Search results for: Michalis Michael
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 666

Search results for: Michalis Michael

276 Playing Safely: An Exploration of Irish Parental Attitudes Towards Risky Play and Its Impact on Play Opportunities for Children

Authors: Fiona Armstrong, David Gaul, Michael Barrett, Lorraine D'Arcy

Abstract:

Playing is an instinctive and universal human behavior, is a child’s way of learning and an outlet for their innate need of activity. Risky play can be defined as any play that is thrilling or exciting involving the risk of injury. The benefits of risky play have been acknowledged as helping children to explore and conquer fears, develop confidence, reduce anxiety, and develop risk-management skills. Studies indicate that children learn sound judgment by assessing and confronting risks in relation to their own capabilities through exposure to carefully managed play experiences. Risky play has been associated with danger and increased risk of injury, with families focusing on risk aversion and protecting children from the risks inherent in the modern world. Despite children needing cultural, social, emotional, physical, and geographical space to play, the opportunity for children to play is diminishing. Aim: This study explores play behaviors and risky play in an Irish context by investigating parental attitudes to risky play. Methodology: This is a mixed methods study involving the State of Play survey and semi-structured interviews exploring parental attitudes to risky play. Data will be quantitatively analyzed using descriptive and inferential statistics using IBM SPSS and qualitatively analyzed via thematic analysis using NVivo. Conclusion: The information gathered could advise stakeholders regarding the creation and provision of developmentally appropriate, challenging, stimulating, adaptable, accessible, and safe as necessary outdoor play areas. This research can inform parents, planners, architects, and authorities involved in creating environments for play and contribute to policy development.

Keywords: child development, parental attitudes, play opportunities, risky play

Procedia PDF Downloads 58
275 Different Motor Inhibition Processes in Action Selection Stage: A Study with Spatial Stroop Paradigm

Authors: German Galvez-Garcia, Javier Albayay, Javiera Peña, Marta Lavin, George A. Michael

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The aim of this research was to investigate whether the selection of the actions needs different inhibition processes during the response selection stage. In Experiment 1, we compared the magnitude of the Spatial Stroop effect, which occurs in response selection stage, in two motor actions (lifting vs reaching) when the participants performed both actions in the same block or in different blocks (mixed block vs. pure blocks).Within pure blocks, we obtained faster latencies when lifting actions were performed, but no differences in the magnitude of the Spatial Stroop effect were observed. Within mixed block, we obtained faster latencies as well as bigger-magnitude for Spatial Stroop effect when reaching actions were performed. We concluded that when no action selection is required (the pure blocks condition), inhibition works as a unitary system, whereas in the mixed block condition, where action selection is required, different inhibitory processes take place within a common processing stage. In Experiment 2, we investigated this common processing stage in depth by limiting participants’ available resources, requiring them to engage in a concurrent auditory task within a mixed block condition. The Spatial Stroop effect interacted with Movement as it did in Experiment 1, but it did not significantly interact with available resources (Auditory task x Spatial Stroop effect x Movement interaction). Thus, we concluded that available resources are distributed equally to both inhibition processes; this reinforces the likelihood of there being a common processing stage in which the different inhibitory processes take place.

Keywords: inhibition process, motor processes, selective inhibition, dual task

Procedia PDF Downloads 392
274 MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligoa

Authors: Anupama Sahoo, Bongyong Lee, Katia Boniface, Julien Seneschal, Sanjaya K. Sahoo, Tatsuya Seki, Chunyan Wang, Soumen Das, Xianlin Han, Michael Steppie, Sudipta Seal, Alain Taieb, Ranjan J. Perera

Abstract:

Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has a complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched miR-211, a known metabolic switch in non-pigmented melanoma cells, was severely downregulated in vitiligo cell line PIG3V and skin biopsies from vitiligo patients, while its novel predicted targets transcriptional co-activator PGC1-α (PPARGC1A), ribonucleotide reductase regulatory subunit M2 (RRM2), and serine-threonine protein kinase TAO1 (TAOK1) were reciprocally upregulated. miR-211 binds to PGC1-α 3’UTR locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated miR-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of miR-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.

Keywords: metabolism, microRNA, mitochondria, vitiligo

Procedia PDF Downloads 367
273 Teaching Practices for Subverting Significant Retentive Learner Errors in Arithmetic

Authors: Michael Lousis

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The systematic identification of the most conspicuous and significant errors made by learners during three-years of testing of their progress in learning Arithmetic throughout the development of the Kassel Project in England and Greece was accomplished. How much retentive these errors were over three-years in the officially provided school instruction of Arithmetic in these countries has also been shown. The learners’ errors in Arithmetic stemmed from a sample, which was comprised of two hundred (200) English students and one hundred and fifty (150) Greek students. The sample was purposefully selected according to the students’ participation in each testing session in the development of the three-year project, in both domains simultaneously in Arithmetic and Algebra. Specific teaching practices have been invented and are presented in this study for subverting these learners’ errors, which were found out to be retentive to the level of the nationally provided mathematical education of each country. The invention and the development of these proposed teaching practices were founded on the rationality of the theoretical accounts concerning the explanation, prediction and control of the errors, on the conceptual metaphor and on an analysis, which tried to identify the required cognitive components and skills of the specific tasks, in terms of Psychology and Cognitive Science as applied to information-processing. The aim of the implementation of these instructional practices is not only the subversion of these errors but the achievement of the mathematical competence, as this was defined to be constituted of three elements: appropriate representations - appropriate meaning - appropriately developed schemata. However, praxis is of paramount importance, because there is no independent of science ‘real-truth’ and because praxis serves as quality control when it takes the form of a cognitive method.

