Black Sea. They reside in shallow sandy and muddy coastal areas at depths of around 70 – 80 meters. Six engineered surfaces (inspired by the Brill fish scale) produced by a 2-photon polymerization (2PP) process were evaluated for their potential as an antifouling solution for incorporation onto tidal energy blades. The micro-textures were analyzed for their AF potential under both static and dynamic laboratory conditions using two laboratory grown diatom species, Amphora coffeaeformis and Nitzschia ovalis. The incorporation of a surface topography was observed to cause a disruption in the growth of A. coffeaeformis and N. ovalis cells on the surface in comparison to control surfaces. This work has demonstrated the importance of understanding cell-surface interaction, in particular, topography for the design of novel antifouling technology. The study concluded that biofouling can be controlled by physical modification, and has contributed significant knowledge to the use of a successful novel bioinspired AF technology, based on Brill, for the first time.Keywords: attachment point theory, biofouling, Scophthalmus rhombus, topography
Procedia PDF Downloads 107333 Assessing Impacts of Climate Variability and Change on Water Productivity and Nutrient Use Efficiency of Maize in the Semi-arid Central Rift Valley of Ethiopia
Authors: Fitih Ademe, Kibebew Kibret, Sheleme Beyene, Mezgebu Getnet, Gashaw Meteke
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Changes in precipitation, temperature and atmospheric CO2 concentration are expected to alter agricultural productivity patterns worldwide. The interactive effects of soil moisture and nutrient availability are the two key edaphic factors that determine crop yield and are sensitive to climatic changes. The study assessed the potential impacts of climate change on maize yield and corresponding water productivity and nutrient use efficiency under climate change scenarios for the Central Rift Valley of Ethiopia by mid (2041-2070) and end century (2071-2100). Projected impacts were evaluated using climate scenarios generated from four General Circulation Models (GCMs) dynamically downscaled by the Swedish RCA4 Regional Climate Model (RCM) in combination with two Representative Concentration Pathways (RCP 4.5 and RCP8.5). Decision Support System for Agro-technology Transfer cropping system model (DSSAT-CSM) was used to simulate yield, water and nutrient use for the study periods. Results indicate that rainfed maize yield might decrease on average by 16.5 and 23% by the 2050s and 2080s, respectively, due to climate change. Water productivity is expected to decline on average by 2.2 and 12% in the CRV by mid and end centuries with respect to the baseline. Nutrient uptake and corresponding nutrient use efficiency (NUE) might also be negatively affected by climate change. Phosphorus uptake probably will decrease in the CRV on average by 14.5 to 18% by 2050s, while N uptake may not change significantly at Melkassa. Nitrogen and P use efficiency indicators showed decreases in the range between 8.5 to 10.5% and between 9.3 to 10.5%, respectively, by 2050s relative to the baseline average. The simulation results further indicated that a combination of increased water availability and optimum nutrient application might increase both water productivity and nutrient use efficiency in the changed climate, which can ensure modest production in the future. Potential options that can improve water availability and nutrient uptake should be identified for the study locations using a crop modeling approach.Keywords: crop model, climate change scenario, nutrient uptake, nutrient use efficiency, water productivity
Procedia PDF Downloads 86332 Estimation of Snow and Ice Melt Contributions to Discharge from the Glacierized Hunza River Basin, Karakoram, Pakistan
Authors: Syed Hammad Ali, Rijan Bhakta Kayastha, Danial Hashmi, Richard Armstrong, Ahuti Shrestha, Iram Bano, Javed Hassan
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This paper presents the results of a semi-distributed modified positive degree-day model (MPDDM) for estimating snow and ice melt contributions to discharge from the glacierized Hunza River basin, Pakistan. The model uses daily temperature data, daily precipitation data, and positive degree day factors for snow and ice melt. The model is calibrated for the period 1995-2001 and validated for 2002-2013, and demonstrates close agreements between observed and simulated discharge with Nash–Sutcliffe Efficiencies of 0.90 and 0.88, respectively. Furthermore, the Weather Research and Forecasting model projected temperature, and precipitation data from 2016-2050 are used for representative concentration pathways RCP4.5 and RCP8.5, and bias correction was done using a statistical approach for future discharge estimation. No drastic changes in future discharge are predicted for the emissions scenarios. The aggregate snow-ice melt contribution