Search results for: drug safety
985 MicroRNA-1246 Expression Associated with Resistance to Oncogenic BRAF Inhibitors in Mutant BRAF Melanoma Cells
Authors: Jae-Hyeon Kim, Michael Lee
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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy
Procedia PDF Downloads 327984 Formulation and Invivo Evaluation of Salmeterol Xinafoate Loaded MDI for Asthma Using Response Surface Methodology
Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth
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The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery
Procedia PDF Downloads 451983 Evaluation of a Method for the Virtual Design of a Software-based Approach for Electronic Fuse Protection in Automotive Applications
Authors: Dominic Huschke, Rudolf Keil
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New driving functionalities like highly automated driving have a major impact on the electrics/electronics architecture of future vehicles and inevitably lead to higher safety requirements. Partly due to these increased requirements, the vehicle industry is increasingly looking at semiconductor switches as an alternative to conventional melting fuses. The protective functionality of semiconductor switches can be implemented in hardware as well as in software. A current approach discussed in science and industry is the implementation of a model of the protected low voltage power cable on a microcontroller to calculate its temperature. Here, the information regarding the current is provided by the continuous current measurement of the semiconductor switch. The signal to open the semiconductor switch is provided by the microcontroller when a previously defined limit for the temperature of the low voltage power cable is exceeded. A setup for the testing of the described principle for electronic fuse protection of a low voltage power cable is built and successfullyvalidated with experiments afterwards. Here, the evaluation criterion is the deviation of the measured temperature of the low voltage power cable from the specified limit temperature when the semiconductor switch is opened. The analysis is carried out with an assumed ambient temperature as well as with a measured ambient temperature. Subsequently, the experimentally performed investigations are simulated in a virtual environment. The explicit focus is on the simulation of the behavior of the microcontroller with an implemented model of a low voltage power cable in a real-time environment. Subsequently, the generated results are compared with those of the experiments. Based on this, the completely virtual design of the described approach is assumed to be valid.Keywords: automotive wire harness, electronic fuse protection, low voltage power cable, semiconductor-based fuses, software-based validation
Procedia PDF Downloads 106982 Theoretical Discussion on the Classification of Risks in Supply Chain Management
Authors: Liane Marcia Freitas Silva, Fernando Augusto Silva Marins, Maria Silene Alexandre Leite
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The adoption of a network structure, like in the supply chains, favors the increase of dependence between companies and, by consequence, their vulnerability. Environment disasters, sociopolitical and economical events, and the dynamics of supply chains elevate the uncertainty of their operation, favoring the occurrence of events that can generate break up in the operations and other undesired consequences. Thus, supply chains are exposed to various risks that can influence the profitability of companies involved, and there are several previous studies that have proposed risk classification models in order to categorize the risks and to manage them. The objective of this paper is to analyze and discuss thirty of these risk classification models by means a theoretical survey. The research method adopted for analyzing and discussion includes three phases: The identification of the types of risks proposed in each one of the thirty models, the grouping of them considering equivalent concepts associated to their definitions, and, the analysis of these risks groups, evaluating their similarities and differences. After these analyses, it was possible to conclude that, in fact, there is more than thirty risks types identified in the literature of Supply Chains, but some of them are identical despite of be used distinct terms to characterize them, because different criteria for risk classification are adopted by researchers. In short, it is observed that some types of risks are identified as risk source for supply chains, such as, demand risk, environmental risk and safety risk. On the other hand, other types of risks are identified by the consequences that they can generate for the supply chains, such as, the reputation risk, the asset depreciation risk and the competitive risk. These results are consequence of the disagreements between researchers on risk classification, mainly about what is risk event and about what is the consequence of risk occurrence. An additional study is in developing in order to clarify how the risks can be generated, and which are the characteristics of the components in a Supply Chain that leads to occurrence of risk.Keywords: sisks classification, survey, supply chain management, theoretical discussion
Procedia PDF Downloads 634981 Slope Stability Analysis and Evaluation of Road Cut Slope in Case of Goro to Abagada Road, Adama
Authors: Ezedin Geta Seid
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Slope failures are among the common geo-environmental natural hazards in the hilly and mountainous terrain of the world causing damages to human life and destruction of infrastructures. In Ethiopia, the demand for the construction of infrastructures, especially highways and railways, has increased to connect the developmental centers. However, the failure of roadside slopes formed due to the difficulty of geographical locations is the major difficulty for this development. As a result, a comprehensive site-specific investigation of destabilizing agents and a suitable selection of slope profiles are needed during design. Hence, this study emphasized the stability analysis and performance evaluation of slope profiles (single slope, multi-slope, and benched slope). The analysis was conducted for static and dynamic loading conditions using limit equilibrium (slide software) and finite element method (Praxis software). The analysis results in selected critical sections show that the slope is marginally stable, with FS varying from 1.2 to 1.5 in static conditions, and unstable with FS below 1 in dynamic conditions. From the comparison of analysis methods, the finite element method provides more valuable information about the failure surface of a slope than limit equilibrium analysis. Performance evaluation of geometric profiles shows that geometric modification provides better and more economical slope stability. Benching provides significant stability for cut slopes (i.e., the use of 2m and 3m bench improves the factor of safety by 7.5% and 12% from a single slope profile). The method is more effective on steep slopes. Similarly, the use of a multi-slope profile improves the stability of the slope in stratified soil with varied strength. The performance is more significant when it is used in combination with benches. The study also recommends drainage control and slope reinforcement as a remedial measure for cut slopes.Keywords: slope failure, slope profile, bench slope, multi slope
Procedia PDF Downloads 34980 Canada's "Flattened Curve": A Geospatail Temporal Analysis of Canada's Amelioration of The Sars-Cov-2 Pandemic Through Coordinated Government Intervention
Authors: John Ahluwalia
