Search results for: Michael Ray Brunt

Authors: Michael Lekan-Kehinde, Abimbola Asojo, Bonnie Sanborn

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Good acoustic performance has been identified as one of the critical Indoor Environmental Quality (IEQ) factors for student learning and development by the National Research Council. Childhood presents the opportunity for children to develop lifelong skills that will support them throughout their adult lives. Acoustic performance of a space has been identified as a factor that can impact language acquisition, concentration, information retention, and general comfort within the environment. Increasingly, students learn by communication between both teachers and fellow students, making speaking and listening crucial. Neurodiversity - while initially coined to describe individuals with autism spectrum disorder (ASD) - widely describes anyone with a different brain process. As the understanding from cognitive and neurosciences increases, the number of people identified as neurodiversity is nearly 30% of the population. This research looks at guidelines and standard for spaces with good acoustical quality and relates it with the experiences of students with autism spectrum disorder (ASD), their parents, teachers, and educators through a mixed methods approach, including selected case studies interviews, and mixed surveys. The information obtained from these sources is used to determine if selected materials, especially properties relating to sound absorption and reverberation reduction, are equally useful in small, medium sized, and large learning spaces and methodologically approaching. The results describe the potential impact of acoustics on Neurodiverse students, considering factors that determine the complexity of sound in relation to the auditory processing capabilities of ASD students. In conclusion, this research extends the knowledge of how materials selection influences the better development of acoustical environments for autism students.

Keywords: acoustics, autism spectrum disorder (ASD), children, education, learning, learning spaces, materials, neurodiversity, sound

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Authors: Michael K. O. Ayomoh, Oyindamola A. Omotuyi

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Autonomous mobile robots deployed to explore or operate in a never explored or an abandoned sub-surface mine requires extreme effectiveness in coordination and communication. In a bid to transmit information from the depth of the mine to the external surface in real-time and amidst diverse physical, chemical and virtual impediments, the concept of unified cooperative robots is seen to be a proficient approach. This paper presents an effective [human → robot → task] coordination framework for effective exploration of an abandoned underground mine. The problem addressed in this research is basically the development of a globalized optimization model premised on time series differentiation and geometrical configurations for effective positioning of the two classes of robots in the cooperation namely the outermost stationary master (OSM) robots and the innermost dynamic task (IDT) robots for effective bi-directional signal transmission. In addition, the synchronization of a vision system and wireless communication system for both categories of robots, fiber optics system for the OSM robots in cases of highly sloppy or vertical mine channels and an autonomous battery recharging capability for the IDT robots further enhanced the proposed concept. The OSM robots are the master robots which are positioned at strategic locations starting from the mine open surface down to its base using a fiber-optic cable or a wireless communication medium all subject to the identified mine geometrical configuration. The OSM robots are usually stationary and function by coordinating the transmission of signals from the IDT robots at the base of the mine to the surface and in a reverse order based on human decisions at the surface control station. The proposed scheme also presents an optimized number of robots required to form the cooperation in a bid to reduce overall operational cost and system complexity.

Keywords: sub-surface mine, wireless communication, outermost stationary master robots, inner-most dynamic robots, fiber optic

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Authors: Tyler Palma, Praveen Damasus, Michael Munther, Mehrdad Mohsenizadeh, Keivan Davami

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The advancement of additive manufacturing, in both research and commercial realms, is highly dependent upon continuing innovations and creativity in materials and designs. Additive manufacturing shows great promise towards revolutionizing various industries, due largely to the fact that design data can be used to create complex products and components, on demand and from the raw materials, for the end user at the point of use. However, it will be critical that the material properties of additively-made parts for engineering purposes be fully understood. As it is a relatively new additive manufacturing method, the response of properties of Multi Jet Fusion (MJF) produced parts to different printing parameters has not been well studied. In this work, testing of mechanical and tribological properties MJF-printed Polyamide 12 parts was performed to determine whether printing orientation in this method results in significantly different part performances. Material properties were studied at macro- and nanoscales. Tensile tests, in combination with tribology tests including steady-state wear, were performed. Results showed a significant difference in resultant part characteristics based on whether they were printed in a vertical or horizontal orientation. Tensile performance of vertically and horizontally printed samples varied, both in ultimate strength and strain. Tribology tests showed that printing orientation has notable effects on the resulting mechanical and wear properties of tested surfaces, due largely to layer orientation and the presence of unfused fused powder grain inclusions. This research advances the understanding of how print orientation affects the mechanical properties of additively manufactured structures, and also how print orientation can be exploited in future engineering design.

