Search results for: single phase flow
Commenced in January 2007
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Edition: International
Paper Count: 12167

Search results for: single phase flow

137 Living in the Edge: Crisis in Indian Tea Industry and Social Deprivation of Tea Garden Workers in Dooars Region of India

Authors: Saraswati Kerketta

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Tea industry is one of the oldest organised sector of India. It employs roughly 1.5 million people directly. Since the last decade Indian tea industry, especially in the northern region is experiencing worst crisis in the post-independence period. Due to many reason the prices of tea show steady decline. The workers are paid one of the lowest wage in tea industry in the world (1.5$ a day) below the UN's $2 a day for extreme poverty. The workers rely on addition benefits from plantation which includes food, housing and medical facilities. These have been effective means of enslavement of generations of labourers by the owners. There is hardly any change in the tea estates where the owners determine the fate of workers. When the tea garden is abandoned or is closed all the facilities disappear immediately. The workers are the descendants of tribes from central India also known as 'tea tribes'. Alienated from their native place, the geographical and social isolation compounded their vulnerability of these people. The economy of the region being totally dependent on tea has resulted in absolute unemployment for the workers of these tea gardens. With no other livelihood and no land to grow food, thousands of workers faced hunger and starvation. The Plantation Labour Act which ensures the decent working and living condition is violated continuously. The labours are forced to migrate and are also exposed to the risk of human trafficking. Those who are left behind suffers from starvation, malnutrition and disease. The condition in the sick tea plantation is no better. Wage are not paid regularly, subsidised food, fuel are also not supplied properly. Health care facilities are in very bad shape. Objectives: • To study the socio-cultural and demographic characteristics of the tea garden labourers in the study area. • To examine the social situation of workers in sick estates in dooars region. • To assess the magnitude of deprivation the impact of economic crisis on abandoned and closed tea estates in the region. Data Base: The study is based on data collected from field survey. Methods: Quantative: Cross-Tabulation, Regression analysis. Qualitative: Household Survey, Focussed Group Discussion, In-depth interview of key informants. Findings: Purchasing power parity has declined since in last three decades. There has been many fold increase in migration. Males migrates long distance towards central and west and south India. Females and children migrates both long and short distance. No one has reported to migrate back to the place of origin of their ancestors. Migrant males work mostly as construction labourers and as factory workers whereas females and children work as domestic help and construction labourers. In about 37 cases either they haven't contacted their families in last six months or are not traceable. The families with single earning members are more likely to migrate. Burden of disease and the duration of sickness, abandonment and closure of plantation are closely related. Death tolls are likely to rise 1.5 times in sick tea gardens and three times in closed tea estates. Sixty percent of the people are malnourished in the sick tea gardens and more than eighty five per cent in abandoned and sick tea gardens.

Keywords: migration, trafficking, starvation death, tea garden workers

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136 Poverty Reduction in European Cities: Local Governments’ Strategies and Programmes to Reduce Poverty; Interview Results from Austria

Authors: Melanie Schinnerl, Dorothea Greiling

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In the context of the 2020 strategy, poverty and its fight returned to the center of national political efforts. This served as motivation for an Austrian research grant-funded project to focus on the under-researched local government level with the aim to identify municipal best-practice cases and to derive policy implications for Austria. Designing effective poverty reduction strategies is a complex challenge which calls for an integrated multi-actor in approach. Cities are increasingly confronted to combat poverty, even in rich EU-member states. By doing so cities face substantial demographic, cultural, economic and social challenges as well as changing welfare state regimes. Furthermore, there is a low willingness of (right-wing) governments to support the poor. Against this background, the research questions are: 1. How do local governments define poverty? 2. Who are the main risk groups and what are the most pressing problems when fighting urban poverty? 3. What is regarded as successful anti-poverty initiatives? 4. What is the underlying welfare state concept? To address the research questions a multi-method approach was chosen, consisting of a systematic literature analysis, a comprehensive document analysis, and expert interviews. For interpreting the data the project follows the qualitative-interpretive paradigm. Municipal approaches for reducing poverty are compared based on deductive, as well as inductive identified criteria. In addition to an intensive literature analysis, interviews (40) were conducted in Austria since the project started in March 2018. From the other countries, 14 responses have been collected, providing a first insight. Regarding the definition of poverty the EU SILC-definition as well as counting the persons who receive need-based minimum social benefits, the Austrian form of social welfare, are the predominant approaches in Austria. In addition to homeless people, single-parent families, un-skilled persons, long-term unemployed persons, migrants (first and second generation), refugees and families with at least 3 children were frequently mentioned. The most pressing challenges for Austrian cities are: expected reductions of social budgets, a great insecurity of the central government's social policy reform plans, the growing number of homeless people and a lack of affordable housing. Together with affordable housing, old-age poverty will gain more importance in the future. The Austrian best practice examples, suggested by interviewees, focused primarily on homeless, children and young people (till 25). Central government’s policy changes have already negative effects on programs for refugees and elderly unemployed. Social Housing in Vienna was frequently mentioned as an international best practice case, other growing cities can learn from. The results from Austria indicate a change towards the social investment state, which primarily focuses on children and labour market integration. The first insights from the other countries indicate that affordable housing and labor market integration are cross-cutting issues. Inherited poverty and old-age poverty seems to be more pressing outside Austria.

Keywords: anti-poverty policies, European cities, empirical study, social investment

Procedia PDF Downloads 93
135 Monte Carlo Risk Analysis of a Carbon Abatement Technology

Authors: Hameed Rukayat Opeyemi, Pericles Pilidis, Pagone Emanuele

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Climate change represents one of the single most challenging problems facing the world today. According to the National Oceanic and Administrative Association, Atmospheric temperature rose almost 25% since 1958, Artic sea ice has shrunk 40% since 1959 and global sea levels have risen more than 5.5 cm since 1990. Power plants are the major culprits of GHG emission to the atmosphere. Several technologies have been proposed to reduce the amount of GHG emitted to the atmosphere from power plant, one of which is the less researched Advanced zero emission power plant. The advanced zero emission power plants make use of mixed conductive membrane (MCM) reactor also known as oxygen transfer membrane (OTM) for oxygen transfer. The MCM employs membrane separation process. The membrane separation process was first introduced in 1899 when Walter Hermann Nernst investigated electric current between metals and solutions. He found that when a dense ceramic is heated, current of oxygen molecules move through it. In the bid to curb the amount of GHG emitted to the atmosphere, the membrane separation process was applied to the field of power engineering in the low carbon cycle known as the Advanced zero emission power plant (AZEP cycle). The AZEP cycle was originally invented by Norsk Hydro, Norway and ABB Alstom power (now known as Demag Delaval Industrial turbo machinery AB), Sweden. The AZEP drew a lot of attention because its ability to capture ~100% CO2 and also boasts of about 30-50 % cost reduction compared to other carbon abatement technologies, the penalty in efficiency is also not as much as its counterparts and crowns it with almost zero NOx emissions due to very low nitrogen concentrations in the working fluid. The advanced zero emission power plants differ from a conventional gas turbine in the sense that its combustor is substituted with the mixed conductive membrane (MCM-reactor). The MCM-reactor is made up of the combustor, low temperature heat exchanger LTHX (referred to by some authors as air pre-heater the mixed conductive membrane responsible for oxygen transfer and the high temperature heat exchanger and in some layouts, the bleed gas heat exchanger. Air is taken in by the compressor and compressed to a temperature of about 723 Kelvin and pressure of 2 Mega-Pascals. The membrane area needed for oxygen transfer is reduced by increasing the temperature of 90% of the air using the LTHX; the temperature is also increased to facilitate oxygen transfer through the membrane. The air stream enters the LTHX through the transition duct leading to inlet of the LTHX. The temperature of the air stream is then increased to about 1150 K depending on the design point specification of the plant and the efficiency of the heat exchanging system. The amount of oxygen transported through the membrane is directly proportional to the temperature of air going through the membrane. The AZEP cycle was developed using the Fortran software and economic analysis was conducted using excel and Matlab followed by optimization case study. This paper discusses techno-economic analysis of four possible layouts of the AZEP cycle. The Simple bleed gas heat exchange layout (100 % CO2 capture), Bleed gas heat exchanger layout with flue gas turbine (100 % CO2 capture), Pre-expansion reheating layout (Sequential burning layout) – AZEP 85 % (85 % CO2 capture) and Pre-expansion reheating layout (Sequential burning layout) with flue gas turbine– AZEP 85 % (85 % CO2 capture). This paper discusses Montecarlo risk analysis of four possible layouts of the AZEP cycle.