Keywords: arithmetic, cognitive science, cognitive psychology, information-processing paradigm, Kassel project, level of the nationally provided mathematical education, praxis, remedial mathematical teaching practices, retentiveness of errors

Procedia PDF Downloads 316
272 Ensuring Safe Operation by Providing an End-To-End Field Monitoring and Incident Management Approach for Autonomous Vehicle Based on ML/Dl SW Stack

Authors: Lucas Bublitz, Michael Herdrich

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By achieving the first commercialization approval in San Francisco the Autonomous Driving (AD) industry proves the technology maturity of the SAE L4 AD systems and the corresponding software and hardware stack. This milestone reflects the upcoming phase in the industry, where the focus is now about scaling and supervising larger autonomous vehicle (AV) fleets in different operation areas. This requires an operation framework, which organizes and assigns responsibilities to the relevant AV technology and operation stakeholders from the AV system provider, the Remote Intervention Operator, the MaaS provider and regulatory & approval authority. This holistic operation framework consists of technological, processual, and organizational activities to ensure safe operation for fully automated vehicles. Regarding the supervision of large autonomous vehicle fleets, a major focus is on the continuous field monitoring. The field monitoring approach must reflect the safety and security criticality of incidents in the field during driving operation. This includes an automatic containment approach, with the overall goal to avoid safety critical incidents and reduce downtime by a malfunction of the AD software stack. An End-to-end (E2E) field monitoring approach detects critical faults in the field, uses a knowledge-based approach for evaluating the safety criticality and supports the automatic containment of these E/E faults. Applying such an approach will ensure the scalability of AV fleets, which is determined by the handling of incidents in the field and the continuous regulatory compliance of the technology after enhancing the Operational Design Domain (ODD) or the function scope by Functions on Demand (FoD) over the entire digital product lifecycle.

Keywords: field monitoring, incident management, multicompliance management for AI in AD, root cause analysis, database approach

Procedia PDF Downloads 75
271 Insight into the Visual Attentional Correlates Underpinning Autistic-Like Traits in Fragile X and Down Syndrome

Authors: Jennifer M. Glennon, Hana D'Souza, Luke Mason, Annette Karmiloff-Smith, Michael S. C. Thomas

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Genetic syndrome groups that feature high rates of autism comorbidity, like Down syndrome (DS) and fragile X syndrome (FXS), have been presented as useful models for understanding risk and protective factors involved in the emergence of autistic traits. Yet despite reaching clinical thresholds, these ‘syndromic’ forms of autism appear to differ in important ways from the idiopathic or ‘non-syndromic’ autism phenotype. To uncover the true nature of these comorbidities, it is necessary to extend definitions of autism to include the cognitive characteristics of the disorder and to then apply this broadened conceptualisation to the study of syndromic autism profiles. The current study employs a variety of well-established eye-tracking paradigms to assess visual attentional performance in children with DS and FXS who reach thresholds for autism on the Social Communication Questionnaire. It investigates whether autism profiles in these children are accompanied by visual orienting difficulties (‘sticky attention’), decreased social attention, and enhanced visual search performance, all of which are characteristic of the idiopathic autism phenotype. Data is collected from children with DS and FXS aged between 6 and 10 years, in addition to two control groups matched on age and intellectual ability (i.e., children with idiopathic autism and neurotypical controls). Cross-sectional developmental trajectory analyses are conducted to enable visuo-attentional profile comparisons. Significant differences in the visuo-attentional processes underpinning autism presentations in children with FXS and DS are hypothesised, supporting notions of syndrome specificity. The study provides insight into the complex heterogeneity associated with syndromic autism presentations and autism per se, with clinical implications for the utility of autism intervention programmes in DS and FXS populations.

Keywords: autism, down syndrome, fragile X syndrome, eye tracking

Procedia PDF Downloads 239
270 The Impact of Dispatching with Rolling Horizon Control in Sizing Thermal Storage for Solar Tower Plant Participating in Wholesale Spot Electricity Market

Authors: Navid Mohammadzadeh, Huy Truong-Ba, Michael Cholette

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The solar tower (ST) plant is a promising technology to exploit large-scale solar irradiation. With thermal energy storage, ST plant has the potential to shift generation to high electricity price periods. However, the size of storage limits the dispatchability of the plant, particularly when it should compete with uncertainty in forecasts of solar irradiation and electricity prices. The purpose of this study is to explore the size of storage when Rolling Horizon Control (RHC) is employed for dispatch scheduling. To this end, RHC is benchmarked against perfect knowledge (PK) forecast and two day-ahead dispatching policies. With optimisation of dispatch planning using PK policy, the optimal achievable profit for a specific size of the storage is determined. A sensitivity analysis using Monte-Carlo simulation is conducted, and the size of storage for RHC and day-ahead policies is determined with the objective of reaching the profit obtained from the PK policy. A case study is conducted for a hypothetical ST plant with thermal storage located in South Australia and intends to dispatch under two market scenarios: 1) fixed price and 2) wholesale spot price. The impact of each individual source of uncertainty on storage size is examined for January and August. The exploration of results shows that dispatching with RH controller reaches optimal achievable profit with ~15% smaller storage compared to that in day-ahead policies. The results of this study may be applied to the CSP plant design procedure.

Keywords: solar tower plant, spot market, thermal storage system, optimized dispatch planning, sensitivity analysis, Monte Carlo simulation

Procedia PDF Downloads 125
269 Comparison of Various Landfill Ground Improvement Techniques for Redevelopment of Closed Landfills to Cater Transport Infrastructure

Authors: Michael D. Vinod, Hadi Khabbaz

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Construction of infrastructure above or adjacent to landfills is becoming more common to capitalize on the limited space available within urban areas. However, development above landfills is a challenging task due to large voids, the presence of organic matter, heterogeneous nature of waste and ambiguity surrounding landfill settlement prediction. Prior to construction of infrastructure above landfills, ground improvement techniques are being employed to improve the geotechnical properties of landfill material. Although the ground improvement techniques have little impact on long term biodegradation and creep related landfill settlement, they have shown some notable short term success with a variety of techniques, including methods for verifying the level of effectiveness of ground improvement techniques. This paper provides geotechnical and landfill engineers a guideline for selection of landfill ground improvement techniques and their suitability to project-specific sites. Ground improvement methods assessed and compared in this paper include concrete injected columns (CIC), dynamic compaction, rapid impact compaction (RIC), preloading, high energy impact compaction (HEIC), vibro compaction, vibro replacement, chemical stabilization and the inclusion of geosynthetics such as geocells. For each ground improvement technique a summary of the existing theory, benefits, limitations, suitable modern ground improvement monitoring methods, the applicability of ground improvement techniques for landfills and supporting case studies are provided. The authors highlight the importance of implementing cost-effective monitoring techniques to allow observation and necessary remediation of the subsidence effects associated with long term landfill settlement. These ground improvement techniques are primarily for the purpose of construction above closed landfills to cater for transport infrastructure loading.