is 39% of total discharge in the period 1993-2013. Snow-ice melt contribution ranges from 35% to 63% during the high flow period (May to October), which constitutes 89% of annual discharge; in the low flow period (November to April) it ranges from 0.02% to 17%, which constitutes 11 % of the annual discharge. The snow-ice melt contribution to total discharge will increase gradually in the future and reach up to 45% in 2041-2050. From a sensitivity analysis, it is found that the combination of a 2°C temperature rise and 20% increase in precipitation shows a 10% increase in discharge. The study allows us to evaluate the impact of climate change in such basins and is also useful for the future prediction of discharge to define hydropower potential, inform other water resource management in the area, to understand future changes in snow-ice melt contribution to discharge, and offer a possible evaluation of future water quantity and availability.Keywords: climate variability, future discharge projection, positive degree day, regional climate model, water resource management
Procedia PDF Downloads 290331 Improvising Grid Interconnection Capabilities through Implementation of Power Electronics
Authors: Ashhar Ahmed Shaikh, Ayush Tandon
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The swift reduction of fossil fuels from nature has crucial need for alternative energy sources to cater vital demand. It is essential to boost alternative energy sources to cover the continuously increasing demand for energy while minimizing the negative environmental impacts. Solar energy is one of the reliable sources that can generate energy. Solar energy is freely available in nature and is completely eco-friendly, and they are considered as the most promising power generating sources due to their easy availability and other advantages for the local power generation. This paper is to review the implementation of power electronic devices through Solar Energy Grid Integration System (SEGIS) to increase the efficiency. This paper will also concentrate on the future grid infrastructure and various other applications in order to make the grid smart. Development and implementation of a power electronic devices such as PV inverters and power controllers play an important role in power supply in the modern energy economy. Solar Energy Grid Integration System (SEGIS) opens pathways for promising solutions for new electronic and electrical components such as advanced innovative inverter/controller topologies and their functions, economical energy management systems, innovative energy storage systems with equipped advanced control algorithms, advanced maximum-power-point tracking (MPPT) suited for all PV technologies, protocols and the associated communications. In addition to advanced grid interconnection capabilities and features, the new hardware design results in small size, less maintenance, and higher reliability. The SEGIS systems will make the 'advanced integrated system' and 'smart grid' evolutionary processes to run in a better way. Since the last few years, there was a major development in the field of power electronics which led to more efficient systems and reduction of the cost per Kilo-watt. The inverters became more efficient and had reached efficiencies in excess of 98%, and commercial solar modules have reached almost 21% efficiency.Keywords: solar energy grid integration systems, smart grid, advanced integrated system, power electronics
Procedia PDF Downloads 184330 A Next Generation Multi-Scale Modeling Theatre for in silico Oncology
Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal
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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling
Procedia PDF Downloads 222329 Community Observatory for Territorial Information Control and Management
Authors: A. Olivi, P. Reyes Cabrera
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Ageing and urbanization are two of the main trends that characterize the twenty-first century. Its trending is especially accelerated in the emerging countries of Asia and Latin America. Chile is one of the countries in the Latin American region, where the demographic transition to ageing is becoming increasingly visible. The challenges that the new demographic scenario poses to urban administrators call for searching innovative solutions to maximize the functional and psycho-social benefits derived from the relationship between older people and the environment in which they live. Although mobility is central to people's everyday practices and social relationships, it is not distributed equitably. On the contrary, it can be considered another factor of inequality in our cities. Older people are a particularly sensitive and vulnerable group to mobility. In this context, based on the ageing in place strategy and following the social innovation approach within a spatial context, the "Community Observatory of