Search results for: Michael J. Tait
217 Biochemical Characterization and Structure Elucidation of a New Cytochrome P450 Decarboxylase
Authors: Leticia Leandro Rade, Amanda Silva de Sousa, Suman Das, Wesley Generoso, Mayara Chagas Ávila, Plinio Salmazo Vieira, Antonio Bonomi, Gabriela Persinoti, Mario Tyago Murakami, Thomas Michael Makris, Leticia Maria Zanphorlin
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Alkenes have an economic appeal, especially in the biofuels field, since they are precursors for drop-in biofuels production, which have similar chemical and physical properties to the conventional fossil fuels, with no oxygen in their composition. After the discovery of the first P450 CYP152 OleTJE in 2011, reported with its unique property of decarboxylating fatty acids (FA), by using hydrogen peroxide as a cofactor and producing 1-alkenes as the main product, the scientific and technological interest in this family of enzymes vastly increased. In this context, the present work presents a new decarboxylase (OleTRN) with low similarity with OleTJE (32%), its biochemical characterization, and structure elucidation. As main results, OleTRN presented a high yield of expression and purity, optimum reaction conditions at 35 °C and pH from 6.5 to 8.0, and higher specificity for oleic acid. Besides that, structure-guided mutations were performed and according to the functional characterizations, it was observed that some mutations presented different specificity and chemoselectivity by varying the chain-length of FA substrates from 12 to 20 carbons. These results are extremely interesting from a biotechnological perspective as those characteristics could diversify the applications and contribute to designing better cytochrome P450 decarboxylases. Considering that peroxygenases have the potential activity of decarboxylating and hydroxylating fatty acids and that the elucidation of the intriguing mechanistic involved in the decarboxylation preferential from OleTJE is still a challenge, the elucidation of OleTRN structure and the functional characterizations of OleTRN and its mutants contribute to new information about CYP152. Besides that, the work also contributed to the discovery of a new decarboxylase with a different selectivity profile from OleTJE, which allows a wide range of applications.Keywords: P450, decarboxylases, alkenes, biofuels
Procedia PDF Downloads 202216 Combine Resection of Talocalcaneal Tarsal Coalition and Calcaneal Lengthening Osteotomy. Short-to-Intermediate Term Results
Authors: Naum Simanovsky, Vladimir Goldman, Michael Zaidman
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Background: The optimal algorithm for the management of symptomatic tarsal coalition is still under discussion in pediatric literature. It's debatable what surgical steps are essential to achieve the best outcome. Method: The investigators retrospectively reviewed the records of twelve patients with symptomatic tarsal coalition that were treated operatively between 2017 and 2019. Only painful flat feet were operated. Two patients were excluded from the study due to lack of sufficient follow-up. Ten of eleven feet were treated with the combination of calcaneal lengthening osteotomy (CLO) and resection of coalition (RC). Only one foot was operated with CLO alone. In half of our patients, Achilles lengthening was performed. For two children, medial plication was added. Short leg cast was applied to all children for 6-8 weeks, and soft shoe insoles for medial arch support were prescribed after. Demographic, clinical, and radiographic records were reviewed. The outcome was evaluated using American Orthopedic Foot and Ankle Society (AOFAS) Ankle Hindfoot Score. Results: There were seven boys and three girls. The mean age at the time of surgery was 13.9 (range 12 to 17) years, and the mean follow-up was 18 (range 8 to 34) months. The early complications included one superficial wound infection and dehiscence. Late complication includes two children with residual forefoot supination. None of our patients required additional operations during the follow-up period. All feet achieved complete deformity correction or dramatic improvement. In the last follow-up, seven feet were painless, and four children had some mild pain after intensive activities. All feet achieved excellent and good scoring on AOFAS. Conclusions: Many patients with talocalcaneal coalition also have rigid or stiff, painful, flat feet. For these patients, the resection of coalition with concomitant CLO can be safely recommended.Keywords: Tarsal coalition, calcaneal lengthening osteotomy., flat foot, coalition resection
Procedia PDF Downloads 65215 Combined Tarsal Coalition Resection and Arthroereisis in Treatment of Symptomatic Rigid Flat Foot in Pediatric Population
Authors: Michael Zaidman, Naum Simanovsky
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Introduction. Symptomatic tarsal coalition with rigid flat foot often demands operative solution. An isolated coalition resection does not guarantee pain relief; correction of co-existing foot deformity may be required. The objective of the study was to analyze the results of combination of tarsal coalition resection and arthroereisis. Patients and methods. We retrospectively reviewed medical records and radiographs of children operatively treated in our institution for symptomatic calcaneonavicular or talocalcaneal coalition between the years 2019 and 2022. Eight patients (twelve feet), 4 boys and 4 girls with mean age 11.2 years, were included in the study. In six patients (10 feet) calcaneonavicular coalition was diagnosed, two patients (two feet) sustained talonavicular coalition. To quantify degrees of foot deformity, we used calcaneal pitch angle, lateral talar-first metatarsal (Meary's) angle, and talonavicular coverage angle. The clinical results were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle Hindfoot Score. Results. The mean follow-up was 28 month. The preoperative mean talonavicular coverage angle was 17,75º as compared with postoperative mean angle of 5.4º. The calcaneal pitch angle improved from mean 6,8º to 16,4º. The mean preoperative Meary’s angle of -11.3º improved to mean 2.8º. The preoperative mean AOFAS score improved from 54.7 to 93.1 points post-operatively. In nine of twelve feet, overall clinical outcome judged by AOFAS scale was excellent (90-100 points), in three feet was good (80-90 points). Six patients (ten feet) obviously improved their subtalar range of motion. Conclusion. For symptomatic stiff or rigid flat feet associated with tarsal coalition, the combination of coalition resection and arthroereisis leads to normalization of radiographic parameters, clinical and functional improvement with good patient’s satisfaction and likely to be more effective than the isolated procedures.Keywords: rigid flat foot, tarsal coalition resection, arthroereisis, outcome
Procedia PDF Downloads 64214 Development of an Optimised, Automated Multidimensional Model for Supply Chains
Authors: Safaa H. Sindi, Michael Roe
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This project divides supply chain (SC) models into seven Eras, according to the evolution of the market’s needs throughout time. The five earliest Eras describe the emergence of supply chains, while the last two Eras are to be created. Research objectives: The aim is to generate the two latest Eras with their respective models that focus on the consumable goods. Era Six contains the Optimal Multidimensional Matrix (OMM) that incorporates most characteristics of the SC and allocates them into four quarters (Agile, Lean, Leagile, and Basic SC). This will help companies, especially (SMEs) plan their optimal SC route. Era Seven creates an Automated Multidimensional Model (AMM) which upgrades the matrix of Era six, as it accounts for all the supply chain factors (i.e. Offshoring, sourcing, risk) into an interactive system with Heuristic Learning that helps larger companies and industries to select the best SC model for their market. Methodologies: The data collection is based on a Fuzzy-Delphi study that analyses statements using Fuzzy Logic. The first round of Delphi study will contain statements (fuzzy rules) about the matrix of Era six. The second round of Delphi contains the feedback given from the first round and so on. Preliminary findings: both models are applicable, Matrix of Era six reduces the complexity of choosing the best SC model for SMEs by helping them identify the best strategy of Basic SC, Lean, Agile and Leagile SC; that’s tailored to their needs. The interactive heuristic learning in the AMM of Era seven will help mitigate error and aid large companies to identify and re-strategize the best SC model and distribution system for their market and commodity, hence increasing efficiency. Potential contributions to the literature: The problematic issue facing many companies is to decide which SC model or strategy to incorporate, due to the many models and definitions developed over the years. This research simplifies this by putting most definition in a template and most models in the Matrix of era six. This research is original as the division of SC into Eras, the Matrix of Era six (OMM) with Fuzzy-Delphi and Heuristic Learning in the AMM of Era seven provides a synergy of tools that were not combined before in the area of SC. Additionally the OMM of Era six is unique as it combines most characteristics of the SC, which is an original concept in itself.Keywords: Leagile, automation, heuristic learning, supply chain models