Keywords: closed landfills, ground improvement, monitoring, settlement, transport infrastructure

Procedia PDF Downloads 224
268 The English as a Foreign Language Teachers’ Perceptions and Practices of Infusing Critical Thinking Skills to Improve Students’ Reading Comprehension

Authors: Michael Amale Kirko, Abebe Gebretsadik

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In the 21st century, developing students’ critical thinking skills has become a prime concern in higher education institutions. Cognizant of this fact, the Ethiopian higher education policy document used critical thinking as one of the guiding principles. The study aims to explore how English as a foreign language (EFL) teachers perceive and practice critical thinking skills (CTS) in teaching reading to improve reading comprehension at Wolaita Sodo University, Ethiopia. A descriptive survey study used an exploratory mixed-methods approach. The study involved 20 EFL instructors and 40 2nd-year English majoring students. The numerical data were collected using teacher and student surveys and classroom observations; the qualitative data were obtained through content analysis and interviews. Teacher survey results indicated that teachers' perceptions are above average (mean = 3.41). And the result of classroom observations showed the practice CTS in class was below average (mean=2.61). The content analysis result revealed instructors utilized fewer higher-order thinking questions during class activities, quizzes, midterm, and final exams. The teachers perceived that teacher, student, and material-related challenges were hindering the practice of CT to improve students’ reading comprehension. Finally, spearman’s rho output showed r=0.97 and p<0.05. Therefore, the results showed that the EFL teachers’ practices of CTS to improve students’ reading comprehension were less frequent; there was a strong, positive, and statistically significant relationship between the teachers’ perceptions and practices of CTS in reading class.

Keywords: perceptions, critical thinking skills, practices, infusing thinking skills, reading comprehension

Procedia PDF Downloads 77
267 Track and Evaluate Cortical Responses Evoked by Electrical Stimulation

Authors: Kyosuke Kamada, Christoph Kapeller, Michael Jordan, Mostafa Mohammadpour, Christy Li, Christoph Guger

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Cortico-cortical evoked potentials (CCEP) refer to responses generated by cortical electrical stimulation at distant brain sites. These responses provide insights into the functional networks associated with language or motor functions, and in the context of epilepsy, they can reveal pathological networks. Locating the origin and spread of seizures within the cortex is crucial for pre-surgical planning. This process can be enhanced by employing cortical stimulation at the seizure onset zone (SOZ), leading to the generation of CCEPs in remote brain regions that may be targeted for disconnection. In the case of a 24-year-old male patient suffering from intractable epilepsy, corpus callosotomy was performed as part of the treatment. DTI-MRI imaging, conducted using a 3T MRI scanner for fiber tracking, along with CCEP, is used as part of an assessment for surgical planning. Stimulation of the SOZ, with alternating monophasic pulses of 300µs duration and 15mA current intensity, resulted in CCEPs on the contralateral frontal cortex, reaching a peak amplitude of 206µV with a latency of 31ms, specifically in the left pars triangularis. The related fiber tracts were identified with a two-tensor unscented Kalman filter (UKF) technique, showing transversal fibers through the corpus callosum. The CCEPs were monitored through the progress of the surgery. Notably, the SOZ-associated CCEPs exhibited a reduction following the resection of the anterior portion of the corpus callosum, reaching the identified connecting fibers. This intervention demonstrated a potential strategy for mitigating the impact of intractable epilepsy through targeted disconnection of identified cortical regions.

Keywords: CCEP, SOZ, Corpus callosotomy, DTI

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266 Examining Neo-colonialism and Power in Global Surgical Missions: An Historical, Practical and Ethical Analysis

Authors: Alex Knighton, Roba Khundkar, Michael Dunn

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Neo-colonialism is defined as the use of economic, political, cultural, or other pressures to control or influence other countries, especially former dependencies, and concerns have been raised about its presence in surgical missions. Surgical missions aim to rectify the huge disparity in surgical access worldwide, but their ethics must be carefully considered. This is especially in light of colonial history which affects international relations and global health today, to ensure that colonial attitudes are not influencing efforts to promote equity. This review examines the history of colonial global health, demonstrating that global health initiatives have consistently been used to benefit those providing them, and then asks whether elements of colonialism are still pervasive in surgical missions today. Data was collected from the literature using specified search terms and snowball searching, as well as from international expert web-based conferences on global surgery ethics. A thematic analysis was then conducted on this data, resulting in the identification of six themes which are identifiable in both past and present global health initiatives. These six themes are power, lack of understanding or respect, feelings of superiority, exploitation, enabling of dependency, and acceptance of poorer standards of care. An ethical analysis follows, concluding that the concerns of power and neo-colonialism in global surgery would be addressed by adopting a framework of procedural justice that promotes a refined governance process in which stakeholders are able to propose and reject decisions that affect them. The paper argues that adopting this model would address concerns of the power disparity in the field directly, as well as promoting an ethical framework to enable the other concerns of power disparity and neo-colonialism identified in the present analysis to be addressed.

Keywords: medical ethics, global surgery, global health, neocolonialism, surgical missions

Procedia PDF Downloads 95
265 Systematic Review and Meta-Analysis of Mid-Term Survival, and Recurrent Mitral Regurgitation for Robotic-Assisted Mitral Valve Repair

Authors: Ramanen Sugunesegran, Michael L. Williams

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Over the past two decades surgical approaches for mitral valve (MV) disease have evolved with the advent of minimally invasive techniques. Robotic mitral valve repair (RMVr) safety and efficacy has been well documented, however, mid- to long-term data are limited. The aim of this review was to provide a comprehensive analysis of the available mid- to long-term term data for RMVr. Electronic searches of five databases were performed to identify all relevant studies reporting minimum 5-year data on RMVr. Pre-defined primary outcomes of interest were overall survival, freedom from MV reoperation and freedom from moderate or worse mitral regurgitation (MR) at 5-years or more post-RMVr. A meta-analysis of proportions or means was performed, utilizing a random effects model, to present the data. Kaplan-Meier curves were aggregated using reconstructed individual patient data. Nine studies totaling 3,300 patients undergoing RMVr were identified. Rates of overall survival at 1-, 5- and 10-years were 99.2%, 97.4% and 92.3%, respectively. Freedom from MV reoperation at 8-years post RMVr was 95.0%. Freedom from moderate or worse MR at 7-years was 86.0%. Rates of early post-operative complications were low with only 0.2% all-cause mortality and 1.0% cerebrovascular accident. Reoperation for bleeding was low at 2.2% and successful RMVr was 99.8%. Mean intensive care unit and hospital stay were 22.4 hours and 5.2 days, respectively. RMVr is a safe procedure with low rates of early mortality and other complications. It can be performed with low complication rates in high volume, experienced centers. Evaluation of available mid-term data post-RMVr suggests favorable rates of overall survival, freedom from MV reoperation and freedom from moderate or worse MR recurrence.

