Search results for: reverse time migration (RTM)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 18998

Search results for: reverse time migration (RTM)

13448 A Novel Rapid Well Control Technique Modelled in Computational Fluid Dynamics Software

Authors: Michael Williams

Abstract:

The ability to control a flowing well is of the utmost important. During the kill phase, heavy weight kill mud is circulated around the well. While increasing bottom hole pressure near wellbore formation, the damage is increased. The addition of high density spherical objects has the potential to minimise this near wellbore damage, increase bottom hole pressure and reduce operational time to kill the well. This operational time saving is seen in the rapid deployment of high density spherical objects instead of building high density drilling fluid. The research aims to model the well kill process using a Computational Fluid Dynamics software. A model has been created as a proof of concept to analyse the flow of micron sized spherical objects in the drilling fluid. Initial results show that this new methodology of spherical objects in drilling fluid agrees with traditional stream lines seen in non-particle flow. Additional models have been created to demonstrate that areas of higher flow rate around the bit can lead to increased probability of wash out of formations but do not affect the flow of micron sized spherical objects. Interestingly, areas that experience dimensional changes such as tool joints and various BHA components do not appear at this initial stage to experience increased velocity or create areas of turbulent flow, which could lead to further borehole stability. In conclusion, the initial models of this novel well control methodology have not demonstrated any adverse flow patterns, which would conclude that this model may be viable under field conditions.

Keywords: well control, fluid mechanics, safety, environment

Procedia PDF Downloads 161
13447 Hip Resurfacing Makes for Easier Surgery with Better Functional Outcomes at Time of Revision: A Case Controlled Study

Authors: O. O. Onafowokan, K. Anderson, M. R. Norton, R. G. Middleton

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Revision total hip arthroplasty (THA) is known to be a challenging procedure with potential for poor outcomes. Due to its lack of metaphyseal encroachment, hip resurfacing arthroplasty (HRA) is classified as a bone conserving procedure. Although the literature postulates that this is an advantage at time of revision surgery, there is no evidence to either support or refute this claim. We identified 129 hips that had undergone HRA and 129 controls undergoing first revision THA. We recorded the clinical assessment and survivorship of implants in a multi-surgeon, single centre, retrospective case control series for both arms. These were matched for age and sex. Data collected included demographics, indications for surgery, Oxford Hip Score (OHS), length of surgery, length of hospital stay, blood transfusion, implant complexity and further surgical procedures. Significance was taken as p < 0.05. Mean follow up was 7.5 years (1 to 15). There was a significant 6 point difference in postoperative OHS in favour of the revision resurfacing group (p=0.0001). The revision HRA group recorded 48 minutes less length of surgery (p<0.0001), 2 days less in length of hospital stay (p=0.018), a reduced need for blood transfusion (p=0.0001), a need for less complexity in revision implants (p=0.001) and a reduced probability of further surgery being required (P=0.003). Whilst we acknowledge the limitations of this study our results suggest that, in contrast to THA, the bone conservation element of HRA may make for a less traumatic revision procedure with better functional outcomes. Use of HRA has seen a dramatic decline as a result of concerns regarding metallosis. However, this information remains of relevance when counselling young active patients about their arthroplasty options and may become pertinent in the future if the promise of ceramic hip resurfacing is ever realized.

Keywords: hip resurfacing, metallosis, revision surgery, total hip arthroplasty

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13446 Retail Strategy to Reduce Waste Keeping High Profit Utilizing Taylor's Law in Point-of-Sales Data

Authors: Gen Sakoda, Hideki Takayasu, Misako Takayasu

Abstract:

Waste reduction is a fundamental problem for sustainability. Methods for waste reduction with point-of-sales (POS) data are proposed, utilizing the knowledge of a recent econophysics study on a statistical property of POS data. Concretely, the non-stationary time series analysis method based on the Particle Filter is developed, which considers abnormal fluctuation scaling known as Taylor's law. This method is extended for handling incomplete sales data because of stock-outs by introducing maximum likelihood estimation for censored data. The way for optimal stock determination with pricing the cost of waste reduction is also proposed. This study focuses on the examination of the methods for large sales numbers where Taylor's law is obvious. Numerical analysis using aggregated POS data shows the effectiveness of the methods to reduce food waste maintaining a high profit for large sales numbers. Moreover, the way of pricing the cost of waste reduction reveals that a small profit loss realizes substantial waste reduction, especially in the case that the proportionality constant  of Taylor’s law is small. Specifically, around 1% profit loss realizes half disposal at =0.12, which is the actual  value of processed food items used in this research. The methods provide practical and effective solutions for waste reduction keeping a high profit, especially with large sales numbers.

Keywords: food waste reduction, particle filter, point-of-sales, sustainable development goals, Taylor's law, time series analysis

Procedia PDF Downloads 119
13445 Analysing Trends in Rice Cropping Intensity and Seasonality across the Philippines Using 14 Years of Moderate Resolution Remote Sensing Imagery

Authors: Bhogendra Mishra, Andy Nelson, Mirco Boschetti, Lorenzo Busetto, Alice Laborte

Abstract:

Rice is grown on over 100 million hectares in almost every country of Asia. It is the most important staple crop for food security and has high economic and cultural importance in Asian societies. The combination of genetic diversity and management options, coupled with the large geographic extent means that there is a large variation in seasonality (when it is grown) and cropping intensity (how often it is grown per year on the same plot of land), even over relatively small distances. Seasonality and intensity can and do change over time depending on climatic, environmental and economic factors. Detecting where and when these changes happen can provide information to better understand trends in regional and even global rice production. Remote sensing offers a unique opportunity to estimate these trends. We apply the recently published PhenoRice algorithm to 14 years of moderate resolution remote sensing (MODIS) data (utilizing 250m resolution 16 day composites from Terra and Aqua) to estimate seasonality and cropping intensity per year and changes over time. We compare the results to the surveyed data collected by International Rice Research Institute (IRRI). The study results in a unique and validated dataset on the extent and change of extent, the seasonality and change in seasonality and the cropping intensity and change in cropping intensity between 2003 and 2016 for the Philippines. Observed trends and their implications for food security and trade policies are also discussed.