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As an affluent first-world nation, Canada took swift and comprehensive action during the outbreak of the SARS-CoV-2 (COVID-19) pandemic compared to other countries in the same socio-economic cohort. The United States has stumbled to overcome obstacles most developed nations have faced, which has led to significantly more per capita cases and deaths. The initial outbreaks of COVID-19 occurred in the US and Canada within days of each other and posed similar potentially catastrophic threats to public health, the economy, and governmental stability. On a macro level, events that take place in the US have a direct impact on Canada. For example, both countries tend to enter and exit economic recessions at approximately the same time, they are each other’s largest trading partners, and their currencies are inexorably linked. Variables intrinsic to Canada’s national infrastructure have been instrumental in the country’s efforts to flatten the curve of COVID-19 cases and deaths. Canada’s coordinated multi-level governmental effort has allowed it to create and enforce policies related to COVID-19 at both the national and provincial levels. Canada’s policy of universal health care is another variable. Health care and public health measures are enforced on a provincial level, and it is within each province’s jurisdiction to dictate standards for public safety based on scientific evidence. Rather than introducing confusion and the possibility of competition for resources such as PPE and vaccines, Canada’s multi-level chain of government authority has provided consistent policies supporting national public health and local delivery of medical care. This paper will demonstrate that the coordinated efforts on provincial and federal levels have been the linchpin in Canada’s relative success in containing the deadly spread of the COVID-19 virus.Keywords: COVID-19, canada, GIS, geospatial analysis
Procedia PDF Downloads 70979 Advance Hybrid Manufacturing Supply Chain System to Get Benefits of Push and Pull Systems
Authors: Akhtar Nawaz, Sahar Noor, Iftikhar Hussain
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This paper considers advanced hybrid manufacturing planning both push and pull system in which each customer order has a due date by demand forecast and customer orders. We present a tool for model for tool development that requires an absolute due dates and customer orders in a manufacturing supply chain. It is vital for the manufacturing companies to face the problem of variations in demands, increase in varieties by maintaining safety stock and to minimize components obsolescence and uselessness. High inventory cost and low delivery lead time is expected in push type of system and on contrary high delivery lead time and low inventory cost is predicted in the pull type. For this tool for model we need an MRP system for the push and pull environment and control of inventories in push parts and lead time in the pull part. To retain process data quickly, completely and to improve responsiveness and minimize inventory cost, a tool is required to deal with the high product variance and short cycle parts. In practice, planning and scheduling are interrelated and should be solved simultaneously with supply chain to ensure that the due dates of customer orders are met. The proposed tool for model considers alternative process plans for job types, with precedence constraints for job operations. Such a tool for model has not been treated in the literature. To solve the model, tool was developed, so a new technique was required to deal with the issue of high product variance and short life cycles in assemble to order.Keywords: hybrid manufacturing system, supply chain system, make to order, make to stock, assemble to order
Procedia PDF Downloads 564978 Water Resources and Sanitation in Public Schools of Datu Odin Sinsuat, Maguindanao
Authors: Lahaina U. Dilangalen
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Using descriptive-experimental research methods, this study aimed to identify the main resources of water, assessed the water quality, sanitation and hygiene practices, and extent of implementation. Complete enumeration was done in 28 elementary public schools of Datu Odin Sinsuat Municipality. Questionnaires were given to the school advisers. Water samples were obtained from the same schools and were submitted to the Department of Science and Technology (DOST) Region XII for microbial analysis, specifically the presence of fecal coliform bacteria. Four water resources such as hand pump, faucet, deep well and spring were found being used in the 28 schools. Of water resources, the only treated was from the faucet. Most of the schools used the water for drinking and washing. Two schools strongly agreed, nine schools agreed and seventeen schools disagreed that they implemented DepEd Order no.56 s. 2009. In addition, two schools strongly agreed and twenty six agreed that they implemented DepEd Order No. 65 s. 2009. Five schools had water supply that were safe to drink while sixteen schools had water supply that were not safe to drink due to high fecal coliform count and did not undergo chemical treatment. The only safe for drinking were water resources that came from faucet because they were chemically treated. Seven out of 28 schools did not have water supply due to their location in mountainous areas. More than half of the schools did not comply with the DepEd Order No. 56 s. 2009 due to the lack of funds and support from the PTA and LGU. It is recommended that the Department of Education must have an urgent assessment of implementing both DepEd Orders No.56 and 65, to assure that the schoolchildren be protected from water and sanitation related ailments. Also, all water resources that are not treated must be used for washing only. Ideally, all the water resources must be treated to assure the safety of all school constituents. Moreover, the school administrators and teachers in the municipality must be provided copies of the results of this study for reference in implementing the said programs.Keywords: assessment, drinking water, fecal coliform, groundwater
Procedia PDF Downloads 253977 The Phenomenon of Biofilm Formation and the Subsequent Management of Foodborne Pathogenic Bacteria
Authors: Raana Babadi Fathipour
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Biofilms, those intricate structures of microbial aggregation that emerge as microorganisms adhere to animate or inanimate surfaces, possess an innate capacity to shield their inhabitants from adversities within the environment whilst fortifying their endurance against antimicrobial agents. This remarkable aspect facilitates the persistence and virulence of said microorganisms, establishing biofilm formation as an integral component of bacterial survival mechanisms. However, should foodborne pathogens adopt this mode of existence, the potentiality for foodborne disease infections becomes alarmingly intensified—an alarming prospect that harbors significant public health hazards and engenders deleterious economic ramifications. Thus, due to these consequences lurking on the horizon, extensive research concentrating upon comprehending biofilms and devising efficacious removal strategies assumes a position imbued with paramount importance within the realm of the food industry. The problem of food waste resulting from spoilage in the food industry continues to present a widespread challenge to both environmental sustainability and the security of our food supplies. In this comprehensive analysis, we delve into the formation of bacterial biofilms, highlighting the specific issues they pose within the realm of food production. Additionally, we provide an overview of various types of common foodborne pathogens that tend to thrive in these biofilms. Furthermore, we summarize existing strategies aimed at tackling or managing detrimental bacterial biofilm growth. We also introduce contemporary approaches that show promise in terms of controlling this issue and highlight their potential for further advancement. Ultimately, our focus lies on outlining prospects for future development as they pertain specifically to combatting bacterial biofilms within the field.Keywords: foodborne pathogens, food safety, biofilm, resistance, quorum-sensing