Keywords: mitral valve disease, mitral valve repair, robotic cardiac surgery, robotic mitral valve repair

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264 An Investigation into the Ideological Facets Involved in Western Interpretations of the History of Communism

Authors: Anna Stoutenburg

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With the rise of the so-called 'new left' within the United States, marked by social democratic figures such as Bernie Sanders and Alexandria Ocasio-Cortez, significant questions have been raised in response to those who would identify with the term 'socialist'. These queries typically revolve around the negatively perceived legacy of past and present countries that share the term in question, with the stark conclusion that not only is socialism a structure that does not work economically, but that it also tends to inflict more harm on those living under it that would be endured in a country functioning under capitalism. In order to examine these claims, the goal of this paper is to examine the legacy of anti-communist historiography in a western context, with the Union of Soviet Socialist Republics, China, and modern Venezuela used as case studies for how this phenomenon operates. Not only will key portions of each nation’s history be re-examined, but there will also be a critical analysis of source cultivation and usage among western historians. The intent of this paper is not merely to deride previous attempts at historicizing and reporting on the events of the nations, but rather to attempt to glean a clearer picture that is free from anti-communist sentiments. Theoretical works that will be consulted in order to define this project are 'The Historiography of Communism' by Michael Brown, as well as 'Beyond Philosophy: Ethics, History, Marxism, and Liberation Theology' by Enrique Dussel. The latter will provide insights concerning why these questions are relevant in a larger context, namely by articulating how the means of liberation understood through an analectic method can be achieved structurally. For a majority of leftists, this question is integral, and by using history as a tool, the ways that political organizing can be used can be better understood, bridging the gap between the common assumption that the communist legacy is a dire one and the idea that it is something which needs to be completely lauded.

Keywords: anti-communism, history, ideology, Marxism

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263 An Energy Transfer Fluorescent Probe System for Glucose Sensor at Biomimetic Membrane Surface

Authors: Hoa Thi Hoang, Stephan Sass, Michael U. Kumke

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Concanavalin A (conA) is a protein has been widely used in sensor system based on its specific binding to α-D-Glucose or α-D-Manose. For glucose sensor using conA, either fluoresence based techniques with intensity based or lifetime based are used. In this research, liposomes made from phospholipids were used as a biomimetic membrane system. In a first step, novel building blocks containing perylene labeled glucose units were added to the system and used to decorate the surface of the liposomes. Upon the binding between rhodamine labeled con A to the glucose units at the biomimetic membrane surface, a Förster resonance energy transfer system can be formed which combines unique fluorescence properties of perylene (e.g., high fluorescence quantum yield, no triplet formation) and its high hydrophobicity for efficient anchoring in membranes to form a novel probe for the investigation of sugar-driven binding reactions at biomimetic surfaces. Two glucose-labeled perylene derivatives were synthesized with different spacer length between the perylene and glucose unit in order to probe the binding of conA. The binding interaction was fully characterized by using high-end fluorescence techniques. Steady-state and time-resolved fluorescence techniques (e.g., fluorescence depolarization) in combination with single-molecule fluorescence spectroscopy techniques (fluorescence correlation spectroscopy, FCS) were used to monitor the interaction with conA. Base on the fluorescence depolarization, the rotational correlation times and the alteration in the diffusion coefficient (determined by FCS) the binding of the conA to the liposomes carrying the probe was studied. Moreover, single pair FRET experiments using pulsed interleaved excitation are used to characterize in detail the binding of conA to the liposome on a single molecule level avoiding averaging out effects.

Keywords: concanavalin A, FRET, sensor, biomimetic membrane

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262 Investigating the Relative Priority of the Factors Affecting Customer Satisfaction in Gaining the Competitive Advantage in Pars-Khazar Company

Authors: Samaneh Pouyanfar, Michael Oliff

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The industry of home appliances may beone of theindustries which has the highest competition, and actually what can guarantee the survival of this industry is discovering the superior services. A trend to provide quality products and services plays an important role in this industry because discovering the services is counted as a vital affair for Manufacturing Organizations’ survival and profitability. Given the importance of the topic, this paper attempts to investigate the relative priority of the factors influencing the customer satisfaction in gaining the competitive advantage in Pars-Khazar Company. In sum, 96 executives of Pars-Khazar Company where investigated in a census. For this purpose, after reviewing the research literature and performing deep interviews between pundits and experts active in the industry, the research questionnaire was made based on variables affecting customer satisfaction and components determining business competitive advantage. Determining the content validity took place by judgement of the experts. The reliability of each structure was measured based on Cronbach’s alpha coefficient. Since the value of Cronbach's alpha was higher than 0.7 for each structure, internal consistency of statements was high and the reliability of the questionnaire was acceptable. The data analysis was also done with Kulmgrf-asmyrnf test and Friedman test using SPSS software. The results showed that in dimension of factors affecting customer satisfaction, the History of trade name (brand), Familiarity with the product brand, Brand reputation and Safety have the highest value of priority respectively, and the variable of firm growth has the highest value of priority among the components determining the performance of competitive advantage.

Keywords: customer satisfaction, competitive advantage, brand history, safety, growth

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261 Incorporation of Growth Factors onto Hydrogels via Peptide Mediated Binding for Development of Vascular Networks

Authors: Katie Kilgour, Brendan Turner, Carly Catella, Michael Daniele, Stefano Menegatti

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In vivo, the extracellular matrix (ECM) provides biochemical and mechanical properties that are instructional to resident cells to form complex tissues with characteristics to develop and support vascular networks. In vitro, the development of vascular networks can be guided by biochemical patterning of substrates via spatial distribution and display of peptides and growth factors to prompt cell adhesion, differentiation, and proliferation. We have developed a technique utilizing peptide ligands that specifically bind vascular endothelial growth factor (VEGF), erythropoietin (EPO), or angiopoietin-1 (ANG1) to spatiotemporally distribute growth factors to cells. This allows for the controlled release of each growth factor, ultimately enhancing the formation of a vascular network. Our engineered tissue constructs (ETCs) are fabricated out of gelatin methacryloyl (GelMA), which is an ideal substrate for tailored stiffness and bio-functionality, and covalently patterned with growth factor specific peptides. These peptides mimic growth factor receptors, facilitating the non-covalent binding of the growth factors to the ETC, allowing for facile uptake by the cells. We have demonstrated in the absence of cells the binding affinity of VEGF, EPO, and ANG1 to their respective peptides and the ability for each to be patterned onto a GelMA substrate. The ability to organize growth factors on an ETC provides different functionality to develop organized vascular networks. Our results demonstrated a method to incorporate biochemical cues into ETCs that enable spatial and temporal control of growth factors. Future efforts will investigate the cellular response by evaluating gene expression, quantifying angiogenic activity, and measuring the speed of growth factor consumption.