Procedia PDF Downloads 389213 Epidemiology of Private Prehospital Calls over the Last Decade in South Africa
Authors: Rhodine Hickman, Craig Wylie, Michael G. McCaul
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Introduction: The World Health Organisation has called on governments around the world to recognise emergency conditions as a global public health problem and respond with appropriate steps for effective preventative strategies. However, to understand the magnitude of the problem, good quality epidemiological data is required. This is especially challenging in low and middle-income countries, where routine data is scarce, specifically within the prehospital setting. Methods: We conducted a retrospective cross-sectional study of a national prehospital private sector EMS database. The database being the property of ER24 (private Emergency Medical Services (EMS) company in South Africa) contains claims submitted by the majority of ambulance services in South Africa during the period between 1 January 2008 to 28 March 2017. We used descriptive statistics and control charts to describe the data using STATA 14. Results: 299,257 calls were included in the analysis. The top clinical conditions requiring ambulance transport were transport accidents (10% of total call volume) and ischaemic heart disease (4.4%). The number of transport accidents consistently increased between 2009 and 2014 and reached beyond the limit for normal variation in 2015. Victims of transport accidents required basic life support services 60% of the time with 80% of injuries being minor to moderate. The frequency of ischaemic heart disease had a steady incline from 2011 to 2016. Advanced life support services were required about 50% of the time, with 60% of patients needing urgent care. Conclusion: Transport accidents, followed by ischaemic heart disease, are the most prevalent conditions in South African private EMS. There is a potential to address these conditions by developing the capacity of low and mid-level providers in trauma and advanced EMS providers in ischaemic heart disease.Keywords: emergency care, emergency medicine, prehospital providers, South Africa
Procedia PDF Downloads 175212 Assessment of the Possible Effects of Biological Control Agents of Lantana camara and Chromolaena odorata in Davao City, Mindanao, Philippines
Authors: Cristine P. Canlas, Crislene Mae L. Gever, Patricia Bea R. Rosialda, Ma. Nina Regina M. Quibod, Perry Archival C. Buenavente, Normandy M. Barbecho, Cynthia Adeline A. Layusa, Michael Day
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Invasive plants have an impact on global biodiversity and ecosystem function, and their management is a complex and formidable task. Two of these invasive plant species, Lantana camara and Chromolaena odorata, are found in the Philippines. Lantana camara has the ability to suppress the growth of and outcompete neighboring plants. Chromolaena odorata causes serious agricultural and economical damage and causes fire hazards during dry season. In addition, both species has been reported to poison livestock. One of the known global management strategies to control invasive plants is the introduction of biological control agents. These natural enemies of the invasive plants reduce population density and impacts of the invasive plants, resulting in the balance of the nature in their invasion. Through secondary data sources, interviews, and field validation (e.g. microhabitat searches, sweep netting, opportunistic sampling, photo-documentation), we investigated whether the biocontrol agents previously released by the Philippine Coconut Authority (PCA) in their Davao Research Center to control these invasive plants are still present and are affecting their respective host weeds. We confirm the presence of the biocontrol agent of L. camara, Uroplata girardi, which was introduced in 1985, and Cecidochares connexa, a biocontrol agent of C. odorata released in 2003. Four other biocontrol agents were found to affect L. camara. Signs of damage (e.g. stem galls in C. odorata, and leaf mines in L. camara) signify that these biocontrol agents have successfully established outside of their release site in Davao. Further investigating the extent of the spread of these biocontrol agents in the Philippines and their damage to the two weeds will contribute to the management of invasive plant species in the country.Keywords: invasive alien species, biological control agent, entomology, worst weeds
Procedia PDF Downloads 374211 Assessing Smallholder Rice and Vegetable Farmers’ Constraints and Needs to Adopt Small-Scale Irrigation in South Tongu District, Ghana
Authors: Tamekloe Michael Kossivi, Kenichi Matsui
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Irrigation access is one of the essential rural development investment options that can significantly improve smallholder farmers’ agriculture productivity. Investment in irrigation infrastructural development to supply adequate water could improve food security, growth in income for farmers, poverty alleviation, and improve business and livelihood. This paper assesses smallholder farmers’ constraints and the needs to adopt small-scale irrigation for crops production in the South Tongu District of Ghana. The data collection involved database search, questionnaire survey, interview, and field work. The structured questionnaire survey was administered from September to November 2020 among 120 respondents in six purposively sampled irrigation communities in the District. The questions focused on small-scale irrigation development constraints and needs. As a result, we found that the respondents relied mainly on rainfall for agriculture production. They did not have adequate irrigation access. Even though the District is blessed with open arable lands and rich water sources for rice and vegetable production on a massive scale, water sources like the Lower Volta River, Tordzi River, and Avu Lagoon were not close enough to the respondents. The respondents faced inadequate credit support (100%), unreliable rainfall (76%), insufficient water supply (54%), and unreliable water delivery challenges on their farms (53%). Physical constraints for the respondents to adopt irrigation included flood (77%), drought (93%), inadequate irrigation technology (59%), and insufficient technical know-how (65%). Farmers were interested in investing in irrigation infrastructural development to enhance productivity on their farms only if they own the farmlands. External support from donors on irrigation systems did not allow smallholder farmers to control irrigation facilities.Keywords: constraints, food security, needs, smallholder farmers, small-scale irrigation
Procedia PDF Downloads 137210 The Impact of Garlic and Citrus Extracts on Energy Retention and Methane Production in Ruminants in vitro
Authors: Michael Graz, Natasha Hurril, Andrew Shearer