Procedia PDF Downloads 59976 Bioanalytical Method Development and Validation of Aminophylline in Rat Plasma Using Reverse Phase High Performance Liquid Chromatography: An Application to Preclinical Pharmacokinetics
Authors: S. G. Vasantharaju, Viswanath Guptha, Raghavendra Shetty
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Introduction: Aminophylline is a methylxanthine derivative belonging to the class bronchodilator. From the literature survey, reported methods reveals the solid phase extraction and liquid liquid extraction which is highly variable, time consuming, costly and laborious analysis. Present work aims to develop a simple, highly sensitive, precise and accurate high-performance liquid chromatography method for the quantification of Aminophylline in rat plasma samples which can be utilized for preclinical studies. Method: Reverse Phase high-performance liquid chromatography method. Results: Selectivity: Aminophylline and the internal standard were well separated from the co-eluted components and there was no interference from the endogenous material at the retention time of analyte and the internal standard. The LLOQ measurable with acceptable accuracy and precision for the analyte was 0.5 µg/mL. Linearity: The developed and validated method is linear over the range of 0.5-40.0 µg/mL. The coefficient of determination was found to be greater than 0.9967, indicating the linearity of this method. Accuracy and precision: The accuracy and precision values for intra and inter day studies at low, medium and high quality control samples concentrations of aminophylline in the plasma were within the acceptable limits Extraction recovery: The method produced consistent extraction recovery at all 3 QC levels. The mean extraction recovery of aminophylline was 93.57 ± 1.28% while that of internal standard was 90.70 ± 1.30%. Stability: The results show that aminophylline is stable in rat plasma under the studied stability conditions and that it is also stable for about 30 days when stored at -80˚C. Pharmacokinetic studies: The method was successfully applied to the quantitative estimation of aminophylline rat plasma following its oral administration to rats. Discussion: Preclinical studies require a rapid and sensitive method for estimating the drug concentration in the rat plasma. The method described in our article includes a simple protein precipitation extraction technique with ultraviolet detection for quantification. The present method is simple and robust for fast high-throughput sample analysis with less analysis cost for analyzing aminophylline in biological samples. In this proposed method, no interfering peaks were observed at the elution times of aminophylline and the internal standard. The method also had sufficient selectivity, specificity, precision and accuracy over the concentration range of 0.5 - 40.0 µg/mL. An isocratic separation technique was used underlining the simplicity of the presented method.Keywords: Aminophyllin, preclinical pharmacokinetics, rat plasma, RPHPLC
Procedia PDF Downloads 223975 An Overview of Technology Availability to Support Remote Decentralized Clinical Trials
Authors: Simone Huber, Bianca Schnalzer, Baptiste Alcalde, Sten Hanke, Lampros Mpaltadoros, Thanos G. Stavropoulos, Spiros Nikolopoulos, Ioannis Kompatsiaris, Lina Pérez- Breva, Vallivana Rodrigo-Casares, Jaime Fons-Martínez, Jeroen de Bruin
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Developing new medicine and health solutions and improving patient health currently rely on the successful execution of clinical trials, which generate relevant safety and efficacy data. For their success, recruitment and retention of participants are some of the most challenging aspects of protocol adherence. Main barriers include: i) lack of awareness of clinical trials; ii) long distance from the clinical site; iii) the burden on participants, including the duration and number of clinical visits and iv) high dropout rate. Most of these aspects could be addressed with a new paradigm, namely the Remote Decentralized Clinical Trials (RDCTs). Furthermore, the COVID-19 pandemic has highlighted additional advantages and challenges for RDCTs in practice, allowing participants to join trials from home and not depend on site visits, etc. Nevertheless, RDCTs should follow the process and the quality assurance of conventional clinical trials, which involve several processes. For each part of the trial, the Building Blocks, existing software and technologies were assessed through a systematic search. The technology needed to perform RDCTs is widely available and validated but is yet segmented and developed in silos, as different software solutions address different parts of the trial and at various levels. The current paper is analyzing the availability of technology to perform RDCTs, identifying gaps and providing an overview of Basic Building Blocks and functionalities that need to be covered to support the described processes.Keywords: architectures and frameworks for health informatics systems, clinical trials, information and communications technology, remote decentralized clinical trials, technology availability
Procedia PDF Downloads 218974 Attitudes and Knowledge of Dental Patients Towards Infection Control Measures in Kuwait University Dental Center
Authors: Fatima Taqi, Abrar Alanzi
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Objectives: The objective of this study is to determine and assess the level of knowledge and attitudes of dental patients attending Kuwait University Dental Clinics (KUDC) regarding the infection control protocols practiced in the clinic. The results would highlight the importance of conducting awareness campaigns in the community to promote good oral healthcare in Kuwait. Materials and Methods: A cross-sectional descriptive survey was carried out among dental patients attending KUDC. A structured questionnaire, in both Arabic and English languages, was used for data collection about the socio-demographic characteristics, knowledge about the dental cross-infection, and attitudes and self-reported practices regarding infection transmission and control in dentistry. Results: A response rate of 80% (202/250) was reported. 47% of respondents had poor knowledge about dental infection transmission, and only 19.8% had satisfactory knowledge. Female participants obtained a higher satisfactory score (14.3%) compared to males (5.5%). Patients with a university degree or higher education had a better level of knowledge compared to patients with a lower educational level (p < 0.05). The majority of participants agreed that the dentist should wear gloves (95.5%), masks (89.6%), safety glasses (70.3%), and gowns (84.7%). Many patients believed that the protection measures are mainly to stop the infection transmission from patient to patient via the dentist. Half of the participants would ask if the instruments are sterilized and might accept treatment from non-vaccinated dentists. Conclusions: Many dental patients attending KUDC have obtained poor knowledge scores regarding infection transmission in the dental clinic. The educational level was significantly associated with their level of knowledge. An overall positive attitude was reported regarding the infection control protocols practiced in the dental clinic. Raising awareness among dental patients about dental infection transmission and protective measures is of utmost importance.Keywords: dental infection, knowledge, dental patients, infection control