Keywords: additive manufacturing, indentation, nano mechanical characterization, print orientation

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Authors: Gary Pattemore, Michael Edgar, Andrew Job, Marina Auad, Kathryn Job

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As critical commodities become more scarce, significant time and resources have been used to better understand complicated ore bodies and extract their full potential. These challenging ore bodies provide several pain points for geologists and engineers to overcome, poor handling of these issues flows downs stream to the processing plant affecting throughput rates and recovery. Many open cut mines utilise blast hole drilling to extract additional information to feed back into the modelling process. This method requires samples to be collected during or after blast hole drilling. Samples are then sent for assay with turnaround times varying from 1 to 12 days. This method is time consuming, costly, requires human exposure on the bench and collects elemental data only. To address this challenge, research has been undertaken to utilise hyperspectral imaging across a broad spectrum to scan samples, collars or take down hole measurements for minerals and moisture content and grade abundances. Automation of this process using unmanned vehicles and on-board processing reduces human in pit exposure to ensure ongoing safety. On-board processing allows data to be integrated into modelling workflows with immediacy. The preliminary results demonstrate numerous direct and indirect benefits from this new technology, including rapid and accurate grade estimates, moisture content and mineralogy. These benefits allow for faster geo modelling updates, better informed mine scheduling and improved downstream blending and processing practices. The paper presents recommendations for implementation of the technology in open cut mining environments.

Keywords: grade control, hyperspectral scanning, artificial intelligence, autonomous mining, machine learning

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Authors: Deyu Yuan

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Discourse analysis as an interdisciplinary approach has more than 60-years-history since it was first named by Zellig Harris in 'Discourse Analysis' on Language in 1952. Ferdinand de Saussure differentiated the 'parole' from the 'langue' that established the principle of focusing on language but not speech. So the rising of discourse analysis can be seen as a discursive turn for the entire language research that closely related to the theory of Speech act. Critical discourse analysis becomes the mainstream of contemporary language research through drawing upon M. A. K. Halliday's socio-semiotic theory and Foucault, Barthes, Bourdieu's views on the sign, discourse, and ideology. So in contrast to general semiotics, social semiotics mainly focuses on parole and the application of semiotic theories to some applicable fields. The article attempts to discuss this applicable sociosemiotics and show the features of it that differ from the Saussurian and Peircian semiotics in four aspects: 1) the sign system is about meaning-generation resource in the social context; 2) the sign system conforms to social and cultural changes with the form of metaphor and connotation; 3) sociosemiotics concerns about five applicable principles including the personal authority principle, non-personal authority principle, consistency principle, model demonstration principle, the expertise principle to deepen specific communication; 4) the study of symbolic functions is targeted to the characteristics of ideational, interpersonal and interactional function in social communication process. Then the paper describes six features which characterize this sociosemiotics as applicable semiotics: social, systematic, usable interdisciplinary, dynamic, and multi-modal characteristics. Thirdly, the paper explores the multi-modal choices of sociosemiotics in the respects of genre, discourse, and style. Finally, the paper discusses the relationship between theory and practice in social semiotics and proposes a relatively comprehensive theoretical framework for social semiotics as applicable semiotics.

Keywords: discourse analysis, sociosemiotics, pragmatics, ideology

Procedia PDF Downloads 351

Authors: Luís Rocha, Adam Gąska, Enrico Savio, Michael Marxer, Christoph Battaglia