Territorial Information Control and Management" project aims at the collective search and validation of solutions for the satisfaction of mobility and accessibility specific needs of urban aged people. Specifically, the Observatory intends to: i) promote the direct participation of the aged population in order to generate relevant information on the territorial situation and the satisfaction of the mobility needs of this group; ii) co-create dynamic and efficient mechanisms for the reporting and updating of territorial information; iii) increase the capacity of the local administration to plan and manage solutions to environmental problems at the neighborhood scale. Based on a participatory mapping methodology and on the application of digital technology, the Observatory designed and developed, together with aged people, a crowdsourcing platform for smartphones, called DIMEapp, for reporting environmental problems affecting mobility and accessibility. DIMEapp has been tested at a prototype level in two neighborhoods of the city of Valparaiso. The results achieved in the testing phase have shown high potential in order to i) contribute to establishing coordination mechanisms with the local government and the local community; ii) improve a local governance system that guides and regulates the allocation of goods and services destined to solve those problems.Keywords: accessibility, ageing, city, digital technology, local governance
Procedia PDF Downloads 131328 Urban Compactness and Sustainability: Beijing Experience
Authors: Xilu Liu, Ameen Farooq
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Beijing has several compact residential housing settings in many of its urban districts. The study in this paper reveals that urban compactness, as predictor of density, may carry an altogether different meaning in the developing world when compared to the U.S for achieving objectives of urban sustainability. Recent urban design studies in the U.S are debating for compact and mixed-use higher density housing to achieve sustainable and energy efficient living environments. While the concept of urban compactness is widely accepted as an approach in modern architectural and urban design fields, this belief may not directly carry well into all areas within cities of developing countries. Beijing’s technology-driven economy, with its historic and rich cultural heritage and a highly speculated real-estate market, extends its urban boundaries into multiple compact urban settings of varying scales and densities. The accelerated pace of migration from the countryside for better opportunities has led to unsustainable and uncontrolled buildups in order to meet the growing population demand within and outside of the urban center. This unwarranted compactness in certain urban zones has produced an unhealthy physical density with serious environmental and ecological challenging basic living conditions. In addition, crowding, traffic congestion, pollution and limited housing surrounding this compactness is a threat to public health. Several residential blocks in close proximity to each other were found quite compacted, or ill-planned, with residential sites due to lack of proper planning in Beijing. Most of them at first sight appear to be compact and dense but further analytical studies revealed that what appear to be dense actually are not as dense as to make a good case that could serve as the corner stone of sustainability and energy efficiency. This study considered several factors including floor area ratio (FAR), ground coverage (GSI), open space ratio (OSR) as indicators in analyzing urban compactness as a predictor of density. The findings suggest that these measures, influencing the density of residential sites under study, were much smaller in density than expected given their compact adjacencies. Further analysis revealed that several residential housing appear to support the notion of density in its compact layout but are actually compacted due to unregulated planning marred by lack of proper urban design standards, policies and guidelines specific to their urban context and condition.Keywords: Beijing, density, sustainability, urban compactness
Procedia PDF Downloads 424327 An Original and Suitable Induction Method of Repeated Hypoxic Stress by Hydralazine to Investigate the Integrity of an in Vitro Contact Co-Culture Blood Brain Barrier Model
Authors: Morgane Chatard, Clémentine Puech, Nathalie Perek, Frédéric Roche