Procedia PDF Downloads 140973 An Intelligent Controller Augmented with Variable Zero Lag Compensation for Antilock Braking System
Authors: Benjamin Chijioke Agwah, Paulinus Chinaenye Eze
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Antilock braking system (ABS) is one of the important contributions by the automobile industry, designed to ensure road safety in such way that vehicles are kept steerable and stable when during emergency braking. This paper presents a wheel slip-based intelligent controller with variable zero lag compensation for ABS. It is required to achieve a very fast perfect wheel slip tracking during hard braking condition and eliminate chattering with improved transient and steady state performance, while shortening the stopping distance using effective braking torque less than maximum allowable torque to bring a braking vehicle to a stop. The dynamic of a vehicle braking with a braking velocity of 30 ms⁻¹ on a straight line was determined and modelled in MATLAB/Simulink environment to represent a conventional ABS system without a controller. Simulation results indicated that system without a controller was not able to track desired wheel slip and the stopping distance was 135.2 m. Hence, an intelligent control based on fuzzy logic controller (FLC) was designed with a variable zero lag compensator (VZLC) added to enhance the performance of FLC control variable by eliminating steady state error, provide improve bandwidth to eliminate the effect of high frequency noise such as chattering during braking. The simulation results showed that FLC- VZLC provided fast tracking of desired wheel slip, eliminate chattering, and reduced stopping distance by 70.5% (39.92 m), 63.3% (49.59 m), 57.6% (57.35 m) and 50% (69.13 m) on dry, wet, cobblestone and snow road surface conditions respectively. Generally, the proposed system used effective braking torque that is less than the maximum allowable braking torque to achieve efficient wheel slip tracking and overall robust control performance on different road surfaces.Keywords: ABS, fuzzy logic controller, variable zero lag compensator, wheel slip tracking
Procedia PDF Downloads 147972 The Effect of Traffic Load on the Maximum Response of a Cable-Stayed Bridge under Blast Loads
Authors: S. K. Hashemi, M. A. Bradford, H. R. Valipour
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The Recent collapse of bridges has raised the awareness about safety and robustness of bridges subjected to extreme loading scenarios such as intentional/unintentional blast loads. The air blast generated by the explosion of bombs or fuel tankers leads to high-magnitude short-duration loading scenarios that can cause severe structural damage and loss of critical structural members. Hence, more attentions need to put towards bridge structures to develop guidelines to increase the resistance of such structures against the probable blast. Recent advancements in numerical methods have brought about the viable and cost effective facilities to simulate complicated blast scenarios and subsequently provide useful reference for safeguarding design of critical infrastructures. In the previous studies common bridge responses to blast load, the traffic load is sometimes not included in the analysis. Including traffic load will increase the axial compression in bridge piers especially when the axial load is relatively small. Traffic load also can reduce the uplift of girders and deck when the bridge experiences under deck explosion. For more complicated structures like cable-stayed or suspension bridges, however, the effect of traffic loads can be completely different. The tension in the cables increase and progressive collapse is likely to happen while traffic loads exist. Accordingly, this study is an attempt to simulate the effect of traffic load cases on the maximum local and global response of an entire cable-stayed bridge subjected to blast loadings using LS-DYNA explicit finite element code. The blast loads ranged from small to large explosion placed at different positions above the deck. Furthermore, the variation of the traffic load factor in the load combination and its effect on the dynamic response of the bridge under blast load is investigated.Keywords: blast, cable-stayed bridge, LS-DYNA, numerical, traffic load
Procedia PDF Downloads 333971 Static Test Pad for Solid Rocket Motors
Authors: Svanik Garg
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Static Test Pads are stationary mechanisms that hold a solid rocket motor, measuring the different parameters of its operation including thrust and temperature to better calibrate it for launch. This paper outlines a specific STP designed to test high powered rocket motors with a thrust upwards of 4000N and limited to 6500N. The design includes a specific portable mechanism with cost an integral part of the design process to make it accessible to small scale rocket developers with limited resources. Using curved surfaces and an ergonomic design, the STP has a delicately engineered façade/case with a focus on stability and axial calibration of thrust. This paper describes the design, operation and working of the STP and its widescale uses given the growing market of aviation enthusiasts. Simulations on the CAD model in Fusion 360 provided promising results with a safety factor of 2 established and stress limited along with the load coefficient A PCB was also designed as part of the test pad design process to help obtain results, with visual output and various virtual terminals to collect data of different parameters. The circuitry was simulated using ‘proteus’ and a special virtual interface with auditory commands was also created for accessibility and wide-scale implementation. Along with this description of the design, the paper also emphasizes the design principle behind the STP including a description of its vertical orientation to maximize thrust accuracy along with a stable base to prevent micromovements. Given the rise of students and professionals alike building high powered rockets, the STP described in this paper is an appropriate option, with limited cost, portability, accuracy, and versatility. There are two types of STP’s vertical or horizontal, the one discussed in this paper is vertical to utilize the axial component of thrust.Keywords: static test pad, rocket motor, thrust, load, circuit, avionics, drag
Procedia PDF Downloads 386970 Bridge Damage Detection and Stiffness Reduction Using Vibration Data: Experimental Investigation on a Small Scale Steel Bridge
Authors: Mirco Tarozzi, Giacomo Pignagnoli, Andrea Benedetti
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The design of planning maintenance of civil structures often requires the evaluation of their level of safety in order to be able to choose which structure, and in which measure, it needs a structural retrofit. This work deals with the evaluation of the stiffness reduction of a scaled steel deck due to the presence of localized damages. The dynamic tests performed on it have shown the variability of its main frequencies linked to the gradual reduction of its rigidity. This deck consists in a steel grillage of four secondary beams and three main beams linked to a concrete slab. This steel deck is 6 m long and 3 m wide and it rests on two abutments made of concrete. By processing the signals of the accelerations due to a random excitation of the deck, the main natural frequencies of this bridge have been extracted. In order to assign more reliable parameters to the numerical model of the deck, some load tests have been performed and the mechanical property of the materials and the supports have been obtained. The two external beams have been cut at one third of their length and the structural strength has been restored by the design of a bolted plate. The gradual loss of the bolts and the plates removal have made the simulation of localized damage possible. In order to define the relationship between frequency variation and loss in stiffness, the identification of its natural frequencies has been performed, before and after the occurrence of the damage, corresponding to each step. The study of the relationship between stiffness losses and frequency shifts has been reported in this paper: the square of the frequency variation due to the presence of the damage is proportional to the ratio between the rigidities. This relationship can be used to quantify the loss in stiffness of a real scale bridge in an efficient way.Keywords: damage detection, dynamic test, frequency shifts, operational modal analysis, steel bridge