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Research on feed supplementation with natural compounds is currently being intensively pursued with a view to improving energy utilisation in ruminants and mitigating the production of methane by these animals. Towards this end, a novel combination of extracts from garlic and bitter orange was therefore selected for trials on the basis of their previously published in vitro anti-methanogenic potential. Three separate in vitro experiments were conducted to determine energy utilisation and greenhouse gas production. These included use of rumen fluid from fistulated cows and sheep in batch culture, the Hohenheim gas test, and the Rusitec technique. Experimental and control arms were utilised, with 5g extracts per kilogram of total dietary dry matter (0.05g/kg active compounds) being used to supplement or not supplement the in vitro systems. Respiratory measurements were conducted on experimental day 1 for the batch culture and Hohenheim gas test and on day 14-21 for the Rusitec Technique (in a 21-day trial). Measurements included methane (CH4) production, total volatile fatty acid (VFA) concentration, molar proportions of acetate, propionate and butyrate and degradation of organic matter (Rusitec). CH4 production was reduced by 82% (±16%), 68% (±11%) and 37% (±4%) in the batch culture, Hohenheim gas test and Rusitec, respectively. Total VFA production was reduced by 13% (±2%) and 2% (±0.1%) in the batch culture and Hohenheim gas test whilst it was increased by 8% (±2%) in the Rusitec. Total VFA production was reduced in all tests between 2 and 10%, whilst acetate production was reduced between 10% and 29%. Propionate production which is an indicator of weight gain was increased in all cases between 16% and 30%. Butyrate production which is considered an indicator of potential milk yield was increased by between 6 and 11%. Degradation of organic matter in the Rusitec experiments was improved by 10% (±0.1%). In conclusion, the study demonstrated the potential of the combination of garlic and citrus extracts to improve digestion, enhance body energy retention and limit CH4 formation in relation to feed intake.Keywords: citrus, garlic, methane, ruminants
Procedia PDF Downloads 330209 A Multi-Criteria Decision Method for the Recruitment of Academic Personnel Based on the Analytical Hierarchy Process and the Delphi Method in a Neutrosophic Environment
Authors: Antonios Paraskevas, Michael Madas
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For a university to maintain its international competitiveness in education, it is essential to recruit qualitative academic staff as it constitutes its most valuable asset. This selection demonstrates a significant role in achieving strategic objectives, particularly by emphasizing a firm commitment to the exceptional student experience and innovative teaching and learning practices of high quality. In this vein, the appropriate selection of academic staff establishes a very important factor of competitiveness, efficiency and reputation of an academic institute. Within this framework, our work demonstrates a comprehensive methodological concept that emphasizes the multi-criteria nature of the problem and how decision-makers could utilize our approach in order to proceed to the appropriate judgment. The conceptual framework introduced in this paper is built upon a hybrid neutrosophic method based on the Neutrosophic Analytical Hierarchy Process (N-AHP), which uses the theory of neutrosophy sets and is considered suitable in terms of a significant degree of ambiguity and indeterminacy observed in the decision-making process. To this end, our framework extends the N-AHP by incorporating the Neutrosophic Delphi Method (N-DM). By applying the N-DM, we can take into consideration the importance of each decision-maker and their preferences per evaluation criterion. To the best of our knowledge, the proposed model is the first which applies the Neutrosophic Delphi Method in the selection of academic staff. As a case study, it was decided to use our method for a real problem of academic personnel selection, having as the main goal to enhance the algorithm proposed in previous scholars’ work, and thus taking care of the inherent ineffectiveness which becomes apparent in traditional multi-criteria decision-making methods when dealing with situations alike. As a further result, we prove that our method demonstrates greater applicability and reliability when compared to other decision models.Keywords: multi-criteria decision making methods, analytical hierarchy process, delphi method, personnel recruitment, neutrosophic set theory
Procedia PDF Downloads 117208 Electron Beam Melting Process Parameter Optimization Using Multi Objective Reinforcement Learning
Authors: Michael A. Sprayberry, Vincent C. Paquit
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Process parameter optimization in metal powder bed electron beam melting (MPBEBM) is crucial to ensure the technology's repeatability, control, and industry-continued adoption. Despite continued efforts to address the challenges via the traditional design of experiments and process mapping techniques, there needs to be more successful in an on-the-fly optimization framework that can be adapted to MPBEBM systems. Additionally, data-intensive physics-based modeling and simulation methods are difficult to support by a metal AM alloy or system due to cost restrictions. To mitigate the challenge of resource-intensive experiments and models, this paper introduces a Multi-Objective Reinforcement Learning (MORL) methodology defined as an optimization problem for MPBEBM. An off-policy MORL framework based on policy gradient is proposed to discover optimal sets of beam power (P) – beam velocity (v) combinations to maintain a steady-state melt pool depth and phase transformation. For this, an experimentally validated Eagar-Tsai melt pool model is used to simulate the MPBEBM environment, where the beam acts as the agent across the P – v space to maximize returns for the uncertain powder bed environment producing a melt pool and phase transformation closer to the optimum. The culmination of the training process yields a set of process parameters {power, speed, hatch spacing, layer depth, and preheat} where the state (P,v) with the highest returns corresponds to a refined process parameter mapping. The resultant objects and mapping of returns to the P-v space show convergence with experimental observations. The framework, therefore, provides a model-free multi-objective approach to discovery without the need for trial-and-error experiments.Keywords: additive manufacturing, metal powder bed fusion, reinforcement learning, process parameter optimization
Procedia PDF Downloads 90207 The Interactions between Phosphorus Leaching and Lime Application in Undisturbed Soil Columns with Different Soil Textures
Authors: Faezeh Eslamian, Zhiming Qi, Michael J. Tate
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Phosphorus losses from agricultural fields through leaching is one of the main contributors to eutrophication of lakes in Quebec as well as North America. The main objective of this study is to evaluate the application of high calcium hydrated lime as a soil amendment in reducing the subsurface transport of phosphorus to water bodies by studying the interactions between phosphorus leaching and lime application in three common agricultural soil textures (sandy loam, loam and clay loam) in Quebec. For this purpose, 6 intact soil columns of 10 cm diameter and 20 cm deep were taken from each of the three different soil textured agricultural fields. Lime (high calcium hydrated lime) was applied to the top 5 cm of half of the intact soil columns while the rest were left as controls. The columns were leached with artificial rainwater in-consecutively at a rate of 3 mm h-1 over a 90-day period. The total amount of water added was equal to the average total rainfall of the region in fall. The leachate samples were collected daily and analyzed for dissolved reactive phosphorus, total dissolved phosphorus, total phosphorus, pH, electrical conductivity, calcium, magnesium, potassium and iron. The results showed that lime was able to significantly reduce dissolved reactive phosphorus concentrations in the leachates by 70 and 40 percent in sandy loam and loam soil columns, respectively, while phosphorus concentration in the clay loam soil leachates were increased by 40 percent. The calcium in lime has P-binding capabilities. Soil chemical properties in sandy and loamy soils can affect phosphorus leaching, whereas, transport mechanisms in clay soils with macropores dominate phosphorus leaching behaviors. The presence of preferential pathways and cracks in the clay soil columns has led to a quick transport of phosphorus through the soil and the less contact time with the soil matrix, therefore, causing less opportunity for P sorption and larger P release. Application of lime to agricultural fields can be considered as a promising measure in mitigating phosphorus loss from sandy loam and loam soils.Keywords: leaching, lime, phosphorus, soil texture
Procedia PDF Downloads 175206 A Multi-criteria Decision Method For The Recruitment Of Academic Personnel Based On The Analytical Hierarchy Process And The Delphi Method In A Neutrosophic Environment (Full Text)
Authors: Antonios Paraskevas, Michael Madas