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The changes observed in the last years in the field of manufacturing and production engineering, popularly known as "Fourth Industry Revolution", utilizes the achievements in the different areas of computer sciences, introducing new solutions at almost every stage of the production process, just to mention such concepts as mass customization, cloud computing, knowledge-based engineering, virtual reality, rapid prototyping, or virtual models of measuring systems. To effectively speed up the production process and make it more flexible, it is necessary to tighten the bonds connecting individual stages of the production process and to raise the awareness and knowledge of employees of individual sectors about the nature and specificity of work in other stages. It is important to discover and develop a suitable education method adapted to the specificities of each stage of the production process, becoming an extremely crucial issue to exploit the potential of the fourth industrial revolution properly. Because of it, the project “Train4Dim” (T4D) intends to develop complex training material for digital manufacturing, including content for design, manufacturing, and quality control, with a focus on coordinate metrology and portable measuring systems. In this paper, the authors present an approach to using an active learning methodology for digital manufacturing. T4D main objective is to develop a multi-degree (apprenticeship up to master’s degree studies) and educational approach that can be adapted to different teaching levels. It’s also described the process of creating the underneath methodology. The paper will share the steps to achieve the aims of the project (training model for digital manufacturing): 1) surveying the stakeholders, 2) Defining the learning aims, 3) producing all contents and curriculum, 4) training for tutors, and 5) Pilot courses test and improvements.

Keywords: learning, Industry 4.0, active learning, digital manufacturing

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Authors: Michael Ryan, Rosemary E. Borgerding, Kimberly L. Oliver

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The objective of this study was to assess the effectiveness of a sports nutrition intervention on body composition in high-school athletes. The study aimed to improve the food and water intake of high-school athletes, evaluate the cost-effectiveness of the intervention, and assess changes in body fat. Data were collected through observations, questionnaires, and interviews. Additionally, bioelectrical impedance analysis was performed to assess the body composition of athletes both before and after the intervention. Athletes (n=25) participated in researcher-monitored training sessions three times a week over the course of 12 weeks. During these sessions, in addition to completing their auxiliary sports training, participants were exposed to educational interventions aimed at improving their nutrition. These included discussions regarding current eating habits, nutritional guidelines for athletes, and individualized recommendations. Food was also made available to athletes for consumption before and after practice. Meals of balanced macronutrient composition were prepared and provided to athletes on four separate occasions throughout the intervention, either prior to or following a competitive event such as a tournament or game. A paired t-test was used to determine the statistical significance of the changes in body fat percentage. The results showed that there was a statistically significant difference between pre and post-intervention body fat percentage (p= .006). Cohen's d of 0.603 was calculated, indicating a moderate effect size. In conclusion, this study provides evidence that a sports nutrition intervention that combines food availability, explicit prescription, and education can be effective in improving the body composition of high-school athletes. However, it's worth noting that this study had a small sample size, and the conclusions cannot be generalized to a larger population. Further research is needed to assess the scalability of this study. This preliminary study demonstrated the feasibility of this type of nutritional intervention and laid the groundwork for a larger, more extensive study to be conducted in the future.

Keywords: bioelectrical impedance, body composition, high-school athletes, sports nutrition, sports pedagogy

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Authors: George Cudjoe Agbemabiese, John Paul Kosiba, Michael Boadi Nyamekye, Vanessa Narkie Tetteh, Caleb Nunoo, Mohammed Muniru Husseini

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The smartphone industry continues to experience massive growth, evidenced by expanding markets and an increasing number of brands, models and manufacturers. As technology advances rapidly, manufacturers of smartphones are consistently introducing new innovations to keep up with the latest evolving industry trends and customer demand for more modern devices. This study aimed to assess the influence of artificial intelligence (AI) voice assistant (VA) on improving customer experience, resulting in the continuous use of mobile brands. Specifically, this article assesses the role of hedonic, utilitarian, and social benefits provided by AIVA on customer experience and the continuance intention to use mobile phone brands. Using a primary data collection instrument, the quantitative approach was adopted to examine the study's variables. Data from 348 valid responses were used for the analysis based on structural equation modeling (SEM) with AMOS version 23. Three main factors were identified to influence customer experience, which results in continuous usage of mobile phone brands. These factors are social benefits, hedonic benefits, and utilitarian benefits. In conclusion, a significant and positive relationship exists between the factors influencing customer experience for continuous usage of mobile phone brands. The study concludes that mobile brands that invest in delivering positive user experiences are in a better position to improve usage and increase preference for their brands. The study recommends that mobile brands consider and research their prospects' and customers' social, hedonic, and utilitarian needs to provide them with desired products and experiences.