Procedia PDF Downloads 160969 Enzyme Producing Psyhrophilic Pseudomonas app. Isolated from Poultry Meats
Authors: Ali Aydin, Mert Sudagidan, Aysen Coban, Alparslan Kadir Devrim
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Pseudomonas spp. (specifically, P. fluorescens and P. fragi) are considered the principal spoilage microorganisms of refrigerated poultry meats. The higher the level psychrophilic spoilage Pseudomonas spp. on carcasses at the end of processing lead to decrease the shelf life of the refrigerated product. The aim of the study was the identification of psychrophilic Pseudomonas spp. having proteolytic and lipolytic activities from poultry meats by 16S rRNA and rpoB gene sequencing, investigation of protease and lipase related genes and determination of proteolytic activity of Pseudomonas spp. In the of isolation procedure, collected chicken meat samples from local markets and slaughterhouses were homogenized and the lysates were incubated on Standard method agar and Skim Milk agar for selection of proteolytic bacteria and tributyrin agar for selection of lipolytic bacteria at +4 °C for 7 days. After detection of proteolytic and lipolytic colonies, the isolates were firstly analyzed by biochemical tests such as Gram staining, catalase and oxidase tests. DNA gene sequencing analysis and comparison with GenBank revealed that 126 strong enzyme Pseudomonas spp. were identified as predominantly P. fluorescens (n=55), P. fragi (n=42), Pseudomonas spp. (n=24), P. cedrina (n=2), P. poae (n=1), P. koreensis (n=1), and P. gessardi (n=1). Additionally, protease related aprX gene was screened in the strains and it was detected in 69/126 strains, whereas, lipase related lipA gene was found in 9 Pseudomonas strains. Protease activity was determined using commercially available protease assay kit and 5 strains showed high protease activity. The results showed that psychrophilic Pseudomonas strains were present in chicken meat samples and they can produce important levels of proteases and lipases for food spoilage to decrease food quality and safety.Keywords: Pseudomonas, chicken meat, protease, lipase
Procedia PDF Downloads 388968 Comparative Study on Productivity, Chemical Composition and Yield Quality of Some Alternative Crops in Romanian Organic Farming
Authors: Maria Toader, Gheorghe Valentin Roman, Alina Maria Ionescu
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Crops diversity and maintaining and enhancing the fertility of agricultural lands are basic principles of organic farming. With a wider range of crops in agroecosystem can improve the ability to control weeds, pests and diseases, and the performance of crops rotation and food safety. In this sense, the main objective of the research was to study the productivity and chemical composition of some alternative crops and their adaptability to soil and climatic conditions of the agricultural area in Southern Romania and to cultivation in the organic farming system. The alternative crops were: lentil (7 genotypes); five species of grain legumes (5 genotypes); four species of oil crops (5 genotypes). The seed production was, on average: 1343 kg/ha of lentil; 2500 kg/ha of field beans; 2400 kg/ha of chick peas and blackeyed peas; more than 2000 kg/ha of atzuki beans, over 1250 kg/ha of fenugreek; 2200 kg/ha of safflower; 570 kg/ha of oil pumpkin; 2150 kg/ha of oil flax; 1518 kg/ha of camelina. Regarding chemical composition, lentil seeds contained: 22.18% proteins, 3.03% lipids, 33.29% glucides, 4.00% minerals, and 259.97 kcal energy values. For field beans: 21.50% proteins, 4.40% lipids, 63.90% glucides, 5.85% minerals, 395.36 kcal energetic value. For chick peas: 21.23% proteins, 4.55% lipids, 53.00% glucides, 3.67% minerals, 348.22 kcal energetic value. For blackeyed peas: 23.30% proteins, 2.10% lipids, 68.10% glucides, 3.93% minerals, 350.14 kcal energetic value. For adzuki beans: 21.90% proteins, 2.60% lipids, 69.30% glucides, 4.10% minerals, 402.48 kcal energetic value. For fenugreek: 21.30% proteins, 4.65% lipids, 63.83% glucides, 5.69% minerals, 396.54 kcal energetic value. For safflower: 12.60% proteins, 28.37% lipids, 46.41% glucides, 3.60% minerals, 505.78 kcal energetic value. For camelina: 20.29% proteins, 31.68% lipids, 36.28% glucides, 4.29% minerals, 526.63 kcal energetic value. For oil pumpkin: 29.50% proteins, 36.92% lipids, 18.50% glucides, 5.41% minerals, 540.15 kcal energetic value. For oil flax: 22.56% proteins, 34.10% lipids, 27.73% glucides, 5.25% minerals, 558.45 kcal energetic value.Keywords: adaptability, alternative crops, chemical composition, organic farming productivity
Procedia PDF Downloads 518967 Solution of Reduced Mass in Solar Glider with Electric Engine
Authors: Piotr Żabicki, Paweł Skutta
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The project of a glider with an electric motor charged by solar power is an step toward the future of Polish gliding. Due to the popularity of the SZD-50-3 glider and its type of usage, the project was developed based on this model. By placing an auxiliary engine in the glider, the pilot is guaranteed a safe return to the airport. Since it is a training glider, and routes are mainly flown by student pilots and instructors, the guarantee of returning to the airport allows flights in more challenging thermal conditions, which contributes to better pilot training. In case of worsening weather, the pilot has a reliable return option, which prevents time loss due to field landings and saves money by avoiding delays in training. The glider uses the NOVA 15 LW engine, a solar installation, and technical modifications to reduce the glider's weight. This includes the Misztal spar solution, previously used in the PZL 19 aircraft. Additionally, the use of lighter coverings and materials that handle loads from pulling, straining, and sharing improves the aerodynamic performance of the glider, enhancing its overall efficiency. Every component added to the glider's construction (battery, engine, etc.) has been placed to avoid shifting loads along the axis, thus preventing unintended spins and flat spins. Safety concerns were also addressed. In the event of a battery or engine fire, the pilot's cabin is designed as a detachable part of the structure and is made of composites covered with non-flammable resin. The batteries are also enclosed in separate boxes located in the former "luggage" compartment. Access to the installation connecting the engine, panel, and battery is convenient due to the detachable cabin from the structure and the fact that the entire installation runs under the structure. The batteries also have easy access due to the current closed hatch. Cooling for the battery is provided this way.Keywords: engineering, girder, glider, solar, spar
Procedia PDF Downloads 12966 Nano-Enhanced In-Situ and Field Up-Gradation of Heavy Oil
Authors: Devesh Motwani, Ranjana S. Baruah