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For a university to maintain its international competitiveness in education, it is essential to recruit qualitative academic staff as it constitutes its most valuable asset. This selection demonstrates a significant role in achieving strategic objectives, particularly by emphasizing a firm commitment to exceptional student experience and innovative teaching and learning practices of high quality. In this vein, the appropriate selection of academic staff establishes a very important factor of competitiveness, efficiency and reputation of an academic institute. Within this framework, our work demonstrates a comprehensive methodological concept that emphasizes on the multi-criteria nature of the problem and on how decision makers could utilize our approach in order to proceed to the appropriate judgment. The conceptual framework introduced in this paper is built upon a hybrid neutrosophic method based on the Neutrosophic Analytical Hierarchy Process (N-AHP), which uses the theory of neutrosophy sets and is considered suitable in terms of significant degree of ambiguity and indeterminacy observed in decision-making process. To this end, our framework extends the N-AHP by incorporating the Neutrosophic Delphi Method (N-DM). By applying the N-DM, we can take into consideration the importance of each decision-maker and their preferences per evaluation criterion. To the best of our knowledge, the proposed model is the first which applies Neutrosophic Delphi Method in the selection of academic staff. As a case study, it was decided to use our method to a real problem of academic personnel selection, having as main goal to enhance the algorithm proposed in previous scholars’ work, and thus taking care of the inherit ineffectiveness which becomes apparent in traditional multi-criteria decision-making methods when dealing with situations alike. As a further result, we prove that our method demonstrates greater applicability and reliability when compared to other decision models.Keywords: analytical hierarchy process, delphi method, multi-criteria decision maiking method, neutrosophic set theory, personnel recruitment
Procedia PDF Downloads 200205 Understanding the Fundamental Driver of Semiconductor Radiation Tolerance with Experiment and Theory
Authors: Julie V. Logan, Preston T. Webster, Kevin B. Woller, Christian P. Morath, Michael P. Short
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Semiconductors, as the base of critical electronic systems, are exposed to damaging radiation while operating in space, nuclear reactors, and particle accelerator environments. What innate property allows some semiconductors to sustain little damage while others accumulate defects rapidly with dose is, at present, poorly understood. This limits the extent to which radiation tolerance can be implemented as a design criterion. To address this problem of determining the driver of semiconductor radiation tolerance, the first step is to generate a dataset of the relative radiation tolerance of a large range of semiconductors (exposed to the same radiation damage and characterized in the same way). To accomplish this, Rutherford backscatter channeling experiments are used to compare the displaced lattice atom buildup in InAs, InP, GaP, GaN, ZnO, MgO, and Si as a function of step-wise alpha particle dose. With this experimental information on radiation-induced incorporation of interstitial defects in hand, hybrid density functional theory electron densities (and their derived quantities) are calculated, and their gradient and Laplacian are evaluated to obtain key fundamental information about the interactions in each material. It is shown that simple, undifferentiated values (which are typically used to describe bond strength) are insufficient to predict radiation tolerance. Instead, the curvature of the electron density at bond critical points provides a measure of radiation tolerance consistent with the experimental results obtained. This curvature and associated forces surrounding bond critical points disfavors localization of displaced lattice atoms at these points, favoring their diffusion toward perfect lattice positions. With this criterion to predict radiation tolerance, simple density functional theory simulations can be conducted on potential new materials to gain insight into how they may operate in demanding high radiation environments.Keywords: density functional theory, GaN, GaP, InAs, InP, MgO, radiation tolerance, rutherford backscatter channeling
Procedia PDF Downloads 174204 Isolation and Characterization of the First Known Inhibitor Cystine Knot Peptide in Sea Anemone: Inhibitory Activity on Acid-Sensing Ion Channels
Authors: Armando A. Rodríguez, Emilio Salceda, Anoland Garateix, André J. Zaharenko, Steve Peigneur, Omar López, Tirso Pons, Michael Richardson, Maylín Díaz, Yasnay Hernández, Ludger Ständker, Jan Tytgat, Enrique Soto
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Acid-sensing ion channels are cation (Na+) channels activated by a pH drop. These proteins belong to the ENaC/degenerin superfamily of sodium channels. ASICs are involved in sensory perception, synaptic plasticity, learning, memory formation, cell migration and proliferation, nociception, and neurodegenerative disorders, among other processes; therefore those molecules that specifically target these channels are of growing pharmacological and biomedical interest. Sea anemones produce a large variety of ion channels peptide toxins; however, those acting on ligand-gated ion channels, such as Glu-gated, Ach-gated ion channels, and acid-sensing ion channels (ASICs), remain barely explored. The peptide PhcrTx1 is the first compound characterized from the sea anemone Phymanthus crucifer, and it constitutes a novel ASIC inhibitor. This peptide was purified by chromatographic techniques and pharmacologically characterized on acid-sensing ion channels of mammalian neurons using patch-clamp techniques. PhcrTx1 inhibited ASIC currents with an IC50 of 100 nM. Edman degradation yielded a sequence of 32 amino acids residues, with a molecular mass of 3477 Da by MALDI-TOF. No similarity to known sea anemone peptides was found in protein databases. The computational analysis of Cys-pattern and secondary structure arrangement suggested that this is a structurally ICK (Inhibitor Cystine Knot)-type peptide, a scaffold that had not been found in sea anemones but in other venomous organisms. These results show that PhcrTx1 represents the first member of a new structural group of sea anemones toxins acting on ASICs. Also, this peptide constitutes a novel template for the development of drugs against pathologies related to ASICs function.Keywords: animal toxin, inhibitor cystine knot, ion channel, sea anemone
Procedia PDF Downloads 310203 Targeting Mre11 Nuclease Overcomes Platinum Resistance and Induces Synthetic Lethality in Platinum Sensitive XRCC1 Deficient Epithelial Ovarian Cancers
Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality
Procedia PDF Downloads 129202 Development of a Novel Antibacterial to Block Growth of Pseudomonas Aeruginosa and Prevent Biofilm Formation
Authors: Clara Franch de la Cal, Christopher J Morris, Michael McArthur
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Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by abnormal transport of chloride and sodium across the lung epithelium, leading to thick and viscous secretions. Within which CF patients suffer from repeated bacterial pulmonary infections, with Pseudomonas aeru-ginosa (PA) eliciting the greatest inflammatory response, causing an irreversible loss of lung func-tion that determines morbidity and mortality. The cell wall of PA is a permeability barrier to many antibacterials and the rise of Mutli-Drug Resistant strains (MDR) is eroding the efficacy of the few remaining clinical options. In addition when PA infection becomes established it forms an antibi-otic-resistant biofilm, embedded in which are slow growing cells that are refractive to drug treat-ment. Making the development of new antibacterials a major challenge. This work describes the development of new type of nanoparticulate oligonucleotide antibacterial capable of tackling PA infections, including MDR strains. It is being developed to both block growth and prevent biofilm formation. These oligonucleotide therapeutics, Transcription Factor Decoys (TFD), act on novel genomic targets by capturing key regulatory proteins to block essential bacterial genes and defeat infection. They have been successfully transfected into a wide range of pathogenic bacteria, both in vitro and in vivo, using a proprietary delivery technology. The surfactant used self-assembles with TFD to form a nanoparticle stable in biological fluids, which protects the TFD from degradation and preferentially transfects prokaryotic membranes. Key challenges are to adapt the nanoparticle so it is active against PA in the context of biofilms and to formulate it for administration by inhalation. This would allow the drug to be delivered to the respiratory tract, thereby achieving drug concentrations sufficient to eradicate the pathogenic organisms at the site of infection.Keywords: antibacterials, transcriptional factor decoys (TFDs), pseudomonas aeruginosa