Keywords: rice, cropping intensity, moderate resolution remote sensing (MODIS), phenology, seasonality

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13444 Modeling Route Selection Using Real-Time Information and GPS Data

Authors: William Albeiro Alvarez, Gloria Patricia Jaramillo, Ivan Reinaldo Sarmiento

Abstract:

Understanding the behavior of individuals and the different human factors that influence the choice when faced with a complex system such as transportation is one of the most complicated aspects of measuring in the components that constitute the modeling of route choice due to that various behaviors and driving mode directly or indirectly affect the choice. During the last two decades, with the development of information and communications technologies, new data collection techniques have emerged such as GPS, geolocation with mobile phones, apps for choosing the route between origin and destination, individual service transport applications among others, where an interest has been generated to improve discrete choice models when considering the incorporation of these developments as well as psychological factors that affect decision making. This paper implements a discrete choice model that proposes and estimates a hybrid model that integrates route choice models and latent variables based on the observation on the route of a sample of public taxi drivers from the city of Medellín, Colombia in relation to its behavior, personality, socioeconomic characteristics, and driving mode. The set of choice options includes the routes generated by the individual service transport applications versus the driver's choice. The hybrid model consists of measurement equations that relate latent variables with measurement indicators and utilities with choice indicators along with structural equations that link the observable characteristics of drivers with latent variables and explanatory variables with utilities.

Keywords: behavior choice model, human factors, hybrid model, real time data

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13443 Microstructure Evolution and Pre-transformation Microstructure Reconstruction in Ti-6Al-4V Alloy

Authors: Shreyash Hadke, Manendra Singh Parihar, Rajesh Khatirkar

Abstract:

In the present investigation, the variation in the microstructure with the changes in the heat treatment conditions i.e. temperature and time was observed. Ti-6Al-4V alloy was subject to solution annealing treatments in β (1066C) and α+β phase (930C and 850C) followed by quenching, air cooling and furnace cooling to room temperature respectively. The effect of solution annealing and cooling on the microstructure was studied by using optical microscopy (OM), scanning electron microscopy (SEM), electron backscattered diffraction (EBSD) and x-ray diffraction (XRD). The chemical composition of the β phase for different conditions was determined with the help of energy dispersive spectrometer (EDS) attached to SEM. Furnace cooling resulted in the development of coarser structure (α+β), while air cooling resulted in much finer structure with widmanstatten morphology of α at the grain boundaries. Quenching from solution annealing temperature formed α’ martensite, their proportion being dependent on the temperature in β phase field. It is well known that the transformation of β to α follows Burger orientation relationship (OR). In order to reconstruct the microstructure of parent β phase, a MATLAB code was written using neighbor-to-neighbor, triplet method and Tari’s method. The code was tested on the annealed samples (1066C solution annealing temperature followed by furnace cooling to room temperature). The parent phase data thus generated was then plotted using the TSL-OIM software. The reconstruction results of the above methods were compared and analyzed. The Tari’s approach (clustering approach) gave better results compared to neighbor-to-neighbor and triplet method but the time taken by the triplet method was least compared to the other two methods.

Keywords: Ti-6Al-4V alloy, microstructure, electron backscattered diffraction, parent phase reconstruction

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13442 The Implantable MEMS Blood Pressure Sensor Model With Wireless Powering And Data Transmission

Authors: Vitaliy Petrov, Natalia Shusharina, Vitaliy Kasymov, Maksim Patrushev, Evgeny Bogdanov

Abstract:

The leading worldwide death reasons are ischemic heart disease and other cardiovascular illnesses. Generally, the common symptom is high blood pressure. Long-time blood pressure control is very important for the prophylaxis, correct diagnosis and timely therapy. Non-invasive methods which are based on Korotkoff sounds are impossible to apply often and for a long time. Implantable devices can combine longtime monitoring with high accuracy of measurements. The main purpose of this work is to create a real-time monitoring system for decreasing the death rate from cardiovascular diseases. These days implantable electronic devices began to play an important role in medicine. Usually implantable devices consist of a transmitter, powering which could be wireless with a special made battery and measurement circuit. Common problems in making implantable devices are short lifetime of the battery, big size and biocompatibility. In these work, blood pressure measure will be the focus because it’s one of the main symptoms of cardiovascular diseases. Our device will consist of three parts: the implantable pressure sensor, external transmitter and automated workstation in a hospital. The Implantable part of pressure sensors could be based on piezoresistive or capacitive technologies. Both sensors have some advantages and some limitations. The Developed circuit is based on a small capacitive sensor which is made of the technology of microelectromechanical systems (MEMS). The Capacitive sensor can provide high sensitivity, low power consumption and minimum hysteresis compared to the piezoresistive sensor. For this device, it was selected the oscillator-based circuit where frequency depends from the capacitance of sensor hence from capacitance one can calculate pressure. The external device (transmitter) used for wireless charging and signal transmission. Some implant devices for these applications are passive, the external device sends radio wave signal on internal LC circuit device. The external device gets reflected the signal from the implant and from a change of frequency is possible to calculate changing of capacitance and then blood pressure. However, this method has some disadvantages, such as the patient position dependence and static using. Developed implantable device doesn’t have these disadvantages and sends blood pressure data to the external part in real-time. The external device continuously sends information about blood pressure to hospital cloud service for analysis by a physician. Doctor’s automated workstation at the hospital also acts as a dashboard, which displays actual medical data of patients (which require attention) and stores it in cloud service. Usually, critical heart conditions occur few hours before heart attack but the device is able to send an alarm signal to the hospital for an early action of medical service. The system was tested with wireless charging and data transmission. These results can be used for ASIC design for MEMS pressure sensor.