Keywords: growth factor, hydrogel, peptide, angiogenesis, vascular, patterning

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260 Sustainable Adaptation: Social Equity and Local-Level Climate Adaptation Planning in U.S. Cities

Authors: Duran Fiack, Jeremy Cumberbatch, Michael Sutherland, Nadine Zerphey

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Civic leaders have increasingly relied upon local climate adaptation plans to identify vulnerabilities, prioritize goals, and implement actions in order to prepare cities for the present and projected effects of global climate change. The concept of sustainability is central to these efforts, as climate adaptation discussions are often framed within the context of economic resilience, environmental protection, and the distribution of climate change impacts across various socioeconomic groups. For urban centers, the climate change issue presents unique challenges for each of these dimensions; however, its potential impacts on marginalized populations are extensive. This study draws from the ‘just sustainabilities’ framework to perform a qualitative analysis of climate adaptation plans prepared by 22 of the 100 largest U.S. cities and examine whether, and to what extent, such initiatives prioritize social equity improvements. Past research has found that the integration of sustainability in urban policy and planning often produces outcomes that favor environmental and economic objectives over social equity improvements. We find that social equity is a particularly prominent theme in local-level climate adaptation efforts, relative to environmental quality and economic development. The findings contribute to the literature on climate adaptation and sustainability within the urban context and offer practical insight for local-level stakeholders concerning potential obstacles and opportunities for the integration of social equity initiatives into climate adaptation planning. Given the likelihood that climate changes will continue to impose unique challenges for marginalized communities in urban areas, advancing our understanding of how social equity concerns are integrated into adaptation efforts is likely to become an increasingly critical area of inquiry.

Keywords: climate adaptation plan, climate change, social equity, sustainability

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259 Modern Construction Methods and Technologies and Their Impacts on Construction Projects

Authors: Michael Anthony Doherty

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Modern Methods of Construction (MMC) is a significant topic in the construction industry; while reviewing (MMC) over different fields that are significant in the modern construction world, the following areas were assessed where (MMC) is developing, supply chain management, automation, digital technology, and new construction technologies. Different methods were considered as an approach to research and exploring areas highlighted within the construction industry that are making advancements using Modern Methods of Construction Methods and Technologies (MCMTs). The research was conducted using the following methodologies, literature review of academic sources, primary and secondary data sources, questionaries, and interviews. The paper is composed of two parts, firstly a literature review and secondly a questionnaire used as the basis for interviews were utilised to achieve the following key objectives: to identify (MCMTs) being implemented in the construction industry, research and compile information with regards to these methods, determine their purpose and their application in the industry, establishing what (MCMTs) are being used in the industry while also determining the success of the methods. The research considers the evolution and development of these methods in projects and within the industry itself. Major findings were as follows; automation technologies such as robotics, offsite fabrication utilising automated production lines are increasingly part of project execution, digital technologies such as AR and VR are increasingly utilised in project co-ordination, (MMCTs) are proving to be a solution to the construction industry problems such as a lack of skilled workforce, hazardous work tasks, and situations, new construction technologies are available and finding their place in mainstream construction, (SCM) and (GSCM) are evolving to new levels using new systems and technologies such as block chain technology as well as Company Size and Project size influence the use of (MMCTs) and the adoption of (MMCTS). In summary the paper endeavours to identify and detail how areas of (MMCTs) are developing and are gaining traction within mainstream construction.

Keywords: automation, digital technology, new construction technologies, supply chain management

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258 Breeding Cotton for Annual Growth Habit: Remobilizing End-of-season Perennial Reserves for Increased Yield

Authors: Salman Naveed, Nitant Gandhi, Grant Billings, Zachary Jones, B. Todd Campbell, Michael Jones, Sachin Rustgi

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Cotton (Gossypium spp.) is the primary source of natural fiber in the U.S. and a major crop in the Southeastern U.S. Despite constant efforts to increase the cotton fiber yield, the yield gain has stagnated. Therefore, we undertook a novel approach to improve the cotton fiber yield by altering its growth habit from perennial to annual. In this effort, we identified genotypes with high-expression alleles of five floral induction and meristem identity genes (FT, SOC1, FUL, LFY, and AP1) from an upland cotton mini-core collection and crossed them in various combinations to develop cotton lines with annual growth habit, optimal flowering time and enhanced productivity. To facilitate the characterization of genotypes with the desired combinations of stacked alleles, we identified markers associated with the gene expression traits via genome-wide association analysis using a 63K SNP Array (Hulse-Kemp et al. 2015 G3 5:1187). Over 14,500 SNPs showed polymorphism and were used for association analysis. A total of 396 markers showed association with expression traits. Out of these 396 markers, 159 mapped to genes, 50 to untranslated regions, and 187 to random genomic regions. Biased genomic distribution of associated markers was observed where more trait-associated markers mapped to the cotton D sub-genome. Many quantitative trait loci coincided at specific genomic regions. This observation has implications as these traits could be bred together. The analysis also allowed the identification of candidate regulators of the expression patterns of these floral induction and meristem identity genes whose functions will be validated via virus-induced gene silencing.

Keywords: cotton, GWAS, QTL, expression traits

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257 Combustion Characteristics of Wet Woody Biomass in a Grate Furnace: Including Measurements within the Bed

Authors: Narges Razmjoo, Hamid Sefidari, Michael Strand

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Biomass combustion is a growing technique for heat and power production due to the increasing stringent regulations with CO2 emissions. Grate-fired systems have been regarded as a common and popular combustion technology for burning woody biomass. However, some grate furnaces are not well optimized and may emit significant amount of unwanted compounds such as dust, NOx, CO, and unburned gaseous components. The combustion characteristics inside the fuel bed are of practical interest, as they are directly related to the release of volatiles and affect the stability and the efficiency of the fuel bed combustion. Although numerous studies have been presented on the grate firing of biomass, to the author’s knowledge, none of them have conducted a detailed experimental study within the fuel bed. It is difficult to conduct measurements of temperature and gas species inside the burning bed of the fuel in full-scale boilers. Results from such inside bed measurements can also be applied by the numerical experts for modeling the fuel bed combustion. The current work presents an experimental investigation into the combustion behavior of wet woody biomass (53 %) in a 4 MW reciprocating grate boiler, by focusing on the gas species distribution along the height of the fuel bed. The local concentrations of gases (CO, CO2, CH4, NO, and O2) inside the fuel bed were measured through a glass port situated on the side wall of the furnace. The measurements were carried out at five different heights of the fuel bed, by means of a bent stainless steel probe containing a type-k thermocouple. The sample gas extracted from the fuel bed, through the probe, was filtered and dried and then was analyzed using two infrared spectrometers. Temperatures of about 200-1100 °C were measured close to the grate, indicating that char combustion is occurring at the bottom of the fuel bed and propagates upward. The CO and CO2 concentration varied in the range of 15-35 vol % and 3-16 vol %, respectively, and NO concentration varied between 10-140 ppm. The profile of the gas concentrations distribution along the bed height provided a good overview of the combustion sub-processes in the fuel bed.