Procedia PDF Downloads 284201 Using a Train-the-Trainer Model to Deliver Post-Partum Haemorrhage Simulation in Rural Uganda
Authors: Michael Campbell, Malaz Elsaddig, Kevin Jones
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Background: Despite encouraging progress, global maternal mortality has remained stubbornly high since the declaration of the Millennium development goals. Sub-Saharan Africa accounts for well over half of maternal deaths with Post-Partum Haemorrhage (PPH) being the lead cause. ‘In house’ simulation training delivered by local doctors may be a sustainable approach for improving emergency obstetric care. The aim of this study was to evaluate the use of a Train-the-Trainer (TtT) model in a rural Ugandan hospital to ascertain whether it can feasibly improve practitioners’ management of PPH. Methods: Three Ugandan doctors underwent a training course to enable them to design and deliver simulation training. These doctors used MamaNatalie® models to simulate PPH scenarios for midwives, nurses and medical students. The main outcome was improvement in participants’ knowledge and confidence, assessed using self-reported scores on a 10-point scale. Results: The TtT model produced significant improvements in the confidence and knowledge scores of the ten participants. The mean confidence score rose significantly (p=0.0005) from 6.4 to 8.6 following the simulation training. There was also a significant increase in the mean knowledge score from 7.2 to 9.0 (p=0.04). Medical students demonstrated the greatest overall increase in confidence scores whilst increases in knowledge scores were largest amongst nurses. Conclusions: This study demonstrates that a TtT model can be used in a low resource setting to improve healthcare professionals’ confidence and knowledge in managing obstetric emergencies. This Train-the-Trainer model represents a sustainable approach to addressing skill deficits in low resource settings. We believe that its expansion across healthcare institutions in Sub-Saharan Africa will help to reduce the region’s high maternal mortality rate and step closer to achieving the ambitions of the Millennium development goals.Keywords: low resource setting, post-partum haemorrhage, simulation training, train the trainer
Procedia PDF Downloads 177200 Two-Protein Modified Gold Nanoparticles for Serological Diagnosis of Borreliosis
Authors: Mohammed Alasel, Michael Keusgen
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Gold is a noble metal; in its nano-scale level (e.g. spherical nanoparticles), the conduction electrons are triggered to collectively oscillate with a resonant frequency when certain wavelengths of electromagnetic radiation interact with its surface; this phenomenon is known as surface plasmon resonance (SPR). SPR is responsible for giving the gold nanoparticles its intense red color depending mainly on its size, shape and distance between nanoparticles. A decreased distance between gold nanoparticles results in aggregation of them causing a change in color from red to blue. This aggregation enables gold nanoparticles to serve as a sensitive biosensoric indicator. In the proposed work, gold nanoparticles were modified with two proteins: i) Borrelia antigen, variable lipoprotein surface-exposed protein (VlsE), and ii) protein A. VlsE antigen induces a strong antibody response against Lyme disease and can be detected from early to late phase during the disease in humans infected with Borrelia. In addition, it shows low cross-reaction with the other non-pathogenic Borrelia strains. The high specificity of VlsE antigen to anti-Borrelia antibodies, combined simultaneously with the high specificity of protein A to the Fc region of all IgG human antibodies, was utilized to develop a rapid test for serological point of care diagnosis of borreliosis in human serum. Only in the presence of anti-Borrelia antibodies in the serum probe, an aggregation of gold nanoparticles can be observed, which is visible by a concentration-dependent colour shift from red (low IgG) to blue (high IgG). Experiments showed it is clearly possible to distinguish between positive and negative sera samples using a simple suspension of the two-protein modified gold nanoparticles in a very short time (30 minutes). The proposed work showed the potential of using such modified gold nanoparticles generally for serological diagnosis. Improved specificity and reduced assay time can be archived in applying increased salt concentrations combined with decreased pH values (pH 5).Keywords: gold nanoparticles, gold aggregation, serological diagnosis, protein A, lyme borreliosis
Procedia PDF Downloads 398199 An Experimental Investigation on Explosive Phase Change of Liquefied Propane During a Bleve Event
Authors: Frederic Heymes, Michael Albrecht Birk, Roland Eyssette
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Boiling Liquid Expanding Vapor Explosion (BLEVE) has been a well know industrial accident for over 6 decades now, and yet it is still poorly predicted and avoided. BLEVE is created when a vessel containing a pressure liquefied gas (PLG) is engulfed in a fire until the tank rupture. At this time, the pressure drops suddenly, leading the liquid to be in a superheated state. The vapor expansion and the violent boiling of the liquid produce several shock waves. This works aimed at understanding the contribution of vapor ad liquid phases in the overpressure generation in the near field. An experimental work was undertaken at a small scale to reproduce realistic BLEVE explosions. Key parameters were controlled through the experiments, such as failure pressure, fluid mass in the vessel, and weakened length of the vessel. Thirty-four propane BLEVEs were then performed to collect data on scenarios similar to common industrial cases. The aerial overpressure was recorded all around the vessel, and also the internal pressure changed during the explosion and ground loading under the vessel. Several high-speed cameras were used to see the vessel explosion and the blast creation by shadowgraph. Results highlight how the pressure field is anisotropic around the cylindrical vessel and highlights a strong dependency between vapor content and maximum overpressure from the lead shock. The time chronology of events reveals that the vapor phase is the main contributor to the aerial overpressure peak. A prediction model is built upon this assumption. Secondary flow patterns are observed after the lead. A theory on how the second shock observed in experiments forms is exposed thanks to an analogy with numerical simulation. The phase change dynamics are also discussed thanks to a window in the vessel. Ground loading measurements are finally presented and discussed to give insight into the order of magnitude of the force.Keywords: phase change, superheated state, explosion, vapor expansion, blast, shock wave, pressure liquefied gas
Procedia PDF Downloads 77198 Everolimus Loaded Polyvinyl Alcohol Microspheres for Sustained Drug Delivery in the Treatment of Subependymal Giant Cell Astrocytoma
Authors: Lynn Louis, Bor Shin Chee, Marion McAfee, Michael Nugent