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Several neurological disorders are linked to repeated hypoxia. The impact of such repeated hypoxic stress, on endothelial cells function of the blood-brain barrier (BBB) is little studied in the literature. Indeed, the study of hypoxic stress in cellular pathways is complex using hypoxia exposure because HIF 1α (factor induced by hypoxia) has a short half life. Our study presents an innovative induction method of repeated hypoxic stress, more reproducible, which allows us to study its impacts on an in vitro contact co-culture BBB model. Repeated hypoxic stress was induced by hydralazine (a mimetic agent of hypoxia pathway) during two hours and repeated during 24 hours. Then, BBB integrity was assessed by permeability measurements (transendothelial electrical resistance and membrane permeability), tight junction protein expressions (cell-ELISA and confocal microscopy) and by studying expression and activity of efflux transporters. First, this study showed that repeated hypoxic stress leads to a BBB’s dysfunction illustrated by a significant increase in permeability. This loss of membrane integrity was linked to a significant decrease of tight junctions’ protein expressions, facilitating a possible transfer of potential cytotoxic compounds in the brain. Secondly, we demonstrated that brain microvascular endothelial cells had set-up defence mechanism. These endothelial cells significantly increased the activity of their efflux transporters which was associated with a significant increase in their expression. In conclusion, repeated hypoxic stress lead to a loss of BBB integrity with a decrease of tight junction proteins. In contrast, endothelial cells increased the expression of their efflux transporters to fight against cytotoxic compounds brain crossing. Unfortunately, enhanced efflux activity could also lead to reducing pharmacological drugs delivering to the brain in such hypoxic conditions.Keywords: BBB model, efflux transporters, repeated hypoxic stress, tigh junction proteins
Procedia PDF Downloads 292326 Interrogating Student-Teachers’ Transformative Learning Role, Resources and Journey Considering Pedagogical Reform in Teacher Education Continuums
Authors: Nji Clement Bang, Rosemary Shafack M., Kum Henry Asei, Yaro Loveline Y
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Scholars perceive learner-centered teaching-learning reform as roles and resources in teacher education (TE) and professional outcome with transformative learning (TL) continuum dimensions. But, teaching-learning reform is fast proliferating amidst debilitating stakeholder systemic dichotomies, resources, commitment, resistance and poor quality outcome that necessitate stronger TE and professional continuums. Scholars keep seeking greater understanding of themes in teaching-learning reform, TE and professional outcome as continuums and how policymakers, student-teachers, teacher trainers and local communities concerned with initial TE can promote continuous holistic quality performance. To sustain the debate continuum and answer the overarching question, we use mixed-methods research-design with diverse literature and 409 sample-data. Onset text, interview and questionnaire analyses reveal debilitating teaching-learning reform in TE continuums that need TL revival. Follow-up focus group discussion and teaching considering TL insights reinforce holistic teaching-learning in TE. Therefore, significant increase in diverse prior-experience articulation1; critical reflection-discourse engagement2; teaching-practice interaction3; complex-activity constrain control4 and formative outcome- reintegration5 reinforce teaching-learning in learning-to-teach role-resource pathways and outcomes. Themes reiterate complex teaching-learning in TE programs that suits TL journeys and student-teachers and students cum teachers, workers/citizens become akin, transformative-learners who evolve personal and collective roles-resources towards holistic-lifelong-learning outcomes. The article could assist debate about quality teaching-learning reform through TL dimensions as TE and professional role-resource continuums.Keywords: transformative learning perspectives, teacher education, initial teacher education, learner-centered pedagogical reform, life-long learning
Procedia PDF Downloads 76325 Multi-Scale Modelling of the Cerebral Lymphatic System and Its Failure
Authors: Alexandra K. Diem, Giles Richardson, Roxana O. Carare, Neil W. Bressloff
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Alzheimer's disease (AD) is the most common form of dementia and although it has been researched for over 100 years, there is still no cure or preventive medication. Its onset and progression is closely related to the accumulation of the neuronal metabolite Aβ. This raises the question of how metabolites and waste products are eliminated from the brain as the brain does not have a traditional lymphatic system. In recent years the rapid uptake of Aβ into cerebral artery walls and its clearance along those arteries towards the lymph nodes in the neck has been suggested and confirmed in mice studies, which has led to the hypothesis that interstitial fluid (ISF), in the basement membranes in the walls of cerebral arteries, provides the pathways for the lymphatic drainage of Aβ. This mechanism, however, requires a net reverse flow of ISF inside the blood vessel