Keywords: MEMS sensor, RF power, wireless data, oscillator-based circuit

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13441 The Intonation of Romanian Greetings: A Sociolinguistics Approach

Authors: Anca-Diana Bibiri, Mihaela Mocanu, Adrian Turculeț

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In a language the inventory of greetings is dynamic with frequent input and output, although this is hardly noticed by the speakers. In this register, there are a number of constant, conservative elements that survive different language models (among them, the classic formulae: bună ziua! (good afternoon!), bună seara! (good evening!), noapte bună! (good night!), la revedere! (goodbye!) and a number of items that fail to pass the test of time, according to language use at a time (ciao!, pa!, bai!). The source of innovation depends both of internal factors (contraction, conversion, combination of classic formulae of greetings), and of external ones (borrowings and calques). Their use imposes their frequencies at once, namely the elimination of the use of others. This paper presents a sociolinguistic approach of contemporary Romanian greetings, based on prosodic surveys in two research projects: AMPRom, and SoRoEs. Romanian language presents a rich inventory of questions (especially partial interrogatives questions/WH-Q) which are used as greetings, alone or, more commonly accompanying a proper greeting. The representative of the typical formulae is Ce mai faci? (How are you?), which, unlike its English counterpart How do you do?, has not become a stereotype, but retains an obvious emotional impact, while serving as a mark of sociolinguistic group. The analyzed corpus consists of structures containing greetings recorded in the main Romanian cultural (urban) centers. From the methodological point of view, the acoustic analysis of the recorded data is performed using software tools (GoldWave, Praat), identifying intonation patterns related to three sociolinguistics variables: age, sex and level of education. The intonation patterns of the analyzed statements are at the interface between partial questions and typical greetings.

Keywords: acoustic analysis, greetings, Romanian language, sociolinguistics

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13440 Foot-and-Mouth Virus Detection in Asymptomatic Dairy Cows without Foot-and-Mouth Disease Outbreak

Authors: Duanghathai Saipinta, Tanittian Panyamongkol, Witaya Suriyasathaporn

Abstract:

Animal management aims to provide a suitable environment for animals allowing maximal productivity in those animals. Prevention of disease is an important part of animal management. Foot-and-mouth disease (FMD) is a highly contagious viral disease in cattle and is an economically important animal disease worldwide. Monitoring the FMD virus in farms is useful management for the prevention of the FMD outbreak. A recent publication indicated collection samples from nasal swabs can be used for monitoring FMD in symptomatic cows. Therefore, the objectives of this study were to determine the FMD virus in asymptomatic dairy cattle using nasal swab samples during the absence of an FMD outbreak. The study was conducted from December 2020 to June 2021 using 185 asymptomatic signs of FMD dairy cattle in Chiang Mai Province, Thailand. By random cow selection, nasal mucosal swabs were used to collect samples from the selected cows and then were to evaluate the presence of FMD viruses using the real-time rt-PCR assay. In total, 4.9% of dairy cattle detected FMD virus, including 2 dairy farms in Mae-on (8 samples; 9.6%) and 1 farm in the Chai-Prakan district (1 sample; 1.2%). Interestingly, both farms in Mae-on were the outbreak of the FMD after this detection for 6 months. This indicated that the FMD virus presented in asymptomatic cattle might relate to the subsequent outbreak of FMD. The outbreak demonstrates the presence of the virus in the environment. In conclusion, monitoring of FMD can be performed by nasal swab collection. Further investigation is needed to show whether the FMD virus presented in asymptomatic FMD cattle could be the cause of the subsequent FMD outbreak or not.

Keywords: cattle, foot-and-mouth disease, nasal swab, real-time rt-PCR assay

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13439 Mikrophonie I (1964) by Karlheinz Stockhausen - Between Idea and Auditory Image

Authors: Justyna Humięcka-Jakubowska

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1. Background in music analysis. Traditionally, when we think about a composer’s sketches, the chances are that we are thinking in terms of the working out of detail, rather than the evolution of an overall concept. Since music is a “time art’, it follows that questions of a form cannot be entirely detached from considerations of time. One could say that composers tend to regard time either as a place gradually and partially intuitively filled, or they can look for a specific strategy to occupy it. In my opinion, one thing that sheds light on Stockhausen's compositional thinking is his frequent use of 'form schemas', that is often a single-page representation of the entire structure of a piece. 2. Background in music technology. Sonic Visualiser is a program used to study a musical recording. It is an open source application for viewing, analysing, and annotating music audio files. It contains a number of visualisation tools, which are designed with useful default parameters for musical analysis. Additionally, the Vamp plugin format of SV supports to provide analysis such as for example structural segmentation. 3. Aims. The aim of my paper is to show how SV may be used to obtain a better understanding of the specific musical work, and how the compositional strategy does impact on musical structures and musical surfaces. I want to show that ‘traditional” music analytic methods don’t allow to indicate interrelationships between musical surface (which is perceived) and underlying musical/acoustical structure. 4. Main Contribution. Stockhausen had dealt with the most diverse musical problems by the most varied methods. A characteristic which he had never ceased to be placed at the center of his thought and works, it was the quest for a new balance founded upon an acute connection between speculation and intuition. In the case with Mikrophonie I (1964) for tam-tam and 6 players Stockhausen makes a distinction between the "connection scheme", which indicates the ground rules underlying all versions, and the form scheme, which is associated with a particular version. The preface to the published score includes both the connection scheme, and a single instance of a "form scheme", which is what one can hear on the CD recording. In the current study, the insight into the compositional strategy chosen by Stockhausen was been compared with auditory image, that is, with the perceived musical surface. Stockhausen's musical work is analyzed both in terms of melodic/voice and timbre evolution. 5. Implications The current study shows how musical structures have determined of musical surface. My general assumption is this, that while listening to music we can extract basic kinds of musical information from musical surfaces. It is shown that an interactive strategies of musical structure analysis can offer a very fruitful way of looking directly into certain structural features of music.

Keywords: automated analysis, composer's strategy, mikrophonie I, musical surface, stockhausen

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13438 Contractors Perspective on Causes of Delays in Power Transmission Projects

Authors: Goutom K. Pall

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At the very heart of the power system, power transmission (PT) acts as an essential link between power generation and distribution. Timely completion of PT infrastructures is therefore crucial to support the development of power system as a whole. Yet despite the importance, studies on PT infrastructure development projects are embryonic and, hence, PT projects undergoing widespread delays worldwide. These delay factors are idiosyncratic and identifying the critical delay factors is essential if the PT industry professionals are to complete their projects efficiently and within the expected timeframes. This study identifies and categorizes 46 causes of PT project delay under ten major groups using six sector expert’s recommendations studied by a preliminary questionnaire survey. Based on the experts’ strong recommendations, two new groups are introduced in the final questionnaire survey: sector specific factors (SSF) and general factors (GF). SSF pertain to delay factors applicable only to the PT projects, while GF represents less biased samples with shared responsibilities of all project parties involved in a project. The study then uses 112 data samples from the contractors to rank the delay factors using relative importance index (RII). The results reveal that SSF, GF and external factors are the most critical groups, while the highest ranked delay factors include the right of way (RoW) problems of transmission lines (TL), delay in payments, frequent changes in TL routes, poor communication and coordination among the project parties and accessibility to TL tower locations. Finally, recommendations are made to minimize the identified delay. The findings are expected to be of substantial benefit to professionals in minimizing time overrun in PT projects implementation, as well as power generation, power distribution, and non-power linear construction projects worldwide.

