Search results for: accuracy ratio
Commenced in January 2007
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Search results for: accuracy ratio

363 Powder Assisted Sheet Forming to Fabricate Ti Capsule Magnetic Hyperthermia Implant

Authors: Keigo Nishitani, Kohei Mizuta Mizuta, Kazuyoshi Kurita, Yukinori Taniguchi

Abstract:

To establish mass production process of Ti capsule which has Fe powder inside as magnetic hyperthermia implant, we assumed that Ti thin sheet can be drawn into a φ1.0 mm die hole through the medium of Fe Powder and becomes outer shell of capsule. This study discusses mechanism of powder assisted deep drawing process by both of numerical simulation and experiment. Ti thin sheet blank was placed on die, and was covered by Fe powder layer without pressurizing. Then upper punch was indented on the Fe powder layer, and the blank can be drawn into die cavity as pressurized powder particles were extruded into die cavity from behind of the drawn blank. Distinct Element Method (DEM) has been used to demonstrate the process. To identify bonding parameters on Fe particles which are cohesion, tensile bond stress and inter particle friction angle, axial and diametrical compression failure test of Fe powder compact was conducted. Several density ratios of powder compacts in range of 0.70 - 0.85 were investigated and relationship between mean stress and equivalent stress was calculated with consideration of critical state line which rules failure criterion in consolidation of Fe powder. Since variation of bonding parameters with density ratio has been experimentally identified, and good agreement has been recognized between several failure tests and its simulation, demonstration of powder assisted sheet forming by using DEM becomes applicable. Results of simulation indicated that indent/drawing length of Ti thin sheet is promoted by smaller Fe particle size, larger indent punch diameter, lower friction coefficient between die surface and Ti sheet and certain degrees of die inlet taper angle. In the deep drawing test, we have made die-set with φ2.4 mm punch and φ1.0 mm die bore diameter. Pure Ti sheet with 100 μm thickness, annealed at 650 deg. C has been tested. After indentation, indented/drawn capsule has been observed by microscope, and its length was measured to discuss the feasibility of this capsulation process. Longer drawing length exists on progressive loading pass comparing with the case of single stroke loading. It is expected that progressive loading has an advantage of which extrusion of powder particle into die cavity with Ti sheet is promoted since powder particle layer can be rebuilt while the punch is withdrawn from the layer in each loading steps. This capsulation phenomenon is qualitatively demonstrated by DEM simulation. Finally, we have fabricated Ti capsule which has Fe powder inside for magnetic hyperthermia cancer care treatment. It is concluded that suggested method is possible to use the manufacturing of Ti capsule implant for magnetic hyperthermia cancer care.

Keywords: metal powder compaction, metal forming, distinct element method, cancer care, magnetic hyperthermia

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362 Thermodynamics of Aqueous Solutions of Organic Molecule and Electrolyte: Use Cloud Point to Obtain Better Estimates of Thermodynamic Parameters

Authors: Jyoti Sahu, Vinay A. Juvekar

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Electrolytes are often used to bring about salting-in and salting-out of organic molecules and polymers (e.g. polyethylene glycols/proteins) from the aqueous solutions. For quantification of these phenomena, a thermodynamic model which can accurately predict activity coefficient of electrolyte as a function of temperature is needed. The thermodynamics models available in the literature contain a large number of empirical parameters. These parameters are estimated using lower/upper critical solution temperature of the solution in the electrolyte/organic molecule at different temperatures. Since the number of parameters is large, inaccuracy can bethe creep in during their estimation, which can affect the reliability of prediction beyond the range in which these parameters are estimated. Cloud point of solution is related to its free energy through temperature and composition derivative. Hence, the Cloud point measurement can be used for accurate estimation of the temperature and composition dependence of parameters in the model for free energy. Hence, if we use a two pronged procedure in which we first use cloud point of solution to estimate some of the parameters of the thermodynamic model and determine the rest using osmotic coefficient data, we gain on two counts. First, since the parameters, estimated in each of the two steps, are fewer, we achieve higher accuracy of estimation. The second and more important gain is that the resulting model parameters are more sensitive to temperature. This is crucial when we wish to use the model outside temperatures window within which the parameter estimation is sought. The focus of the present work is to prove this proposition. We have used electrolyte (NaCl/Na2CO3)-water-organic molecule (Iso-propanol/ethanol) as the model system. The model of Robinson-Stokes-Glukauf is modified by incorporating the temperature dependent Flory-Huggins interaction parameters. The Helmholtz free energy expression contains, in addition to electrostatic and translational entropic contributions, three Flory-Huggins pairwise interaction contributions viz., and (w-water, p-polymer, s-salt). These parameters depend both on temperature and concentrations. The concentration dependence is expressed in the form of a quadratic expression involving the volume fractions of the interacting species. The temperature dependence is expressed in the form .To obtain the temperature-dependent interaction parameters for organic molecule-water and electrolyte-water systems, Critical solution temperature of electrolyte -water-organic molecules is measured using cloud point measuring apparatus The temperature and composition dependent interaction parameters for electrolyte-water-organic molecule are estimated through measurement of cloud point of solution. The model is used to estimate critical solution temperature (CST) of electrolyte water-organic molecules solution. We have experimentally determined the critical solution temperature of different compositions of electrolyte-water-organic molecule solution and compared the results with the estimates based on our model. The two sets of values show good agreement. On the other hand when only osmotic coefficients are used for estimation of the free energy model, CST predicted using the resulting model show poor agreement with the experiments. Thus, the importance of the CST data in the estimation of parameters of the thermodynamic model is confirmed through this work.

Keywords: concentrated electrolytes, Debye-Hückel theory, interaction parameters, Robinson-Stokes-Glueckauf model, Flory-Huggins model, critical solution temperature

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361 p-Type Multilayer MoS₂ Enabled by Plasma Doping for Ultraviolet Photodetectors Application

Authors: Xiao-Mei Zhang, Sian-Hong Tseng, Ming-Yen Lu

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Two-dimensional (2D) transition metal dichalcogenides (TMDCs), such as MoS₂, have attracted considerable attention owing to the unique optical and electronic properties related to its 2D ultrathin atomic layer structure. MoS₂ is becoming prevalent in post-silicon digital electronics and in highly efficient optoelectronics due to its extremely low thickness and its tunable band gap (Eg = 1-2 eV). For low-power, high-performance complementary logic applications, both p- and n-type MoS₂ FETs (NFETs and PFETs) must be developed. NFETs with an electron accumulation channel can be obtained using unintentionally doped n-type MoS₂. However, the fabrication of MoS₂ FETs with complementary p-type characteristics is challenging due to the significant difficulty of injecting holes into its inversion channel. Plasma treatments with different species (including CF₄, SF₆, O₂, and CHF₃) have also been found to achieve the desired property modifications of MoS₂. In this work, we demonstrated a p-type multilayer MoS₂ enabled by selective-area doping using CHF₃ plasma treatment. Compared with single layer MoS₂, multilayer MoS₂ can carry a higher drive current due to its lower bandgap and multiple conduction channels. Moreover, it has three times the density of states at its minimum conduction band. Large-area growth of MoS₂ films on 300 nm thick SiO₂/Si substrate is carried out by thermal decomposition of ammonium tetrathiomolybdate, (NH₄)₂MoS₄, in a tube furnace. A two-step annealing process is conducted to synthesize MoS₂ films. For the first step, the temperature is set to 280 °C for 30 min in an N₂ rich environment at 1.8 Torr. This is done to transform (NH₄)₂MoS₄ into MoS₃. To further reduce MoS₃ into MoS₂, the second step of annealing is performed. For the second step, the temperature is set to 750 °C for 30 min in a reducing atmosphere consisting of 90% Ar and 10% H₂ at 1.8 Torr. The grown MoS₂ films are subjected to out-of-plane doping by CHF₃ plasma treatment using a Dry-etching system (ULVAC original NLD-570). The radiofrequency power of this dry-etching system is set to 100 W and the pressure is set to 7.5 mTorr. The final thickness of the treated samples is obtained by etching for 30 s. Back-gated MoS₂ PFETs were presented with an on/off current ratio in the order of 10³ and a field-effect mobility of 65.2 cm²V⁻¹s⁻¹. The MoS₂ PFETs photodetector exhibited ultraviolet (UV) photodetection capability with a rapid response time of 37 ms and exhibited modulation of the generated photocurrent by back-gate voltage. This work suggests the potential application of the mild plasma-doped p-type multilayer MoS₂ in UV photodetectors for environmental monitoring, human health monitoring, and biological analysis.