wall compared to the blood flow and the driving forces for such a mechanism remain unknown. While possible driving mechanisms have been studied using mathematical models in the past, a mechanism for net reverse flow has not been discovered yet. Here, we aim to address the question of the driving force of this reverse lymphatic drainage of Aβ (also called perivascular drainage) by using multi-scale numerical and analytical modelling. The numerical simulation software COMSOL Multiphysics 4.4 is used to develop a fluid-structure interaction model of a cerebral artery, which models blood flow and displacements in the artery wall due to blood pressure changes. An analytical model of a layer of basement membrane inside the wall governs the flow of ISF and, therefore, solute drainage based on the pressure changes and wall displacements obtained from the cerebral artery model. The findings suggest that an active role in facilitating a reverse flow is played by the components of the basement membrane and that stiffening of the artery wall during age is a major risk factor for the impairment of brain lymphatics. Additionally, our model supports the hypothesis of a close association between cerebrovascular diseases and the failure of perivascular drainage.Keywords: Alzheimer's disease, artery wall mechanics, cerebral blood flow, cerebral lymphatics
Procedia PDF Downloads 526324 Comparison of Patient Stay at Withy Bush Same Day Emergency Care and Then Those at the Emergency Department
Authors: Joshua W. Edefo, Shafiul Azam, Murray D. Smith
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Introduction: In April 2022, the Welsh Government introduced the six goals for urgent and emergency care programs. One of these goals was to provide access to clinically safe alternatives, leading to the establishment of the Same Day Emergency Care (SDEC) program. The SDEC initiative aims to offer viable options that maintain patient safety while avoiding unnecessary hospital stays. The aim of the study is to determine the duration of patient stay in SDEC and compare it with that of Emergency department (ED) stay to ascertain if one of the objectives of SDEC is achieved. Methods: Patient stays and attendance datasets were constructed from Withybush SDEC and ED patient records. These records were provided by Hywel Dda University Health Board Informatics. Some hypothetical pathways were identified, notably SDEC visits involving a single attendance and ED visits then immediately transferred to SDEC. Descriptive statistics were used to summarise the data, and hypothesis tests for mean differences used the student t-test. Propensity scoring was employed to match a set of ED patient stays to SDEC patient stays which were then used to determine the average treatment effect (ATE) to compare durations of stay in SDEC with ED. Regression methods were used to model the natural logarithm of the duration of SDEC attendance, and the level of statistical significance was set to 0.05. Results: SDEC visits involving a single attendance (170 of 384; 44.3%) is the most frequently observed pathway with patient length of stay at 256 minutes (95%CI 237.4 - 275.1). The next most frequently observed pathway of patient stay was SDEC attendance after presenting to ED (80 of 384; 20.8%) and gave the length of stay of 440 minutes (95%CI 351.6 - 529.2). Time spent in this pathway significantly increased by 184 minutes (95%CI 118.0 - 250.2, support for no difference p<0.001) compared to the most seen pathway. When SDEC data were compared with ED, the estimate for the ATE from SDEC single attendance was -272 minutes (95%CI -334.1 - -210.5; p<0.001), while that of ED then SDEC pathway was -50.6 min (95%CI -182.7-81.5; p=0.453). Conclusion: When patients are admitted to SDEC and successfully discharged, their stays are significantly shorter, approximately 4.5 hours, compared to patients who spend their entire stay in the Emergency Department. That difference vanishes when the patient stay includes a period spent previously in ED before transfer to SDEC.Keywords: attendance, emergency-department, patient-stay, same-day-emergency-care
Procedia PDF Downloads 45323 The Structure and Development of a Wing Tip Vortex under the Effect of Synthetic Jet Actuation
Authors: Marouen Dghim, Mohsen Ferchichi