Keywords: artificial intelligence, continuance usage, customer experience, smartphone industry

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Authors: Smruti Mahapatra, Dipankar Biswas, Richard Um, Michael Meggyesy, Riccardo Serra, Noah Gorelick, Steven Marra, Amir Manbachi, Mark G. Luciano

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Intracranial pressure (ICP) is profoundly regulated by the effects of cardiac pulsation and the volume of the incoming blood. Furthermore, these effects on ICP are incremented by the presence of a rigid skull that does not allow for changes in total volume during the cardiac cycle. These factors play a pivotal role in cerebrospinal fluid (CSF) dynamics and distribution, with consequences that are not well understood to this date and that may have a deep effect on the Central Nervous System (CNS) functioning. We designed this study with two specific aims: (a) To study how pulsatility influences local CSF flow, and (b) To study how modulating intracranial pressure affects drug distribution throughout the SAS globally. In order to achieve these aims, we built an elaborate in-vitro model of the SAS closely mimicking the dimensions and flow rates of physiological systems. To modulate intracranial pressure, we used an intracranially implanted, cardiac-gated, volume-oscillating balloon (CADENCE device). Commercially available dye was used to visualize changes in CSF flow. We first implemented two control cases, seeing how the tracer behaves in the presence of pulsations from the brain phantom and the balloon individually. After establishing the controls, we tested 2 cases, having the brain and the balloon pulsate together in sync and out of sync. We then analyzed the distribution area using image processing software. The in-sync case produced a significant increase, 5x times, in the tracer distribution area relative to the out-of-sync case. Assuming that the tracer fluid would mimic blood flow movement, a drug introduced in the SAS with such a system in place would enhance drug distribution and increase the bioavailability of therapeutic drugs to a wider spectrum of brain tissue.

Keywords: blood-brain barrier, cardiac-gated, cerebrospinal fluid, drug delivery, neurosurgery

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Authors: Mehwish Ishfaq, Aiman Kamran

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This study aimed at impact of perceived parental attitude on life orientation with moderating role of body dysmorphic symptoms. Perceived parental attitude comprised of parental autonomy support & psychological control to their child for development of individuality, self-regulation, and bodily construction that includes cognitive, social, and affective development. This perceived parental attitude have significant relationship with life orientation on individual’s self. Data was collected from schools and universities residing in Islamabad and Rawalpindi and was also obtained through online survey. Instrument used to measure perceived parental attitude was Perceived Parental Autonomy Support Scale (PPASS). Through The Life Orientation Test (LOT-R) which was developed by Michael F. Scheier in 1994, level of optimism and pessimism was assessed. For measuring body dysmorphic disorder, the Body Dysmorphic Questionnaire (BDDQ) which was developed by Dr. Katherine A. Phillips in 2009, a screening scale was used. The present study includes a total sample size of (N= 100) females and was conducted through cross-sectional survey. The findings of current study suggested that perceived parental attitude showed negative relationship with life orientation and this relationship was moderated by body dysmorphic disorder symptoms in females. There was significant age difference in body dysmorphia, perceived parental attitude, and life orientation. Body dysmorphic symptoms were more common in females with age 20-29 (M= 1.33, S.D=1.91) as compared to 12-19 (M=1.16, S.D=1.95). Participants also reported that affected relationship with either parent caused problems in daily life, including school, public interactions and activities leading to low dispositional optimism in life orientation. This study gives us insight about maintaining factors for body dysmorphic disorder symptoms which is beneficial for therapeutic approaches.

Keywords: body dysmorphic disorder, perceived parental attitude, parental autonomy support, psychological control, dispositional optimism

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Authors: Julian Y. Raheema, Michael R. Hess, Raymond C. Provost, Mark Bilinski

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The world is rapidly moving towards advancing and utilizing artificial intelligence and autonomous robotics. The ground-breaking Boston Dynamics quadruped robot, SPOT, was designed for industrial and commercial tasks requiring limited autonomous navigation. Out of the box, SPOT has route memorization and playback – it can repeat a path that it has been manually piloted through, but it cannot autonomously navigate an area that has not been previously explored. The presented SPOT payload package is built on ROS framework to support autonomous navigation and mapping of an unexplored environment. The package is fully integrated with SPOT to take advantage of motor controls and collision avoidance that comes natively with the robot. The payload runs all computations onboard, takes advantage of visual odometry SLAM and uses an Intel RealSense depth camera and Velodyne LiDAR sensor to generate 2D and 3D maps while in autonomous navigation mode. These maps are fused into the navigation stack to generate a costmap to enable the robot to safely navigate the environment without causing damage to the surroundings or the robot. The operator defines the operational zone and start location and then sends the explore command to have SPOT explore, generate 2D and 3D maps of the environment and return to the start location to await the operator's next command. The benefit of the presented package is that it is much lighter weight and less expensive than previous approaches and, importantly, operates in GPS-denied scenarios, which is ideal for indoor mapping. There are numerous applications that are hazardous to humans for SPOT enhanced with the autonomy payload, including disaster response, nuclear inspection, mine inspection, and so on. Other less extreme uses cases include autonomous 3D and 2D scanning of facilities for inspection, engineering and construction purposes.