Keywords: photodetection, p-type doping, multilayers, MoS₂

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360 Follicular Thyroid Carcinoma in a Developing Country: A Retrospective Study of 10 Years

Authors: Abdul Aziz, Muhammad Qamar Masood, Saadia Sattar, Saira Fatima, Najmul Islam

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Introduction: The most common endocrine tumor is thyroid cancer. Follicular Thyroid Carcinoma (FTC) accounts for 5%–10% of all thyroid cancers. Patients with FTC frequently present with more advanced stage diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery, while radioactive iodine therapy is the main adjuvant therapy as per ATA guidelines. In many developing countries, surgical facilities and radioactive iodine are in short supply; therefore, understanding follicular thyroid cancer trends may help developing countries plan and use resources more effectively. Methodology: It was a retrospective observational study of FTC patients of age 18 years and above conducted at Aga Khan University Hospital, Karachi, from 1st January 2010 to 31st December 2019. Results: There were 404 patients with thyroid carcinoma, out of which forty (10.1%) were FTC. 50% of the patients were in the 41-60 years age group, and the female to male ratio was 1.5: 1. Twenty-four patients (60%) presented with complain of neck swelling followed by metastasis (20%) and compressive symptoms (20%). The most common site of metastasis was bone (87.5%), followed by lung (12.5%). The pre-operative thyroglobulin level was done in six out of eight metastatic patients (75%) in which it was elevated. This emphasizes the importance of checking thyroglobulin level in unusual presentation (bone pain, fractures) of a patient having neck swelling also to help in establishing the primary source of tumor. There was no complete documentation of ultrasound features of the thyroid gland in all the patients, which is an important investigation done in the initial evaluation of thyroid nodule. On FNAC, 50% (20 patients) had Bethesda category III-IV nodules, while 10% ( 4 patients ) had Bethesda category II. In sixteen patients, FNAC was not done as they presented with compressive symptoms or metastasis. Fifty percent had a total thyroidectomy and 50% had subtotal followed by completion thyroidectomy, plus ten patients had lymph node dissection, out of which seven had histopathological lymph node involvement. On histopathology, twenty-three patients (57.5%) had minimally invasive, while seventeen (42.5%) had widely invasive follicular thyroid carcinoma. The capsular invasion was present in thirty-three patients (82.5%); one patient had no capsular invasion, but there was a vascular invasion. Six patients' histopathology had no record of capsular invasion. In contrast, the lymphovascular invasion was present in twenty-six patients (65%). In this study, 65 % of the patients had clinical stage 1 disease, while 25% had stage 2 and 10% had clinical stage 4. Seventeen patients (42.5%) had received RAI 30-100 mCi, while ten patients (25%) received more than 100 mCi. Conclusion: FTC demographic and clinicopathological presentation are the same in Pakistan as compared to other countries. Surgery followed by RAI is the mainstay of treatment. Thus understanding the trend of FTC and proper planning and utilization of the resources will help the developing countries in effectively treating the FTC.

Keywords: thyroid carcinoma, follicular thyroid carcinoma, clinicopathological features, developing countries

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359 Optimizing Stormwater Sampling Design for Estimation of Pollutant Loads

Authors: Raja Umer Sajjad, Chang Hee Lee

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Stormwater runoff is the leading contributor to pollution of receiving waters. In response, an efficient stormwater monitoring program is required to quantify and eventually reduce stormwater pollution. The overall goals of stormwater monitoring programs primarily include the identification of high-risk dischargers and the development of total maximum daily loads (TMDLs). The challenge in developing better monitoring program is to reduce the variability in flux estimates due to sampling errors; however, the success of monitoring program mainly depends on the accuracy of the estimates. Apart from sampling errors, manpower and budgetary constraints also influence the quality of the estimates. This study attempted to develop optimum stormwater monitoring design considering both cost and the quality of the estimated pollutants flux. Three years stormwater monitoring data (2012 – 2014) from a mix land use located within Geumhak watershed South Korea was evaluated. The regional climate is humid and precipitation is usually well distributed through the year. The investigation of a large number of water quality parameters is time-consuming and resource intensive. In order to identify a suite of easy-to-measure parameters to act as a surrogate, Principal Component Analysis (PCA) was applied. Means, standard deviations, coefficient of variation (CV) and other simple statistics were performed using multivariate statistical analysis software SPSS 22.0. The implication of sampling time on monitoring results, number of samples required during the storm event and impact of seasonal first flush were also identified. Based on the observations derived from the PCA biplot and the correlation matrix, total suspended solids (TSS) was identified as a potential surrogate for turbidity, total phosphorus and for heavy metals like lead, chromium, and copper whereas, Chemical Oxygen Demand (COD) was identified as surrogate for organic matter. The CV among different monitored water quality parameters were found higher (ranged from 3.8 to 15.5). It suggests that use of grab sampling design to estimate the mass emission rates in the study area can lead to errors due to large variability. TSS discharge load calculation error was found only 2 % with two different sample size approaches; i.e. 17 samples per storm event and equally distributed 6 samples per storm event. Both seasonal first flush and event first flush phenomena for most water quality parameters were observed in the study area. Samples taken at the initial stage of storm event generally overestimate the mass emissions; however, it was found that collecting a grab sample after initial hour of storm event more closely approximates the mean concentration of the event. It was concluded that site and regional climate specific interventions can be made to optimize the stormwater monitoring program in order to make it more effective and economical.

Keywords: first flush, pollutant load, stormwater monitoring, surrogate parameters

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358 Ways to Prevent Increased Wear of the Drive Box Parts and the Central Drive of the Civil Aviation Turbo Engine Based on Tribology

Authors: Liudmila Shabalinskaya, Victor Golovanov, Liudmila Milinis, Sergey Loponos, Alexander Maslov, D. O. Frolov

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The work is devoted to the rapid laboratory diagnosis of the condition of aircraft friction units, based on the application of the nondestructive testing method by analyzing the parameters of wear particles, or tribodiagnostics. The most important task of tribodiagnostics is to develop recommendations for the selection of more advanced designs, materials and lubricants based on data on wear processes for increasing the life and ensuring the safety of the operation of machines and mechanisms. The object of tribodiagnostics in this work are the tooth gears of the central drive and the gearboxes of the gas turbine engine of the civil aviation PS-90A type, in which rolling friction and sliding friction with slip occur. The main criterion for evaluating the technical state of lubricated friction units of a gas turbine engine is the intensity and rate of wear of the friction surfaces of the friction unit parts. When the engine is running, oil samples are taken and the state of the friction surfaces is evaluated according to the parameters of the wear particles contained in the oil sample, which carry important and detailed information about the wear processes in the engine transmission units. The parameters carrying this information include the concentration of wear particles and metals in the oil, the dispersion composition, the shape, the size ratio and the number of particles, the state of their surfaces, the presence in the oil of various mechanical impurities of non-metallic origin. Such a morphological analysis of wear particles has been introduced into the order of monitoring the status and diagnostics of various aircraft engines, including a gas turbine engine, since the type of wear characteristic of the central drive and the drive box is surface fatigue wear and the beginning of its development, accompanied by the formation of microcracks, leads to the formation of spherical, up to 10 μm in size, and in the aftermath of flocculent particles measuring 20-200 μm in size. Tribodiagnostics using the morphological analysis of wear particles includes the following techniques: ferrography, filtering, and computer analysis of the classification and counting of wear particles. Based on the analysis of several series of oil samples taken from the drive box of the engine during their operating time, a study was carried out of the processes of wear kinetics. Based on the results of the study and comparing the series of criteria for tribodiagnostics, wear state ratings and statistics of the results of morphological analysis, norms for the normal operating regime were developed. The study allowed to develop levels of wear state for friction surfaces of gearing and a 10-point rating system for estimating the likelihood of the occurrence of an increased wear mode and, accordingly, prevention of engine failures in flight.

Keywords: aviation, box of drives, morphological analysis, tribodiagnostics, tribology, ferrography, filtering, wear particle

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357 Dental Caries among Children in Bazartete, Timor-Leste and the impact of Maluk Timor School Outreach Program

Authors: A. Flaviana da Silva, B. Jenifer Apriani Ximenes, C. Efigenia dos Santos Pereira

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The World Health Organization's 2022 Global Oral Health Status Report reveals a staggering statistic: more than 3.5 billion people, or half of the world's population, currently suffer from untreated oral diseases, encompassing issues like tooth loss, gum disease, and oral cancers. Among these, dental caries, commonly known as tooth decay, affects over 2.5 billion people globally. Dental caries result from acid erosion of teeth due to plaque build-up and consumption of free sugars. Despite being preventable through basic measures such as regular tooth-brushing with fluoride toothpaste and reduced sugar intake, untreated dental caries poses a significant and growing public health crisis. In children, dental caries stands as the most prevalent non-communicable disease worldwide, affecting 60-90% of school children to some extent. This condition severely impacts their physical, emotional, and social well-being, hindering essential activities and overall quality of life. Timor-Leste, a small nation in South-east Asia, grapples with the escalating problem of childhood dental caries, exacerbated by its unique challenges including poor access to healthcare services and limited resources. Methods: This study analysed Secondary, cross-sectional data collected by Maluk Timor in 2022 during the School Outreach Program. A total of 1,008 children aged 4-16 from eight primary schools in the Bazartete administrative post were examined for dental caries in their primary and permanent teeth. All students were invited to participate, and consent was obtained from parents and children. A team comprising one dentist and two dental nurses conducted health promotion sessions, dental examinations, and SDF treatment. A screening form based on WHO guidelines collected demographic data and caries diagnosis, categorized as decayed or healthy. Data analysis involved entering the data into Google Sheets, verifying its accuracy, and importing it into Microsoft Excel for analysis. Variables were created to identify students with carious lesions, and prevalence tables were generated, stratified by age group, gender, and location. Results: Among the 1,008 children analysed, 58.3% had dental caries. Caries prevalence was higher in primary teeth (36.7%) compared to permanent teeth (29.5%). Conclusion: In summary, this report highlights the alarming prevalence of dental caries among children in Timor-Leste and the efforts of Maluk Timor's School Outreach Program in addressing this critical issue. The results emphasize the need for effective preventive measures and improved access to oral healthcare in this region.