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The effect of synthetic jet actuation on the roll-up and the development of a wing tip vortex downstream a square-tipped rectangular wing was investigated experimentally using hotwire anemometry. The wing is equipped with a hallow cavity designed to generate a high aspect ratio synthetic jets blowing at an angles with respect to the spanwise direction. The structure of the wing tip vortex under the effect of fluidic actuation was examined at a chord Reynolds number Re_c=8×10^4. An extensive qualitative study on the effect of actuation on the spanwise pressure distribution at c⁄4 was achieved using pressure scanner measurements in order to determine the optimal actuation parameters namely, the blowing momentum coefficient, Cμ, and the non-dimensionalized actuation frequency, F^+. A qualitative study on the effect of actuation parameters on the spanwise pressure distribution showed that optimal actuation frequencies of the synthetic jet were found within the range amplified by both long and short wave instabilities where spanwise pressure coefficients exhibited a considerable decrease by up to 60%. The vortex appeared larger and more diffuse than that of the natural vortex case. Operating the synthetic jet seemed to introduce unsteadiness and turbulence into the vortex core. Based on the ‘a priori’ optimal selected parameters, results of the hotwire wake survey indicated that the actuation achieved a reduction and broadening of the axial velocity deficit. A decrease in the peak tangential velocity associated with an increase in the vortex core radius was reported as a result of the accelerated radial transport of angular momentum. Peak vorticity level near the core was also found to be largely diffused as a direct result of the increased turbulent mixing within the vortex. The wing tip vortex a exhibited a reduced strength and a diffused core as a direct result of increased turbulent mixing due to the presence of turbulent small scale vortices within its core. It is believed that the increased turbulence within the vortex due to the synthetic jet control was the main mechanism associated with the decreased strength and increased size of the wing tip vortex as it evolves downstream. A comparison with a ‘non-optimal’ case was included to demonstrate the effectiveness of selecting the appropriate control parameters. The Synthetic Jet will be operated at various actuation configurations and an extensive parametric study is projected to determine the optimal actuation parameters.Keywords: flow control, hotwire anemometry, synthetic jet, wing tip vortex
Procedia PDF Downloads 436322 An Investigation of Peptide Functionalized Gold Nanoparticles On Colon Cancer Cells For Biomedical Application
Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1
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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.
Procedia PDF Downloads 94321 Participatory Action Research for Strengthening Health Systems: A Freirian Critique from a Community Based Study Conducted in the Northern Areas of Pakistan
Authors: Sohail Bawani, Kausar S. Khan, Rozina Karmaliani, Shehnaz Mir
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Action research (AR) is one of the types of health systems research (HSR), and participatory action research (PAR) is known for being effective in health systems strengthening (HSS). The current literature on PAR for HSS cites numerous examples and case studies that led to improve health services; build child health information system; increase knowledge and awareness of people about health problems, and identify pathways for institutional and policy change by engaging people in research. But examples of marginalized communities being agents of change in health governance are not common in health systems research (HSR). This approach to PAR is at the heart of Paolo Freire’s Social Transformation Theory and Critical Consciousness building, which was used to design a community-based PAR study in the Northern/mountainous areas of Pakistan. The purpose of the study was to understand the place and role of marginalized communities in strengthening existing health governance structure (health facility and village health committees and health boards) by taking marginalized communities as partners. Community meetings were carried out to identify who is living at the social, political, cultural and economic margins in 40 different villages. Participatory reflection and analysis (PRA) tools were used during the meeting to facilitate identification. Focus group discussions were conducted with marginalized groups using PRA tools and family ethnographies with marginalized families identified through group discussions. Findings of the study revealed that for the marginalized health systems constitute more than just delivery of health services, but it also embraces social determinants that surround systems and its governance. The paper argues that from Frerian perspective people’s participation should not only be limited to knowledge generation. People must be seen active users of the knowledge that they generate for achieving better health outcomes that they want to achieve in the time to come. PAR provides a pathway to the marginalized in playing a role in health governance. The study dissemination planned shall engage the marginalized in a dialogue with service providers so that together a role for the marginalized can be outlined.Keywords: participatory action research, health systems, marginalized, health services
Procedia PDF Downloads 283