Keywords: delay, project delay, power transmission projects, time-overruns

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13437 Intelligent Control of Bioprocesses: A Software Application

Authors: Mihai Caramihai, Dan Vasilescu

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The main research objective of the experimental bioprocess analyzed in this paper was to obtain large biomass quantities. The bioprocess is performed in 100 L Bioengineering bioreactor with 42 L cultivation medium made of peptone, meat extract and sodium chloride. The reactor was equipped with pH, temperature, dissolved oxygen, and agitation controllers. The operating parameters were 37 oC, 1.2 atm, 250 rpm and air flow rate of 15 L/min. The main objective of this paper is to present a case study to demonstrate that intelligent control, describing the complexity of the biological process in a qualitative and subjective manner as perceived by human operator, is an efficient control strategy for this kind of bioprocesses. In order to simulate the bioprocess evolution, an intelligent control structure, based on fuzzy logic has been designed. The specific objective is to present a fuzzy control approach, based on human expert’ rules vs. a modeling approach of the cells growth based on bioprocess experimental data. The kinetic modeling may represent only a small number of bioprocesses for overall biosystem behavior while fuzzy control system (FCS) can manipulate incomplete and uncertain information about the process assuring high control performance and provides an alternative solution to non-linear control as it is closer to the real world. Due to the high degree of non-linearity and time variance of bioprocesses, the need of control mechanism arises. BIOSIM, an original developed software package, implements such a control structure. The simulation study has showed that the fuzzy technique is quite appropriate for this non-linear, time-varying system vs. the classical control method based on a priori model.

Keywords: intelligent, control, fuzzy model, bioprocess optimization

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13436 Research on Level Adjusting Mechanism System of Large Space Environment Simulator

Authors: Han Xiao, Zhang Lei, Huang Hai, Lv Shizeng

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Space environment simulator is a device for spacecraft test. KM8 large space environment simulator built in Tianjing Space City is the largest as well as the most advanced space environment simulator in China. Large deviation of spacecraft level will lead to abnormally work of the thermal control device in spacecraft during the thermal vacuum test. In order to avoid thermal vacuum test failure, level adjusting mechanism system is developed in the KM8 large space environment simulator as one of the most important subsystems. According to the level adjusting requirements of spacecraft’s thermal vacuum tests, the four fulcrums adjusting model is established. By means of collecting level instruments and displacement sensors data, stepping motors controlled by PLC drive four supporting legs simultaneous movement. In addition, a PID algorithm is used to control the temperature of supporting legs and level instruments which long time work under the vacuum cold and black environment in KM8 large space environment simulator during thermal vacuum tests. Based on the above methods, the data acquisition and processing, the analysis and calculation, real time adjustment and fault alarming of the level adjusting mechanism system are implemented. The level adjusting accuracy reaches 1mm/m, and carrying capacity is 20 tons. Debugging showed that the level adjusting mechanism system of KM8 large space environment simulator can meet the thermal vacuum test requirement of the new generation spacecraft. The performance and technical indicators of the level adjusting mechanism system which provides important support for the development of spacecraft in China have been ahead of similar equipment in the world.

Keywords: space environment simulator, thermal vacuum test, level adjusting, spacecraft, parallel mechanism

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13435 A Framework for Incorporating Non-Linear Degradation of Conductive Adhesive in Environmental Testing

Authors: Kedar Hardikar, Joe Varghese

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Conductive adhesives have found wide-ranging applications in electronics industry ranging from fixing a defective conductor on printed circuit board (PCB) attaching an electronic component in an assembly to protecting electronics components by the formation of “Faraday Cage.” The reliability requirements for the conductive adhesive vary widely depending on the application and expected product lifetime. While the conductive adhesive is required to maintain the structural integrity, the electrical performance of the associated sub-assembly can be affected by the degradation of conductive adhesive. The degradation of the adhesive is dependent upon the highly varied use case. The conventional approach to assess the reliability of the sub-assembly involves subjecting it to the standard environmental test conditions such as high-temperature high humidity, thermal cycling, high-temperature exposure to name a few. In order to enable projection of test data and observed failures to predict field performance, systematic development of an acceleration factor between the test conditions and field conditions is crucial. Common acceleration factor models such as Arrhenius model are based on rate kinetics and typically rely on an assumption of linear degradation in time for a given condition and test duration. The application of interest in this work involves conductive adhesive used in an electronic circuit of a capacitive sensor. The degradation of conductive adhesive in high temperature and humidity environment is quantified by the capacitance values. Under such conditions, the use of established models such as Hallberg-Peck model or Eyring Model to predict time to failure in the field typically relies on linear degradation rate. In this particular case, it is seen that the degradation is nonlinear in time and exhibits a square root t dependence. It is also shown that for the mechanism of interest, the presence of moisture is essential, and the dominant mechanism driving the degradation is the diffusion of moisture. In this work, a framework is developed to incorporate nonlinear degradation of the conductive adhesive for the development of an acceleration factor. This method can be extended to applications where nonlinearity in degradation rate can be adequately characterized in tests. It is shown that depending on the expected product lifetime, the use of conventional linear degradation approach can overestimate or underestimate the field performance. This work provides guidelines for suitability of linear degradation approximation for such varied applications

Keywords: conductive adhesives, nonlinear degradation, physics of failure, acceleration factor model.