Keywords: gas turbine, global warming, green house gases, power plants

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134 Oncolytic Efficacy of Thymidine Kinase-Deleted Vaccinia Virus Strain Tiantan (oncoVV-TT) in Glioma

Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi

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Oncolytic viruses, which only replicate in tumor cells, are being extensively studied for their use in cancer therapy. A particular virus known as the vaccinia virus, a member of the poxvirus family, has demonstrated oncolytic abilities glioma. Treating Glioma with traditional methods such as chemotherapy and radiotherapy is quite challenging. Even though oncolytic viruses have shown immense potential in cancer treatment, their effectiveness in glioblastoma treatment is still low. Therefore, there is a need to improve and optimize immunotherapies for better results. In this study, we have designed oncoVV-TT, which can more effectively target tumor cells while minimizing replication in normal cells by replacing the thymidine kinase gene with a luc-p2a-GFP gene expression cassette. Human glioblastoma cell line U251 MG, rat glioblastoma cell line C6, and non-tumor cell line HFF were plated at 105 cells in a 12-well plates in 2 mL of DMEM-F2 medium with 10% FBS added to each well. Then incubated at 37°C. After 16 hours, the cells were treated with oncoVV-TT at an MOI of 0.01, 0.1 and left in the incubator for a further 24, 48, 72 and 96 hours. Viral replication assay, fluorescence imaging and viability tests, including trypan blue and crystal violet, were conducted to evaluate the cytotoxic effect of oncoVV-TT. The finding shows that oncoVV-TT had significantly higher cytotoxic activity and proliferation rates in tumor cells in a dose and time-dependent manner, with the strongest effect observed in U251 MG. To conclude, oncoVV-TT has the potential to be a promising oncolytic virus for cancer treatment, with a more cytotoxic effect in human glioblastoma cells versus rat glioma cells. To assess the effectiveness of vaccinia virus-mediated viral therapy, we have tested U251mg and C6 tumor cell lines taken from human and rat gliomas, respectively. The study evaluated oncoVV-TT's ability to replicate and lyse cells and analyzed the survival rates of the tested cell lines when treated with different doses of oncoVV-TT. Additionally, we compared the sensitivity of human and mouse glioma cell lines to the oncolytic vaccinia virus. All experiments regarding viruses were conducted under biosafety level 2. We engineered a Vaccinia-based oncolytic virus called oncoVV-TT to replicate specifically in tumor cells. To propagate the oncoVV-TT virus, HeLa cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 10 MOI virus was added. After 48 h, cells were harvested by scraping, and viruses were collected by 3 sequential freezing and thawing cycles followed by removal of cell debris by centrifugation (1500 rpm, 5 min). The supernatant was stored at −80 ◦C for the following experiments. To measure the replication of the virus in Hela, cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 5 MOI virus or equal dilution of PBS was added. At the treatment time of 0 h, 24 h, 48 h, 72 h and 96 h, the viral titers were determined under the fluorescence microscope (BZ-X700; Keyence, Osaka, Japan). Fluorescence intensity was quantified using the imagej software according to the manufacturer’s protocol. For the isolation of single-virus clones, HeLa cells seeded in six-well plates (5×105 cells/well). After 24 h (100% confluent), the cells were infected with a 10-fold dilution series of TianTan green fluorescent protein (GFP)virus and incubated for 4 h. To examine the cytotoxic effect of oncoVV-TT virus ofn U251mg and C6 cell, trypan blue and crystal violet assay was used.

Keywords: oncolytic virus, immune therapy, glioma, vaccinia virus

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133 Development of Advanced Virtual Radiation Detection and Measurement Laboratory (AVR-DML) for Nuclear Science and Engineering Students

Authors: Lily Ranjbar, Haori Yang

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Online education has been around for several decades, but the importance of online education became evident after the COVID-19 pandemic. Eventhough the online delivery approach works well for knowledge building through delivering content and oversight processes, it has limitations in developing hands-on laboratory skills, especially in the STEM field. During the pandemic, many education institutions faced numerous challenges in delivering lab-based courses, especially in the STEM field. Also, many students worldwide were unable to practice working with lab equipment due to social distancing or the significant cost of highly specialized equipment. The laboratory plays a crucial role in nuclear science and engineering education. It can engage students and improve their learning outcomes. In addition, online education and virtual labs have gained substantial popularity in engineering and science education. Therefore, developing virtual labs is vital for institutions to deliver high-class education to their students, including their online students. The School of Nuclear Science and Engineering (NSE) at Oregon State University, in partnership with SpectralLabs company, has developed an Advanced Virtual Radiation Detection and Measurement Lab (AVR-DML) to offer a fully online Master of Health Physics program. It was essential for us to use a system that could simulate nuclear modules that accurately replicate the underlying physics, the nature of radiation and radiation transport, and the mechanics of the instrumentations used in the real radiation detection lab. It was all accomplished using a Realistic, Adaptive, Interactive Learning System (RAILS). RAILS is a comprehensive software simulation-based learning system for use in training. It is comprised of a web-based learning management system that is located on a central server, as well as a 3D-simulation package that is downloaded locally to user machines. Users will find that the graphics, animations, and sounds in RAILS create a realistic, immersive environment to practice detecting different radiation sources. These features allow students to coexist, interact and engage with a real STEM lab in all its dimensions. It enables them to feel like they are in a real lab environment and to see the same system they would in a lab. Unique interactive interfaces were designed and developed by integrating all the tools and equipment needed to run each lab. These interfaces provide students full functionality for data collection, changing the experimental setup, and live data collection with real-time updates for each experiment. Students can manually do all experimental setups and parameter changes in this lab. Experimental results can then be tracked and analyzed in an oscilloscope, a multi-channel analyzer, or a single-channel analyzer (SCA). The advanced virtual radiation detection and measurement laboratory developed in this study enabled the NSE school to offer a fully online MHP program. This flexibility of course modality helped us to attract more non-traditional students, including international students. It is a valuable educational tool as students can walk around the virtual lab, make mistakes, and learn from them. They have an unlimited amount of time to repeat and engage in experiments. This lab will also help us speed up training in nuclear science and engineering.

Keywords: advanced radiation detection and measurement, virtual laboratory, realistic adaptive interactive learning system (rails), online education in stem fields, student engagement, stem online education, stem laboratory, online engineering education

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132 Implications of Agricultural Subsidies Since Green Revolution: A Case Study of Indian Punjab

Authors: Kriti Jain, Sucha Singh Gill

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Subsidies have been a major part of agricultural policies around the world, and more extensively since the green revolution in developing countries, for the sake of attaining higher agricultural productivity and achieving food security. But entrenched subsidies lead to distorted incentives and promote inefficiencies in the agricultural sector, threatening the viability of these very subsidies and sustainability of the agricultural production systems, posing a threat to the livelihood of farmers and laborers dependent on it. This paper analyzes the economic and ecological sustainability implications of prolonged input and output subsidies in agriculture by studying the case of Indian Punjab, an agriculturally developed state responsible for ensuring food security in the country when it was facing a major food crisis. The paper focuses specifically on the environmentally unsustainable cropping pattern changes as a result of Minimum Support Price (MSP) and assured procurement and on the resource use efficiency and cost implications of power subsidy for irrigation in Punjab. The study is based on an analysis of both secondary and primary data sources. Using secondary data, a time series analysis was done to capture the changes in Punjab’s cropping pattern, water table depth, fertilizer consumption, and electrification of agriculture. This has been done to examine the role of price and output support adopted to encourage the adoption of green revolution technology in changing the cropping structure of the state, resulting in increased input use intensities (especially groundwater and fertilizers), which harms the ecological balance and decreases factor productivity. Evaluation of electrification of Punjab agriculture helped evaluate the trend in electricity productivity of agriculture and how free power imposed further pressure on the extant agricultural ecosystem. Using data collected from a primary survey of 320 farmers in Punjab, the extent of wasteful application of groundwater irrigation, water productivity of output, electricity usage, and cost of irrigation driven electricity subsidy to the exchequer were estimated for the dominant cropping pattern amongst farmers. The main findings of the study revealed how because of a subsidy has driven agricultural framework, Punjab has lost area under agro climatically suitable and staple crops and moved towards a paddy-wheat cropping system, that is gnawing away the state’s natural resources like water table has been declining at a significant rate of 25 cms per year since 1975-76, and excessive and imbalanced fertilizer usage has led to declining soil fertility in the state. With electricity-driven tubewells as the major source of irrigation within a regime of free electricity and water-intensive crop cultivation, there is both wasteful application of irrigation water and electricity in the cultivation of paddy crops, burning an unproductive hole in the exchequer’s pocket. There is limited access to both agricultural extension services and water-conserving technology, along with policy imbalance, keeping farmers in an intensive and unsustainable production system. Punjab agriculture is witnessing diminishing returns to factor, which under the business-as-usual scenario, will soon enter the phase of negative returns to factor.

Keywords: cropping pattern, electrification, subsidy, sustainability

Procedia PDF Downloads 158
131 Techno-Economic Assessment of Distributed Heat Pumps Integration within a Swedish Neighborhood: A Cosimulation Approach

Authors: Monica Arnaudo, Monika Topel, Bjorn Laumert

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Within the Swedish context, the current trend of relatively low electricity prices promotes the electrification of the energy infrastructure. The residential heating sector takes part in this transition by proposing a switch from a centralized district heating system towards a distributed heat pumps-based setting. When it comes to urban environments, two issues arise. The first, seen from an electricity-sector perspective, is related to the fact that existing networks are limited with regards to their installed capacities. Additional electric loads, such as heat pumps, can cause severe overloads on crucial network elements. The second, seen from a heating-sector perspective, has to do with the fact that the indoor comfort conditions can become difficult to handle when the operation of the heat pumps is limited by a risk of overloading on the distribution grid. Furthermore, the uncertainty of the electricity market prices in the future introduces an additional variable. This study aims at assessing the extent to which distributed heat pumps can penetrate an existing heat energy network while respecting the technical limitations of the electricity grid and the thermal comfort levels in the buildings. In order to account for the multi-disciplinary nature of this research question, a cosimulation modeling approach was adopted. In this way, each energy technology is modeled in its customized simulation environment. As part of the cosimulation methodology: a steady-state power flow analysis in pandapower was used for modeling the electrical distribution grid, a thermal balance model of a reference building was implemented in EnergyPlus to account for space heating and a fluid-cycle model of a heat pump was implemented in JModelica to account for the actual heating technology. With the models set in place, different scenarios based on forecasted electricity market prices were developed both for present and future conditions of Hammarby Sjöstad, a neighborhood located in the south-east of Stockholm (Sweden). For each scenario, the technical and the comfort conditions were assessed. Additionally, the average cost of heat generation was estimated in terms of levelized cost of heat. This indicator enables a techno-economic comparison study among the different scenarios. In order to evaluate the levelized cost of heat, a yearly performance simulation of the energy infrastructure was implemented. The scenarios related to the current electricity prices show that distributed heat pumps can replace the district heating system by covering up to 30% of the heating demand. By lowering of 2°C, the minimum accepted indoor temperature of the apartments, this level of penetration can increase up to 40%. Within the future scenarios, if the electricity prices will increase, as most likely expected within the next decade, the penetration of distributed heat pumps can be limited to 15%. In terms of levelized cost of heat, a residential heat pump technology becomes competitive only within a scenario of decreasing electricity prices. In this case, a district heating system is characterized by an average cost of heat generation 7% higher compared to a distributed heat pumps option.