Keywords: dental caries, timor-leste, oral health, children, public health, primary health care, teeth

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356 Predicting Susceptibility to Coronary Artery Disease using Single Nucleotide Polymorphisms with a Large-Scale Data Extraction from PubMed and Validation in an Asian Population Subset

Authors: K. H. Reeta, Bhavana Prasher, Mitali Mukerji, Dhwani Dholakia, Sangeeta Khanna, Archana Vats, Shivam Pandey, Sandeep Seth, Subir Kumar Maulik

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Introduction Research has demonstrated a connection between coronary artery disease (CAD) and genetics. We did a deep literature mining using both bioinformatics and manual efforts to identify the susceptible polymorphisms in coronary artery disease. Further, the study sought to validate these findings in an Asian population. Methodology In first phase, we used an automated pipeline which organizes and presents structured information on SNPs, Population and Diseases. The information was obtained by applying Natural Language Processing (NLP) techniques to approximately 28 million PubMed abstracts. To accomplish this, we utilized Python scripts to extract and curate disease-related data, filter out false positives, and categorize them into 24 hierarchical groups using named Entity Recognition (NER) algorithms. From the extensive research conducted, a total of 466 unique PubMed Identifiers (PMIDs) and 694 Single Nucleotide Polymorphisms (SNPs) related to coronary artery disease (CAD) were identified. To refine the selection process, a thorough manual examination of all the studies was carried out. Specifically, SNPs that demonstrated susceptibility to CAD and exhibited a positive Odds Ratio (OR) were selected, and a final pool of 324 SNPs was compiled. The next phase involved validating the identified SNPs in DNA samples of 96 CAD patients and 37 healthy controls from Indian population using Global Screening Array. ResultsThe results exhibited out of 324, only 108 SNPs were expressed, further 4 SNPs showed significant difference of minor allele frequency in cases and controls. These were rs187238 of IL-18 gene, rs731236 of VDR gene, rs11556218 of IL16 gene and rs5882 of CETP gene. Prior researches have reported association of these SNPs with various pathways like endothelial damage, susceptibility of vitamin D receptor (VDR) polymorphisms, and reduction of HDL-cholesterol levels, ultimately leading to the development of CAD. Among these, only rs731236 had been studied in Indian population and that too in diabetes and vitamin D deficiency. For the first time, these SNPs were reported to be associated with CAD in Indian population. Conclusion: This pool of 324 SNP s is a unique kind of resource that can help to uncover risk associations in CAD. Here, we validated in Indian population. Further, validation in different populations may offer valuable insights and contribute to the development of a screening tool and may help in enabling the implementation of primary prevention strategies targeted at the vulnerable population.

Keywords: coronary artery disease, single nucleotide polymorphism, susceptible SNP, bioinformatics

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355 The Photovoltaic Panel at End of Life: Experimental Study of Metals Release

Authors: M. Tammaro, S. Manzo, J. Rimauro, A. Salluzzo, S. Schiavo

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The solar photovoltaic (PV) modules are considered to have a negligible environmental impact compared to the fossil energy. Therefore also the waste management and the corresponding potential environmental hazard needs to be considered. The case of the photovoltaic panel is unique because the time lag from the manufacturing to the decommissioning as waste usually takes 25-30 years. Then the environmental hazard associated with end life of PV panels has been largely related to their metal contents. The principal concern regards the presence of heavy metals as Cd in thin film (TF) modules or Pb and Cr in crystalline silicon (c-Si) panels. At the end of life of PV panels, these dangerous substances could be released in the environment, if special requirements for their disposal are not adopted. Nevertheless, in literature, only a few experimental study about metal emissions from silicon crystalline/thin film panels and the corresponding environmental effect are present. As part of a study funded by the Italian national consortium for the waste collection and recycling (COBAT), the present work was aimed to analyze experimentally the potential release into the environment of hazardous elements, particularly metals, from PV waste. In this paper, for the first time, eighteen releasable metals a large number of photovoltaic panels, by c-Si and TF, manufactured in the last 30 years, together with the environmental effects by a battery of ecotoxicological tests, were investigated. Leaching tests are conducted on the crushed samples of PV module. The test is conducted according to Italian and European Standard procedure for hazard assessment of the granular waste and of the sludge. The sample material is shaken for 24 hours in HDPE bottles with an overhead mixer Rotax 6.8 VELP at indoor temperature and using pure water (18 MΩ resistivity) as leaching solution. The liquid-to-solid ratio was 10 (L/S=10, i.e. 10 liters of water per kg of solid). The ecotoxicological tests were performed in the subsequent 24 hours. A battery of toxicity test with bacteria (Vibrio fisheri), algae (Pseudochirneriella subcapitata) and crustacea (Daphnia magna) was carried out on PV panel leachates obtained as previously described and immediately stored in dark and at 4°C until testing (in the next 24 hours). For understand the actual pollution load, a comparison with the current European and Italian benchmark limits was performed. The trend of leachable metal amount from panels in relation to manufacturing years was then highlighted in order to assess the environmental sustainability of PV technology over time. The experimental results were very heterogeneous and show that the photovoltaic panels could represent an environmental hazard. The experimental results showed that the amounts of some hazardous metals (Pb, Cr, Cd, Ni), for c-Si and TF, exceed the law limits and they are a clear indication of the potential environmental risk of photovoltaic panels "as a waste" without a proper management.

Keywords: photovoltaic panel, environment, ecotoxicity, metals emission

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354 Ichthyofauna and Population Status at Indus River Downstream, Sindh-Pakistan

Authors: M. K. Sheikh, Y. M. Laghari., P. K. Lashari., N. T. Narejo

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The Indus River is one of the longest important rivers of the world in Asia that flows southward through Pakistan, merges into the Arabian Sea near the port city of Karachi in Sindh Province, and forms the Indus Delta. Fish are an important resource for humans worldwide, especially as food. In fish, healthy nutriments are present which are not found in any other meat source because it have a huge quantity of omega- 3 fatty acids, which are very essential for the human body. Ichthyologic surveys were conducted to explore the diversity of freshwater fishes, distribution, abundance and current status of the fishes at different spatial scale of the downstream, Indus River. Total eight stations were selected namely Railo Miyan (RM), Karokho (Kk), Khanpur (Kp), Mullakatiyar (Mk), Wasi Malook Shah (WMS), Branch Morie (BM), Sujawal (Sj) and Jangseer (JS). The study was carried in the period of January 2016 to December 2019 to identify River and biodiversity threats and to suggest recommendations for conservation. The data were analysed by different population diversity index. Altogether, 124 species were recorded belonging to 12 Orders and 43 Families from the downstream of Indus River. Among 124 species, 29% belong to high commercial value and 35% were trash fishes. 31% of fishes were identified as marine/estuarine origin (migratory) and 05% were exotic fish species. Perciformes is the most predominated order, contributing to 41% of families. Among 43 families, the family Cyprinidae was the richest family from all localities of downstream, represented by 24% of fish species demonstrating a significant dominance in the number of species. A significant difference was observed for species abundance in between all sites, the maximum abundance species were found at first location RM having 115 species and minimum observed at the last station JS 56 genera. In the recorded Ichthyofauna, seven groups were found according to the International Union for Conservation of Nature status (IUCN), where a high species ratio was collected, in Least Concern (LC) having 94 species, 11 were found as not evaluated (NE), whereas 8 was identified as near threatened (NT), 1 was recorded as critically endangered (CR), 11 were collected as data deficient (DD), and while 8 was observed as vulnerable (VU) and 3 endangered (EN) species. Different diversity index has been used extensively in environmental studies to estimate the species richness and abundance of ecosystems outputs of their wellness; a positive environment (biodiversity rich) with species at RM had an environmental wellness and biodiversity levels of 4.566% while a negative control environment (biodiversity poor) on last station JS had an environmental wellness and biodiversity levels of 3.931%. The status of fish biodiversity and river has been found under serious threat. Due to the lower diversity of fishes, it became not only venerable for fish but also risky for fishermen. Necessary steps are recommended to protect the biodiversity by conducting further conservative research in this area.

Keywords: ichthyofaunal biodiversity, threatened species, diversity index, Indus River downstream

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353 High Speed Motion Tracking with Magnetometer in Nonuniform Magnetic Field

Authors: Jeronimo Cox, Tomonari Furukawa

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Magnetometers have become more popular in inertial measurement units (IMU) for their ability to correct estimations using the earth's magnetic field. Accelerometer and gyroscope-based packages fail with dead-reckoning errors accumulated over time. Localization in robotic applications with magnetometer-inclusive IMUs has become popular as a way to track the odometry of slower-speed robots. With high-speed motions, the accumulated error increases over smaller periods of time, making them difficult to track with IMU. Tracking a high-speed motion is especially difficult with limited observability. Visual obstruction of motion leaves motion-tracking cameras unusable. When motions are too dynamic for estimation techniques reliant on the observability of the gravity vector, the use of magnetometers is further justified. As available magnetometer calibration methods are limited with the assumption that background magnetic fields are uniform, estimation in nonuniform magnetic fields is problematic. Hard iron distortion is a distortion of the magnetic field by other objects that produce magnetic fields. This kind of distortion is often observed as the offset from the origin of the center of data points when a magnetometer is rotated. The magnitude of hard iron distortion is dependent on proximity to distortion sources. Soft iron distortion is more related to the scaling of the axes of magnetometer sensors. Hard iron distortion is more of a contributor to the error of attitude estimation with magnetometers. Indoor environments or spaces inside ferrite-based structures, such as building reinforcements or a vehicle, often cause distortions with proximity. As positions correlate to areas of distortion, methods of magnetometer localization include the production of spatial mapping of magnetic field and collection of distortion signatures to better aid location tracking. The goal of this paper is to compare magnetometer methods that don't need pre-productions of magnetic field maps. Mapping the magnetic field in some spaces can be costly and inefficient. Dynamic measurement fusion is used to track the motion of a multi-link system with us. Conventional calibration by data collection of rotation at a static point, real-time estimation of calibration parameters each time step, and using two magnetometers for determining local hard iron distortion are compared to confirm the robustness and accuracy of each technique. With opposite-facing magnetometers, hard iron distortion can be accounted for regardless of position, Rather than assuming that hard iron distortion is constant regardless of positional change. The motion measured is a repeatable planar motion of a two-link system connected by revolute joints. The links are translated on a moving base to impulse rotation of the links. Equipping the joints with absolute encoders and recording the motion with cameras to enable ground truth comparison to each of the magnetometer methods. While the two-magnetometer method accounts for local hard iron distortion, the method fails where the magnetic field direction in space is inconsistent.