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13434 Using Open Source Data and GIS Techniques to Overcome Data Deficiency and Accuracy Issues in the Construction and Validation of Transportation Network: Case of Kinshasa City

Authors: Christian Kapuku, Seung-Young Kho

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An accurate representation of the transportation system serving the region is one of the important aspects of transportation modeling. Such representation often requires developing an abstract model of the system elements, which also requires important amount of data, surveys and time. However, in some cases such as in developing countries, data deficiencies, time and budget constraints do not always allow such accurate representation, leaving opportunities to assumptions that may negatively affect the quality of the analysis. With the emergence of Internet open source data especially in the mapping technologies as well as the advances in Geography Information System, opportunities to tackle these issues have raised. Therefore, the objective of this paper is to demonstrate such application through a practical case of the development of the transportation network for the city of Kinshasa. The GIS geo-referencing was used to construct the digitized map of Transportation Analysis Zones using available scanned images. Centroids were then dynamically placed at the center of activities using an activities density map. Next, the road network with its characteristics was built using OpenStreet data and other official road inventory data by intersecting their layers and cleaning up unnecessary links such as residential streets. The accuracy of the final network was then checked, comparing it with satellite images from Google and Bing. For the validation, the final network was exported into Emme3 to check for potential network coding issues. Results show a high accuracy between the built network and satellite images, which can mostly be attributed to the use of open source data.

Keywords: geographic information system (GIS), network construction, transportation database, open source data

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13433 Time-Dependent Reliability Analysis of Corrosion Affected Cast Iron Pipes with Mixed Mode Fracture

Authors: Chun-Qing Li, Guoyang Fu, Wei Yang

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A significant portion of current water networks is made of cast iron pipes. Due to aging and deterioration with corrosion being the most predominant mechanism, the failure rate of cast iron pipes is very high. Although considerable research has been carried out in the past few decades, most are on the effect of corrosion on the structural capacity of pipes using strength theory as the failure criterion. This paper presents a reliability-based methodology for the assessment of corrosion affected cast iron pipe cracking failures. A nonlinear limit state function taking into account all three fracture modes is proposed for brittle metal pipes with mixed mode fracture. A stochastic model of the load effect is developed, and time-dependent reliability method is employed to quantify the probability of failure and predict the remaining service life. A case study is carried out using the proposed methodology, followed by sensitivity analysis to investigate the effects of the random variables on the probability of failure. It has been found that the larger the inclination angle or the Mode I fracture toughness is, the smaller the probability of pipe failure is. It has also been found that the multiplying and exponential coefficients k and n in the power law corrosion model and the internal pressure have the most influence on the probability of failure for cast iron pipes. The methodology presented in this paper can assist pipe engineers and asset managers in developing a risk-informed and cost-effective strategy for better management of corrosion-affected pipelines.

Keywords: corrosion, inclined surface cracks, pressurized cast iron pipes, stress intensity

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13432 Dual Set Point Governor Control Structure with Common Optimum Temporary Droop Settings for both Islanded and Grid Connected Modes

Authors: Deepen Sharma, Eugene F. Hill

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For nearly 100 years, hydro-turbine governors have operated with only a frequency set point. This natural governor action means that the governor responds with changing megawatt output to disturbances in system frequency. More and more, power system managers are demanding that governors operate with constant megawatt output. One way of doing this is to introduce a second set point in the control structure called a power set point. The control structure investigated and analyzed in this paper is unique in the way that it utilizes a power reference set point in addition to the conventional frequency reference set point. An optimum set of temporary droop parameters derived based on the turbine-generator inertia constant and the penstock water start time for stable islanded operation are shown to be also equally applicable for a satisfactory rate of generator loading during its grid connected mode. A theoretical development shows why this is the case. The performance of the control structure has been investigated and established based on the simulation study made in MATLAB/Simulink as well as through testing the real time controller performance on a 15 MW Kaplan Turbine and generator. Recordings have been made using the labVIEW data acquisition platform. The hydro-turbine governor control structure and its performance investigated in this paper thus eliminates the need to have a separate set of temporary droop parameters, one valid for islanded mode and the other for interconnected operations mode.

Keywords: frequency set point, hydro governor, interconnected operation, isolated operation, power set point

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13431 An Efficient Machine Learning Model to Detect Metastatic Cancer in Pathology Scans Using Principal Component Analysis Algorithm, Genetic Algorithm, and Classification Algorithms

Authors: Bliss Singhal

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Machine learning (ML) is a branch of Artificial Intelligence (AI) where computers analyze data and find patterns in the data. The study focuses on the detection of metastatic cancer using ML. Metastatic cancer is the stage where cancer has spread to other parts of the body and is the cause of approximately 90% of cancer-related deaths. Normally, pathologists spend hours each day to manually classifying whether tumors are benign or malignant. This tedious task contributes to mislabeling metastasis being over 60% of the time and emphasizes the importance of being aware of human error and other inefficiencies. ML is a good candidate to improve the correct identification of metastatic cancer, saving thousands of lives and can also improve the speed and efficiency of the process, thereby taking fewer resources and time. So far, the deep learning methodology of AI has been used in research to detect cancer. This study is a novel approach to determining the potential of using preprocessing algorithms combined with classification algorithms in detecting metastatic cancer. The study used two preprocessing algorithms: principal component analysis (PCA) and the genetic algorithm, to reduce the dimensionality of the dataset and then used three classification algorithms: logistic regression, decision tree classifier, and k-nearest neighbors to detect metastatic cancer in the pathology scans. The highest accuracy of 71.14% was produced by the ML pipeline comprising of PCA, the genetic algorithm, and the k-nearest neighbor algorithm, suggesting that preprocessing and classification algorithms have great potential for detecting metastatic cancer.

Keywords: breast cancer, principal component analysis, genetic algorithm, k-nearest neighbors, decision tree classifier, logistic regression

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13430 Software-Defined Architecture and Front-End Optimization for DO-178B Compliant Distance Measuring Equipment

Authors: Farzan Farhangian, Behnam Shakibafar, Bobda Cedric, Rene Jr. Landry

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Among the air navigation technologies, many of them are capable of increasing aviation sustainability as well as accuracy improvement in Alternative Positioning, Navigation, and Timing (APNT), especially avionics Distance Measuring Equipment (DME), Very high-frequency Omni-directional Range (VOR), etc. The integration of these air navigation solutions could make a robust and efficient accuracy in air mobility, air traffic management and autonomous operations. Designing a proper RF front-end, power amplifier and software-defined transponder could pave the way for reaching an optimized avionics navigation solution. In this article, the possibility of reaching an optimum front-end to be used with single low-cost Software-Defined Radio (SDR) has been investigated in order to reach a software-defined DME architecture. Our software-defined approach uses the firmware possibilities to design a real-time software architecture compatible with a Multi Input Multi Output (MIMO) BladeRF to estimate an accurate time delay between a Transmission (Tx) and the reception (Rx) channels using the synchronous scheduled communication. We could design a novel power amplifier for the transmission channel of the DME to pass the minimum transmission power. This article also investigates designing proper pair pulses based on the DO-178B avionics standard. Various guidelines have been tested, and the possibility of passing the certification process for each standard term has been analyzed. Finally, the performance of the DME was tested in the laboratory environment using an IFR6000, which showed that the proposed architecture reached an accuracy of less than 0.23 Nautical mile (Nmi) with 98% probability.