Keywords: experimental, fuel bed, grate firing, wood combustion

Procedia PDF Downloads 326
256 Effect of Cooking Time, Seed-To-Water Ratio and Soaking Time on the Proximate Composition and Functional Properties of Tetracarpidium conophorum (Nigerian Walnut) Seeds

Authors: J. O. Idoko, C. N. Michael, T. O. Fasuan

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This study investigated the effects of cooking time, seed-to-water ratio and soaking time on proximate and functional properties of African walnut seed using Box-Behnken design and Response Surface Methodology (BBD-RSM) with a view to increase its utilization in the food industry. African walnut seeds were sorted washed, soaked, cooked, dehulled, sliced, dried and milled. Proximate analysis and functional properties of the samples were evaluated using standard procedures. Data obtained were analyzed using descriptive and inferential statistics. Quadratic models were obtained to predict the proximate and functional qualities as a function of cooking time, seed-to-water ratio and soaking time. The results showed that the crude protein ranged between 11.80% and 23.50%, moisture content ranged between 1.00% and 4.66%, ash content ranged between 3.35% and 5.25%, crude fibre ranged from 0.10% to 7.25% and carbohydrate ranged from 1.22% to 29.35%. The functional properties showed that soluble protein ranged from 16.26% to 42.96%, viscosity ranged from 23.43 mPas to 57 mPas, emulsifying capacity ranged from 17.14% to 39.43% and water absorption capacity ranged from 232% to 297%. An increase in the volume of water used during cooking resulted in loss of water soluble protein through leaching, the length of soaking time and the moisture content of the dried product are inversely related, ash content is inversely related to the cooking time and amount of water used, extraction of fat is enhanced by increase in soaking time while increase in cooking and soaking times result into decrease in fibre content. The results obtained indicated that African walnut could be used in several food formulations as protein supplement and binder.

Keywords: African walnut, functional properties, proximate analysis, response surface methodology

Procedia PDF Downloads 396
255 Identifying Strategies and Techniques for the Egyptian Medium and Large Size Contractors to Respond to Economic Hardship

Authors: Michael Salib, Samer Ezeldin, Ahmed Waly

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There are numerous challenges and problems facing the construction industry in several countries in the Middle East, as a result of numerous economic and political effects. As an example in Egypt, several construction companies have shut down and left the market since 2016. The closure of these companies occurred, as they did not respond with the suitable techniques and strategies that will enable them to survive during this economic turmoil period. A research is conducted in order to identify adequate strategies to be implemented by the Egyptian contractors that could allow them survive and keep competing during such economic hardship period. Two different techniques were used in order to identify these startegies. First, a deep research were conducted on the companies located in countries that suffered similar economic harship to identify the strategies they used in order to survive. Second, interviews were conducted with experts in the construction field in order to list the effective strategies they used that allowed them to survive. Moreover, at the end of each interview, the experts were asked to rate the applicability of the previously identified strategies used in the foreign countries, then the efficiency of each strategy if used in Egypt. A framework model is developed in order to assist the construction companies in choosing the suitable techniques to their company size, through identifying the top ranked strategies and techniques that should be adopted by the company based on the parameters given to the model. In order to verify this framework, the financial statements of two leading companies in the Egyptian construction market were studied. The first Contractor has applied nearly all the top ranked strategies identified in this paper, while the other contractor has applied only few of the identified top ranked strategies. Finally, another expert interviews were conducted in order to validate the framework. These experts were asked to test the model and rate through a questionnaire its applicability and effectiveness.

Keywords: construction management, economic hardship, recession, survive

Procedia PDF Downloads 126
254 Project Progress Prediction in Software Devlopment Integrating Time Prediction Algorithms and Large Language Modeling

Authors: Dong Wu, Michael Grenn

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Managing software projects effectively is crucial for meeting deadlines, ensuring quality, and managing resources well. Traditional methods often struggle with predicting project timelines accurately due to uncertain schedules and complex data. This study addresses these challenges by combining time prediction algorithms with Large Language Models (LLMs). It makes use of real-world software project data to construct and validate a model. The model takes detailed project progress data such as task completion dynamic, team Interaction and development metrics as its input and outputs predictions of project timelines. To evaluate the effectiveness of this model, a comprehensive methodology is employed, involving simulations and practical applications in a variety of real-world software project scenarios. This multifaceted evaluation strategy is designed to validate the model's significant role in enhancing forecast accuracy and elevating overall management efficiency, particularly in complex software project environments. The results indicate that the integration of time prediction algorithms with LLMs has the potential to optimize software project progress management. These quantitative results suggest the effectiveness of the method in practical applications. In conclusion, this study demonstrates that integrating time prediction algorithms with LLMs can significantly improve the predictive accuracy and efficiency of software project management. This offers an advanced project management tool for the industry, with the potential to improve operational efficiency, optimize resource allocation, and ensure timely project completion.