Keywords: cosimulation, distributed heat pumps, district heating, electrical distribution grid, integrated energy systems

Procedia PDF Downloads 123
130 The Use of Non-Parametric Bootstrap in Computing of Microbial Risk Assessment from Lettuce Consumption Irrigated with Contaminated Water by Sanitary Sewage in Infulene Valley

Authors: Mario Tauzene Afonso Matangue, Ivan Andres Sanchez Ortiz

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The Metropolitan area of Maputo (Mozambique Capital City) is located in semi-arid zone (800 mm annual rainfall) with 1101170 million inhabitants. On the west side, there are the flatlands of Infulene where the Mulauze River flows towards to the Indian Ocean, receiving at this site, the storm water contaminated with sanitary sewage from Maputo, transported through a concrete open channel. In Infulene, local communities grow salads crops such as tomato, onion, garlic, lettuce, and cabbage, which are then commercialized and consumed in several markets in Maputo City. Lettuce is the most daily consumed salad crop in different meals, generally in fast-foods, breakfasts, lunches, and dinners. However, the risk of infection by several pathogens due to the consumption of lettuce, using the Quantitative Microbial Risk Assessment (QMRA) tools, is still unknown since there are few studies or publications concerning to this matter in Mozambique. This work is aimed at determining the annual risk arising from the consumption of lettuce grown in Infulene valley, in Maputo, using QMRA tools. The exposure model was constructed upon the volume of contaminated water remaining in the lettuce leaves, the empirical relations between the number of pathogens and the indicator of microorganisms (E. coli), the consumption of lettuce (g) and reduction of pathogens (days). The reference pathogens were Vibrio cholerae, Cryptosporidium, norovirus, and Ascaris. The water quality samples (E. coli) were collected in the storm water channel from January 2016 to December 2018, comprising 65 samples, and the urban lettuce consumption data were collected through inquiry in Maputo Metropolis covering 350 persons. A non-parametric bootstrap was performed involving 10,000 iterations over the collected dataset, namely, water quality (E. coli) and lettuce consumption. The dose-response models were: Exponential for Cryptosporidium, Kummer Confluent hypergeomtric function (1F1) for Vibrio and Ascaris Gaussian hypergeometric function (2F1-(a,b;c;z) for norovirus. The annual infection risk estimates were performed using R 3.6.0 (CoreTeam) software by Monte Carlo (Latin hypercubes), a sampling technique involving 10,000 iterations. The annual infection risks values expressed by Median and the 95th percentile, per person per year (pppy) arising from the consumption of lettuce are as follows: Vibrio cholerae (1.00, 1.00), Cryptosporidium (3.91x10⁻³, 9.72x 10⁻³), nororvirus (5.22x10⁻¹, 9.99x10⁻¹) and Ascaris (2.59x10⁻¹, 9.65x10⁻¹). Thus, the consumption of the lettuce would result in greater risks than the tolerable levels ( < 10⁻³ pppy or 10⁻⁶ DALY) for all pathogens, and the Vibrio cholerae is the most virulent pathogens, according to the hit-single models followed by the Ascaris lumbricoides and norovirus. The sensitivity analysis carried out in this work pointed out that in the whole QMRA, the most important input variable was the reduction of pathogens (Spearman rank value was 0.69) between harvest and consumption followed by water quality (Spearman rank value was 0.69). The decision-makers (Mozambique Government) must strengthen the prevention measures related to pathogens reduction in lettuce (i.e., washing) and engage in wastewater treatment engineering.

Keywords: annual infections risk, lettuce, non-parametric bootstrapping, quantitative microbial risk assessment tools

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129 Evaluation of Polymerisation Shrinkage of Randomly Oriented Micro-Sized Fibre Reinforced Dental Composites Using Fibre-Bragg Grating Sensors and Their Correlation with Degree of Conversion

Authors: Sonam Behl, Raju, Ginu Rajan, Paul Farrar, B. Gangadhara Prusty

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Reinforcing dental composites with micro-sized fibres can significantly improve the physio-mechanical properties of dental composites. The short fibres can be oriented randomly within dental composites, thus providing quasi-isotropic reinforcing efficiency unlike unidirectional/bidirectional fibre reinforced composites enhancing anisotropic properties. Thus, short fibres reinforced dental composites are getting popular among practitioners. However, despite their popularity, resin-based dental composites are prone to failure on account of shrinkage during photo polymerisation. The shrinkage in the structure may lead to marginal gap formation, causing secondary caries, thus ultimately inducing failure of the restoration. The traditional methods to evaluate polymerisation shrinkage using strain gauges, density-based measurements, dilatometer, or bonded-disk focuses on average value of volumetric shrinkage. Moreover, the results obtained from traditional methods are sensitive to the specimen geometry. The present research aims to evaluate the real-time shrinkage strain at selected locations in the material with the help of optical fibre Bragg grating (FBG) sensors. Due to the miniature size (diameter 250 µm) of FBG sensors, they can be easily embedded into small samples of dental composites. Furthermore, an FBG array into the system can map the real-time shrinkage strain at different regions of the composite. The evaluation of real-time monitoring of shrinkage values may help to optimise the physio-mechanical properties of composites. Previously, FBG sensors have been able to rightfully measure polymerisation strains of anisotropic (unidirectional or bidirectional) reinforced dental composites. However, very limited study exists to establish the validity of FBG based sensors to evaluate volumetric shrinkage for randomly oriented fibres reinforced composites. The present study aims to fill this research gap and is focussed on establishing the usage of FBG based sensors for evaluating the shrinkage of dental composites reinforced with randomly oriented fibres. Three groups of specimens were prepared by mixing the resin (80% UDMA/20% TEGDMA) with 55% of silane treated BaAlSiO₂ particulate fillers or by adding 5% of micro-sized fibres of diameter 5 µm, and length 250/350 µm along with 50% of silane treated BaAlSiO₂ particulate fillers into the resin. For measurement of polymerisation shrinkage strain, an array of three fibre Bragg grating sensors was embedded at a depth of 1 mm into a circular Teflon mould of diameter 15 mm and depth 2 mm. The results obtained are compared with the traditional method for evaluation of the volumetric shrinkage using density-based measurements. Degree of conversion was measured using FTIR spectroscopy (Spotlight 400 FT-IR from PerkinElmer). It is expected that the average polymerisation shrinkage strain values for dental composites reinforced with micro-sized fibres can directly correlate with the measured degree of conversion values, implying that more C=C double bond conversion to C-C single bond values also leads to higher shrinkage strain within the composite. Moreover, it could be established the photonics approach could help assess the shrinkage at any point of interest in the material, suggesting that fibre-Bragg grating sensors are a suitable means for measuring real-time polymerisation shrinkage strain for randomly fibre reinforced dental composites as well.

Keywords: dental composite, glass fibre, polymerisation shrinkage strain, fibre-Bragg grating sensors

Procedia PDF Downloads 126
128 Detection of Mustard Traces in Food by an Official Food Safety Laboratory

Authors: Clara Tramuta, Lucia Decastelli, Elisa Barcucci, Sandra Fragassi, Samantha Lupi, Enrico Arletti, Melissa Bizzarri, Daniela Manila Bianchi

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Introdution: Food allergies occurs, in the Western World, 2% of adults and up to 8% of children. The protection of allergic consumers is guaranted, in Eurrope, by Regulation (EU) No 1169/2011 of the European Parliament which governs the consumer's right to information and identifies 14 food allergens to be mandatory indicated on the label. Among these, mustard is a popular spice added to enhance the flavour and taste of foods. It is frequently present as an ingredient in spice blends, marinades, salad dressings, sausages, and other products. Hypersensitivity to mustard is a public health problem since the ingestion of even low amounts can trigger severe allergic reactions. In order to protect the allergic consumer, high performance methods are required for the detection of allergenic ingredients. Food safety laboratories rely on validated methods that detect hidden allergens in food to ensure the safety and health of allergic consumers. Here we present the test results for the validation and accreditation of a Real time PCR assay (RT-PCR: SPECIALfinder MC Mustard, Generon), for the detection of mustard traces in food. Materials and Methods. The method was tested on five classes of food matrices: bakery and pastry products (chocolate cookies), meats (ragù), ready-to-eat (mixed salad), dairy products (yogurt), grains, and milling products (rice and barley flour). Blank samples were spiked starting with the mustard samples (Sinapis Alba), lyophilized and stored at -18 °C, at a concentration of 1000 ppm. Serial dilutions were then prepared to a final concentration of 0.5 ppm, using the DNA extracted by ION Force FAST (Generon) from the blank samples. The Real Time PCR reaction was performed by RT-PCR SPECIALfinder MC Mustard (Generon), using CFX96 System (BioRad). Results. Real Time PCR showed a limit of detection (LOD) of 0.5 ppm in grains and milling products, ready-to-eat, meats, bakery, pastry products, and dairy products (range Ct 25-34). To determine the exclusivity parameter of the method, the ragù matrix was contaminated with Prunus dulcis (almonds), peanut (Arachis hypogaea), Glycine max (soy), Apium graveolens (celery), Allium cepa (onion), Pisum sativum (peas), Daucus carota (carrots), and Theobroma cacao (cocoa) and no cross-reactions were observed. Discussion. In terms of sensitivity, the Real Time PCR confirmed, even in complex matrix, a LOD of 0.5 ppm in five classes of food matrices tested; these values are compatible with the current regulatory situation that does not consider, at international level, to establish a quantitative criterion for the allergen considered in this study. The Real Time PCR SPECIALfinder kit for the detection of mustard proved to be easy to use and particularly appreciated for the rapid response times considering that the amplification and detection phase has a duration of less than 50 minutes. Method accuracy was rated satisfactory for sensitivity (100%) and specificity (100%) and was fully validated and accreditated. It was found adequate for the needs of the laboratory as it met the purpose for which it was applied. This study was funded in part within a project of the Italian Ministry of Health (IZS PLV 02/19 RC).