Keywords: motion tracking, sensor fusion, magnetometer, state estimation

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352 Preparation, Solid State Characterization of Etraverine Co-Crystals with Improved Solubility for the Treatment of Human Immunodeficiency Virus

Authors: B. S. Muddukrishna, Karthik Aithal, Aravind Pai

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Introduction: Preparation of binary cocrystals of Etraverine (ETR) by using Tartaric Acid (TAR) as a conformer was the main focus of this study. Etravirine is a Class IV drug, as per the BCS classification system. Methods: Cocrystals were prepared by slow evaporation technique. A mixture of total 500mg of ETR: TAR was weighed in molar ratios of 1:1 (371.72mg of ETR and 128.27mg of TAR). Saturated solution of Etravirine was prepared in Acetone: Methanol (50:50) mixture in which tartaric acid is dissolved by sonication and then this solution was stirred using a magnetic stirrer until the solvent got evaporated. Shimadzu FTIR – 8300 system was used to acquire the FTIR spectra of the cocrystals prepared. Shimadzu thermal analyzer was used to achieve DSC measurements. X-ray diffractometer was used to obtain the X-ray powder diffraction pattern. Shake flask method was used to determine the equilibrium dynamic solubility of pure, physical mixture and cocrystals of ETR. USP buffer (pH 6.8) containing 1% of Tween 80 was used as the medium. The pure, physical mixture and the optimized cocrystal of ETR were accurately weighed sufficient to maintain the sink condition and were filled in hard gelatine capsules (size 4). Electrolab-Tablet Dissolution tester using basket apparatus at a rotational speed of 50 rpm and USP phosphate buffer (900 mL, pH = 6.8, 37 ˚C) + 1% Tween80 as a media, was used to carry out dissolution. Shimadzu LC-10 series chromatographic system was used to perform the analysis with PDA detector. An Hypersil BDS C18 (150mm ×4.6 mm ×5 µm) column was used for separation with mobile phase comprising of a mixture of ace¬tonitrile and phosphate buffer 20mM, pH 3.2 in the ratio 60:40 v/v. The flow rate was 1.0mL/min and column temperature was set to 30°C. The detection was carried out at 304 nm for ETR. Results and discussions: The cocrystals were subjected to various solid state characterization and the results confirmed the formation of cocrystals. The C=O stretching vibration (1741cm-1) in tartaric acid was disappeared in the cocrystal and the peak broadening of primary amine indicates hydrogen bond formation. The difference in the melting point of cocrystals when compared to pure Etravirine (265 °C) indicates interaction between the drug and the coformer which proves that first ordered transformation i.e. melting endotherm has disappeared. The difference in 2θ values of pure drug and cocrystals indicates the interaction between the drug and the coformer. Dynamic solubility and dissolution studies were also conducted by shake flask method and USP apparatus one respectively and 3.6 fold increase in the dynamic solubility were observed and in-vitro dissolution study shows four fold increase in the solubility for the ETR: TAR (1:1) cocrystals. The ETR: TAR (1:1) cocrystals shows improved solubility and dissolution as compared to the pure drug which was clearly showed by solid state characterization and dissolution studies.

Keywords: dynamic solubility, Etraverine, in vitro dissolution, slurry method

Procedia PDF Downloads 323
351 Field Performance of Cement Treated Bases as a Reflective Crack Mitigation Technique for Flexible Pavements

Authors: Mohammad R. Bhuyan, Mohammad J. Khattak

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Deterioration of flexible pavements due to crack reflection from its soil-cement base layer is a major concern around the globe. The service life of flexible pavement diminishes significantly because of the reflective cracks. Highway agencies are struggling for decades to prevent or mitigate these cracks in order to increase pavement service lives. The root cause of reflective cracks is the shrinkage crack which occurs in the soil-cement bases during the cement hydration process. The primary factor that causes the shrinkage is the cement content of the soil-cement mixture. With the increase of cement content, the soil-cement base gains strength and durability, which is necessary to withstand the traffic loads. But at the same time, higher cement content creates more shrinkage resulting in more reflective cracks in pavements. Historically, various states of USA have used the soil-cement bases for constructing flexile pavements. State of Louisiana (USA) had been using 8 to 10 percent of cement content to manufacture the soil-cement bases. Such traditional soil-cement bases yield 2.0 MPa (300 psi) 7-day compressive strength and are termed as cement stabilized design (CSD). As these CSD bases generate significant reflective cracks, another design of soil-cement base has been utilized by adding 4 to 6 percent of cement content called cement treated design (CTD), which yields 1.0 MPa (150 psi) 7-day compressive strength. The reduction of cement content in the CTD base is expected to minimize shrinkage cracks thus increasing pavement service lives. Hence, this research study evaluates the long-term field performance of CTD bases with respect to CSD bases used in flexible pavements. Pavement Management System of the state of Louisiana was utilized to select flexible pavement projects with CSD and CTD bases that had good historical record and time-series distress performance data. It should be noted that the state collects roughness and distress data for 1/10th mile section every 2-year period. In total, 120 CSD and CTD projects were analyzed in this research, where more than 145 miles (CTD) and 175 miles (CSD) of roadways data were accepted for performance evaluation and benefit-cost analyses. Here, the service life extension and area based on distress performance were considered as benefits. It was found that CTD bases increased 1 to 5 years of pavement service lives based on transverse cracking as compared to CSD bases. On the other hand, the service lives based on longitudinal and alligator cracking, rutting and roughness index remain the same. Hence, CTD bases provide some service life extension (2.6 years, on average) to the controlling distress; transverse cracking, but it was inexpensive due to its lesser cement content. Consequently, CTD bases become 20% more cost-effective than the traditional CSD bases, when both bases were compared by net benefit-cost ratio obtained from all distress types.

Keywords: cement treated base, cement stabilized base, reflective cracking , service life, flexible pavement

Procedia PDF Downloads 149
350 Cobb Angle Measurement from Coronal X-Rays Using Artificial Neural Networks

Authors: Andrew N. Saylor, James R. Peters

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Scoliosis is a complex 3D deformity of the thoracic and lumbar spines, clinically diagnosed by measurement of a Cobb angle of 10 degrees or more on a coronal X-ray. The Cobb angle is the angle made by the lines drawn along the proximal and distal endplates of the respective proximal and distal vertebrae comprising the curve. Traditionally, Cobb angles are measured manually using either a marker, straight edge, and protractor or image measurement software. The task of measuring the Cobb angle can also be represented by a function taking the spine geometry rendered using X-ray imaging as input and returning the approximate angle. Although the form of such a function may be unknown, it can be approximated using artificial neural networks (ANNs). The performance of ANNs is affected by many factors, including the choice of activation function and network architecture; however, the effects of these parameters on the accuracy of scoliotic deformity measurements are poorly understood. Therefore, the objective of this study was to systematically investigate the effect of ANN architecture and activation function on Cobb angle measurement from the coronal X-rays of scoliotic subjects. The data set for this study consisted of 609 coronal chest X-rays of scoliotic subjects divided into 481 training images and 128 test images. These data, which included labeled Cobb angle measurements, were obtained from the SpineWeb online database. In order to normalize the input data, each image was resized using bi-linear interpolation to a size of 500 × 187 pixels, and the pixel intensities were scaled to be between 0 and 1. A fully connected (dense) ANN with a fixed cost function (mean squared error), batch size (10), and learning rate (0.01) was developed using Python Version 3.7.3 and TensorFlow 1.13.1. The activation functions (sigmoid, hyperbolic tangent [tanh], or rectified linear units [ReLU]), number of hidden layers (1, 3, 5, or 10), and number of neurons per layer (10, 100, or 1000) were varied systematically to generate a total of 36 network conditions. Stochastic gradient descent with early stopping was used to train each network. Three trials were run per condition, and the final mean squared errors and mean absolute errors were averaged to quantify the network response for each condition. The network that performed the best used ReLU neurons had three hidden layers, and 100 neurons per layer. The average mean squared error of this network was 222.28 ± 30 degrees2, and the average mean absolute error was 11.96 ± 0.64 degrees. It is also notable that while most of the networks performed similarly, the networks using ReLU neurons, 10 hidden layers, and 1000 neurons per layer, and those using Tanh neurons, one hidden layer, and 10 neurons per layer performed markedly worse with average mean squared errors greater than 400 degrees2 and average mean absolute errors greater than 16 degrees. From the results of this study, it can be seen that the choice of ANN architecture and activation function has a clear impact on Cobb angle inference from coronal X-rays of scoliotic subjects.