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This article aims to develop a sustained release formulation of microspheres containing the mTOR inhibitor Everolimus (EVR) using Polyvinyl alcohol (PVA) to enhance the bioavailability of the drug and to overcome poor solubility characteristics of Everolimus. This paper builds on recent work in the manufacture of microspheres using the sessile droplet technique by freezing the polymer-drug solution by suspending the droplets into pre-cooled ethanol vials immersed in liquid nitrogen. The spheres were subjected to 6 freezing cycles and 3 freezing cycles with thawing to obtain proper geometry, prevent aggregation, and achieve physical cross-linking. The prepared microspheres were characterised for surface morphology by SEM, where a 3-D porous structure was observed. The in vitro release studies showed a 62.17% release over 12.5 days, indicating a sustained release due to good encapsulation. This result is comparatively much more than the 49.06% release achieved within 4 hours from the solvent cast Everolimus film as a control with no freeze-thaw cycles performed. The solvent cast films were made in this work for comparison. A prolonged release of Everolimus using a polymer-based drug delivery system is essential to reach optimal therapeutic concentrations in treating SEGA tumours without systemic exposure. These results suggest that the combination of PVA and Everolimus via a rheological synergism enhanced the bioavailability of the hydrophobic drug Everolimus. Physical-chemical characterisation using DSC and FTIR analysis showed compatibility of the drug with the polymer, and the stability of the drug was maintained owing to the high molecular weight of the PVA. The obtained results indicate that the developed PVA/EVR microsphere is highly suitable as a potential drug delivery system with improved bioavailability in treating Subependymal Giant cell astrocytoma (SEGA).Keywords: drug delivery system, everolimus, freeze-thaw cycles, polyvinyl alcohol
Procedia PDF Downloads 127197 Outcomes of the Gastrocnemius Flap Performed by Orthopaedic Surgeons in Salvage Revision Knee Arthroplasty: A Retrospective Study at a Tertiary Orthopaedic Centre
Authors: Amirul Adlan, Robert McCulloch, Scott Evans, Michael Parry, Jonathan Stevenson, Lee Jeys
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Background and Objectives: The gastrocnemius myofascial flap is used to manage soft-tissue defects over the anterior aspect of the knee in the context of a patient presenting with a sinus and periprosthetic joint infection (PJI) or extensor mechanism failure. The aim of this study was twofold: firstly, to evaluate the outcomes of gastrocnemius flaps performed by appropriately trained orthopaedic surgeons in the context of PJI and, secondly, to evaluate the infection-free survival of this patient group. Methods: We retrospectively reviewed 30 patients who underwent gastrocnemius flap reconstruction during staged revision total knee arthroplasty for prosthetic joint infection (PJI). All flaps were performed by an orthopaedic surgeon with orthoplastics training. Patients had a mean age of 68.9 years (range 50–84) and were followed up for a mean of 50.4 months (range 2–128 months). A total of 29 patients (97 %) were categorized into Musculoskeletal Infection Society (MSIS) local extremity grade 3 (greater than two compromising factors), and 52 % of PJIs were polymicrobial. The primary outcome measure was flap failure, and the secondary outcome measure was a recurrent infection. Results: Flap survival was 100% with no failures or early returns to theatre for flap problems such as necrosis or haematoma. Overall infection-free survival during the study period was 48% (13 of 27 infected cases). Using limb salvage as the outcome, 77% (23 of 30 patients) retained the limb. Infection recurrence occurred in 48% (10 patients) in the type B3 cohort and 67% (4 patients) in the type C3 cohort (p = 0.65). Conclusion: The surgical technique for a gastrocnemius myofascial flap is reliable and reproducible when performed by appropriately trained orthopaedic surgeons, even in high-risk groups. However, the risks of recurrent infection and amputation remain high within our series due to poor host and extremity factors.Keywords: gastrocnemius flap, limb salvage, revision arthroplasty, outcomes
Procedia PDF Downloads 111196 Knowledge of Risk Factors and Health Implications of Fast Food Consumption among Undergraduate in Nigerian Polytechnic
Authors: Adebusoye Michael, Anthony Gloria, Fasan Temitope, Jacob Anayo
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Background: The culture of fast food consumption has gradually become a common lifestyle in Nigeria especially among young people in urban areas, in spite of the associated adverse health consequences. The adolescent pattern of fast foods consumption and their perception of this practice, as a risk factor for Non-Communicable Diseases (NCDs), have not been fully explored. This study was designed to assess fast food consumption pattern and the perception of it as a risk factor for NCDs among undergraduates of Federal Polytechnic, Bauchi. Methodology: The study was descriptive cross-sectional in design. One hundred and eighty-five students were recruited using systematic random sampling method from the two halls of residence. A structured questionnaire was used to assess the consumption pattern of fast foods. Data collected from the questionnaires were analysed using statistical package for the social sciences (SPSS) version 16. Simple descriptive statistics, such as frequency counts and percentages were used to interpret the data. Results: The age range of respondents was 18-34 years, 58.4% were males, 93.5% singles and 51.4% of their parents were employed. The majority (100%) were aware of fast foods and (75%) agreed to its implications as NCD. Fast foods consumption distribution included meat pie (4.9%), beef roll/ sausage (2.7%), egg roll (13.5%), doughnut (16.2%), noodles(18%) and carbonated drinks (3.8%). 30.3% consumed thrice in a week and 71% attached workload to high consumption of fast food. Conclusion: It was revealed that a higher social pressure from peers, time constraints, class pressure and school programme had the strong influence on high percentages of higher institutions’ students consume fast foods and therefore nutrition educational campaigns for campus food outlets or vendors and behavioural change communication on healthy nutrition and lifestyles among young people are hereby advocated.Keywords: fast food consumption, Nigerian polytechnic, risk factors, undergraduate
Procedia PDF Downloads 471195 Mindfulness in a Secular Age: Framing and Contextualising the Conversation in the Irish Context
Authors: Thomas P. Carroll
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The phenomenon of mindfulness has become ever more popular in an increasingly pluralist Western society. Mindfulness practice has penetrated secular contexts that would otherwise be closed to religious influence, including state schools, hospitals, and commerce. The contemporary understanding of mindfulness has its origins in Buddhist meditation. However, since Jon Kabat-Zinn’s pioneering work in Mindfulness-Based Interventions, the concept has developed and sometimes mutated into various forms of practice which are disembedded from their original spiritual philosophy. This project will explore the spiritual climate within which mindfulness is currently flourishing through dialogue with three interlocutors. The first interlocutor is the Canadian philosopher Charles Taylor whose seminal work, ‘A Secular Age’, outlines three distinct modes of secularity. Taylor examines how the conditions of belief have changed and how the self seeks meaning in an age where belief in the divine is no longer axiomatic. The next interlocutor is Czech theologian and psychotherapist Tomáš Halík who offers a unique perspective of a Catholic who belongs to a section of society outnumbered by secular counterparts, with a theological hermeneutic best described as 'Den Fremden verstehen- understanding the stranger'. Finally, Irish theologian Michael Paul Gallagher offers a theological perspective on how the Christian faith can be translated into dialogue with Irish secular culture, as well as addressing the crisis of imagination and culture rather than the crisis of faith in Ireland. These interlocutors will illustrate that there are sometimes striking differences in how to interpret the religious signs of the times. However, these approaches also reveal significant similarities in how they address and explore the meaning of religious belief and experience today. In this way, themes will emerge that will help to frame the conversation about mindfulness in the West. These themes will include; the failure of the secularization thesis to pass, the growth of a diverse marketplace of religions and beliefs and the growth of a demographic who identify as spiritual but not religious. Such research is paramount in enabling a richer dialogue between Christian faith and mindfulness in a fragmented, postmodern Western context.Keywords: culture, mindfulness, secularism, spirituality
Procedia PDF Downloads 113194 Characterising Rates of Renal Dysfunction and Sarcoidosis in Patients with Elevated Serum Angiotensin-Converting Enzyme
Authors: Fergal Fouhy, Alan O’Keeffe, Sean Costelloe, Michael Clarkson