Keywords: allergens, food, mustard, real time PCR

Procedia PDF Downloads 137
127 Spatial Assessment of Creek Habitats of Marine Fish Stock in Sindh Province

Authors: Syed Jamil H. Kazmi, Faiza Sarwar

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The Indus delta of Sindh Province forms the largest creeks zone of Pakistan. The Sindh coast starts from the mouth of Hab River and terminates at Sir Creek area. In this paper, we have considered the major creeks from the site of Bin Qasim Port in Karachi to Jetty of Keti Bunder in Thatta District. A general decline in the mangrove forest has been observed that within a span of last 25 years. The unprecedented human interventions damage the creeks habitat badly which includes haphazard urban development, industrial and sewage disposal, illegal cutting of mangroves forest, reduced and inconsistent fresh water flow mainly from Jhang and Indus rivers. These activities not only harm the creeks habitat but affected the fish stock substantially. Fishing is the main livelihood of coastal people but with the above-mentioned threats, it is also under enormous pressure by fish catches resulted in unchecked overutilization of the fish resources. This pressure is almost unbearable when it joins with deleterious fishing methods, uncontrolled fleet size, increase trash and by-catch of juvenile and illegal mesh size. Along with these anthropogenic interventions study area is under the red zone of tropical cyclones and active seismicity causing floods, sea intrusion, damage mangroves forests and devastation of fish stock. In order to sustain the natural resources of the Indus Creeks, this study was initiated with the support of FAO, WWF and NIO, the main purpose was to develop a Geo-Spatial dataset for fish stock assessment. The study has been spread over a year (2013-14) on monthly basis which mainly includes detailed fish stock survey, water analysis and few other environmental analyses. Environmental analysis also includes the habitat classification of study area which has done through remote sensing techniques for 22 years’ time series (1992-2014). Furthermore, out of 252 species collected, fifteen species from estuarine and marine groups were short-listed to measure the weight, health and growth of fish species at each creek under GIS data through SPSS system. Furthermore, habitat suitability analysis has been conducted by assessing the surface topographic and aspect derivation through different GIS techniques. The output variables then overlaid in GIS system to measure the creeks productivity. Which provided the results in terms of subsequent classes: extremely productive, highly productive, productive, moderately productive and less productive. This study has revealed the Geospatial tools utilization along with the evaluation of the fisheries resources and creeks habitat risk zone mapping. It has also been identified that the geo-spatial technologies are highly beneficial to identify the areas of high environmental risk in Sindh Creeks. This has been clearly discovered from this study that creeks with high rugosity are more productive than the creeks with low levels of rugosity. The study area has the immense potential to boost the economy of Pakistan in terms of fish export, if geo-spatial techniques are implemented instead of conventional techniques.

Keywords: fish stock, geo-spatial, productivity analysis, risk

Procedia PDF Downloads 222
126 Synthesis of Carbonyl Iron Particles Modified with Poly (Trimethylsilyloxyethyl Methacrylate) Nano-Grafts

Authors: Martin Cvek, Miroslav Mrlik, Michal Sedlacik, Tomas Plachy

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Magnetorheological elastomers (MREs) are multi-phase composite materials containing micron-sized ferromagnetic particles dispersed in an elastomeric matrix. Their properties such as modulus, damping, magneto-striction, and electrical conductivity can be controlled by an external magnetic field and/or pressure. These features of the MREs are used in the development of damping devices, shock attenuators, artificial muscles, sensors or active elements of electric circuits. However, imperfections on the particle/matrix interfaces result in the lower performance of the MREs when compared with theoretical values. Moreover, magnetic particles are susceptible to corrosion agents such as acid rains or sea humidity. Therefore, the modification of particles is an effective tool for the improvement of MRE performance due to enhanced compatibility between particles and matrix as well as improvements of their thermo-oxidation and chemical stability. In this study, the carbonyl iron (CI) particles were controllably modified with poly(trimethylsilyloxyethyl methacrylate) (PHEMATMS) nano-grafts to develop magnetic core–shell structures exhibiting proper wetting with various elastomeric matrices resulting in improved performance within a frame of rheological, magneto-piezoresistance, pressure-piezoresistance, or radio-absorbing properties. The desired molecular weight of PHEMATMS nano-grafts was precisely tailored using surface-initiated atom transfer radical polymerization (ATRP). The CI particles were firstly functionalized using a 3-aminopropyltriethoxysilane agent, followed by esterification reaction with α-bromoisobutyryl bromide. The ATRP was performed in the anisole medium using ethyl α-bromoisobutyrate as a macroinitiator, N, N´, N´´, N´´-pentamethyldiethylenetriamine as a ligand, and copper bromide as an initiator. To explore the effect PHEMATMS molecular weights on final properties, two variants of core-shell structures with different nano-graft lengths were synthesized, while the reaction kinetics were designed through proper reactant feed ratios and polymerization times. The PHEMATMS nano-grafts were characterized by nuclear magnetic resonance and gel permeation chromatography proving information to their monomer conversions, molecular chain lengths, and low polydispersity indexes (1.28 and 1.35) as the results of the executed ATRP. The successful modifications were confirmed via Fourier transform infrared- and energy-dispersive spectroscopies while expected wavenumber outputs and element presences, respectively, of constituted PHEMATMS nano-grafts, were occurring in the spectra. The surface morphology of bare CI and their PHEMATMS-grafted analogues was further studied by scanning electron microscopy, and the thicknesses of grafted polymeric layers were directly observed by transmission electron microscopy. The contact angles as a measure of particle/matrix compatibility were investigated employing the static sessile drop method. The PHEMATMS nano-grafts enhanced compatibility of hydrophilic CI with low-surface-energy hydrophobic polymer matrix in terms of their wettability and dispersibility in an elastomeric matrix. Thus, the presence of possible defects at the particle/matrix interface is reduced, and higher performance of modified MREs is expected.

Keywords: atom transfer radical polymerization, core-shell, particle modification, wettability

Procedia PDF Downloads 178
125 Railway Composite Flooring Design: Numerical Simulation and Experimental Studies

Authors: O. Lopez, F. Pedro, A. Tadeu, J. Antonio, A. Coelho

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The future of the railway industry lies in the innovation of lighter, more efficient and more sustainable trains. Weight optimizations in railway vehicles allow reducing power consumption and CO₂ emissions, increasing the efficiency of the engines and the maximum speed reached. Additionally, they reduce wear of wheels and rails, increase the space available for passengers, etc. Among the various systems that integrate railway interiors, the flooring system is one which has greater impact both on passenger safety and comfort, as well as on the weight of the interior systems. Due to the high weight saving potential, relative high mechanical resistance, good acoustic and thermal performance, ease of modular design, cost-effectiveness and long life, the use of new sustainable composite materials and panels provide the latest innovations for competitive solutions in the development of flooring systems. However, one of the main drawbacks of the flooring systems is their relatively poor resistance to point loads. Point loads in railway interiors can be caused by passengers or by components fixed to the flooring system, such as seats and restraint systems, handrails, etc. In this way, they can originate higher fatigue solicitations under service loads or zones with high stress concentrations under exceptional loads (higher longitudinal, transverse and vertical accelerations), thus reducing its useful life. Therefore, to verify all the mechanical and functional requirements of the flooring systems, many physical prototypes would be created during the design phase, with all of the high costs associated with it. Nowadays, the use of virtual prototyping methods by computer-aided design (CAD) and computer-aided engineering (CAE) softwares allow validating a product before committing to making physical test prototypes. The scope of this work was to current computer tools and integrate the processes of innovation, development, and manufacturing to reduce the time from design to finished product and optimise the development of the product for higher levels of performance and reliability. In this case, the mechanical response of several sandwich panels with different cores, polystyrene foams, and composite corks, were assessed, to optimise the weight and the mechanical performance of a flooring solution for railways. Sandwich panels with aluminum face sheets were tested to characterise its mechanical performance and determine the polystyrene foam and cork properties when used as inner cores. Then, a railway flooring solution was fully modelled (including the elastomer pads to provide the required vibration isolation from the car body) and perform structural simulations using FEM analysis to comply all the technical product specifications for the supply of a flooring system. Zones with high stress concentrations are studied and tested. The influence of vibration modes on the comfort level and stability is discussed. The information obtained with the computer tools was then completed with several mechanical tests performed on some solutions, and on specific components. The results of the numerical simulations and experimental campaign carried out are presented in this paper. This research work was performed as part of the POCI-01-0247-FEDER-003474 (coMMUTe) Project funded by Portugal 2020 through COMPETE 2020.