Keywords: scoliosis, artificial neural networks, cobb angle, medical imaging

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349 The Effect of TiO₂ Nanoparticles on Zebrafish Embryos

Authors: Elena Maria Scalisi

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Currently, photodegradation by nanoparticles (NPs) is a common solution for wastewater treatment. Nanoparticles are efficient for removing organic and inorganic pollutants, heavy metals from wastewater and killing microorganisms through environmentally friendly. In this context, the major representative of photocatalytic technology for industrial wastewater treatment are TiO₂ nanoparticles (TiO₂-NPs). TiO₂-NPs have a strong catalytic activity that depends to their physicochemical properties. Thanks to their small size (between 1-100 nm), nanoparticles occupy less volume, then their surface area increases. The increase in the surface-to-volume ratio results in the increase of the particle surface energy, which improve their reactivity potential. However, these unique properties represent risks to the ecosystems and organisms when unintentionally TiO₂-NPs are release into the environment and absorbed by living organisms. Several studies confirm that there is a high level of interest concerning the safety of TiO₂-NPs in the aquatic environment, furthermore, ecotoxicological tools are useful to correctly evaluate their toxicity. In the current study, we aimed to characterize potential toxic effects of TiO₂-NP suspension to zebrafish during embryo-larval stages to evaluate parameters such as survival rates, malformation, hatching, the overall length of the larvae heartbeat, and biochemical biomarkers that reflect the acute toxicity and sublethal effects of TiO₂-NPs. Zebrafish embryos were exposed to titanium dioxide nanoparticles (TiO₂-NPs at 1mg/L, 2mg/L, and 4mg/L) from fertilization to the free swimming stage (144hpf). Every day, we recorded the toxicological endpoints, moreover, immunohistochemical analysis has been performed at the end of the exposure. In particular, we have evaluate the expression of the following biomarkers: Heat Shock Protein 70 (HSP70), Poly ADP-Ribose Polymerase-1 (PARP-1), Metallothioneins (MTs). Our results have shown that hatch ability, survival, and malformation rate were not affected by TiO₂ NPs at these exposure levels. However, TiO₂-NPs caused an increase of heartbeat and reduction of body length; at the same time, TiO₂-NPs have inducted the production of ROS and the expression of oxidative stress biomarkers HSP70 and PARP-1. Hight positivity for PARP-1 at all concentration tested was observed. As regards MT, positivity was found in the expression of this biomarker in the whole body of the embryo, with the exception of the end of the tail. Metallothioneins (MT) are biomarkers widely used in environmental monitoring programs for aquatic creatures. At the light of our results i.e. no death until the end of the experiment (144hpf), no malformation and expression of the biomarkers mentioned, it is evident that zebrafish larvae with their natural detoxification pathways are able to resist the presence of toxic substances and then they can tolerate the presence of metal concentrations. However, an excessive oxidative state can compromise cell function, therefore the uncontrolled release of nanoparticles into the environment is severe and must be constantly monitored.

Keywords: nanoparticles, embryo zebrafish, HSP70, PARP-1

Procedia PDF Downloads 119
348 Vehicle Timing Motion Detection Based on Multi-Dimensional Dynamic Detection Network

Authors: Jia Li, Xing Wei, Yuchen Hong, Yang Lu

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Detecting vehicle behavior has always been the focus of intelligent transportation, but with the explosive growth of the number of vehicles and the complexity of the road environment, the vehicle behavior videos captured by traditional surveillance have been unable to satisfy the study of vehicle behavior. The traditional method of manually labeling vehicle behavior is too time-consuming and labor-intensive, but the existing object detection and tracking algorithms have poor practicability and low behavioral location detection rate. This paper proposes a vehicle behavior detection algorithm based on the dual-stream convolution network and the multi-dimensional video dynamic detection network. In the videos, the straight-line behavior of the vehicle will default to the background behavior. The Changing lanes, turning and turning around are set as target behaviors. The purpose of this model is to automatically mark the target behavior of the vehicle from the untrimmed videos. First, the target behavior proposals in the long video are extracted through the dual-stream convolution network. The model uses a dual-stream convolutional network to generate a one-dimensional action score waveform, and then extract segments with scores above a given threshold M into preliminary vehicle behavior proposals. Second, the preliminary proposals are pruned and identified using the multi-dimensional video dynamic detection network. Referring to the hierarchical reinforcement learning, the multi-dimensional network includes a Timer module and a Spacer module, where the Timer module mines time information in the video stream and the Spacer module extracts spatial information in the video frame. The Timer and Spacer module are implemented by Long Short-Term Memory (LSTM) and start from an all-zero hidden state. The Timer module uses the Transformer mechanism to extract timing information from the video stream and extract features by linear mapping and other methods. Finally, the model fuses time information and spatial information and obtains the location and category of the behavior through the softmax layer. This paper uses recall and precision to measure the performance of the model. Extensive experiments show that based on the dataset of this paper, the proposed model has obvious advantages compared with the existing state-of-the-art behavior detection algorithms. When the Time Intersection over Union (TIoU) threshold is 0.5, the Average-Precision (MP) reaches 36.3% (the MP of baselines is 21.5%). In summary, this paper proposes a vehicle behavior detection model based on multi-dimensional dynamic detection network. This paper introduces spatial information and temporal information to extract vehicle behaviors in long videos. Experiments show that the proposed algorithm is advanced and accurate in-vehicle timing behavior detection. In the future, the focus will be on simultaneously detecting the timing behavior of multiple vehicles in complex traffic scenes (such as a busy street) while ensuring accuracy.

Keywords: vehicle behavior detection, convolutional neural network, long short-term memory, deep learning

Procedia PDF Downloads 107
347 Analysis on the Converged Method of Korean Scientific and Mathematical Fields and Liberal Arts Programme: Focusing on the Intervention Patterns in Liberal Arts

Authors: Jinhui Bak, Bumjin Kim

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The purpose of this study is to analyze how the scientific and mathematical fields (STEM) and liberal arts (A) work together in the STEAM program. In the future STEAM programs that have been designed and developed, the humanities will act not just as a 'tool' for science technology and mathematics, but as a 'core' content to have an equivalent status. STEAM was first introduced to the Republic of Korea in 2011 when the Ministry of Education emphasized fostering creative convergence talent. Many programs have since been developed under the name STEAM, but with the majority of programs focusing on technology education, arts and humanities are considered secondary. As a result, arts is most likely to be accepted as an option that can be excluded from the teachers who run the STEAM program. If what we ultimately pursue through STEAM education is in fostering STEAM literacy, we should no longer turn arts into a tooling area for STEM. Based on this consciousness, this study analyzed over 160 STEAM programs in middle and high schools, which were produced and distributed by the Ministry of Education and the Korea Science and Technology Foundation from 2012 to 2017. The framework of analyses referenced two criteria presented in the related prior studies: normative convergence and technological convergence. In addition, we divide Arts into fine arts and liberal arts and focused on Korean Language Course which is in liberal arts and analyzed what kind of curriculum standards were selected, and what kind of process the Korean language department participated in teaching and learning. In this study, to ensure the reliability of the analysis results, we have chosen to cross-check the individual analysis results of the two researchers and only if they are consistent. We also conducted a reliability check on the analysis results of three middle and high school teachers involved in the STEAM education program. Analyzing 10 programs selected randomly from the analyzed programs, Cronbach's α .853 showed a reliable level. The results of this study are summarized as follows. First, the convergence ratio of the liberal arts was lowest in the department of moral at 14.58%. Second, the normative convergence is 28.19%, which is lower than that of the technological convergence. Third, the language and achievement criteria selected for the program were limited to functional areas such as listening, talking, reading and writing. This means that the convergence of Korean language departments is made only by the necessary tools to communicate opinions or promote scientific products. In this study, we intend to compare these results with the STEAM programs in the United States and abroad to explore what elements or key concepts are required for the achievement criteria for Korean language and curriculum. This is meaningful in that the humanities field (A), including Korean, provides basic data that can be fused into 'equivalent qualifications' with science (S), technical engineering (TE) and mathematics (M).

Keywords: Korean STEAM Programme, liberal arts, STEAM curriculum, STEAM Literacy, STEM

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346 Ibrutinib and the Potential Risk of Cardiac Failure: A Review of Pharmacovigilance Data

Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.

Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection

Procedia PDF Downloads 107
345 Phonological Processing and Its Role in Pseudo-Word Decoding in Children Learning to Read Kannada Language between 5.6 to 8.6 Years

Authors: Vangmayee. V. Subban, Somashekara H. S, Shwetha Prabhu, Jayashree S. Bhat