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Background: Sarcoidosis is a systemic, non-infectious disease of unknown aetiology, characterized by non-caseating granulomatous inflammation. The lung is most often affected (90%); however, the condition can affect all organs, including the kidneys. There is limited evidence describing the incidence and characteristics of renal involvement in sarcoidosis. Serum angiotensin-converting enzyme (ACE) is a recognised biomarker used in the diagnosis and monitoring of sarcoidosis. Methods: A single-centre, retrospective cohort study of patients presenting to Cork University Hospital (CUH) in 2015 with first-time elevations of serum ACE was performed. This included an initial database review of ACE and other biochemistry results, followed by a medical chart review to confirm the presence or absence of sarcoidosis and management thereof. Acute kidney injury (AKI) was staged using the AKIN criteria, and chronic kidney disease (CKD) was staged using the KDIGO criteria. Follow-up was assessed over five years tracking serum creatinine, serum calcium, and estimated glomerular filtration rates (eGFR). Results: 119 patients were identified as having a first raised serum ACE in 2015. Seventy-nine male patients and forty female patients were identified. The mean age of patients identified was 47 years old. 11% had CKD at baseline. 18% developed an AKI at least once within the next five years. A further 6% developed CKD during this time period. 13% developed hypercalcemia. The patients within the lowest quartile of serums ACE had an incidence of sarcoidosis of 5%. None of this group developed hypercalcemia, 23% developed AKI, and 7% developed CKD. Of the patients with a serum ACE in the highest quartile, almost all had documented diagnoses of sarcoidosis with an incidence of 96%. 3% of this group developed hypercalcemia, 13% AKI and 3% developed CKD. Conclusions: There was an unexpectedly high incidence of AKI in patients who had a raised serum ACE. Not all patients with a raised serum ACE had a confirmed diagnosis of sarcoidosis. There does not appear to be a relationship between increased serum ACE levels and increased incidence of hypercalcaemia, AKI, and CKD. Ideally, all patients should have biopsy-proven sarcoidosis. This is an initial study that should be replicated with larger numbers and including multiple centres.Keywords: sarcoidosis, acute kidney injury, chronic kidney disease, hypercalcemia
Procedia PDF Downloads 103193 Bioengineering of a Plant System to Sustainably Remove Heavy Metals and to Harvest Rare Earth Elements (REEs) from Industrial Wastes
Authors: Edmaritz Hernandez-Pagan, Kanjana Laosuntisuk, Alex Harris, Allison Haynes, David Buitrago, Michael Kudenov, Colleen Doherty
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Rare Earth Elements (REEs) are critical metals for modern electronics, green technologies, and defense systems. However, due to their dispersed nature in the Earth’s crust, frequent co-occurrence with radioactive materials, and similar chemical properties, acquiring and purifying REEs is costly and environmentally damaging, restricting access to these metals. Plants could serve as resources for bioengineering REE mining systems. Although there is limited information on how REEs affect plants at a cellular and molecular level, plants with high REE tolerance and hyperaccumulation have been identified. This dissertation aims to develop a plant-based system for harvesting REEs from industrial waste material with a focus on Acid Mine Drainage (AMD), a toxic coal mining product. The objectives are 1) to develop a non-destructive, in vivo detection method for REE detection in Phytolacca plants (REE hyperaccumulator) plants utilizing fluorescence spectroscopy and with a primary focus on dysprosium, 2) to characterize the uptake of REE and Heavy Metals in Phytolacca americana and Phytolacca acinosa (REE hyperaccumulator) in AMD for potential implementation in the plant-based system, 3) to implement the REE detection method to identify REE-binding proteins and peptides for potential enhancement of uptake and selectivity for targeted REEs in the plants implemented in the plant-based system. The candidates are known REE-binding peptides or proteins, orthologs of known metal-binding proteins from REE hyperaccumulator plants, and novel proteins and peptides identified by comparative plant transcriptomics. Lanmodulin, a high-affinity REE-binding protein from methylotrophic bacteria, is used as a benchmark for the REE-protein binding fluorescence assays and expression in A. thaliana to test for changes in REE plant tolerance and uptake.Keywords: phytomining, agromining, rare earth elements, pokeweed, phytolacca
Procedia PDF Downloads 15192 Loss of Function of Only One of Two CPR5 Paralogs Causes Resistance Against Rice Yellow Mottle Virus
Authors: Yugander Arra, Florence Auguy, Melissa Stiebner, Sophie Chéron, Michael M. Wudick, Van Schepler-Luu, Sébastien Cunnac, Wolf B. Frommer, Laurence Albar
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Rice yellow mottle virus (RYMV) is one of the most important diseases affecting rice in Africa. The most promising strategy to reduce yield losses is the use of highly resistant varieties. The resistance gene RYMV2 is homolog of the Arabidopsis constitutive expression of pathogenesis related protein-5 (AtCPR5) nucleoporin gene. Resistance alleles are originating from African cultivated rice Oryza glaberrima, rarely cultivated, and are characterized by frameshifts or early stop codons, leading to a non-functional or truncated protein. Rice possesses two paralogs of CPR5 and function of these genes are unclear. Here, we evaluated the role of the two rice candidate nucleoporin paralogs OsCPR5.1 (pathogenesis-related gene 5; RYMV2) and OsCPR5.2 by CRISPR/Cas9 genome editing. Despite striking sequence and structural similarity, only loss-of-function of OsCPR5.1 led to full resistance, while loss-of-function oscpr5.2 mutants remained susceptible. Short N-terminal deletions in OsCPR5.1 also did not lead to resistance. In contrast to Atcpr5 mutants, neither OsCPR5.1 nor OsCPR5.2 knock out mutants showed substantial growth defects. Taken together, the candidate nucleoporin OsCPR5.1, but not its close homolog OsCPR5.2, plays a specific role for the susceptibility to RYMV, possibly by impairing the import of viral RNA or protein into the nucleus. Whereas gene introgression from O. glaberrima to high yielding O. sativa varieties is impaired by strong sterility barriers and the negative impact of linkage drag, genome editing of OsCPR5.1, while maintaining OsCPR5.2 activity, thus provides a promising strategy to generate O. sativa elite lines that are resistant to RYMV.Keywords: CRISPR Cas9, genome editing, knock out mutant, recessive resistance, rice yellow mottle virus
Procedia PDF Downloads 118191 MicroRNA in Bovine Corpus Luteum during Early Pregnancy
Authors: Rreze Gecaj, Corina Schanzenbach, Benedikt Kirchner, Michael Pfaffl, Bajram Berisha
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The maintenance of corpus lutem (CL) during early pregnancy in cattle is a critical and multifarious process. A luteotrophic mechanism originating from the embryo is widely accepted as the triggering signal for the CL maintenance. In the cattle, it is the interferon-tau (IFNT) secretion form conceptus that prevents CL regression and ensures progesterone production for the establishment of pregnancy. In addition to endocrine and paracrine signals, microRNA (miRNA) can also support CL sustainability during early pregnancy. MiRNA are small non-coding nucleic acids that regulate gene expression post-transcriptionally and are shown to be involved in the modulation of CL function. However, the examination of miRNAs in corpus luteum function at the early pregnancy still remains largely uncovered. This study aims at profiling the expression of miRNA in CL during the early pregnancy in cattle by comparing it with the CL form late cycle and with the regressed CL. Corpora lutea were assigned in two different groups during the cycle (C13 group, late CL: days 13-18 and C18, regressed CL group: day >18) and during the early pregnancy (group P: 1-2 month). The estrous cycle was determined by macroscopic examination and to age the fetus crown-rump length measurement was applied. A total of 9 corpora lutea from individual animals were included in the study, three corpora lutea for each group. MiRNAs population was profiled using small RNA next-generation sequencing and biologically significant miRNAs were evaluated for their differential expression using the DESeq2-methodology. We show that 6 differentially expressed miRNAs (bta-mir-2890, -2332, -2441-3p, -148b, -1248 and -29c) are common to both comparisons, P vs C13 and P vs C18. While for each stage individually we have identified unique miRNAs differentially expressed only for the given comparison. bta-miR-23a and -769 were unique miRNAs differentially expressed in P vs C13, whereas forty-four unique miRNAs were identified as differentially expressed in P vs C18. These data confirm that miRNAs are highly abundant in luteal tissue during early pregnancy and potentially regulate the CL maintenance at this stage of fetus development.Keywords: bovine, corpus luteum, microRNA, pregnancy, RNA-Seq