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The prime incentive behind up gradation of heavy oil is to increase its API gravity for ease of transportation to refineries, thus expanding the market access of bitumen-based crude to the refineries. There has always been a demand for an integrated approach that aims at simplifying the upgrading scheme, making it adaptable to the production site in terms of economics, environment, and personnel safety. Recent advances in nanotechnology have facilitated the development of two lines of heavy oil upgrading processes that make use of nano-catalysts for producing upgraded oil: In Situ Upgrading and Field Upgrading. The In-Situ upgrading scheme makes use of Hot Fluid Injection (HFI) technique where heavy fractions separated from produced oil are injected into the formations to reintroduce heat into the reservoir along with suspended nano-catalysts and hydrogen. In the presence of hydrogen, catalytic exothermic hydro-processing reactions occur that produce light gases and volatile hydrocarbons which contribute to increased oil detachment from the rock resulting in enhanced recovery. In this way the process is a combination of enhanced heavy oil recovery along with up gradation that effectively handles the heat load within the reservoirs, reduces hydrocarbon waste generation and minimizes the need for diluents. By eliminating most of the residual oil, the Synthetic Crude Oil (SCO) is much easier to transport and more amenable for processing in refineries. For heavy oil reservoirs seriously impacted by the presence of aquifers, the nano-catalytic technology can still be implemented on field though with some additional investments and reduced synergies; however still significantly serving the purpose of production of transportable oil with substantial benefits with respect to both large scale upgrading, and known commercial field upgrading technologies currently on the market. The paper aims to delve deeper into the technology discussed, and the future compatibility.Keywords: upgrading, synthetic crude oil, nano-catalytic technology, compatibility
Procedia PDF Downloads 408965 Investigation of the Material Behaviour of Polymeric Interlayers in Broken Laminated Glass
Authors: Martin Botz, Michael Kraus, Geralt Siebert
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The use of laminated glass gains increasing importance in structural engineering. For safety reasons, at least two glass panes are laminated together with a polymeric interlayer. In case of breakage of one or all of the glass panes, the glass fragments are still connected to the interlayer due to adhesion forces and a certain residual load-bearing capacity is left in the system. Polymer interlayers used in the laminated glass show a viscoelastic material behavior, e.g. stresses and strains in the interlayer are dependent on load duration and temperature. In the intact stage only small strains appear in the interlayer, thus the material can be described in a linear way. In the broken stage, large strains can appear and a non-linear viscoelasticity material theory is necessary. Relaxation tests on two different types of polymeric interlayers are performed at different temperatures and strain amplitudes to determine the border to the non-linear material regime. Based on the small-scale specimen results further tests on broken laminated glass panes are conducted. So-called ‘through-crack-bending’ (TCB) tests are performed, in which the laminated glass has a defined crack pattern. The test set-up is realized in a way that one glass layer is still able to transfer compressive stresses but tensile stresses have to be transferred by the interlayer solely. The TCB-tests are also conducted under different temperatures but constant force (creep test). Aims of these experiments are to elaborate if the results of small-scale tests on the interlayer are transferable to a laminated glass system in the broken stage. In this study, limits of the applicability of linear-viscoelasticity are established in the context of two commercially available polymer-interlayers. Furthermore, it is shown that the results of small-scale tests agree to a certain degree to the results of the TCB large-scale experiments. In a future step, the results can be used to develop material models for the post breakage performance of laminated glass.Keywords: glass breakage, laminated glass, relaxation test, viscoelasticity
Procedia PDF Downloads 123964 Piracy in Southeast Asian Waters: Problems, Legal Measures and Way Forward
Authors: Ahmad Almaududy Amri
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Southeast Asia is considered as an area which is important in terms of piratical studies. There are several reasons to this argument: firstly, it has the second highest figure of piracy attacks in the world from 2008 to 2012. Only the African Region transcends the number of piracies that were committed in Southeast Asia. Secondly, the geographical location of the region is very important to world trade. There are several sea lanes and straits which are normally used for international navigation mainly for trade purposes. In fact, there are six out of 25 busiest ports all over the world located in Southeast Asia. In ancient times, the main drivers of piracy were raiding for plunder and capture of slaves; however, in modern times, developments in politics, economics and even military technology have drastically altered the universal crime of piracy. There are a variety of motives behind modern day piracy including economic gains from receiving ransoms from government or ship companies, political and even terrorist reasons. However, it cannot be denied that piratical attacks persist and continue. States have taken measures both at the international and regional level in order to eradicate piratical attacks. The United Nations Convention on the Law of the Sea and the Convention on the Suppression of Unlawful Act against the Safety of Navigation served as the two main international legal frameworks in combating piracy. At the regional level, Regional Cooperation Agreement against Piracy and Armed Robbery and ASEAN measures are regard as prominent in addressing the piracy problem. This paper will elaborate the problems of piracy in Southeast Asia and examine the adequacy of legal frameworks at both the international and regional levels in order address the current legal measures in combating piracy. Furthermore, it will discuss current challenges in the implementation of anti-piracy measures at the international and regional levels as well as the way forward in addressing the issue.Keywords: piracy, Southeast Asia, maritime security, legal frameworks
Procedia PDF Downloads 504963 Discussion on the Impact and Improvement Strategy of Bike Sharing on Urban Space
Authors: Bingying Liu, Dandong Ge, Xinlan Zhang, Haoyang Liang
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Over the past two years, a new generation of No-Pile Bike sharing, represented by the Ofo, Mobike and HelloBike, has sprung up in various cities in China, and spread rapidly in countries such as Britain, Japan, the United States and Singapore. As a new green public transportation mode, bike sharing can bring a series of benefits to urban space. At first, this paper analyzes the specific impact of bike sharing on urban space in China. Based on the market research and data analyzing, it is found that bike sharing can improve the quality of urban space in three aspects: expanding the radius of public transportation service, filling service blind spots, alleviating urban traffic congestion, and enhancing the vitality of urban space. On the other hand, due to the immature market and the imperfect system, bike sharing has gradually revealed some difficulties, such as parking chaos, malicious damage, safety problems, imbalance between supply and demand, and so on. Then the paper investigates the characteristics of shared bikes, business model, operating mechanism on Chinese market currently. Finally, in order to make bike sharing serve urban construction better, this paper puts forward some specific countermeasures from four aspects. In terms of market operations, it is necessary to establish a public-private partnership model and set up a unified bike-sharing integrated management platform. From technical methods level, the paper proposes to develop an intelligent parking system for regulating parking. From policy formulation level, establishing a bike-sharing assessment mechanism would strengthen supervision. As to urban planning, sharing data and redesigning slow roadway is beneficial for transportation and spatial planning.Keywords: bike sharing, impact analysis, improvement strategy, urban space