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Introduction and Need: Phonological processing is critical in learning to read alphabetical and non-alphabetical languages. However, its role in learning to read Kannada an alphasyllabary is equivocal. The literature has focused on the developmental role of phonological awareness on reading. To the best of authors knowledge, the role of phonological memory and phonological naming has not been addressed in alphasyllabary Kannada language. Therefore, there is a need to evaluate the comprehensive role of the phonological processing skills in Kannada on word decoding skills during the early years of schooling. Aim and Objectives: The present study aimed to explore the phonological processing abilities and their role in learning to decode pseudowords in children learning to read the Kannada language during initial years of formal schooling between 5.6 to 8.6 years. Method: In this cross sectional study, 60 typically developing Kannada speaking children, 20 each from Grade I, Grade II, and Grade III between the age range of 5.6 to 6.6 years, 6.7 to 7.6 years and 7.7 to 8.6 years respectively were selected from Kannada medium schools. Phonological processing abilities were assessed using an assessment tool specifically developed to address the objectives of the present research. The assessment tool was content validated by subject experts and had good inter and intra-subject reliability. Phonological awareness was assessed at syllable level using syllable segmentation, blending, and syllable stripping at initial, medial and final position. Phonological memory was assessed using pseudoword repetition task and phonological naming was assessed using rapid automatized naming of objects. Both phonological awareneness and phonological memory measures were scored for the accuracy of the response, whereas Rapid Automatized Naming (RAN) was scored for total naming speed. Results: The mean scores comparison using one-way ANOVA revealed a significant difference (p ≤ 0.05) between the groups on all the measures of phonological awareness, pseudoword repetition, rapid automatized naming, and pseudoword reading. Subsequent post-hoc grade wise comparison using Bonferroni test revealed significant differences (p ≤ 0.05) between each of the grades for all the tasks except (p ≥ 0.05) for syllable blending, syllable stripping, and pseudoword repetition between Grade II and Grade III. The Pearson correlations revealed a highly significant positive correlation (p=0.000) between all the variables except phonological naming which had significant negative correlations. However, the correlation co-efficient was higher for phonological awareness measures compared to others. Hence, phonological awareness was chosen a first independent variable to enter in the hierarchical regression equation followed by rapid automatized naming and finally, pseudoword repetition. The regression analysis revealed syllable awareness as a single most significant predictor of pseudoword reading by explaining the unique variance of 74% and there was no significant change in R² when RAN and pseudoword repetition were added subsequently to the regression equation. Conclusion: Present study concluded that syllable awareness matures completely by Grade II, whereas the phonological memory and phonological naming continue to develop beyond Grade III. Amongst phonological processing skills, phonological awareness, especially syllable awareness is crucial for word decoding than phonological memory and naming during initial years of schooling.

Keywords: phonological awareness, phonological memory, phonological naming, phonological processing, pseudo-word decoding

Procedia PDF Downloads 148
344 A Comparison of Methods for Estimating Dichotomous Treatment Effects: A Simulation Study

Authors: Jacqueline Y. Thompson, Sam Watson, Lee Middleton, Karla Hemming

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Introduction: The odds ratio (estimated via logistic regression) is a well-established and common approach for estimating covariate-adjusted binary treatment effects when comparing a treatment and control group with dichotomous outcomes. Its popularity is primarily because of its stability and robustness to model misspecification. However, the situation is different for the relative risk and risk difference, which are arguably easier to interpret and better suited to specific designs such as non-inferiority studies. So far, there is no equivalent, widely acceptable approach to estimate an adjusted relative risk and risk difference when conducting clinical trials. This is partly due to the lack of a comprehensive evaluation of available candidate methods. Methods/Approach: A simulation study is designed to evaluate the performance of relevant candidate methods to estimate relative risks to represent conditional and marginal estimation approaches. We consider the log-binomial, generalised linear models (GLM) with iteratively weighted least-squares (IWLS) and model-based standard errors (SE); log-binomial GLM with convex optimisation and model-based SEs; log-binomial GLM with convex optimisation and permutation tests; modified-Poisson GLM IWLS and robust SEs; log-binomial generalised estimation equations (GEE) and robust SEs; marginal standardisation and delta method SEs; and marginal standardisation and permutation test SEs. Independent and identically distributed datasets are simulated from a randomised controlled trial to evaluate these candidate methods. Simulations are replicated 10000 times for each scenario across all possible combinations of sample sizes (200, 1000, and 5000), outcomes (10%, 50%, and 80%), and covariates (ranging from -0.05 to 0.7) representing weak, moderate or strong relationships. Treatment effects (ranging from 0, -0.5, 1; on the log-scale) will consider null (H0) and alternative (H1) hypotheses to evaluate coverage and power in realistic scenarios. Performance measures (bias, mean square error (MSE), relative efficiency, and convergence rates) are evaluated across scenarios covering a range of sample sizes, event rates, covariate prognostic strength, and model misspecifications. Potential Results, Relevance & Impact: There are several methods for estimating unadjusted and adjusted relative risks. However, it is unclear which method(s) is the most efficient, preserves type-I error rate, is robust to model misspecification, or is the most powerful when adjusting for non-prognostic and prognostic covariates. GEE estimations may be biased when the outcome distributions are not from marginal binary data. Also, it seems that marginal standardisation and convex optimisation may perform better than GLM IWLS log-binomial.

Keywords: binary outcomes, statistical methods, clinical trials, simulation study

Procedia PDF Downloads 93
343 A Geographic Information System Mapping Method for Creating Improved Satellite Solar Radiation Dataset Over Qatar

Authors: Sachin Jain, Daniel Perez-Astudillo, Dunia A. Bachour, Antonio P. Sanfilippo

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The future of solar energy in Qatar is evolving steadily. Hence, high-quality spatial solar radiation data is of the uttermost requirement for any planning and commissioning of solar technology. Generally, two types of solar radiation data are available: satellite data and ground observations. Satellite solar radiation data is developed by the physical and statistical model. Ground data is collected by solar radiation measurement stations. The ground data is of high quality. However, they are limited to distributed point locations with the high cost of installation and maintenance for the ground stations. On the other hand, satellite solar radiation data is continuous and available throughout geographical locations, but they are relatively less accurate than ground data. To utilize the advantage of both data, a product has been developed here which provides spatial continuity and higher accuracy than any of the data alone. The popular satellite databases: National Solar radiation Data Base, NSRDB (PSM V3 model, spatial resolution: 4 km) is chosen here for merging with ground-measured solar radiation measurement in Qatar. The spatial distribution of ground solar radiation measurement stations is comprehensive in Qatar, with a network of 13 ground stations. The monthly average of the daily total Global Horizontal Irradiation (GHI) component from ground and satellite data is used for error analysis. The normalized root means square error (NRMSE) values of 3.31%, 6.53%, and 6.63% for October, November, and December 2019 were observed respectively when comparing in-situ and NSRDB data. The method is based on the Empirical Bayesian Kriging Regression Prediction model available in ArcGIS, ESRI. The workflow of the algorithm is based on the combination of regression and kriging methods. A regression model (OLS, ordinary least square) is fitted between the ground and NSBRD data points. A semi-variogram is fitted into the experimental semi-variogram obtained from the residuals. The kriging residuals obtained after fitting the semi-variogram model were added to NSRBD data predicted values obtained from the regression model to obtain the final predicted values. The NRMSE values obtained after merging are respectively 1.84%, 1.28%, and 1.81% for October, November, and December 2019. One more explanatory variable, that is the ground elevation, has been incorporated in the regression and kriging methods to reduce the error and to provide higher spatial resolution (30 m). The final GHI maps have been created after merging, and NRMSE values of 1.24%, 1.28%, and 1.28% have been observed for October, November, and December 2019, respectively. The proposed merging method has proven as a highly accurate method. An additional method is also proposed here to generate calibrated maps by using regression and kriging model and further to use the calibrated model to generate solar radiation maps from the explanatory variable only when not enough historical ground data is available for long-term analysis. The NRMSE values obtained after the comparison of the calibrated maps with ground data are 5.60% and 5.31% for November and December 2019 month respectively.

Keywords: global horizontal irradiation, GIS, empirical bayesian kriging regression prediction, NSRDB

Procedia PDF Downloads 71
342 A 1H NMR-Linked PCR Modelling Strategy for Tracking the Fatty Acid Sources of Aldehydic Lipid Oxidation Products in Culinary Oils Exposed to Simulated Shallow-Frying Episodes

Authors: Martin Grootveld, Benita Percival, Sarah Moumtaz, Kerry L. Grootveld

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Objectives/Hypotheses: The adverse health effect potential of dietary lipid oxidation products (LOPs) has evoked much clinical interest. Therefore, we employed a 1H NMR-linked Principal Component Regression (PCR) chemometrics modelling strategy to explore relationships between data matrices comprising (1) aldehydic LOP concentrations generated in culinary oils/fats when exposed to laboratory-simulated shallow frying practices, and (2) the prior saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acid (PUFA) contents of such frying media (FM), together with their heating time-points at a standard frying temperature (180 oC). Methods: Corn, sunflower, extra virgin olive, rapeseed, linseed, canola, coconut and MUFA-rich algae frying oils, together with butter and lard, were heated according to laboratory-simulated shallow-frying episodes at 180 oC, and FM samples were collected at time-points of 0, 5, 10, 20, 30, 60, and 90 min. (n = 6 replicates per sample). Aldehydes were determined by 1H NMR analysis (Bruker AV 400 MHz spectrometer). The first (dependent output variable) PCR data matrix comprised aldehyde concentration scores vectors (PC1* and PC2*), whilst the second (predictor) one incorporated those from the fatty acid content/heating time variables (PC1-PC4) and their first-order interactions. Results: Structurally complex trans,trans- and cis,trans-alka-2,4-dienals, 4,5-epxy-trans-2-alkenals and 4-hydroxy-/4-hydroperoxy-trans-2-alkenals (group I aldehydes predominantly arising from PUFA peroxidation) strongly and positively loaded on PC1*, whereas n-alkanals and trans-2-alkenals (group II aldehydes derived from both MUFA and PUFA hydroperoxides) strongly and positively loaded on PC2*. PCR analysis of these scores vectors (SVs) demonstrated that PCs 1 (positively-loaded linoleoylglycerols and [linoleoylglycerol]:[SFA] content ratio), 2 (positively-loaded oleoylglycerols and negatively-loaded SFAs), 3 (positively-loaded linolenoylglycerols and [PUFA]:[SFA] content ratios), and 4 (exclusively orthogonal sampling time-points) all powerfully contributed to aldehydic PC1* SVs (p 10-3 to < 10-9), as did all PC1-3 x PC4 interaction ones (p 10-5 to < 10-9). PC2* was also markedly dependent on all the above PC SVs (PC2 > PC1 and PC3), and the interactions of PC1 and PC2 with PC4 (p < 10-9 in each case), but not the PC3 x PC4 contribution. Conclusions: NMR-linked PCR analysis is a valuable strategy for (1) modelling the generation of aldehydic LOPs in heated cooking oils and other FM, and (2) tracking their unsaturated fatty acid (UFA) triacylglycerol sources therein.