Keywords: software project management, time prediction algorithms, large language models (LLMS), forecast accuracy, project progress prediction

Procedia PDF Downloads 79
253 dynr.mi: An R Program for Multiple Imputation in Dynamic Modeling

Authors: Yanling Li, Linying Ji, Zita Oravecz, Timothy R. Brick, Michael D. Hunter, Sy-Miin Chow

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Assessing several individuals intensively over time yields intensive longitudinal data (ILD). Even though ILD provide rich information, they also bring other data analytic challenges. One of these is the increased occurrence of missingness with increased study length, possibly under non-ignorable missingness scenarios. Multiple imputation (MI) handles missing data by creating several imputed data sets, and pooling the estimation results across imputed data sets to yield final estimates for inferential purposes. In this article, we introduce dynr.mi(), a function in the R package, Dynamic Modeling in R (dynr). The package dynr provides a suite of fast and accessible functions for estimating and visualizing the results from fitting linear and nonlinear dynamic systems models in discrete as well as continuous time. By integrating the estimation functions in dynr and the MI procedures available from the R package, Multivariate Imputation by Chained Equations (MICE), the dynr.mi() routine is designed to handle possibly non-ignorable missingness in the dependent variables and/or covariates in a user-specified dynamic systems model via MI, with convergence diagnostic check. We utilized dynr.mi() to examine, in the context of a vector autoregressive model, the relationships among individuals’ ambulatory physiological measures, and self-report affect valence and arousal. The results from MI were compared to those from listwise deletion of entries with missingness in the covariates. When we determined the number of iterations based on the convergence diagnostics available from dynr.mi(), differences in the statistical significance of the covariate parameters were observed between the listwise deletion and MI approaches. These results underscore the importance of considering diagnostic information in the implementation of MI procedures.

Keywords: dynamic modeling, missing data, mobility, multiple imputation

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252 Formulation and Characterization of NaCS-PDMDAAC Capsules with Immobilized Chlorella vulgaris for Phycoremediation of Palm Oil Mill Effluent

Authors: Quin Emparan, Razif Harun, Dayang R. A. Biak, Rozita Omar, Michael K. Danquah

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Cultivation of immobilized microalgae cells is on the rise for biotechnological applications. In this study, cultivation of Chlorella vulgaris was carried out in the form of suspended free-cell and immobilized cells system. NaCS-PDMDAAC capsules were used to immobilize C. vulgaris. Initially, the synthesized NaCS with C. vulgaris culture were prepared at various concentration of 5- 20% (w/v) using a 6% hardening solution (PDMDAAC) to investigate the capsules' gel stability and suitability for microalgae cells growth. Then, the capsules produced from 15% NaCS with C. vulgaris culture were furthered investigated using 5%, 10%, and 15% (w/v) of PDMDAAC solution. The capsules' gel stability was evaluated through dissolution time and loss of uniform spherical shape of capsules, while suitability for microalgae cells growth was evaluated through the optical density of microalgae. In this study, the 15% NaCS-10% PDMDAAC capsules were found to be the most suitable to sustain the capsules' gel stability and microalgae cells growth in MLA. For that reason, the C. vulgaris immobilized in the 15% NaCS-10% PDMDAAC capsules were further characterized using physicochemical analysis in terms of morphological, carbon (C), hydrogen (H) and nitrogen (N), Fourier transform-infrared (FT-IR), scanning electron microscopy-energy dispersive X-ray (SEM-EDX), zeta potential and Brunauer-Emmet-Teller (BET) analyses. The results revealed that the presence of sulfonates in the synthesized NaCS and NaCS-PDMDAAC capsules without and with C. vulgaris proves that cellulose alcohol group was successfully bonded by sulfo group. Besides that, immobilized microalgae cells have a smaller cell size of 6.29 ± 1.09 µm and zeta potential of -11.93 ± 0.91 mV than suspended free-cells microalgae culture. It can be summarized that immobilization of C. vulgaris in the 15% NaCS-10% PDMDAAC capsules are relevant as a bioremediator for wastewater treatment purposes due to its suitable size of pore and capsules as well as structural and compositional properties.

Keywords: biological capsules, immobilized cultivation, microalgae, physico-chemical analysis

Procedia PDF Downloads 172
251 Cellular Senescence and Neuroinflammation Following Controlled Cortical Impact Traumatic Brain Injury in Juvenile Mice

Authors: Zahra F. Al-Khateeb, Shenel Shekerzade, Hasna Boumenar, Siân M. Henson, Jordi L. Tremoleda, A. T. Michael-Titus

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Traumatic brain injury (TBI) is the leading cause of disability and death in young adults and also increases the risk ofneurodegeneration. The mechanisms linking moderate to severe TBI to neurodegeneration are not known. It has been proposed that cellular senescence inductionpost-injury could amplify neuroinflammation and induce long-term changes. The impact of these processes after injury to an immature brain has not been characterised yet. We carried out a controlled cortical impact injury (CCI) in juvenile 1 month-old male CD1 mice. Animals were anesthetised and received a unilateral CCI injury. The sham group received anaesthesia and had a craniotomy. A naïve group had no intervention. The brain tissue was analysed at 5 days and 35 days post-injury using immunohistochemistry and markers for microglia, astrocytes, and senescence. Compared tonaïve animals, injured mice showed an increased microglial and astrocytic reaction early post-injury, as reflected in Iba1 and GFAP markers, respectively; the GFAP increase persisted in the later phase. The senescence analysis showed a significant increase inγH2AX-53BP1 nuclear foci, 8-oxoguanine, p19ARF, p16INK4a, and p53 expression in naïve vs. sham groups and naïve vs. CCI groups, at 5 dpi. At 35 days, the difference was no longer statistically significant in all markers. The injury induced a decrease p21 expression vs. the naïve group, at 35 dpi. These results indicate the induction of a complex senescence response after immature brain injury. Some changes occur early and may reflect the activation/proliferation of non-neuronal cells post-injury that had been hindered, whereas changes such as p21 downregulation may reflect a delayed response and pro-repair processes.

Keywords: cellular senescence, traumatic brain injury, brain injury, controlled cortical impact

Procedia PDF Downloads 139
250 Investigation of the Material Behaviour of Polymeric Interlayers in Broken Laminated Glass

Authors: Martin Botz, Michael Kraus, Geralt Siebert

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The use of laminated glass gains increasing importance in structural engineering. For safety reasons, at least two glass panes are laminated together with a polymeric interlayer. In case of breakage of one or all of the glass panes, the glass fragments are still connected to the interlayer due to adhesion forces and a certain residual load-bearing capacity is left in the system. Polymer interlayers used in the laminated glass show a viscoelastic material behavior, e.g. stresses and strains in the interlayer are dependent on load duration and temperature. In the intact stage only small strains appear in the interlayer, thus the material can be described in a linear way. In the broken stage, large strains can appear and a non-linear viscoelasticity material theory is necessary. Relaxation tests on two different types of polymeric interlayers are performed at different temperatures and strain amplitudes to determine the border to the non-linear material regime. Based on the small-scale specimen results further tests on broken laminated glass panes are conducted. So-called ‘through-crack-bending’ (TCB) tests are performed, in which the laminated glass has a defined crack pattern. The test set-up is realized in a way that one glass layer is still able to transfer compressive stresses but tensile stresses have to be transferred by the interlayer solely. The TCB-tests are also conducted under different temperatures but constant force (creep test). Aims of these experiments are to elaborate if the results of small-scale tests on the interlayer are transferable to a laminated glass system in the broken stage. In this study, limits of the applicability of linear-viscoelasticity are established in the context of two commercially available polymer-interlayers. Furthermore, it is shown that the results of small-scale tests agree to a certain degree to the results of the TCB large-scale experiments. In a future step, the results can be used to develop material models for the post breakage performance of laminated glass.