Keywords: cork agglomerate core, mechanical performance, numerical simulation, railway flooring system

Procedia PDF Downloads 156
124 Factors Associated with Risky Sexual Behaviour in Adolescent Girls and Young Women in Cambodia: A Systematic Review

Authors: Farwa Rizvi, Joanne Williams, Humaira Maheen, Elizabeth Hoban

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There is an increase in risky sexual behavior and unsafe sex in adolescent girls and young women aged 15 to 24 years in Cambodia, which negatively affects their reproductive health by increasing the risk of contracting sexually transmitted infections and unintended pregnancies. Risky sexual behavior includes ‘having sex at an early age, having multiple sexual partners, having sex while under the influence of alcohol or drugs, and unprotected sexual behaviors’. A systematic review of quantitative research conducted in Cambodia was undertaken, using the theoretical framework of the Social Ecological Model to identify the personal, social and cultural factors associated with risky sexual behavior and unsafe sex in young Cambodian women. PRISMA guidelines were used to search databases including Medline Complete, PsycINFO, CINAHL Complete, Academic Search Complete, Global Health, and Social Work Abstracts. Additional searches were conducted in Science Direct, Google Scholar and in the grey literature sources. A risk-of-bias tool developed explicitly for the systematic review of cross-sectional studies was used. Summary item on the overall risk of study bias after the inter-rater response showed that the risk-of-bias was high in two studies, moderate in one study and low in one study. The search strategy included a combination of subject terms and free text terms. The medical subject headings (MeSH) terms included were; contracept* or ‘birth control’ or ‘family planning’ or pregnan* or ‘safe sex’ or ‘protected intercourse’ or ‘unprotected intercourse’ or ‘protected sex’ or ‘unprotected sex’ or ‘risky sexual behaviour*’ or ‘abort*’ or ‘planned parenthood’ or ‘unplanned pregnancy’ AND ( barrier* or obstacle* or challenge* or knowledge or attitude* or factor* or determinant* or choic* or uptake or discontinu* or acceptance or satisfaction or ‘needs assessment’ or ‘non-use’ or ‘unmet need’ or ‘decision making’ ) AND Cambodia*. Initially, 300 studies were identified by using key words and finally, four quantitative studies were selected based on the inclusion criteria. The four studies were published between 2010 and 2016. The study participants ranged in age from 10-24 years, single or married, with 3 to 10 completed years of education. The mean age at sexual debut was reported to be 18 years. Using the perspective of the Social Ecological Model, risky sexual behavior was associated with individual-level factors including young age at sexual debut, low education, unsafe sex under the influence of alcohol and substance abuse, multiple sexual partners or transactional sex. Family level factors included living away from parents, orphan status and low levels of family support. Peer and partner level factors included peer delinquency and lack of condom use. Low socioeconomic status at the society level was also associated with risky sexual behaviour. There is scant research on sexual and reproductive health of adolescent girls and young women in Cambodia. Individual, family and social factors were significantly associated with risky sexual behaviour. More research is required to inform potential preventive strategies and policies that address young women’s sexual and reproductive health.

Keywords: adolescents, high-risk sex, sexual activity, unplanned pregnancies

Procedia PDF Downloads 215
123 Mapping Iron Content in the Brain with Magnetic Resonance Imaging and Machine Learning

Authors: Gabrielle Robertson, Matthew Downs, Joseph Dagher

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Iron deposition in the brain has been linked with a host of neurological disorders such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. While some treatment options exist, there are no objective measurement tools that allow for the monitoring of iron levels in the brain in vivo. An emerging Magnetic Resonance Imaging (MRI) method has been recently proposed to deduce iron concentration through quantitative measurement of magnetic susceptibility. This is a multi-step process that involves repeated modeling of physical processes via approximate numerical solutions. For example, the last two steps of this Quantitative Susceptibility Mapping (QSM) method involve I) mapping magnetic field into magnetic susceptibility and II) mapping magnetic susceptibility into iron concentration. Process I involves solving an ill-posed inverse problem by using regularization via injection of prior belief. The end result from Process II highly depends on the model used to describe the molecular content of each voxel (type of iron, water fraction, etc.) Due to these factors, the accuracy and repeatability of QSM have been an active area of research in the MRI and medical imaging community. This work aims to estimate iron concentration in the brain via a single step. A synthetic numerical model of the human head was created by automatically and manually segmenting the human head on a high-resolution grid (640x640x640, 0.4mm³) yielding detailed structures such as microvasculature and subcortical regions as well as bone, soft tissue, Cerebral Spinal Fluid, sinuses, arteries, and eyes. Each segmented region was then assigned tissue properties such as relaxation rates, proton density, electromagnetic tissue properties and iron concentration. These tissue property values were randomly selected from a Probability Distribution Function derived from a thorough literature review. In addition to having unique tissue property values, different synthetic head realizations also possess unique structural geometry created by morphing the boundary regions of different areas within normal physical constraints. This model of the human brain is then used to create synthetic MRI measurements. This is repeated thousands of times, for different head shapes, volume, tissue properties and noise realizations. Collectively, this constitutes a training-set that is similar to in vivo data, but larger than datasets available from clinical measurements. This 3D convolutional U-Net neural network architecture was used to train data-driven Deep Learning models to solve for iron concentrations from raw MRI measurements. The performance was then tested on both synthetic data not used in training as well as real in vivo data. Results showed that the model trained on synthetic MRI measurements is able to directly learn iron concentrations in areas of interest more effectively than other existing QSM reconstruction methods. For comparison, models trained on random geometric shapes (as proposed in the Deep QSM method) are less effective than models trained on realistic synthetic head models. Such an accurate method for the quantitative measurement of iron deposits in the brain would be of important value in clinical studies aiming to understand the role of iron in neurological disease.

Keywords: magnetic resonance imaging, MRI, iron deposition, machine learning, quantitative susceptibility mapping

Procedia PDF Downloads 100
122 A Copula-Based Approach for the Assessment of Severity of Illness and Probability of Mortality: An Exploratory Study Applied to Intensive Care Patients

Authors: Ainura Tursunalieva, Irene Hudson

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Continuous improvement of both the quality and safety of health care is an important goal in Australia and internationally. The intensive care unit (ICU) receives patients with a wide variety of and severity of illnesses. Accurately identifying patients at risk of developing complications or dying is crucial to increasing healthcare efficiency. Thus, it is essential for clinicians and researchers to have a robust framework capable of evaluating the risk profile of a patient. ICU scoring systems provide such a framework. The Acute Physiology and Chronic Health Evaluation III and the Simplified Acute Physiology Score II are ICU scoring systems frequently used for assessing the severity of acute illness. These scoring systems collect multiple risk factors for each patient including physiological measurements then render the assessment outcomes of individual risk factors into a single numerical value. A higher score is related to a more severe patient condition. Furthermore, the Mortality Probability Model II uses logistic regression based on independent risk factors to predict a patient’s probability of mortality. An important overlooked limitation of SAPS II and MPM II is that they do not, to date, include interaction terms between a patient’s vital signs. This is a prominent oversight as it is likely there is an interplay among vital signs. The co-existence of certain conditions may pose a greater health risk than when these conditions exist independently. One barrier to including such interaction terms in predictive models is the dimensionality issue as it becomes difficult to use variable selection. We propose an innovative scoring system which takes into account a dependence structure among patient’s vital signs, such as systolic and diastolic blood pressures, heart rate, pulse interval, and peripheral oxygen saturation. Copulas will capture the dependence among normally distributed and skewed variables as some of the vital sign distributions are skewed. The estimated dependence parameter will then be incorporated into the traditional scoring systems to adjust the points allocated for the individual vital sign measurements. The same dependence parameter will also be used to create an alternative copula-based model for predicting a patient’s probability of mortality. The new copula-based approach will accommodate not only a patient’s trajectories of vital signs but also the joint dependence probabilities among the vital signs. We hypothesise that this approach will produce more stable assessments and lead to more time efficient and accurate predictions. We will use two data sets: (1) 250 ICU patients admitted once to the Chui Regional Hospital (Kyrgyzstan) and (2) 37 ICU patients’ agitation-sedation profiles collected by the Hunter Medical Research Institute (Australia). Both the traditional scoring approach and our copula-based approach will be evaluated using the Brier score to indicate overall model performance, the concordance (or c) statistic to indicate the discriminative ability (or area under the receiver operating characteristic (ROC) curve), and goodness-of-fit statistics for calibration. We will also report discrimination and calibration values and establish visualization of the copulas and high dimensional regions of risk interrelating two or three vital signs in so-called higher dimensional ROCs.

Keywords: copula, intensive unit scoring system, ROC curves, vital sign dependence

Procedia PDF Downloads 129
121 Post Liberal Perspective on Minorities Visibility in Contemporary Visual Culture: The Case of Mizrahi Jews

Authors: Merav Alush Levron, Sivan Rajuan Shtang

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From as early as their emergence in Europe and the US, postmodern and post-colonial paradigm have formed the backbone of the visual culture field of study. The self-representation project of political minorities is studied, described and explained within the premises and perspectives drawn from these paradigms, addressing the key issues they had raised: modernism’s crisis of representation. The struggle for self-representation, agency and multicultural visibility sought to challenge the liberal pretense of universality and equality, hitting at its different blind spots, on issues such as class, gender, race, sex, and nationality. This struggle yielded subversive identity and hybrid performances, including reclaiming, mimicry and masquerading. These performances sought to defy the uniform, universal self, which forms the basis for the liberal, rational, enlightened subject. The argument of this research runs that this politics of representation itself is confined within liberal thought. Alongside post-colonialism and multiculturalism’s contribution in undermining oppressive structures of power, generating diversity in cultural visibility, and exposing the failure of liberal colorblindness, this subversion is constituted in the visual field by way of confrontation, flying in the face of the universal law and relying on its ongoing comparison and attribution to this law. Relying on Deleuze and Guattari, this research set out to draw theoretic and empiric attention to an alternative, post-liberal occurrence which has been taking place in the visual field in parallel to the contra-hegemonic phase and as a product of political reality in the aftermath of the crisis of representation. It is no longer a counter-representation; rather, it is a motion of organic minor desire, progressing in the form of flows and generating what Deleuze and Guattari termed deterritorialization of social structures. This discussion shall have its focus on current post-liberal performances of ‘Mizrahim’ (Jewish Israelis of Arab and Muslim extraction) in the visual field in Israel. In television, video art and photography, these performances challenge the issue of representation and generate concrete peripheral Mizrahiness, realized in the visual organization of the photographic frame. Mizrahiness then transforms from ‘confrontational’ representation into a 'presence', flooding the visual sphere in our plain sight, in a process of 'becoming'. The Mizrahi desire is exerted on the plains of sound, spoken language, the body and the space where they appear. It removes from these plains the coding and stratification engendered by European dominance and rational, liberal enlightenment. This stratification, adhering to the hegemonic surface, is flooded not by way of resisting false consciousness or employing hybridity, but by way of the Mizrahi identity’s own productive, material immanent yearning. The Mizrahi desire reverberates with Mizrahi peripheral 'worlds of meaning', where post-colonial interpretation almost invariably identifies a product of internalized oppression, and a recurrence thereof, rather than a source in itself - an ‘offshoot, never a wellspring’, as Nissim Mizrachi clarifies in his recent pioneering work. The peripheral Mizrahi performance ‘unhook itself’, in Deleuze and Guattari words, from the point of subjectification and interpretation and does not correspond with the partialness, absence, and split that mark post-colonial identities.