Procedia PDF Downloads 171962 Design and Implementation of 3kVA Grid-Tied Transformerless Power Inverter for Solar Photovoltaic Application
Authors: Daniel O. Johnson, Abiodun A. Ogunseye, Aaron Aransiola, Majors Samuel
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Power Inverter is a very important device in renewable energy use particularly for solar photovoltaic power application because it is the effective interface between the DC power generator and the load or the grid. Transformerless inverter is getting more and more preferred to the power converter with galvanic isolation transformer and may eventually supplant it. Transformerless inverter offers advantages of improved DC to AC conversion and power delivery efficiency; and reduced system cost, weight and complexity. This work presents thorough analysis of the design and prototyping of 3KVA grid-tie transformerless inverter. The inverter employs electronic switching method with minimised heat generation in the system and operates based on the principle of pulse-width modulation (PWM). The design is such that it can take two inputs, one from PV arrays and the other from Battery Energy Storage BES and addresses the safety challenge of leakage current. The inverter system was designed around microcontroller system, modeled with Proteus® software for simulation and testing of the viability of the designed inverter circuit. The firmware governing the operation of the grid-tied inverter is written in C language and was developed using MicroC software by Mikroelectronica® for writing sine wave signal code for synchronization to the grid. The simulation results show that the designed inverter circuit performs excellently with very high efficiency, good quality sinusoidal output waveform, negligible harmonics and gives very stable performance under voltage variation from 36VDC to 60VDC input. The prototype confirmed the simulated results and was successfully synchronized with the utility supply. The comprehensive analyses of the circuit design, the prototype and explanation on overall performance will be presented.Keywords: grid-tied inverter, leakage current, photovoltaic system, power electronic, transformerless inverter
Procedia PDF Downloads 292961 From Dog to Dog: Potential Probiotic and Immunomodulatory Strains Isolated from Canine Milk
Authors: Paula Buldres, Jorge Toledo
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Objectives: This study aimed to characterize potential probiotic strains isolated from canine breast milk for use in dogs with enteropathies. Methodology: Six canine breast milk strains, one canine colostrum strain, and one control porcine breast milk strain were characterized. According to its functional properties of resistance to acids, different concentrations of bile salts, and pancreatin, its presumptive properties of safety and inhibitory effect on pathogens, non-cytotoxic characteristics, and adhesion to the intestine. The immunomodulatory effect of formulations with better probiotic characterization in vitro and in vivo was also analyzed. Results: Two strains characterized as potential probiotics were obtained, which corresponded to the canine strains (TUCO-16 and TUCO-17), presenting resistance to acidic pH, bile salts, and pancreatin, as well as an inhibitory effect on pathogenic Escherichia coli, Salmonella sp., and Clostridium perfringens. Strains TUCO-16 and TUCO-17 induced a significant increase in the expression of TNF-α and IL-8 in canine macrophages, respectively. Expression analyses of pattern recognition receptors in DH82 cells suggest that TUCO-16 and TUCO-17 might increase the TLR2 expression marker, and porcine strain (TUCO-4) increases the NOD2 expression marker. Based on the count obtained and the encapsulation yield, the best formulations correspond to FOS-Inulin for the TUCO-17 and TUCO-4 strains; Maltodextrin-Inulin for TUCO-16. All the strains are non-cytotoxic. The strain that showed the highest adhesion to intestinal epithelial cells was TUCO-17 with the FOS-Inulin formulation. On the other hand, the probiotics decreased the expression of pro-inflammatory markers in vivo, both in the intestine and in the spleen of mice. Conclusion: The combination of these three strains under study (TUCO-16, TUCO-17, and TUCO-4) would cover the probiotic properties in formulation and immunomodulation of all the markers under study.Keywords: probiotics, gastrointestinal infec, dog, probiotic formulation, immunomodulatory probiotics
Procedia PDF Downloads 69960 Multicenter Baseline Survey to Outline Antimicrobial Prescribing Practices at Six Public Sectortertiary Care Hospitals in a Low Middle Income Country
Authors: N. Khursheed, M. Fatima, S. Jamal, A. Raza, S. Rattani, Q. Ahsan, A. Rasheed, M. Jawed
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Introduction: Antibiotics are among the commonly prescribed medicines to treat bacterial infections. Their misuse intensifies resistance, and overuse incurs heavy losses to the healthcare system in terms of increased treatment costs and enhanced disease burden. Studies show that 40% of empirically used antibiotics are irrationally utilized. The objective of this study was to evaluate prescribing pattern of antibiotics at six public sector tertiary care hospitals across Pakistan. Methods: A multicenter cross-sectional point prevalence survey (PPS) was conducted in selected wards of six public sector tertiary care hospitals in Pakistan as part of the Clinical Engagement program by Fleming Fund Country Grant Pakistan in collaboration with Indus Hospital & Health Network (IHHN) from February to March 2021, these included Jinnah Postgraduate Medical Center and Dr. Ruth K. M. Pfau Civil Hospital from Karachi, Sheikh Zayed Hospital Lahore, Nishtar Medical University Hospital Multan, Medical Teaching Institute Hayatabad Medical Complex Peshawar, and Provincial Headquarters Hospital Gilgit. WHO PPS methodology was used for data collection (Hospital, ward, and patient level data was collected). Data was entered into the open-source Kobo Collect application and was analyzed using SPSS (version 22.0). Findings: Medical records of 837 in-patients were surveyed, of which the prevalence of antibiotics use was 78.5%. The most commonly prescribed antimicrobial was Ceftriaxone (21.7%) which is categorized in the Watch group of WHO AWaRe Classification, followed by Metronidazole (17.3%), Cefoperazone/Sulbactam (8.4%), Co-Amoxiclav (6.3%) and Piperacillin/Tazobactam (5.9%). The antibiotics were prescribed largely for surgical prophylaxis (36.7%), followed by community-acquired infections (24.7%). One antibiotic was prescribed to 46.7%, two to 39.9%, and three or more to 12.5 %. Two of six (30%) hospitals had functional drug and therapeutic committees, three (50%) had infection prevention and control committees, and one facility had an antibiotic formulary. Conclusion: Findings demonstrate high consumption of broad-spectrum antimicrobials and emphasizes the importance of expanding the antimicrobial stewardship program. Mentoring clinical teams will help to rationalize antimicrobial use.Keywords: antimicrobial resistance, antimicrobial stewardship, point prevalence survey, antibiotics