Keywords: autonomous, SLAM, quadruped, mapping, exploring, ROS, robotics, navigation

Procedia PDF Downloads 90

Authors: Jonathan R. Olsen, Natalie Nicholls, Jenna Panter, Hannah Burnett, Michael Tornow, Richard Mitchell

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The 20-minute neighborhood is a policy priority for governments worldwide and a key feature of this policy is providing access to natural space within 800 meters of home. The study aims were to (1) examine the association between distance to nearest natural space and frequent use over time and (2) examine whether frequent use and changes in use were patterned by income and housing tenure over time. Bi-annual Scottish Household Survey data were obtained for 2013 to 2019 (n:42128 aged 16+). Adults were asked the walking distance to their nearest natural space, the frequency of visits to this space and their housing tenure, as well as age, sex and income. We examined the association between distance from home of nearest natural space, housing tenure, and the likelihood of frequent natural space use (visited once a week or more). Two-way interaction terms were further applied to explore variation in the association between tenure and frequent natural space use over time. We found that 87% of respondents lived within 10 minute walk of a natural space, meeting the policy specification for a 20-minute neighbourhood. Greater proximity to natural space was associated with increased use; individuals living a 6 to 10 minute walk and over 10 minute walk were respectively 53% and 78% less likely to report frequent natural space use than those living within a 5 minute walk. Housing tenure was an important predictor of frequent natural space use; private renters and homeowners were more likely to report frequent natural space use than social renters. Our findings provide evidence that proximity to natural space is a strong predictor of frequent use. Our study provides important evidence that time-based access measures alone do not consider deep-rooted socioeconomic variation in use of Natural space. Policy makers should ensure a nuanced lens is applied to operationalising and monitoring the 20-minute neighbourhood to safeguard against exacerbating existing inequalities.

Keywords: natural space, housing, inequalities, 20-minute neighbourhood, urban design

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Authors: Mark Linden, Rachel Leonard, Trisha Forbes, Michael Brown, Lynne Marsh, Stuart Todd, Nathan Hughes, Maria Truesdale

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Background: Current interventions which aim to improve the mental health of family carers are often face to face, which can create barriers to full participation. Online interventions can offer flexibility in delivery compared to face to face approaches. The primary objective of this study is to determine the feasibility of delivering the Carers-ID online intervention, while the secondary outcome is to improve the mental health of family carers of people with intellectual disabilities. Methods: Family carers (n = 120) will be randomised to receive the intervention (n=60) or assigned to a wait-list control (n=60) group. The intervention (www.Carers-ID.com) consists of fourteen modules which cover topics including promoting resilience, providing peer support, reducing anxiety, managing stress, accessing local supports, managing family conflict and information for siblings who are carers. Primary outcomes for this study include acceptability and feasibility of the outcome measures, recruitment, participation and retention rates and effect sizes. Secondary outcomes will be completed at three time points (baseline, following intervention completion and three months after completion). Secondary outcomes include, depression, anxiety, stress, well-being , resilience and social connectedness. Participants (n=12) who have taken part in the intervention arm of the research will be invited to participate in semi-structured interviews as part of the process evaluation. Discussion: To determine whether a full-scale randomised controlled effectiveness trial is warranted, feasibility testing of the intervention and trial procedures is a necessary first step. The Carers-ID intervention provides an accessible resource for family carers to support their mental health and well-being.