Keywords: avionics, DME, software defined radio, navigation

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13429 Attitude of Staff Nurses on Nursing Research and Its Utilization

Authors: Y. N. Shashidhara, B. S. Shakuntala

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Introduction: Nursing practice is undergoing tremendous changes and challenges. In order to meet social challenges and needs, nursing practice must be research based. Research is needed to evaluate the effectiveness of nursing treatment modalities, to determine the impact of nursing care on the health of the patients or to test the theory of nursing practice. Objective of the study to explore the attitude of staff nurses on Nursing research and its utilization Methodology: The descriptive study design was adopted and 300 staff nurses were selected by systematic random sampling technique from eight hospitals. The attitude on nursing research was assessed by validated and reliable self-administered attitude scale which consists of 40 items. Results: The overall attitude mean score 130.2 (SD 11.5) regarding attitude on Nursing research and its utilization. Some of the findings are the majority of staff nurses (51% agreed and 18.3% strongly agreed) that they have all the motivation to use research findings if they get support. Nearly 25.3 percent of staff nurses agreed and 10.7 percent strongly agreed that they do not have time to conduct research. The majority of staff nurses 53.7 percent agreed that research will help in updating Nursing profession. Nearly 32.6 percent of staff nurses agreed and 20.5 percent strongly agreed that being able to use will make them better nurses. About 45.3 percent and 17.3 percent agreed and strongly agreed that knowledge gained through experience is more useful than research. Most (40%) of nurses agreed that thy do not have the authority to change the patient care practice. The majority of staff nurses (45.7 percent agreed and 13 percent strongly agreed) feel the research will consume their personal time. Majority, 50 percent of staff nurses agreed and 16.7 percent strongly agreed that to conduct and utilize research findings requires financial support. Majority 50 percent of staff nurses agreed and 12 percent strongly agreed that physicians will cooperate and value nursing research findings. Majority 67.3 percent of staff nurses had moderate positive and 32.7 percent of staff nurses had highly positive attitude towards Nursing research and its utilization. Conclusion: With this study we understanding that, the staff nurses have positive attitude regarding nursing research. If the nurses are supported and motivated for research utilization we can improve the patient care.

Keywords: nurses, attitude, nursing research, research utilization

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13428 Atom Probe Study of Early Stage of Precipitation on Binary Al-Li, Al-Cu Alloys and Ternary Al-Li-Cu Alloys

Authors: Muna Khushaim

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Aluminum-based alloys play a key role in modern engineering, especially in the aerospace industry. Introduction of solute atoms such as Li and Cu is the main approach to improve the strength in age-hardenable Al alloys via the precipitation hardening phenomenon. Knowledge of the decomposition process of the microstructure during the precipitation reaction is particularly important for future technical developments. The objective of this study is to investigate the nano-scale chemical composition in the Al-Cu, Al-Li and Al-Li-Cu during the early stage of the precipitation sequence and to describe whether this compositional difference correlates with variations in the observed precipitation kinetics. Comparing the random binomial frequency distribution and the experimental frequency distribution of concentrations in atom probe tomography data was used to investigate the early stage of decomposition in the different binary and ternary alloys which were experienced different heat treatments. The results show that an Al-1.7 at.% Cu alloy requires a long ageing time of approximately 8 h at 160 °C to allow the diffusion of Cu atoms into Al matrix. For the Al-8.2 at.% Li alloy, a combination of both the natural ageing condition (48 h at room temperature) and a short artificial ageing condition (5 min at 160 °C) induces increasing on the number density of the Li clusters and hence increase number of precipitated δ' particles. Applying this combination of natural ageing and short artificial ageing conditions onto the ternary Al-4 at.% Li-1.7 at.% Cu alloy induces the formation of a Cu-rich phase. Increasing the Li content in the ternary alloy up to 8 at.% and increasing the ageing time to 30 min resulted in the precipitation processes ending with δ' particles. Thus, the results contribute to the understanding of Al-alloy design.

Keywords: aluminum alloy, atom probe tomography, early stage, decomposition

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13427 Elasticity Model for Easing Peak Hour Demand for Metrorail Transport System

Authors: P. K. Sarkar, Amit Kumar Jain

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The demand for Urban transportation is characterised by a large scale temporal and spatial variations which causes heavy congestion inside metro trains in peak hours near Centre Business District (CBD) of the city. The conventional approach to address peak hour congestion, metro trains has been to increase the supply by way of introduction of more trains, increasing the length of the trains, optimising the time table to increase the capacity of the system. However, there is a limitation of supply side measures determined by the design capacity of the systems beyond which any addition in the capacity requires huge capital investments. The demand side interventions are essentially required to actually spread the demand across the time and space. In this study, an attempt has been made to identify the potential Transport Demand Management tools applicable to Urban Rail Transportation systems with a special focus on differential pricing. A conceptual price elasticity model has been developed to analyse the effect of various combinations of peak and nonpeak hoursfares on demands. The elasticity values for peak hour, nonpeak hour and cross elasticity have been assumed from the relevant literature available in the field. The conceptual price elasticity model so developed is based on assumptions which need to be validated with actual values of elasticities for different segments of passengers. Once validated, the model can be used to determine the peak and nonpeak hour fares with an objective to increase overall ridership, revenue, demand levelling and optimal utilisation of assets.