Keywords: frying oils, lipid oxidation products, frying episodes, chemometrics, principal component regression, NMR Analysis, cytotoxic/genotoxic aldehydes

Procedia PDF Downloads 153
341 Structural Analysis of a Composite Wind Turbine Blade

Authors: C. Amer, M. Sahin

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The design of an optimised horizontal axis 5-meter-long wind turbine rotor blade in according with IEC 61400-2 standard is a research and development project in order to fulfil the requirements of high efficiency of torque from wind production and to optimise the structural components to the lightest and strongest way possible. For this purpose, a research study is presented here by focusing on the structural characteristics of a composite wind turbine blade via finite element modelling and analysis tools. In this work, first, the required data regarding the general geometrical parts are gathered. Then, the airfoil geometries are created at various sections along the span of the blade by using CATIA software to obtain the two surfaces, namely; the suction and the pressure side of the blade in which there is a hat shaped fibre reinforced plastic spar beam, so-called chassis starting at 0.5m from the root of the blade and extends up to 4 m and filled with a foam core. The root part connecting the blade to the main rotor differential metallic hub having twelve hollow threaded studs is then modelled. The materials are assigned as two different types of glass fabrics, polymeric foam core material and the steel-balsa wood combination for the root connection parts. The glass fabrics are applied using hand wet lay-up lamination with epoxy resin as METYX L600E10C-0, is the unidirectional continuous fibres and METYX XL800E10F having a tri-axial architecture with fibres in the 0,+45,-45 degree orientations in a ratio of 2:1:1. Divinycell H45 is used as the polymeric foam. The finite element modelling of the blade is performed via MSC PATRAN software with various meshes created on each structural part considering shell type for all surface geometries, and lumped mass were added to simulate extra adhesive locations. For the static analysis, the boundary conditions are assigned as fixed at the root through aforementioned bolts, where for dynamic analysis both fixed-free and free-free boundary conditions are made. By also taking the mesh independency into account, MSC NASTRAN is used as a solver for both analyses. The static analysis aims the tip deflection of the blade under its own weight and the dynamic analysis comprises normal mode dynamic analysis performed in order to obtain the natural frequencies and corresponding mode shapes focusing the first five in and out-of-plane bending and the torsional modes of the blade. The analyses results of this study are then used as a benchmark prior to modal testing, where the experiments over the produced wind turbine rotor blade has approved the analytical calculations.

Keywords: dynamic analysis, fiber reinforced composites, horizontal axis wind turbine blade, hand-wet layup, modal testing

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340 Assessment Environmental and Economic of Yerba Mate as a Feed Additive on Feedlot Lamb

Authors: Danny Alexander R. Moreno, Gustavo L. Sartorello, Yuli Andrea P. Bermudez, Richard R. Lobo, Ives Claudio S. Bueno, Augusto H. Gameiro

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Meat production is a significant sector for Brazil's economy; however, the agricultural segment has suffered censure regarding the negative impacts on the environment, which consequently results in climate change. Therefore, it is essential the implementation of nutritional strategies that can improve the environmental performance of livestock. This research aimed to estimate the environmental impact and profitability of the use of yerba mate extract (Ilex paraguariensis) as an additive in the feeding of feedlot lamb. Thirty-six castrated male lambs (average weight of 23.90 ± 3.67 kg and average age of 75 days) were randomly assigned to four experimental diets with different levels of inclusion of yerba mate extract (0, 1, 2, and 4 %) based on dry matter. The animals were confined for fifty-three days and fed with 60:40 corn silage to concentrate ratio. As an indicator of environmental impact, the carbon footprint (CF) was measured as kg of CO₂ equivalent (CO₂-eq) per kg of body weight produced (BWP). The greenhouse gas (GHG) emissions such as methane (CH₄) generated from enteric fermentation, were calculated using the sulfur hexafluoride gas tracer (SF₆) technique; while the CH₄, nitrous oxide (N₂O - emissions generated by feces and urine), and carbon dioxide (CO₂ - emissions generated by concentrate and silage processing) were estimated using the Intergovernmental Panel on Climate Change (IPCC) methodology. To estimate profitability, the gross margin was used, which is the total revenue minus the total cost; the latter is composed of the purchase of animals and food. The boundaries of this study considered only the lamb fattening system. The enteric CH₄ emission from the lamb was the largest source of on-farm GHG emissions (47%-50%), followed by CH₄ and N₂O emissions from manure (10%-20%) and CO₂ emission from the concentrate, silage, and fossil energy (17%-5%). The treatment that generated the least environmental impact was the group with 4% of yerba mate extract (YME), which showed a 3% reduction in total GHG emissions in relation to the control (1462.5 and 1505.5 kg CO₂-eq, respectively). However, the scenario with 1% YME showed an increase in emissions of 7% compared to the control group. In relation to CF, the treatment with 4% YME had the lowest value (4.1 kg CO₂-eq/kg LW) compared with the other groups. Nevertheless, although the 4% YME inclusion scenario showed the lowest CF, the gross margin decreased by 36% compared to the control group (0% YME), due to the cost of YME as a food additive. The results showed that the extract has the potential for use in reducing GHG. However, the cost of implementing this input as a mitigation strategy increased the production cost. Therefore, it is important to develop political strategies that help reduce the acquisition costs of input that contribute to the search for the environmental and economic benefit of the livestock sector.

Keywords: meat production, natural additives, profitability, sheep

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339 Stock Prediction and Portfolio Optimization Thesis

Authors: Deniz Peksen

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This thesis aims to predict trend movement of closing price of stock and to maximize portfolio by utilizing the predictions. In this context, the study aims to define a stock portfolio strategy from models created by using Logistic Regression, Gradient Boosting and Random Forest. Recently, predicting the trend of stock price has gained a significance role in making buy and sell decisions and generating returns with investment strategies formed by machine learning basis decisions. There are plenty of studies in the literature on the prediction of stock prices in capital markets using machine learning methods but most of them focus on closing prices instead of the direction of price trend. Our study differs from literature in terms of target definition. Ours is a classification problem which is focusing on the market trend in next 20 trading days. To predict trend direction, fourteen years of data were used for training. Following three years were used for validation. Finally, last three years were used for testing. Training data are between 2002-06-18 and 2016-12-30 Validation data are between 2017-01-02 and 2019-12-31 Testing data are between 2020-01-02 and 2022-03-17 We determine Hold Stock Portfolio, Best Stock Portfolio and USD-TRY Exchange rate as benchmarks which we should outperform. We compared our machine learning basis portfolio return on test data with return of Hold Stock Portfolio, Best Stock Portfolio and USD-TRY Exchange rate. We assessed our model performance with the help of roc-auc score and lift charts. We use logistic regression, Gradient Boosting and Random Forest with grid search approach to fine-tune hyper-parameters. As a result of the empirical study, the existence of uptrend and downtrend of five stocks could not be predicted by the models. When we use these predictions to define buy and sell decisions in order to generate model-based-portfolio, model-based-portfolio fails in test dataset. It was found that Model-based buy and sell decisions generated a stock portfolio strategy whose returns can not outperform non-model portfolio strategies on test dataset. We found that any effort for predicting the trend which is formulated on stock price is a challenge. We found same results as Random Walk Theory claims which says that stock price or price changes are unpredictable. Our model iterations failed on test dataset. Although, we built up several good models on validation dataset, we failed on test dataset. We implemented Random Forest, Gradient Boosting and Logistic Regression. We discovered that complex models did not provide advantage or additional performance while comparing them with Logistic Regression. More complexity did not lead us to reach better performance. Using a complex model is not an answer to figure out the stock-related prediction problem. Our approach was to predict the trend instead of the price. This approach converted our problem into classification. However, this label approach does not lead us to solve the stock prediction problem and deny or refute the accuracy of the Random Walk Theory for the stock price.

Keywords: stock prediction, portfolio optimization, data science, machine learning

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338 Wage Differentials in Pakistan by Focusing on Wage Differentials in Public and Private Sectors, Formal and Informal Sectors, and Major Occupational Groups

Authors: Asghar Ali, Narjis Khatoon

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This study focuses on the presence of wage differentials in Pakistan and also on the determinants that originate it. Since there are a smaller number of studies that are conducted on this topic in Pakistan, the current study aims to contribute in bridging the existing gap in this particular research genre. Hence, this study not only generates the desired results specific focus but it also contributes to the overall empirical work on the Pakistan economy. The preceding works which have been done to research wage determinants and wage differentials have used numerous different theories and approaches to reach their goals. The current study, in order to analyze the determinants of wage differentials in the developing economy, deals with the study of a number of such theories and approaches that are supposed as being beneficial for the purpose. This study undertakes the explanation of wage differentials in Pakistan by focusing on wage differentials in public and private sectors, formal and informal sectors, and major occupational groups. The study uses 'Wage Theory' to examine wage differentials among male and female employees in public and private sectors on varied levels of working conditions. This study also uses 'Segmented Labor Market Theory' to determine the wage differential in both public and private sectors, formal and informal, and major occupational groups in Pakistan. So the author has used various econometric techniques in order to explain and test these theories and to find out the required results. This study has employed seven different cross-sectional Labour Force Surveys for the time period between 2006-07 to 2012-13. Gender equality is not only a policy reform agenda for developing countries but also an important goal of Millennium Development Goals. This study investigates the nexus between wage inequality and economic growth and detects co-integration between gender wage differential and economic growth using ARDL bound test. It is confirmed from the empirical results that there exists long-run relationship between economic growth and wage differential. Our study indicated that half of the total female employees from fourteen major cities of Pakistan were employed in the public sector. Out of total female employees in private sector, 66 percent are employed in the formal sector, and 33 percent are working in the informal sector. Results also indicated that both men and women were paid more in the public sector compared to the private sector counterparts. Among the total female employees, only 9 percent had received any formal training, 52% were married and average years of schooling were 11 years. Further, our findings regarding wage differential between genders indicate that wage gap is lower in public sector as compared to private sector. In proportion, gender wage ratio was found to be 0.96, 0.62 and 0.66 in public, formal private and informal private sectors respectively. This suggests that in this case, private sector female employees with the same pay structure are compensated at a lower endowments rate as then public sector workers as compared to their counter parts.