Keywords: desire, minority, Mizrahi Jews, post-colonialism, post-liberalism, visibility, Deleuze and Guattari

Procedia PDF Downloads 299
120 On the Utility of Bidirectional Transformers in Gene Expression-Based Classification

Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of the flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on the spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts, as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with an attention mechanism. In previous works on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work, with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on the presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: machine learning, classification and regression, gene circuit design, bidirectional transformers

Procedia PDF Downloads 35
119 Pharmacokinetics of First-Line Tuberculosis Drugs in South African Patients from Kwazulu-Natal: Effects of Pharmacogenetic Variation on Rifampicin and Isoniazid Concentrations

Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

Abstract:

Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

Procedia PDF Downloads 158
118 Design of Experiment for Optimizing Immunoassay Microarray Printing

Authors: Alex J. Summers, Jasmine P. Devadhasan, Douglas Montgomery, Brittany Fischer, Jian Gu, Frederic Zenhausern

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Immunoassays have been utilized for several applications, including the detection of pathogens. Our laboratory is in the development of a tier 1 biothreat panel utilizing Vertical Flow Assay (VFA) technology for simultaneous detection of pathogens and toxins. One method of manufacturing VFA membranes is with non-contact piezoelectric dispensing, which provides advantages, such as low-volume and rapid dispensing without compromising the structural integrity of antibody or substrate. Challenges of this processinclude premature discontinuation of dispensing and misaligned spotting. Preliminary data revealed the Yp 11C7 mAb (11C7)reagent to exhibit a large angle of failure during printing which may have contributed to variable printing outputs. A Design of Experiment (DOE) was executed using this reagent to investigate the effects of hydrostatic pressure and reagent concentration on microarray printing outputs. A Nano-plotter 2.1 (GeSIM, Germany) was used for printing antibody reagents ontonitrocellulose membrane sheets in a clean room environment. A spotting plan was executed using Spot-Front-End software to dispense volumes of 11C7 reagent (20-50 droplets; 1.5-5 mg/mL) in a 6-test spot array at 50 target membrane locations. Hydrostatic pressure was controlled by raising the Pressure Compensation Vessel (PCV) above or lowering it below our current working level. It was hypothesized that raising or lowering the PCV 6 inches would be sufficient to cause either liquid accumulation at the tip or discontinue droplet formation. After aspirating 11C7 reagent, we tested this hypothesis under stroboscope.75% of the effective raised PCV height and of our hypothesized lowered PCV height were used. Humidity (55%) was maintained using an Airwin BO-CT1 humidifier. The number and quality of membranes was assessed after staining printed membranes with dye. The droplet angle of failure was recorded before and after printing to determine a “stroboscope score” for each run. The DOE set was analyzed using JMP software. Hydrostatic pressure and reagent concentration had a significant effect on the number of membranes output. As hydrostatic pressure was increased by raising the PCV 3.75 inches or decreased by lowering the PCV -4.5 inches, membrane output decreased. However, with the hydrostatic pressure closest to equilibrium, our current working level, membrane output, reached the 50-membrane target. As the reagent concentration increased from 1.5 to 5 mg/mL, the membrane output also increased. Reagent concentration likely effected the number of membrane output due to the associated dispensing volume needed to saturate the membranes. However, only hydrostatic pressure had a significant effect on stroboscope score, which could be due to discontinuation of dispensing, and thus the stroboscope check could not find a droplet to record. Our JMP predictive model had a high degree of agreement with our observed results. The JMP model predicted that dispensing the highest concentration of 11C7 at our current PCV working level would yield the highest number of quality membranes, which correlated with our results. Acknowledgements: This work was supported by the Chemical Biological Technologies Directorate (Contract # HDTRA1-16-C-0026) and the Advanced Technology International (Contract # MCDC-18-04-09-002) from the Department of Defense Chemical and Biological Defense program through the Defense Threat Reduction Agency (DTRA).

Keywords: immunoassay, microarray, design of experiment, piezoelectric dispensing

Procedia PDF Downloads 151
117 Optimized Electron Diffraction Detection and Data Acquisition in Diffraction Tomography: A Complete Solution by Gatan

Authors: Saleh Gorji, Sahil Gulati, Ana Pakzad

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Continuous electron diffraction tomography, also known as microcrystal electron diffraction (MicroED) or three-dimensional electron diffraction (3DED), is a powerful technique, which in combination with cryo-electron microscopy (cryo-ED), can provide atomic-scale 3D information about the crystal structure and composition of different classes of crystalline materials such as proteins, peptides, and small molecules. Unlike the well-established X-ray crystallography method, 3DED does not require large single crystals and can collect accurate electron diffraction data from crystals as small as 50 – 100 nm. This is a critical advantage as growing larger crystals, as required by X-ray crystallography methods, is often very difficult, time-consuming, and expensive. In most cases, specimens studied via 3DED method are electron beam sensitive, which means there is a limitation on the maximum amount of electron dose one can use to collect the required data for a high-resolution structure determination. Therefore, collecting data using a conventional scintillator-based fiber coupled camera brings additional challenges. This is because of the inherent noise introduced during the electron-to-photon conversion in the scintillator and transfer of light via the fibers to the sensor, which results in a poor signal-to-noise ratio and requires a relatively higher and commonly specimen-damaging electron dose rates, especially for protein crystals. As in other cryo-EM techniques, damage to the specimen can be mitigated if a direct detection camera is used which provides a high signal-to-noise ratio at low electron doses. In this work, we have used two classes of such detectors from Gatan, namely the K3® camera (a monolithic active pixel sensor) and Stela™ (that utilizes DECTRIS hybrid-pixel technology), to address this problem. The K3 is an electron counting detector optimized for low-dose applications (like structural biology cryo-EM), and Stela is also a counting electron detector but optimized for diffraction applications with high speed and high dynamic range. Lastly, data collection workflows, including crystal screening, microscope optics setup (for imaging and diffraction), stage height adjustment at each crystal position, and tomogram acquisition, can be one of the other challenges of the 3DED technique. Traditionally this has been all done manually or in a partly automated fashion using open-source software and scripting, requiring long hours on the microscope (extra cost) and extensive user interaction with the system. We have recently introduced Latitude® D in DigitalMicrograph® software, which is compatible with all pre- and post-energy-filter Gatan cameras and enables 3DED data acquisition in an automated and optimized fashion. Higher quality 3DED data enables structure determination with higher confidence, while automated workflows allow these to be completed considerably faster than before. Using multiple examples, this work will demonstrate how to direct detection electron counting cameras enhance 3DED results (3 to better than 1 Angstrom) for protein and small molecule structure determination. We will also show how Latitude D software facilitates collecting such data in an integrated and fully automated user interface.

Keywords: continuous electron diffraction tomography, direct detection, diffraction, Latitude D, Digitalmicrograph, proteins, small molecules

Procedia PDF Downloads 64
116 Electromyographic Analysis of Biceps Brachii during Golf Swing and Review of Its Impact on Return to Play Following Tendon Surgery

Authors: Amin Masoumiganjgah, Luke Salmon, Julianne Burnton, Fahimeh Bagheri, Gavin Lenton, S. L. Ezekial Tan

Abstract:

Introduction: The incidence of proximal biceps tenodesis and acute distal biceps repair is increasing, and rehabilitation protocols following both are variable. Golf is a popular sport within Australia, and the Gold Coast has become a Mecca for golfers, with more courses per capita than anywhere else in the world. Currently, there are no clear guidelines regarding return to golf play following biceps procedures. The aim of this study was to determine biceps brachii activation during the golf swing through electromyographic analysis, and subsequently, aid in rehabilitation guidelines and return to golf following tenodesis and repair. Methods: Subjects were amateur golfers with no previous upper limb surgery. Surface electromyography (EMG) and high-speed video recording were used to analyse activation of the left and right biceps brachii and the anterior deltoid during the golf swing. Each participant’s maximum voluntary contraction (MVC) was recorded, and they were then required to hit a golf ball aiming for specific distances of 2, 50, 100 and 150 metres at a driving range. Noraxon myoResearch and Matlab were used for data analysis. Mean % MVC was calculated for leading and trailing arms during the full swing and its’ 4 phases: back-swing, acceleration, early follow-through and late follow-through. Results: 12 golfers (2 female and 10 male), participated in the study. Median age was 27 (25 – 38), with all being right handed. Over all distances, the mean activation of the short and long head of biceps brachii was < 10% through the full swing. When breaking down the 50, 100 and 150m swing into phases, mean MVC activation was lowest in backswing (5.1%), followed by acceleration (9.7%), early follow-through (9.2%), and late follow-through (21.4%). There was more variation and slightly higher activation in the right biceps (trailing arm) in backswing, acceleration, and early follow-through; with higher activation in the leading arm in late follow-through (25.4% leading, 17.3% trailing). 2m putts resulted in low MVC values (3.1% ) with little variation across swing phases. There was considerable individual variation in results – one tense subject averaged 11.0% biceps MVC through the 2m putting stroke and others recorded peak mean MVC biceps activations of 68.9% at 50m, 101.3% at 100m, and 111.3% at 150m. Discussion: Previous studies have investigated the role of rotator cuff, spine, and hip muscles during the golf swing however, to our knowledge, this is the first study that investigates the activation of biceps brachii. Many rehabilitation programs following a biceps tenodesis or repair allow active range against gravity and restrict strengthening exercises until 6 weeks, and this does not appear to be associated with any adverse outcome. Previous studies demonstrate a range of < 10% MVC is similar to the unloaded biceps brachii during walking(1), active elbow flexion with the hand positioned either in pronation or supination will produce MVC < 20% throughout range(2) and elbow flexion with a 4kg dumbbell can produce mean MVC’s of around 40%(3). Our study demonstrates that increasing activation is associated with the leading arm, increasing shot distance and the late follow-through phase. Although the cohort mean MVC of the biceps brachii is <10% through the full swing, variability is high and biceps activation reach peak mean MVC’s of over 100% in different swing phases for some individuals. Given these EMG values, caution is advised when advising patients post biceps procedures to return to long distance golf shots, particularly when the leading arm is involved. Even though it would appear that putting would be as safe as having an unloaded hand out of a sling following biceps procedures, the variability of activation patterns across different golfers would lead us to caution against accelerated golf rehabilitation in those who may be particularly tense golfers. The 50m short iron shot was too long to consider as a chip shot and more work can be done in this area to determine the safety of chipping.