Keywords: urban transport, differential fares, congestion, transport demand management, elasticity

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13426 Numerical Investigation of the Effects of Surfactant Concentrations on the Dynamics of Liquid-Liquid Interfaces

Authors: Bamikole J. Adeyemi, Prashant Jadhawar, Lateef Akanji

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Theoretically, there exist two mathematical interfaces (fluid-solid and fluid-fluid) when a liquid film is present on solid surfaces. These interfaces overlap if the mineral surface is oil-wet or mixed wet, and therefore, the effects of disjoining pressure are significant on both boundaries. Hence, dewetting is a necessary process that could detach oil from the mineral surface. However, if the thickness of the thin water film directly in contact with the surface is large enough, disjoining pressure can be thought to be zero at the liquid-liquid interface. Recent studies show that the integration of fluid-fluid interactions with fluid-rock interactions is an important step towards a holistic approach to understanding smart water effects. Experiments have shown that the brine solution can alter the micro forces at oil-water interfaces, and these ion-specific interactions lead to oil emulsion formation. The natural emulsifiers present in crude oil behave as polyelectrolytes when the oil interfaces with low salinity water. Wettability alteration caused by low salinity waterflooding during Enhanced Oil Recovery (EOR) process results from the activities of divalent ions. However, polyelectrolytes are said to lose their viscoelastic property with increasing cation concentrations. In this work, the influence of cation concentrations on the dynamics of viscoelastic liquid-liquid interfaces is numerically investigated. The resultant ion concentrations at the crude oil/brine interfaces were estimated using a surface complexation model. Subsequently, the ion concentration parameter is integrated into a mathematical model to describe its effects on the dynamics of a viscoelastic interfacial thin film. The film growth, stability, and rupture were measured after different time steps for three types of fluids (Newtonian, purely elastic and viscoelastic fluids). The interfacial films respond to exposure time in a similar manner with an increasing growth rate, which resulted in the formation of more droplets with time. Increased surfactant accumulation at the interface results in a higher film growth rate which leads to instability and subsequent formation of more satellite droplets. Purely elastic and viscoelastic properties limit film growth rate and consequent film stability compared to the Newtonian fluid. Therefore, low salinity and reduced concentration of the potential determining ions in injection water will lead to improved interfacial viscoelasticity.

Keywords: liquid-liquid interfaces, surfactant concentrations, potential determining ions, residual oil mobilization

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13425 Benefits of PRP in Third Molar Surgery - A Review of the Literature

Authors: Nitesh Kumar, Adel Elrasheed, Antonio Gagliardilugo

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Introduction and aims: PRP has been increasing in popularity over the past decade. It is used in many facets of medicine and dentistry such as osteoarthritis, hair loss, skin rejunavation, healing of tendons after injury. Due to the increasing popularity of PRP in third molar surgery in dentistry, this study aims to identify the role of platelet rich plasma and its function in third molar surgery. Methodology: Three databases were chosen to source the articles for review: pubmed, science direct, and Cochrane. The keywords “platelet rich plasma”, “third molar extraction” and “wisdom tooth extraction” and literature review were used to search for relevant articles. Articles that were not in English were omitted and only systematic reviews relevant to the study were collected. All systematic reviews abstracts pertinent to the study were read by two reviewers to avoid bias. Results/statistics: 20 review articles were obtained of which 13 fulfilled the criteria. The Amstar tool validified the strength of these review articles. There is strong evidence in the literature that PRP in third molar surgery decreases post op pain, swelling and recovery time. 20 review articles were obtained of which 13 fulfilled the criteria. The Amstar tool validified the strength of these review articles. There is strong evidence in the literature that PRP in third molar surgery decreases post op pain, swelling and recovery time. Conclusions/clinical relevance: Platelet rich plasma plays a crucial role in patient recovery following the extraction of third molars and should be considered and offered as a routine part of third molar therapy.

Keywords: PRP, third molar, extractions, wisdom teeth

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13424 Ultrasound-Assisted Extraction of Bioactive Compounds from Cocoa Shell and Their Encapsulation in Gum Arabic and Maltodextrin: A Technology to Produce Functional Food Ingredients

Authors: Saeid Jafari, Khursheed Ahmad Sheikh, Randy W. Worobo, Kitipong Assatarakul

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In this study, the extraction of cocoa shell powder (CSP) was optimized, and the optimized extracts were spray-dried for encapsulation purposes. Temperature (45-65 ◦C), extraction time (30–60 min), and ethanol concentration (60–100%) were the extraction parameters. The response surface methodology analysis revealed that the model was significant (p ≤ 0.05) in interactions between all variables (total phenolic compound, total flavonoid content, and antioxidant activity as measured by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP assays), with a lack of fit test for the model being insignificant (p > 0.05). Temperature (55 ◦C), time (45 min), and ethanol concentration (60%) were found to be the optimal extraction conditions. For spray-drying encapsulation, some quality metrics (e.g., water solubility, water activity) were insignificant (p > 0.05). The microcapsules were found to be spherical in shape using a scanning electron microscope. Thermogravimetric and differential thermogravimetric measurements of the microcapsules revealed nearly identical results. The gum arabic + maltodextrin microcapsule (GMM) showed potential antibacterial (zone of inhibition: 11.50 mm; lower minimum inhibitory concentration: 1.50 mg/mL) and antioxidant (DPPH: 1063 mM trolox/100g dry wt.) activities (p ≤ 0.05). In conclusion, the microcapsules in this study, particularly GMM, are promising antioxidant and antibacterial agents to be fortified as functional food ingredients for the production of nutraceutical foods with health-promoting properties.

Keywords: functional foods, coco shell powder, antioxidant activity, encapsulation, extraction

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13423 An Audit of Restaging Transurethral Resection of Bladder Tumor (Re-TURBT) Quality in a District General Hospital

Authors: Rizwan Iqbal

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Introduction: Re-TURBT has been recommended by international guidelines for patients with non-muscle invasive bladder cancer (NMIBC) who are deemed high-risk. Indications for re-TURBTs remain controversial and studies show mixed outcomes. It should be performed when the initial TURBT specimen lacks detrusor muscle, has tumor stage pT1 or G3/high-grade, or where resection is deemed incomplete. This ensures complete resection of tumors that have a high risk of recurrence as well as accurately identifying any tumors which have been upstaged. The aim of this audit was to evaluate the quality of re-TURBTs in a district general hospital. Method: Data were retrospectively collected from 31 patients who had re-TURBTs between April 2021 and September 2022. Data included baseline demographics, time from initial to re-TURBT, quality of operation note, presence of residual tumor, complications, and administration of chemotherapy within 24 hours of the initial TURBT. Data collection remains ongoing at the time of writing. Results: The mean age was 76 years old and 71.0% of patients were male. 32.3% of patients had their re-TURBT within six weeks and 32.3% had intravesical chemotherapy administered within 24 hours of the initial TURBT. 74.2% of initial TURBTs had detrusor muscle present in the specimen. 48.4% of patients had residual disease following re-TURBT. Just one patient had their pathology upstaged at re-TURBT. The use of the TURBT proforma on the operation note was variable, with 51.6% and 38.7% of surgeons using the proforma after the initial and re-TURBT. Conclusion: Re-TURBT improves bladder cancer staging and is necessary in patients who are deemed high-risk in order to identify any upstaging or recurrence of the disease.