Procedia PDF Downloads 259190 Mitigating Self-Regulation Issues in the Online Instruction of Math
Authors: Robert Vanderburg, Michael Cowling, Nicholas Gibson
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Mathematics is one of the core subjects taught in the Australian K-12 education system and is considered an important component for future studies in areas such as engineering and technology. In addition to this, Australia has been a world leader in distance education due to the vastness of its geographic landscape. Despite this, research is still needed on distance math instruction. Even though delivery of curriculum has given way to online studies, and there is a resultant push for computer-based (PC, tablet, smartphone) math instruction, much instruction still involves practice problems similar to those original curriculum packs, without the ability for students to self-regulate their learning using the full interactive capabilities of these devices. Given this need, this paper addresses issues students have during online instruction. This study consists of 32 students struggling with mathematics enrolled in a math tutorial conducted in an online setting. The study used a case study design to understand some of the blockades hindering the students’ success. Data was collected by tracking students practice and quizzes, tracking engagement of the site, recording one-on-one tutorials, and collecting data from interviews with the students. Results revealed that when students have cognitively straining tasks in an online instructional setting, the first thing to dissipate was their ability to self-regulate. The results also revealed that instructors could ameliorate the situation and provided useful data on strategies that could be used for designing future online tasks. Specifically, instructors could utilize cognitive dissonance strategies to reduce the cognitive drain of the tasks online. They could segment the instruction process to reduce the cognitive demands of the tasks and provide in-depth self-regulatory training, freeing mental capacity for the mathematics content. Finally, instructors could provide specific scheduling and assignment structure changes to reduce the amount of student centered self-regulatory tasks in the class. These findings will be discussed in more detail and summarized in a framework that can be used for future work.Keywords: digital education, distance education, mathematics education, self-regulation
Procedia PDF Downloads 136189 Internet Health: A Cross-Sectional Survey Exploring Identified Risks and Online Safety Measures in Parent and Children with Neurodevelopmental Disorders
Authors: Abdirahim Mohamed, Sarita Rana Chhetri, Michael Sleath, Nadia Saleem
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Rationale: Internet usage has been very much integrated into our daily lives. Internet usage within a neurodevelopmental disorder population is also on the increase. Nevertheless, there is very little empirical research on how this population virtually protect themselves; along with how their parents can keep them safe online. This topic was an ever-growing concern to the parents within our services and in many cases would add to the stresses and mental health of parents. This ignited an idea within our team to conduct research to explore the perceived online risks within this population and how they keep themselves safe. In conjunction, we also explored how parents and caregivers monitor and safeguard their young people to the potential threats online. Our hypothesis was that the perceived risks will heavily outnumber the safeguarding measures implemented by this population. Method: Within the Coventry and Warwickshire NHS Partnership Trust Child and Adolescent Mental Health Service (CAMHS), we distributed qualitative questionnaires to all the clinical bases (N=80). Questions explored topics such as daily internet usage, safeguarding measures, and perceived threats. The researchers requested for all CAMHS clinicians to identify participants. Participants in this study were accessing CAMHS for neurodevelopmental specific interventions. Results: The data were analysed using both Excel and SPSS. Within SPSS, a MANOVA was conducted and found a significant difference between safeguarding measures and perceived online risks within responses (p ≤ 0.5). This supports our hypothesis that participants in this population are well versed in the safeguarding issues of the internet; however, struggle to implement appropriate preventative measures. Data were also screened using Excel and found that all parents and carers stated they 'monitored their child’s internet use'. Conclusion: Data suggest that parents/carers may require more specific intervention to equip them with preventative measures due to the clear discrepancy between perceived risks and safeguarding measures. More research may also need to be conducted around this area to determine appropriate methodology to explore this topic further.Keywords: Internet, health , how safe are we , internet health check
Procedia PDF Downloads 268188 Using Serious Games to Integrate the Potential of Mass Customization into the Fuzzy Front-End of New Product Development
Authors: Michael N. O'Sullivan, Con Sheahan
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Mass customization is the idea of offering custom products or services to satisfy the needs of each individual customer while maintaining the efficiency of mass production. Technologies like 3D printing and artificial intelligence have many start-ups hoping to capitalize on this dream of creating personalized products at an affordable price, and well established companies scrambling to innovate and maintain their market share. However, the majority of them are failing as they struggle to understand one key question – where does customization make sense? Customization and personalization only make sense where the value of the perceived benefit outweighs the cost to implement it. In other words, will people pay for it? Looking at the Kano Model makes it clear that it depends on the product. In products where customization is an inherent need, like prosthetics, mass customization technologies can be highly beneficial. However, for products that already sell as a standard, like headphones, offering customization is likely only an added bonus, and so the product development team must figure out if the customers’ perception of the added value of this feature will outweigh its premium price tag. This can be done through the use of a ‘serious game,’ whereby potential customers are given a limited budget to collaboratively buy and bid on potential features of the product before it is developed. If the group choose to buy customization over other features, then the product development team should implement it into their design. If not, the team should prioritize the features on which the customers have spent their budget. The level of customization purchased can also be translated to an appropriate production method, for example, the most expensive type of customization would likely be free-form design and could be achieved through digital fabrication, while a lower level could be achieved through short batch production. Twenty-five teams of final year students from design, engineering, construction and technology tested this methodology when bringing a product from concept through to production specification, and found that it allowed them to confidently decide what level of customization, if any, would be worth offering for their product, and what would be the best method of producing it. They also found that the discussion and negotiations between players during the game led to invaluable insights, and often decided to play a second game where they offered customers the option to buy the various customization ideas that had been discussed during the first game.Keywords: Kano model, mass customization, new product development, serious game
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