Keywords: glass breakage, laminated glass, relaxation test, viscoelasticity

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249 Hydrodynamics of Periphyton Biofilters in Recirculating Aquaculture

Authors: Adam N. Bell, Sarina J. Ergas, Michael Nystrom, Nathan P. Brennan, Kevan L. Main

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Integrated Multi-Trophic Aquaculture systems (IMTA) have the potential to improve the sustainability of seafood production, generate organic fertilizer and feed, remove waste discharges and reduce energy use. IMTA can include periphyton biofilters where algae and microbes grow on surfaces, along with caught detritus and amphipods. Periphyton biofilters provide many advantages: nitrification, denitrification, primary production and ecological diversity. The goal of this study was to determine how biofilter hydraulic residence time (τ) effects periphyton biomass production, dissolved oxygen (DO) and nutrient removal. A pilot scale recirculating aquaculture system (RAS) was designed, constructed and operated at different hydraulic residence times (τ= 1, 2, 4, 6, 8 hours per tank). For each τ, a conservative tracer study was conducted to investigate system hydrodynamics. Data on periphyton weights, pH, nitrogen species, phosphorus, temperature and DO were collected. The tracer study for τ =1 hour revealed that the normalized time < τ, indicating short-circuiting. Periphyton biomass production rate was relatively unaffected by τ (R_e<1 for all τ). Average ammonia nitrogen removal was > 75% for all trials. Nitrate and nitrite did not accumulate in the RAS for τ≥4 hours due to enhanced denitrification in anoxic zones. For τ≥4 hours DO concentration was at a maximum of 4 mg L-1 after 14:00, and decreased to 0 mg L-1 during nighttime. At τ=1 hour, the RAS stayed > 2 mg L-1 and DO was more evenly distributed. For the validation trial, the culture tank was stocked with Centropomus undecimalis (common snook) and the system was operated at τ= 1 hr. Preliminary results showed that a RAS with an integrated periphyton biofilter could support fish health with low nutrient concentrations DO > 6 mg L-1.

Keywords: sustainable aquaculture, resource recovery, nitrogen, microalgae, hydrodynamics, integrated multi-trophic aquaculture

Procedia PDF Downloads 131
248 Breeding for Hygienic Behavior in Honey Bees

Authors: Michael Eickermann, Juergen Junk

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The Western honey (Apis mellifera) is threatened by a number of parasites, especially the devastating Varroa mite (Varroa destructor) is responsible for a high level of mortality over winter, e.g., in Europe and USA. While the use of synthetic pesticides or organic acids has been preferred so far to control this parasite, breeding strategies for less susceptible honey bees are in early stages. Hygienic behavior can be an important tool for controlling Varroa destructor. Worker bees with a high level of this behavior are able to detect infested brood in the cells under the wax lid during pupation and remove them out of the hive. The underlying processes of this behavior are only partly investigated, but it is for sure that hygienic behavior is heritable and therefore, can be integrated into commercial breeding lines. In a first step, breeding lines with a high level of phenotypic hygienic behavior have been identified by using a bioassay for accurate assessment of this trait in a long-term national breeding program in Luxembourg since 2015. Based on the artificial infestation of nucleus colonies with 150 phoretic Varroa destructor mites, the level of phenotypic hygienic behavior was detected by counting the number of mites in all stages, twelve days after infestation. A nucleus with a high level of hygienic behavior was overwintered and used for breeding activities in the following years. Artificial insemination was used to combine different breeding lines. Buckfast lines, as well as Carnica lines, were used. While Carnica lines offered only a low increase of hygienic behavior up to maximum 62.5%, Buckfast lines performed much better with mean levels of more than 87.5%. Some mating ends up with a level of 100%. But even with a level of 82.5% Varroa mites are not able to reproduce in the colony anymore. In a final step, a nucleus with a high level of hygienic behavior were build up to full colonies and located at two places in Luxembourg to build up a drone congregation area. Local beekeepers can bring their nucleus to this location for mating the queens with drones offering a high level of hygienic behavior.

Keywords: agiculture, artificial insemination, honey bee, varroa destructor

Procedia PDF Downloads 136
247 Development of a Humanized Anti-CEA Antibody for the Near Infrared Optical Imaging of Cancer

Authors: Paul J Yazaki, Michael Bouvet, John Shively

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Surgery for solid gastrointestinal (GI) cancers such as pancreatic, colorectal, and gastric adenocarcinoma remains the mainstay of curative therapy. Complete resection of the primary tumor with negative margins (R0 resection), its draining lymph nodes, and distant metastases offers the optimal surgical benefit. Real-time fluorescence guided surgery (FGS) promises to improve GI cancer outcomes and is rapidly advancing with tumor-specific antibody conjugated fluorophores that can be imaged using near infrared (NIR) technology. Carcinoembryonic Antigen (CEA) is a non-internalizing tumor antigen validated as a surface tumor marker expressed in >95% of colorectal, 80% of gastric, and 60% of pancreatic adenocarcinomas. Our humanized anti-CEA hT84.66-M5A (M5A) monoclonal antibody (mAb)was conjugated with the NHS-IRDye800CW fluorophore and shown it can rapidly and effectively NIRoptical imageorthotopically implanted human colon and pancreatic cancer in mouse models. A limitation observed is that these NIR-800 dye conjugated mAbs have a rapid clearance from the blood, leading to a narrow timeframe for FGS and requiring high doses for effective optical imaging. We developed a novel antibody-fluorophore conjugate by incorporating a PEGylated sidearm linker to shield or mask the IR800 dye’s hydrophobicity which effectively extended the agent’s blood circulation half-life leading to increased tumor sensitivity and lowered normal hepatic uptake. We hypothesized that our unique anti-CEA linked to the fluorophore, IR800 by PEGylated sidewinder, M5A-SW-IR800 will become the next generation optical imaging agent, safe, effective, and widely applicable for intraoperative image guided surgery in CEA expressing GI cancers.

Keywords: optical imaging, anti-CEA, cancer, fluorescence-guided surgery

Procedia PDF Downloads 147