Keywords: urology, bladder cancer, turbt, cancer

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13422 Thermal Effects on Wellbore Stability and Fluid Loss in High-Temperature Geothermal Drilling

Authors: Mubarek Alpkiray, Tan Nguyen, Arild Saasen

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Geothermal drilling operations contain numerous challenges that are encountered to increase the well cost and nonproductive time. Fluid loss is one of the most undesirable troublesome that can cause well abandonment in geothermal drilling. Lost circulation can be seen due to natural fractures, high mud weight, and extremely high formation temperatures. This challenge may cause wellbore stability problems and lead to expensive drilling operations. Wellbore stability is the main domain that should be considered to mitigate or prevent fluid loss into the formation. This paper describes the causes of fluid loss in the Pamukoren geothermal field in Turkey. A geomechanics approach integration and assessment is applied to help the understanding of fluid loss problems. In geothermal drillings, geomechanics is primarily based on rock properties, in-situ stress characterization, the temperature of the rock, determination of stresses around the wellbore, and rock failure criteria. Since a high-temperature difference between the wellbore wall and drilling fluid is presented, temperature distribution through the wellbore is estimated and implemented to the wellbore stability approach. This study reviewed geothermal drilling data to analyze temperature estimation along the wellbore, the cause of fluid loss and stored electric capacity of the reservoir. Our observation demonstrates the geomechanical approach's significant role in understanding safe drilling operations on high-temperature wells. Fluid loss is encountered due to thermal stress effects around the borehole. This paper provides a wellbore stability analysis for a geothermal drilling operation to discuss the causes of lost circulation resulting in nonproductive time and cost.

Keywords: geothermal wells, drilling, wellbore stresses, drilling fluid loss, thermal stress

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13421 Design and Synthesis of Copper-Zeolite Composite for Antimicrobial Activity and Heavy Metal Removal From Waste Water

Authors: Feleke Terefe Fanta

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Background: The existence of heavy metals and coliform bacteria contaminants in aquatic system of Akaki river basin, a sub city of Addis Ababa, Ethiopia has become a public concern as human population increases and land development continues. Hence, it is the right time to design treatment technologies that can handle multiple pollutants. Results: In this study, we prepared a synthetic zeolites and copper doped zeolite composite adsorbents as cost effective and simple approach to simultaneously remove heavy metals and total coliforms from wastewater of Akaki river. The synthesized copper–zeolite X composite was obtained by ion exchange method of copper ions into zeolites frameworks. Iodine test, XRD, FTIR and autosorb IQ automated gas sorption analyzer were used to characterize the adsorbents. The mean concentrations of Cd, Cr, and Pb in untreated sample were 0.795, 0.654 and 0.7025 mg/L respectively. These concentrations decreased to Cd (0.005 mg/L), Cr (0.052 mg/L) and Pb (bellow detection limit, BDL) for sample treated with bare zeolite X while a further decrease in concentration of Cd (0.005 mg/L), Cr (BDL) and Pb (BDL) was observed for the sample treated with copper–zeolite composite. Zeolite X and copper-modified zeolite X showed complete elimination of total coliforms after 90 and 50 min contact time respectively. Conclusion: The results obtained in this study showed high antimicrobial disinfection and heavy metal removal efficiencies of the synthesized adsorbents. Furthermore, these sorbents are efficient in significantly reducing physical parameters such as electrical conductivity, turbidity, BOD and COD.

Keywords: WASTE WATER, COPPER DOPED ZEOITE X, ADSORPITION, HEAVY METAL, DISINFECTION, AKAKI RIVER

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13420 An As-Is Analysis and Approach for Updating Building Information Models and Laser Scans

Authors: Rene Hellmuth

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Factory planning has the task of designing products, plants, processes, organization, areas, and the construction of a factory. The requirements for factory planning and the building of a factory have changed in recent years. Regular restructuring of the factory building is becoming more important in order to maintain the competitiveness of a factory. Restrictions in new areas, shorter life cycles of product and production technology as well as a VUCA world (Volatility, Uncertainty, Complexity & Ambiguity) lead to more frequent restructuring measures within a factory. A building information model (BIM) is the planning basis for rebuilding measures and becomes an indispensable data repository to be able to react quickly to changes. Use as a planning basis for restructuring measures in factories only succeeds if the BIM model has adequate data quality. Under this aspect and the industrial requirement, three data quality factors are particularly important for this paper regarding the BIM model: up-to-dateness, completeness, and correctness. The research question is: how can a BIM model be kept up to date with required data quality and which visualization techniques can be applied in a short period of time on the construction site during conversion measures? An as-is analysis is made of how BIM models and digital factory models (including laser scans) are currently being kept up to date. Industrial companies are interviewed, and expert interviews are conducted. Subsequently, the results are evaluated, and a procedure conceived how cost-effective and timesaving updating processes can be carried out. The availability of low-cost hardware and the simplicity of the process are of importance to enable service personnel from facility mnagement to keep digital factory models (BIM models and laser scans) up to date. The approach includes the detection of changes to the building, the recording of the changing area, and the insertion into the overall digital twin. Finally, an overview of the possibilities for visualizations suitable for construction sites is compiled. An augmented reality application is created based on an updated BIM model of a factory and installed on a tablet. Conversion scenarios with costs and time expenditure are displayed. A user interface is designed in such a way that all relevant conversion information is available at a glance for the respective conversion scenario. A total of three essential research results are achieved: As-is analysis of current update processes for BIM models and laser scans, development of a time-saving and cost-effective update process and the conception and implementation of an augmented reality solution for BIM models suitable for construction sites.

Keywords: building information modeling, digital factory model, factory planning, restructuring

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13419 Use of Zikani’s Ribosome Modulating Agents for Treating Recessive Dystrophic & Junctional Epidermolysis Bullosa with Nonsense Mutations

Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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