Keywords: wage differentials, formal, informal, economic growth

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337 Electrical Degradation of GaN-based p-channel HFETs Under Dynamic Electrical Stress

Authors: Xuerui Niu, Bolin Wang, Xinchuang Zhang, Xiaohua Ma, Bin Hou, Ling Yang

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The application of discrete GaN-based power switches requires the collaboration of silicon-based peripheral circuit structures. However, the packages and interconnection between the Si and GaN devices can introduce parasitic effects to the circuit, which has great impacts on GaN power transistors. GaN-based monolithic power integration technology is an emerging solution which can improve the stability of circuits and allow the GaN-based devices to achieve more functions. Complementary logic circuits consisting of GaN-based E-mode p-channel heterostructure field-effect transistors (p-HFETs) and E-mode n-channel HEMTs can be served as the gate drivers. E-mode p-HFETs with recessed gate have attracted increasing interest because of the low leakage current and large gate swing. However, they suffer from a poor interface between the gate dielectric and polarized nitride layers. The reliability of p-HFETs is analyzed and discussed in this work. In circuit applications, the inverter is always operated with dynamic gate voltage (VGS) rather than a constant VGS. Therefore, dynamic electrical stress has been simulated to resemble the operation conditions for E-mode p-HFETs. The dynamic electrical stress condition is as follows. VGS is a square waveform switching from -5 V to 0 V, VDS is fixed, and the source grounded. The frequency of the square waveform is 100kHz with the rising/falling time of 100 ns and duty ratio of 50%. The effective stress time is 1000s. A number of stress tests are carried out. The stress was briefly interrupted to measure the linear IDS-VGS, saturation IDS-VGS, As VGS switches from -5 V to 0 V and VDS = 0 V, devices are under negative-bias-instability (NBI) condition. Holes are trapped at the interface of oxide layer and GaN channel layer, which results in the reduction of VTH. The negative shift of VTH is serious at the first 10s and then changes slightly with the following stress time. However, different phenomenon is observed when VDS reduces to -5V. VTH shifts negatively during stress condition, and the variation in VTH increases with time, which is different from that when VDS is 0V. Two mechanisms exists in this condition. On the one hand, the electric field in the gate region is influenced by the drain voltage, so that the trapping behavior of holes in the gate region changes. The impact of the gate voltage is weakened. On the other hand, large drain voltage can induce the hot holes generation and lead to serious hot carrier stress (HCS) degradation with time. The poor-quality interface between the oxide layer and GaN channel layer at the gate region makes a major contribution to the high-density interface traps, which will greatly influence the reliability of devices. These results emphasize that the improved etching and pretreatment processes needs to be developed so that high-performance GaN complementary logics with enhanced stability can be achieved.

Keywords: GaN-based E-mode p-HFETs, dynamic electric stress, threshold voltage, monolithic power integration technology

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336 The Effects of Aging on Visuomotor Behaviors in Reaching

Authors: Mengjiao Fan, Thomson W. L. Wong

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It is unavoidable that older adults may have to deal with aging-related motor problems. Aging is highly likely to affect motor learning and control as well. For example, older adults may suffer from poor motor function and quality of life due to age-related eye changes. These adverse changes in vision results in impairment of movement automaticity. Reaching is a fundamental component of various complex movements, which is therefore beneficial to explore the changes and adaptation in visuomotor behaviors. The current study aims to explore how aging affects visuomotor behaviors by comparing motor performance and gaze behaviors between two age groups (i.e., young and older adults). Visuomotor behaviors in reaching under providing or blocking online visual feedback (simulated visual deficiency) conditions were investigated in 60 healthy young adults (Mean age=24.49 years, SD=2.12) and 37 older adults (Mean age=70.07 years, SD=2.37) with normal or corrected-to-normal vision. Participants in each group were randomly allocated into two subgroups. Subgroup 1 was provided with online visual feedback of the hand-controlled mouse cursor. However, in subgroup 2, visual feedback was blocked to simulate visual deficiency. The experimental task required participants to complete 20 times of reaching to a target by controlling the mouse cursor on the computer screen. Among all the 20 trials, start position was upright in the center of the screen and target appeared at a randomly selected position by the tailor-made computer program. Primary outcomes of motor performance and gaze behaviours data were recorded by the EyeLink II (SR Research, Canada). The results suggested that aging seems to affect the performance of reaching tasks significantly in both visual feedback conditions. In both age groups, blocking online visual feedback of the cursor in reaching resulted in longer hand movement time (p < .001), longer reaching distance away from the target center (p<.001) and poorer reaching motor accuracy (p < .001). Concerning gaze behaviors, blocking online visual feedback increased the first fixation duration time in young adults (p<.001) but decreased it in older adults (p < .001). Besides, under the condition of providing online visual feedback of the cursor, older adults conducted a longer fixation dwell time on target throughout reaching than the young adults (p < .001) although the effect was not significant under blocking online visual feedback condition (p=.215). Therefore, the results suggested that different levels of visual feedback during movement execution can affect gaze behaviors differently in older and young adults. Differential effects by aging on visuomotor behaviors appear on two visual feedback patterns (i.e., blocking or providing online visual feedback of hand-controlled cursor in reaching). Several specific gaze behaviors among the older adults were found, which imply that blocking of visual feedback may act as a stimulus to seduce extra perceptive load in movement execution and age-related visual degeneration might further deteriorate the situation. It indeed provides us with insight for the future development of potential rehabilitative training method (e.g., well-designed errorless training) in enhancing visuomotor adaptation for our aging population in the context of improving their movement automaticity by facilitating their compensation of visual degeneration.

Keywords: aging effect, movement automaticity, reaching, visuomotor behaviors, visual degeneration

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335 Switchable Lipids: From a Molecular Switch to a pH-Sensitive System for the Drug and Gene Delivery

Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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334 Numerical Model of Crude Glycerol Autothermal Reforming to Hydrogen-Rich Syngas

Authors: A. Odoom, A. Salama, H. Ibrahim

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Hydrogen is a clean source of energy for power production and transportation. The main source of hydrogen in this research is biodiesel. Glycerol also called glycerine is a by-product of biodiesel production by transesterification of vegetable oils and methanol. This is a reliable and environmentally-friendly source of hydrogen production than fossil fuels. A typical composition of crude glycerol comprises of glycerol, water, organic and inorganic salts, soap, methanol and small amounts of glycerides. Crude glycerol has limited industrial application due to its low purity thus, the usage of crude glycerol can significantly enhance the sustainability and production of biodiesel. Reforming techniques is an approach for hydrogen production mainly Steam Reforming (SR), Autothermal Reforming (ATR) and Partial Oxidation Reforming (POR). SR produces high hydrogen conversions and yield but is highly endothermic whereas POR is exothermic. On the downside, PO yields lower hydrogen as well as large amount of side reactions. ATR which is a fusion of partial oxidation reforming and steam reforming is thermally neutral because net reactor heat duty is zero. It has relatively high hydrogen yield, selectivity as well as limits coke formation. The complex chemical processes that take place during the production phases makes it relatively difficult to construct a reliable and robust numerical model. Numerical model is a tool to mimic reality and provide insight into the influence of the parameters. In this work, we introduce a finite volume numerical study for an 'in-house' lab-scale experiment of ATR. Previous numerical studies on this process have considered either using Comsol or nodal finite difference analysis. Since Comsol is a commercial package which is not readily available everywhere and lab-scale experiment can be considered well mixed in the radial direction. One spatial dimension suffices to capture the essential feature of ATR, in this work, we consider developing our own numerical approach using MATLAB. A continuum fixed bed reactor is modelled using MATLAB with both pseudo homogeneous and heterogeneous models. The drawback of nodal finite difference formulation is that it is not locally conservative which means that materials and momenta can be generated inside the domain as an artifact of the discretization. Control volume, on the other hand, is locally conservative and suites very well problems where materials are generated and consumed inside the domain. In this work, species mass balance, Darcy’s equation and energy equations are solved using operator splitting technique. Therefore, diffusion-like terms are discretized implicitly while advection-like terms are discretized explicitly. An upwind scheme is adapted for the advection term to ensure accuracy and positivity. Comparisons with the experimental data show very good agreements which build confidence in our modeling approach. The models obtained were validated and optimized for better results.

Keywords: autothermal reforming, crude glycerol, hydrogen, numerical model

Procedia PDF Downloads 121