Procedia PDF Downloads 105959 Identification, Synthesis, and Biological Evaluation of the Major Human Metabolite of NLRP3 Inflammasome Inhibitor MCC950
Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson
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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3
Procedia PDF Downloads 252958 Impact of Emerging Nano-Agrichemicals on the Simultaneous Control of Arsenic and Cadmium in Rice Paddies
Authors: Xingmao Ma, Wenjie Sun
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Rice paddies are frequently co-contaminated by arsenic (As) and cadmium (Cd), both of which demonstrate a high propensity for accumulation in rice grains and cause global food safety and public health concern. Even though different agricultural management strategies have been explored for their simultaneous control in rice grains, a viable solution is yet to be developed. Interestingly, several nanoagrichemicals, such as the zinc nanofertilizer and copper nanopesticide have displayed strong potential to reduce As or Cd accumulation in rice tissues. In order to determine whether these nanoagrichemicals can lower the accumulation of both As and Cd in rice, a series of bench studies were performed. Our results show that zinc oxide nanoparticles at 100 mg/Kg significantly lowered both As, and Cd in rice roots and shoots in flood irrigated rice seedlings, while equivalent amount of zinc ions only reduced As concentration in rice shoots. Zinc ions significantly increased Cd concentration in rice shoots by almost 30%. The results demonstrate a unique 'nano-effect' of zinc oxide nanoparticles, which is ascribed to the slow releasing of zinc ions from nanoparticles and the formation of different transformation products in these two treatments. We also evaluated the effect of nanoscale soil amendment, silicon oxide nanoparticles (SiO₂NPs) on the simultaneous reduction in both flooding and alternate wet and dry irrigation scheme. The effect of SiO₂NPs on As and Cd accumulation in rice tissues was strongly affected by the irrigation scheme. While 2000 mg/kg of SiO₂NPs significantly reduced As in rice roots and insignificantly reduced As in rice shoots in flooded rice, it increased As concentration in rice shoots in alternate wet and dry irrigation. In both irrigation scenarios, SiO₂NPs significantly reduced Cd concentration in rice roots, but only reduced Cd concentration in rice shoots in alternate wet and dry irrigation. Our results demonstrate a marked effect of nanoagrichemicals on the accumulation of As and Cd in rice and can be a potential solution to simultaneously control both in certain conditions.Keywords: arsenic, cadmium, rice, nanoagrichemicals
Procedia PDF Downloads 161957 Empirical Investigations on Speed Differentiations of Traffic Flow: A Case Study on a Basic Freeway Segment of O-2 in Istanbul
Authors: Hamed Rashid Sarand, Kemal Selçuk Öğüt
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Speed is one of the fundamental variables of road traffic flow that stands as an important evaluation criterion for traffic analyses in several aspects. In particular, varieties of speed variable, such as average speed, free flow speed, optimum speed (capacity speed), acceleration/deceleration speed and so on, have been explicitly considered in the analysis of not only road safety but also road capacity. In the purpose of realizing 'road speed – maximum speed difference across lanes' and 'road flow rate – maximum speed difference across lanes' relations on freeway traffic, this study presents a case study conducted on a basic freeway segment of O-2 in Istanbul. The traffic data employed in this study have been obtained from 5 remote traffic microwave sensors operated by Istanbul Metropolitan Municipality. The study stretch is located between two successive freeway interchanges: Ümraniye and Kavacık. Daily traffic data of 4 years (2011-2014) summer months, July and August are used. The speed data are analyzed into two main flow areas such as uncongested and congested flows. In this study, the regression analyses were carried out in order to examine the relationship between maximum speed difference across lanes and road speed. These investigations were implemented at uncongested and congested flows, separately. Moreover, the relationship between maximum speed difference across lanes and road flow rate were evaluated by applying regression analyses for both uncongested and congested flows separately. It is concluded that there is the moderate relationship between maximum speed difference across lanes and road speed in 50% cases. Additionally, it is indicated that there is the moderate relationship between maximum speed difference across lanes and road flow rate in 30% cases. The maximum speed difference across lanes decreases as the road flow rate increases.Keywords: maximum speed difference, regression analysis, remote traffic microwave sensor, speed differentiation, traffic flow
Procedia PDF Downloads 367956 Vitex agnus-castus Anti-Inflammatory, Antioxidants Characters and Anti-Tumor Effect in Ehrlich Ascites Carcinoma Model
Authors: Abeer Y. Ibrahim, Faten M. Ibrahim, Samah A. El-Newary, Saber F. Hendawy
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Objective: Appreciation of in-vitro anti-inflammatory and antioxidant characters of Vitex agnus-castus berries alcoholic extract and fractions, as well as in-vivo antitumor ability of alcoholic extract and chloroform fraction against Ehrlich ascites carcinoma is the aim of this study. Material and methods: Antioxidant properties of crude alcoholic extract of vitex berries as well as petroleum ether, chloroform, ethyl acetate and butanol fractions were evaluated, in-vitro assessments, as compared with standard materials, l-ascorbic acid (vitamin C) and butylated hydroxyl toluene(BHT). The anti-inflammatory activity was investigated in cyclooxygenase (COX)-1 and COX-2 inhibition assays. Moreover, in-vivo antitumor effect of vitex berries alcoholic and chloroform extracts were evaluated using Ehrlich ascites carcinoma model. Data were presented as mean±SE, and data were analyzed by one-way analysis of variance test. Results and conclusion: Berries crude extract showed potent antioxidant activity followed with its fractions ethyl acetate and chloroform as compared with standard (V.C and BHT). Ethyl acetate fraction showed good reduction capability, metal ion chelation, hydrogen peroxide scavenging, nitric oxide scavenging and superoxide anion scavenging. Meanwhile, chloroform fraction produced the highest free radical scavenging activity and total antioxidant capacity. In respectable of lipid peroxidation inhibition, crude alcoholic extract and its fractions cleared weak inhibition in comparing with standard materials. Anti-inflammatory activity of V. agnus-castus berries chloroform fraction of vitex was best COX-2 inhibitor (IC₅₀, 135.41 µg/ ml) as compared to vitex alcoholic extract or ethyl acetate fraction with weak inhibitory effect on COX-1 (IC50, 778.432 µg/ ml), where the lowest effect on COX-1 was recorded with alcoholic extract. Alcoholic extract and its fractions showed weak COX-1 inhibition activity, whereas COX-2 was inhibited (100%), compared with celecoxib drug (72% at 1000ppm). The crude alcoholic and chloroform extracts of V. agnus-castus barries significantly reduced the viable Ehrlich cell count and increased nonviable count with amelioration of all hematological parameters. This amelioration was reflected on increasing median survival time and significant increase (P < 0.05) in lifespan.Keywords: anti-inflammatory, antioxidants, ehrlich ascites carcinoma, Vitex agnus-castus
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