Keywords: electromyographic analysis, biceps brachii rupture, golf swing, tendon surgery

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115 Bio-Inspired Information Complexity Management: From Ant Colony to Construction Firm

Authors: Hamza Saeed, Khurram Iqbal Ahmad Khan

Abstract:

Effective information management is crucial for any construction project and its success. Primary areas of information generation are either the construction site or the design office. There are different types of information required at different stages of construction involving various stakeholders creating complexity. There is a need for effective management of information flows to reduce uncertainty creating complexity. Nature provides a unique perspective in terms of dealing with complexity, in particular, information complexity. System dynamics methodology provides tools and techniques to address complexity. It involves modeling and simulation techniques that help address complexity. Nature has been dealing with complex systems since its creation 4.5 billion years ago. It has perfected its system by evolution, resilience towards sudden changes, and extinction of unadaptable and outdated species that are no longer fit for the environment. Nature has been accommodating the changing factors and handling complexity forever. Humans have started to look at their natural counterparts for inspiration and solutions for their problems. This brings forth the possibility of using a biomimetics approach to improve the management practices used in the construction sector. Ants inhabit different habitats. Cataglyphis and Pogonomyrmex live in deserts, Leafcutter ants reside in rainforests, and Pharaoh ants are native to urban developments of tropical areas. Detailed studies have been done on fifty species out of fourteen thousand discovered. They provide the opportunity to study the interactions in diverse environments to generate collective behavior. Animals evolve to better adapt to their environment. The collective behavior of ants emerges from feedback through interactions among individuals, based on a combination of three basic factors: The patchiness of resources in time and space, operating cost, environmental stability, and the threat of rupture. If resources appear in patches through time and space, the response is accelerating and non-linear, and if resources are scattered, the response follows a linear pattern. If the acquisition of energy through food is faster than energy spent to get it, the default is to continue with an activity unless it is halted for some reason. If the energy spent is rather higher than getting it, the default changes to stay put unless activated. Finally, if the environment is stable and the threat of rupture is low, the activation and amplification rate is slow but steady. Otherwise, it is fast and sporadic. To further study the effects and to eliminate the environmental bias, the behavior of four different ant species were studied, namely Red Harvester ants (Pogonomyrmex Barbatus), Argentine ants (Linepithema Humile), Turtle ants (Cephalotes Goniodontus), Leafcutter ants (Genus: Atta). This study aims to improve the information system in the construction sector by providing a guideline inspired by nature with a systems-thinking approach, using system dynamics as a tool. Identified factors and their interdependencies were analyzed in the form of a causal loop diagram (CLD), and construction industry professionals were interviewed based on the developed CLD, which was validated with significance response. These factors and interdependencies in the natural system corresponds with the man-made systems, providing a guideline for effective use and flow of information.

Keywords: biomimetics, complex systems, construction management, information management, system dynamics

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114 Effect of Cerebellar High Frequency rTMS on the Balance of Multiple Sclerosis Patients with Ataxia

Authors: Shereen Ismail Fawaz, Shin-Ichi Izumi, Nouran Mohamed Salah, Heba G. Saber, Ibrahim Mohamed Roushdi

Abstract:

Background: Multiple sclerosis (MS) is a chronic, inflammatory, mainly demyelinating disease of the central nervous system, more common in young adults. Cerebellar involvement is one of the most disabling lesions in MS and is usually a sign of disease progression. It plays a major role in the planning, initiation, and organization of movement via its influence on the motor cortex and corticospinal outputs. Therefore, it contributes to controlling movement, motor adaptation, and motor learning, in addition to its vast connections with other major pathways controlling balance, such as the cerebellopropriospinal pathways and cerebellovestibular pathways. Hence, trying to stimulate the cerebellum by facilitatory protocols will add to our motor control and balance function. Non-invasive brain stimulation, both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), has recently emerged as effective neuromodulators to influence motor and nonmotor functions of the brain. Anodal tDCS has been shown to improve motor skill learning and motor performance beyond the training period. Similarly, rTMS, when used at high frequency (>5 Hz), has a facilitatory effect on the motor cortex. Objective: Our aim was to determine the effect of high-frequency rTMS over the cerebellum in improving balance and functional ambulation of multiple sclerosis patients with Ataxia. Patients and methods: This was a randomized single-blinded placebo-controlled prospective trial on 40 patients. The active group (N=20) received real rTMS sessions, and the control group (N=20) received Sham rTMS using a placebo program designed for this treatment. Both groups received 12 sessions of high-frequency rTMS over the cerebellum, followed by an intensive exercise training program. Sessions were given three times per week for four weeks. The active group protocol had a frequency of 10 Hz rTMS over the cerebellar vermis, work period 5S, number of trains 25, and intertrain interval 25s. The total number of pulses was 1250 pulses per session. The control group received Sham rTMS using a placebo program designed for this treatment. Both groups of patients received an intensive exercise program, which included generalized strengthening exercises, endurance and aerobic training, trunk abdominal exercises, generalized balance training exercises, and task-oriented training such as Boxing. As a primary outcome measure the Modified ICARS was used. Static Posturography was done with: Patients were tested both with open and closed eyes. Secondary outcome measures included the expanded Disability Status Scale (EDSS) and 8 Meter walk test (8MWT). Results: The active group showed significant improvements in all the functional scales, modified ICARS, EDSS, and 8-meter walk test, in addition to significant differences in static Posturography with open eyes, while the control group did not show such differences. Conclusion: Cerebellar high-frequency rTMS could be effective in the functional improvement of balance in MS patients with ataxia.

Keywords: brain neuromodulation, high frequency rTMS, cerebellar stimulation, multiple sclerosis, balance rehabilitation

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113 Anesthesia for Spinal Stabilization Using Neuromuscular Blocking Agents in Dog: Case Report

Authors: Agata Migdalska, Joanna Berczynska, Ewa Bieniek, Jacek Sterna

Abstract:

Muscle relaxation is considered important during general anesthesia for spine stabilization. In a presented case peripherally acting muscle relaxant was applied during general anesthesia for spine stabilization surgery. The patient was a dog, 11-years old, 26 kg, male, mix breed. Spine fracture was situated between Th13-L1-L2, probably due to the car accident. Preanesthetic physical examination revealed no sign underlying health issues. The dog was premedicated with midazolam 0.2 mg IM and butorphanol 2.4 mg IM. General anesthesia was induced with propofol IV. After the induction, the dog was intubated with an endotracheal tube and connected to an open-ended rebreathing system and maintained with the use of inhalation anesthesia with isoflurane in oxygen. 0,5 mg/ kg of rocuronium was given IV. Use of muscle relaxant was accompanied by an assessment of the degree of neuromuscular blockade by peripheral nerve stimulator. Electrodes were attached to the skin overlying at the peroneal nerve at the lateral cranial tibia. Four electrical pulses were applied to the nerve over a 2 second period. When satisfying nerve block was detected dog was prepared for the surgery. No further monitoring of the effectiveness of blockade was performed during surgery. Mechanical ventilation was kept during anesthesia. During surgery dog maintain stable, and no anesthesiological complication occur. Intraoperatively surgeon claimed that neuromuscular blockade results in a better approach to the spine and easier muscle manipulation which was helpful in order to see the fracture and replace bone fragments. Finally, euthanasia was performed intraoperatively as a result of vast myelomalacia process of the spinal cord. This prevented examination of the recovering process. Neuromuscular blocking agents act at the neuromuscular junction to provide profound muscle relaxation throughout the body. Muscle blocking agents are neither anesthetic nor analgesic; therefore inappropriately used may cause paralysis in fully conscious and feeling pain patient. They cause paralysis of all skeletal muscles, also diaphragm and intercostal muscles when given in higher doses. Intraoperative management includes maintaining stable physiological conditions, which involves adjusting hemodynamic parameters, ensuring proper ventilation, avoiding variations in temperature, maintain normal blood flow to promote proper oxygen exchange. Neuromuscular blocking agent can cause many side effects like residual paralysis, anaphylactic or anaphylactoid reactions, delayed recovery from anesthesia, histamine release, recurarization. Therefore reverse drug like neostigmine (with glikopyrolat) or edrofonium (with atropine) should be used in case of a life-threatening situation. Another useful drug is sugammadex, although the cost of this drug strongly limits its use. Muscle relaxant improves surgical conditions during spinal surgery, especially in heavily muscled individuals. They are also used to facilitate the replacement of dislocated joints as they improve conditions during fracture reduction. It is important to emphasize that in a patient with muscle weakness neuromuscular blocking agents may result in intraoperative and early postoperative cardiovascular and respiratory complications, as well as prolonged recovery from anesthesia. This should not appear in patients with recent spine fracture or luxation. Therefore it is believed that neuromuscular blockers could be useful during spine stabilization procedures.