Keywords: intellectual disability, family carer, feasibility trial, online intervention

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Authors: Michael Scott Evans, Andrew Smith

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The feeling of fatigue at work could potentially have devastating consequences. The aim of this study was to investigate whether the well-established objective indicator of fatigue – the Fatigue Risk Index (FRI) calculator used by the rail industry is an effective indicator to the number of safety incidents, in which fatigue could have been a contributing factor. The study received ethics approval from Cardiff University’s Ethics Committee (EC.16.06.14.4547). A total of 901 safety incidents were recorded from a single British rail franchise between 1st June 2010 – 31st December 2016, into the Safety Management Information System (SMIS). The safety incident types identified that fatigue could have been a contributing factor were: Signal Passed at Danger (SPAD), Train Protection & Warning System (TPWS) activation, Automatic Warning System (AWS) slow to cancel, failed to call, and station overrun. From the 901 recorded safety incidents, the scheduling system CrewPlan was used to extract the Fatigue Index (FI) score and Risk Index (RI) score of all train drivers on the day of the safety incident. Only the working rosters of 64.2% (N = 578) (550 men and 28 female) ranging in age from 24 – 65 years old (M = 47.13, SD = 7.30) were accessible for analyses. Analysis from all 578 train drivers who were involved in safety incidents revealed that 99.8% (N = 577) of Fatigue Index (FI) scores fell within or below the identified guideline threshold of 45 as well as 97.9% (N = 566) of Risk Index (RI) scores falling below the 1.6 threshold range. Their scores represent good practice within the rail industry. These findings seem to indicate that the current objective indicator, i.e. the FRI calculator used in this study by the British rail franchise was not an effective predictor of train driver’s FI scores and RI scores, as safety incidents in which fatigue could have been a contributing factor represented only 0.2% of FI scores and 2.1% of RI scores. Further research is needed to determine whether there are other contributing factors that could provide a better indication as to why there is such a significantly large proportion of train drivers who are involved in safety incidents, in which fatigue could have been a contributing factor have such low FI and RI scores.

Keywords: fatigue risk index calculator, objective indicator of fatigue, rail industry, safety incident

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Authors: Maria Ahmad, Alexandra Valetopoulou, Michael D. Christian

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Background: London’s Air Ambulance (LAA) provides advanced pre-hospital trauma care across London, bringing specialist resources and expert trauma teams to patients. Since its inception 32 years ago, LAA has treated over 40,000 pre-hospital patients and significantly contributed to pre-hospital patient care in London. To the authors’ best knowledge, this is the first analysis to quantify the magnitude of the publication impact of LAA on the international field of pre-hospital medicine. Method: We searched the Scopus, Web of Science, Google Scholar and PubMed databases to identify LAA focused articles. These were defined as articles on the topic of pre-hospital medicine which either utilised data from LAA, or focused on LAA patients, or were authored by LAA clinicians. A bibliometric analysis was conducted and the impact of each eligible article was classified as either: high (article directly influenced the change or creation of clinical guidelines); medium (the article was referenced in clinical guidelines or had >20 Google Scholar citations or >10 PubMed citations); or low impact (article had <20 Google Scholar citations or <10 PubMed citations). Results: The literature search yielded 1,120 articles in total. 198 articles met our inclusion criteria, and their full text was analysed to determine the level of impact. 19 articles were classified as high-impact, 76 as medium-impact, and 103 as low-impact. 20 of the 76 medium-impact articles were referenced in clinical guidelines but had not prompted changes to the guidelines. Conclusion: To our knowledge, this review is the first to quantify the significant publication impact of LAA within the field of pre-hospital medicine over the last 32 years. LAA publications have focused on and driven clinical innovations in trauma care, particularly in pre-hospital anaesthesia, haemorrhage control, and major incidents, with many impacting national and international guidelines. We recommend a greater emphasis on multidisciplinary pre-hospital collaboration in publications in future research and quality improvement projects across all pre-hospital services.

Keywords: air ambulance, pre-hospital medicine, London’s Air Ambulance, London HEMS

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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

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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

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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

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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

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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 175

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

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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 137

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 329

Authors: Antonios Paraskevas, Michael Madas

Abstract:

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

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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

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Authors: Faezeh Eslamian, Zhiming Qi, Michael J. Tate

Abstract:

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 175

Authors: Antonios Paraskevas, Michael Madas

Abstract:

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 200

Authors: Julie V. Logan, Preston T. Webster, Kevin B. Woller, Christian P. Morath, Michael P. Short

Abstract:

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 174

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

Abstract:

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 308

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

Abstract:

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 129