Keywords: anesthesia, dog, neuromuscular block, spine surgery

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112 Phenotype and Psychometric Characterization of Phelan-Mcdermid Syndrome Patients

Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

Abstract:

Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

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111 From Modelled Design to Reality through Material and Machinery Lab and Field Tests: Porous Concrete Carparks at the Wanda Metropolitano Stadium in Madrid

Authors: Manuel de Pazos-Liano, Manuel Cifuentes-Antonio, Juan Fisac-Gozalo, Sara Perales-Momparler, Carlos Martinez-Montero

Abstract:

The first-ever game in the Wanda Metropolitano Stadium, the new home of the Club Atletico de Madrid, was played on September 16, 2017, thanks to the work of a multidisciplinary team that made it possible to combine urban development with sustainability goals. The new football ground sits on a 1.2 km² land owned by the city of Madrid. Its construction has dramatically increased the sealed area of the site (transforming the runoff coefficient from 0.35 to 0.9), and the surrounding sewer network has no capacity for that extra flow. As an alternative to enlarge the existing 2.5 m diameter pipes, it was decided to detain runoff on site by means of an integrated and durable infrastructure that would not blow up the construction cost nor represent a burden on the municipality’s maintenance tasks. Instead of the more conventional option of building a large concrete detention tank, the decision was taken on the use of pervious pavement on the 3013 car parking spaces for sub-surface water storage, a solution aligned with the city water ordinance and the Madrid + Natural project. Making the idea a reality, in only five months and during the summer season (which forced to pour the porous concrete only overnight), was a challenge never faced before in Spain, that required of innovation both at the material as well as the machinery side. The process consisted on: a) defining the characteristics required for the porous concrete (compressive strength of 15 N/mm2 and 20% voids); b) testing of different porous concrete dosages at the construction company laboratory; c) stablishing the cross section in order to provide structural strength and sufficient water detention capacity (20 cm porous concrete over a 5 cm 5/10 gravel, that sits on a 50 cm coarse 40/50 aggregate sub-base separated by a virgin fiber polypropylene geotextile fabric); d) hydraulic computer modelling (using the Full Hydrograph Method based on the Wallingford Procedure) to estimate design peak flows decrease (an average of 69% at the three car parking lots); e) use of a variety of machinery for the application of the porous concrete to achieve both structural strength and permeable surface (including an inverse rotating rolling imported from USA, and the so-called CMI, a sliding concrete paver used in the construction of motorways with rigid pavements); f) full-scale pilots and final construction testing by an accredited laboratory (pavement compressive strength average value of 15 N/mm2 and 0,0032 m/s permeability). The continuous testing and innovating construction process explained in detail within this article, allowed for a growing performance with time, finally proving the use of the CMI valid also for large porous car park applications. All this process resulted in a successful story that converts the Wanda Metropolitano Stadium into a great demonstration site that will help the application of the Spanish Royal Decree 638/2016 (it also counts with rainwater harvesting for grass irrigation).

Keywords: construction machinery, permeable carpark, porous concrete, SUDS, sustainable develpoment

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110 Hybrid Materials on the Basis of Magnetite and Magnetite-Gold Nanoparticles for Biomedical Application

Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko

Abstract:

During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.

Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity

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109 Application of Electrical Resistivity Surveys on Constraining Causes of Highway Pavement Failure along Ajaokuta-Anyigba Road, North Central Nigeria

Authors: Moroof, O. Oloruntola, Sunday Oladele, Daniel, O. Obasaju, Victor, O Ojekunle, Olateju, O. Bayewu, Ganiyu, O. Mosuro

Abstract:

Integrated geophysical methods involving Vertical Electrical Sounding (VES) and 2D resistivity survey were deployed to gain an insight into the influence of the two varying rock types (mica-schist and granite gneiss) underlying the road alignment to the incessant highway failure along Ajaokuta-Anyigba, North-central Nigeria. The highway serves as a link-road for the single largest cement factory in Africa (Dangote Cement Factory) and two major ceramic industries to the capital (Abuja) via Lokoja. 2D Electrical Resistivity survey (Dipole-Dipole Array) and Vertical Electrical Sounding (VES) (Schlumberger array) were employed. Twenty-two (22) 2D profiles were occupied, twenty (20) conducted about 1 m away from the unstable section underlain by mica-schist with profile length each of approximately 100 m. Two (2) profiles were conducted about 1 m away from the stable section with a profile length of 100 m each due to barriers caused by the drainage system and outcropping granite gneiss at the flanks of the road. A spacing of 2 m was used for good image resolution of the near-surface. On each 2D profile, a range of 1-3 VES was conducted; thus, forty-eight (48) soundings were acquired. Partial curve matching and WinResist software were used to obtain the apparent and true resistivity values of the 1D survey, while DiprofWin software was used for processing the 2-D survey. Two exposed lithologic sections caused by abandoned river channels adjacent to two profiles as well as the knowledge of the geology of the area helped to constrain the VES and 2D processing and interpretation. Generally, the resistivity values obtained reflect the parent rock type, degree of weathering, moisture content and competency of the tested area. Resistivity values < 100; 100 – 950; 1000 – 2000 and > 2500 ohms-m were interpreted as clay, weathered layer, partly weathered layer and fresh basement respectively. The VES results and 2-D resistivity structures along the unstable segment showed similar lithologic characteristics and sequences dominated by clayey substratum for depths range of 0 – 42.2 m. The clayey substratum is a product of intensive weathering of the parent rock (mica-schist) and constitutes weak foundation soils, causing highway failure. This failure is further exacerbated by several heavy-duty trucks which ply the section round the clock due to proximity to two major ceramic industries in the state and lack of drainage system. The two profiles on the stable section show 2D structures that are remarkably different from those of the unstable section with very thin topsoils, higher resistivity weathered substratum (indicating the presence of coarse fragments from the parent rock) and shallow depth to the basement (1.0 – 7. 1 m). Also, the presence of drainage and lower volume of heavy-duty trucks are contributors to the pavement stability of this section of the highway. The resistivity surveys effectively delineated two contrasting soil profiles of the subbase/subgrade that reflect variation in the mineralogy of underlying parent rocks.

Keywords: clay, geophysical methods, pavement, resistivity

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108 Preliminary Results on a Study of Antimicrobial Susceptibility Testing of Bacillus anthracis Strains Isolated during Anthrax Outbreaks in Italy from 2001 to 2017

Authors: Viviana Manzulli, Luigina Serrecchia, Adelia Donatiello, Valeria Rondinone, Sabine Zange, Alina Tscherne, Antonio Parisi, Antonio Fasanella

Abstract:

Anthrax is a zoonotic disease that affects a wide range of animal species (primarily ruminant herbivores), and can be transmitted to humans through consumption or handling of contaminated animal products. The etiological agent B.anthracis is able to survive in unfavorable environmental conditions by forming endospore which remain viable in the soil for many decades. Furthermore, B.anthracis is considered as one of the most feared agents to be potentially misused as a biological weapon and the importance of the disease and its treatment in humans has been underscored before the bioterrorism events in the United States in 2001. Due to the often fatal outcome of human cases, antimicrobial susceptibility testing plays especially in the management of anthrax infections an important role. In Italy, animal anthrax is endemic (predominantly found in the southern regions and on islands) and is characterized by sporadic outbreaks occurring mainly during summer. Between 2012 and 2017 single human cases of cutaneous anthrax occurred. In this study, 90 diverse strains of B.anthracis, isolated in Italy from 2001 to 2017, were screened to their susceptibility to sixteen clinically relevant antimicrobial agents by using the broth microdilution method. B.anthracis strains selected for this study belong to the strain collection stored at the Anthrax Reference Institute of Italy located inside the Istituto Zooprofilattico Sperimentale of Puglia and Basilicata. The strains were isolated at different time points and places from various matrices (human, animal and environmental). All strains are a representative of over fifty distinct MLVA 31 genotypes. The following antibiotics were used for testing: gentamicin, ceftriaxone, streptomycin, penicillin G, clindamycin, chloramphenicol, vancomycin, linezolid, cefotaxime, tetracycline, erythromycin, rifampin, amoxicillin, ciprofloxacin, doxycycline and trimethoprim. A standard concentration of each antibiotic was prepared in a specific diluent, which were then twofold serial diluted. Therefore, each wells contained: bacterial suspension of 1–5x104 CFU/mL in Mueller-Hinton Broth (MHB), the antibiotic to be tested at known concentration and resazurin, an indicator of cell growth. After incubation overnight at 37°C, the wells were screened for color changes caused by the resazurin: a change from purple to pink/colorless indicated cell growth. The lowest concentration of antibiotic that prevented growth represented the minimal inhibitory concentration (MIC). This study suggests that B.anthracis remains susceptible in vitro to many antibiotics, in addition to doxycycline (MICs ≤ 0,03 µg/ml), ciprofloxacin (MICs ≤ 0,03 µg/ml) and penicillin G (MICs ≤ 0,06 µg/ml), recommend by CDC for the treatment of human cases and for prophylactic use after exposure to the spores. In fact, the good activity of gentamicin (MICs ≤ 0,25 µg/ml), streptomycin (MICs ≤ 1 µg/ml), clindamycin (MICs ≤ 0,125 µg/ml), chloramphenicol(MICs ≤ 4 µg/ml), vancomycin (MICs ≤ 2 µg/ml), linezolid (MICs ≤ 2 µg/ml), tetracycline (MICs ≤ 0,125 µg/ml), erythromycin (MICs ≤ 0,25 µg/ml), rifampin (MICs ≤ 0,25 µg/ml), amoxicillin (MICs ≤ 0,06 µg/ml), towards all tested B.anthracis strains demonstrates an appropriate alternative choice for prophylaxis and/or treatment. All tested B.anthracis strains showed intermediate susceptibility to the cephalosporins (MICs ≥ 16 µg/ml) and resistance to trimethoprim (MICs ≥ 128 µg/ml).

Keywords: Bacillus anthracis, antibiotic susceptibility, treatment, minimum inhibitory concentration

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